A Texas-size defense against Short-lived menstruation changes Phloem flow controls

storms and sea-level rise p. 698 after COVID-19 vaccination p. 704 root outgrowth p. 762

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Zhejiang Lab’s research team members discuss chip design and testing plans.

Intelligent computing connects everything

At Zhejiang Lab, scientists develop new tools and techniques that will expand our computer interaction,” Shi says. “Driven by the intelligent data reactor engine, it
understanding of the universe, improve health care, and open up new avenues schedules different computing tasks with the optimal computing resources, adapts
of research. the best computing methods, and forms the optimal results.”
For FAST and the future FAST array, the Astronomical Big Data Intelligent
The Internet of Everything (IoE) will connect people, processes, and devices. Computing and Service Platform will support, as several examples, discoveries
Scientists at Zhejiang Lab in Hangzhou, China see the IoE as a symbol of the new era of pulsars, fast radio bursts, and extragalactic galaxies. It’s already been used to
of digital civilization, with intelligent computing encompassing computing methods propose a unified mechanism that can explain the evolution of the polarization
and systems complemented by other technical capabilities that will drive the IoE. At frequency of repeated fast radio bursts.
Zhejiang Lab, scientists work on chips, algorithms, software, and novel computing In addition, this facility at Zhejiang Lab will advance other fields. As Shi says, “It
architectures for intelligent computing. will provide new methods, new tools, and new paradigms for scientific discovery,
““We take advantage of intelligent computing and novel research paradigms social governance, and the digital economy, and promote work in health care and
to revolutionarily advance the research in pertinent disciplines and develop new other fields.”
research models,” says Tuo Shi, research specialist at Zhejiang Lab’s Research
Center for Intelligent Computing Hardware. Making a material genome
To drive this research, Zhejiang Lab created its Intelligent Computing Data “Although many people know about the genetic genome and other ’omes, the
Reactor. This facility collects virtually any type of data in real time and analyzes it material genome refers to the acceleration of the discovery and design of novel
with intelligent computing. As Shi explains, the reactor “efficiently uses intelligent- materials using high value datasets and computational technologies,” Shi explains.
computing clusters, intelligent supercomputers, brain-like computers, as well as “Based on reliable experimental results obtained from characterization platforms
intelligent-computing software and hardware.” and their databases involving chemical compositions, crystal structures, and
PHOTOS: LEFT: © ZHENGZAISHURU/SHUTTERSTOCK.COM; RIGHT: PROVIDED BY ZHEJIANG LAB

That collection of intelligent-computing technology can be applied to a wide physical properties, the relation between a material’s structure and device
range of fields including astronomy, genetics, materials and medical treatments. performance can be established via theoretical predictions and simulations, leading
to the discovery of new materials for innovative commercial purposes.”
Fostering FAST advances Zhejiang Lab’s Material Intelligent Computing Platform combines big data,
In Guizhou, a mountainous region in southwest China, scientists built a radio artificial intelligence, and domain knowledge to develop new approaches to creating
telescope known as FAST (Five-hundred-meter Aperture Spherical radio Telescope). intelligent materials. For example, artificial proteins can be developed for advanced
With a diameter of 500 meters, which is more than 1.5 times the height of the Eiffel cancer treatments and other disease treatments.
Tower, FAST is the world’s largest single-dish radio telescope, but that’s just the The future of connecting people and technology will change how we see and
beginning. As Shi notes, “The future ‘FAST array’ will be a large-scale telescope interact with the world. Intelligent computing will create the foundation of
cluster consisting of up to five FASTs.” This array will be used to explore the early those advances.
universe, detect gravitational waves, and more. Sponsored by
To analyze data from projects like FAST, Zhejiang Lab developed its Astronomical
Big Data Intelligent Computing and Service Platform. “The service platform takes
the computing facility and intelligent technology as the base, and then uses
data, algorithms, models, and knowledge to build a public knowledge base, and
six engines, which include operation management, collaborative computing,
knowledge construction, simulation deduction, data processing, and human–

1118Product.indd 679 11/10/22 2:55 PM

 CONTENTS
1 8 N O V E M B E R 2 0 2 2 • VO LU M E 3 7 8 • I S S U E 6 6 2 1

698
Houston’s petrochemical plants are at risk from hurricane-driven flooding.

NEWS 697 Billionaire’s crypto company

collapse strands scientists
As FTX files for bankruptcy, the grantees
709 Potential bias in genetic correlations
Mating patterns across two traits can inflate
estimates of genetic overlap
its foundations supported may not see all By A. D. Grotzinger and M. C. Keller
IN BRIEF of their pledged money By R. F. Service RESEARCH ARTICLE p. 754

690 News at a glance FEATURES

710 Adding functions to pyridines
IN DEPTH 698 Shelter from the storm Chemical reactions break a pyridine ring to
A plan to wall off Houston and nearby allow its modification By J. M. Joo
692 Science community braces for industry from flooding caused by REPORTS pp. 773 & 779
divided government hurricanes will cost tens of billions of
Split control of Congress could produce fiery dollars. Will it be enough?
hearings and limit new funding By J. Mervis By W. Cornwall
712 Using mirrors to control molecular
dynamics
693 Tumors can teem with microbes. An optical cavity mixes molecular vibrations
But what are they doing there?
New study suggests microbiomes can
promote cancer by suppressing immune
INSIGHTS with light and changes chemical reactivity
By L. Chuntonov
REPORT p. 790
response and seeding metastases By G. Sinha
PERSPECTIVES POLICY FORUM
694 Whistleblower finds possible

PHOTO: WITOLD SKRYPCZAK/ALAMY STOCK PHOTO

misconduct in his own papers 704 COVID-19 vaccination and 713 Research under China’s personal
Matthew Schrag confronts a mentor after menstruation information law
their joint work is flagged on the PubPeer COVID-19 vaccination causes small changes The new law may present obstacles to some
website By C. Piller to menstruation that quickly resolve kinds of research By X. Li et al.
By V. Male
696 Booming trade in mammoth ivory may BOOKS ET AL.
be bad news for elephants 706 Defining the onset of the
Paleontologists are urged to take a stand Anthropocene 716 The Gaia letters
against a market that may provide cover for Twelve sites are considered for defining the Contextualized correspondence traces the
continued poaching By M. Price Anthropocene geological epoch emergence of a provocative hypothesis
PODCAST By C. N. Waters and S. D. Turner By P. Falkowski

680 18 NOVEMBER 2022 • VOL 378 ISSUE 6621 science.org SCIENCE

1118 TOC_16198450.indd 680 11/15/22 5:36 PM

 717 Aquatic life and its parallels
Blurring the personal and the scientific, SPECIAL SECTION
an author probes the beauty, terror, and
richness of the natural world By J. Berwald 75 YEARS OF TRANSISTORS
LETTERS
INTRODUCTION ON THE COVER
718 Editorial Retraction 720 From one transistor… A hand holds a portable radio origi-
By H. H. Thorp nally presented at the 21st Radio and
PERSPECTIVES Television Show at the Porte de
718 Brazil’s preventable bridge disasters Versailles Exhibition Center in Paris,
By W. E. Magnusson 722 Moore’s law: The journey ahead
France, on 9 September 1959. The
M. S. Lundstrom and M. A. Alam
invention of transistors 75 years ago
718 Welcoming Taiwan’s diaspora spurred innovations that affected
724 Toward gallium oxide power
scientists communication, computation, control
electronics M. J. Tadjer systems, instrumentation, and other
By J. Huang
REVIEWS technologies. Today, the development of
719 Life in Science: The elephant new transistor tech-
in the inbox 726 Carbon nanotube transistors: nologies continues
By C. T. A. Lewis Making electronics from molecules on many fronts.
A. D. Franklin et al. See the special
section beginning

RESEARCH
733 Toward attoJoule switching energy on page 720. Photo:
in logic transistors S. Datta et al. Keystone-France/
Gamma-Rapho via
SEE ALSO EDITORIAL p. 683 Getty Images
IN BRIEF
741 From Science and other journals
747 Solar cells Organic chemistry
RESEARCH ARTICLES Initializing film homogeneity to retard phase 773 Halogenation of the 3-position
segregation for stable perovskite solar cells of pyridines through Zincke imine
744 Developmental biology Y. Bai et al. intermediates B. T. Boyle et al.
Hippo signaling instructs ectopic but not 779 Radical and ionic meta-C–H
normal organ growth W. Kowalczyk et al. 754 Human genomics functionalization of pyridines, quinolines,
RESEARCH ARTICLE SUMMARY; FOR FULL TEXT: Cross-trait assortative mating is widespread and isoquinolines H. Cao et al.
DOI.ORG/10.1126/SCIENCE.ABG3679
and inflates genetic correlation estimates PERSPECTIVE p. 710
R. Border et al.
745 Human fertility PERSPECTIVE p. 709 785 Quantum physics
The mechanism of acentrosomal spindle Noise-resilient edge modes on a chain
assembly in human oocytes T. Wu et al. 762 Plant science of superconducting qubits
RESEARCH ARTICLE SUMMARY; FOR FULL TEXT: Hydraulic flux–responsive hormone X. Mi et al.
DOI.ORG/10.1126/SCIENCE.ABQ7361
redistribution determines root branching
P. Mehra et al. 790 Chemical physics
746 Cancer Cavity-enabled enhancement of ultrafast
Aberrant hyperexpression of the RNA binding intramolecular vibrational redistribution over
REPORTS
protein FMRP in tumors mediates immune pseudorotation T.-T. Chen et al.
evasion Q. Zeng et al. 768 3D printing PERSPECTIVE p. 712
RESEARCH ARTICLE SUMMARY; FOR FULL TEXT: Mechanical nanolattices printed using
DOI.ORG/10.1126/SCIENCE.ABL7207 nanocluster-based photoresists Q. Li et al.
DEPARTMENTS
683 Editorial
746 Shockley was a racist and eugenicist
By H. H. Thorp
75 YEARS OF TRANSISTORS SECTION p. 720

798 Working Life

Silent no longer By W. P. Suza

Science Staff ............................................. 682

Killer T cells (red) attack susceptible cancer cells (green). Science Careers .........................................796
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682 18 NOVEMBER 2022 • VOL 378 ISSUE 6621 science.org SCIENCE

 EDITORIAL

Shockley was a racist and eugenicist

T
his week’s issue on the 75th anniversary of the overtly in favor of eugenics as was Shockley, but he was a
transistor describes a triumph of both basic and strong advocate for genetic determinism, even claiming
applied science. What started out as studies on at the behest of the cigarette industry that tobacco itself
the fundamental physics of silicon led to the was not harmful because genetics determined whether
device that makes it possible to read this article smokers would ultimately contract lung cancer.
online. The coinventor of the transistor, William Following Shockley’s death in 1989, Nature correctly
Shockley, who along with John Bardeen and Wal- called out his racism in an obituary, but then published
ter Brattain won the 1956 Nobel Prize in Physics, is cor- a letter from Seitz defending Shockley and claiming H. Holden Thorp
rectly recognized as a primary architect of the comput- that the reason Shockley became a eugenicist was be-
Editor-in-Chief,
er age. Gordon Moore (cofounder of Intel Corporation) cause of physical trauma he experienced in a near-fatal
Science journals.
famously said that Shockley put the silicon in “Silicon car accident. When Science wrote about this dustup,
[email protected];
Valley.” Appallingly, Shockley devoted the latter part of it referred to Shockley’s ideas as merely “unpopular”
his life to promoting racist views, arguing that higher and “extremely controversial.” It then ran a letter from @hholdenthorp
IQs among Blacks were correlated with higher extents an even more notorious eugenicist, J. Philippe Rush-
of Caucasian ancestry, and advo- ton, who argued that by merely
cating for voluntary sterilization covering the disagreement at
of Black women. At the time, Nature, Science was deliver-
Science did not condemn Shock-
ley for what he was: a charlatan
“The process ing an “ad hominem attack.” In
addition to an ill-advised deci-
who used his scientific creden-
tials to advance racist ideology.
of science is one of sion to publish Rushton’s letter,
Science posted a response saying,
The failure of Science to con-
demn Shockley began in 1968,
continual revision, “no criticism of Shockley was in-
tended.” Yikes.
when it published a letter la-
menting the fact that he was
but it’s also Looking back, it’s clear that
what was intended as an attempt
prohibited from speaking at the
Polytechnic Institute of Brook-
one that must have to make room for dissent and
discussion only served to abet
lyn. The letter repeated the fa-
miliar trope that Shockley was a conscience.” Shockley and his cohorts in their
effort to build support for eugen-
simply asking questions about ics. Science gave them a platform
the role of race in intelligence. and inadequate scorn. The les-
But Shockley had no scientific basis for doing so, he was son is that we at Science need to make more effort to
not submitting peer-reviewed papers on the topic, and think about everything that we do, not only from the
most importantly, he was using his ideas as the basis standpoint of communicating science to the public, but
for promoting eugenics. Such a debate had no place in also as an organization that above all, supports all of
this journal. humanity. The process of science is one of continual
Shockley was part of a cadre of physicists who ad- revision, but it’s also one that must have a conscience.
vanced ideas outside of their area of expertise to pro- It was only a few months ago, in a commentary on
mote a right-wing agenda. He was a close friend of racism in science by Ebony Omotola McGee, that Shock-
Frederick Seitz—president of both the National Acad- ley was described in our pages in the terms he deserved.
emy of Sciences and Rockefeller University—who, But as recently as 2001, Science described him simply as
following a career in physics, became a purveyor of mis- a “transistor inventor and race theorist.” That won’t cut
information on tobacco, nuclear weapons, and climate it anymore. As of today, a link to this editorial will ap-
change. Like Shockley, Seitz carried out his nonphysics pear along with any mention of Shockley in this journal.
work through op-eds and conservative think tanks, not Make no mistake. Shockley was a racist. Shockley was
through the accepted mechanism of peer review that he a eugenicist. That’s all.
used in doing physics. Seitz was not, at least publicly, as –H. Holden Thorp
PHOTO: CAMERON DAVIDSON

10.1126/science.adf8117

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 Advertorial

The multi(dimension)verse of computing

Communications technology is changing the way we live at an ever-faster pace. announced its “Q-LEAP” initiative, committing hundreds of millions more into
Massive amounts of data can be transferred around the world in a flash, and research on hardware and software related to quantum computing. All this is in
mathematical problems that have eluded the best minds can now be solved in anticipation of a market size that is estimated to increase almost 10-fold in the
mere months by supercomputing. The arrival of quantum computing, however, next 5 years.
will make these technologies archaic. If its expected potential is realized, then The impressive contributions by Japanese government and industry
quantum computing will be as superior to supercomputing as the works of are matched by the discoveries made through Japan’s academia–industry
Shakespeare compared to the output of a monkey at a typewriter. collaborations. Building on its recognized strengths in semiconductors
Supercomputing remains the pinnacle of digital computing; it works by taking and high-performance computing, Japan has achieved a number of firsts in
classical bits of information and, with enough energy, making an extraordinary quantum computing. Quantum key distribution and quantum annealing are
number of calculations to find a solution to complex problems. However, just two of the areas it excels in as it advances into the commercial market,
whereas a classical bit only takes one of two states (either a 0 or a 1), a qubit, pushed by companies such as Fujitsu, Toshiba, and NEC, among many others.
the information basis of quantum computing, can represent a superposition Commercialization is also being facilitated by organizations like the Quantum ICT
of the two states. This distinction allows quantum computers to analyze Forum, which is bringing the best minds in the field to translate technologies and
multidimensional spaces to recognize patterns that simply cannot be observed guide policy.
by classical computers. Not only does this new perspective reduce the time Quantum computers will not be in commission for another decade or two
needed to calculate a solution, but it also expands by leaps and bounds the types because of the many functional challenges that remain, such as the short
of problems that can be solved. coherence time of qubits and the large error rates in quantum operations.
The applications are endless and will impact every area of our lives. These Ironically, these problems will be solved iteratively, much in the way digital
computers will be better at designing drugs, planning global supply chains, computing works. In the meantime, Japan is already producing quantum-

PHOTO: © DMITRIY RYBIN/SHUTTERSTOCK.COM

reducing financial risk, and predicting the weather. They could even reveal the inspired digital technologies that solve many of the combinatorial optimization
elusive secrets of the universe. problems eluding even the best supercomputers. Although not as fast as true
Quantum computing may not get the same attention as the space race did quantum computers, these quantum-based devices can reduce problem-
many decades ago, but countries of all sizes recognize the implications of this solving time from months to hours and from days to seconds. Moreover, they are
technology and are competing to take the lead. Included in this list is Japan, available right now.
which aims to announce four new quantum computing research centers by the For decades, Japan has been a herald of the future. From its bullet trains
end of the fiscal year. Japanese government funding agencies have invested to its robot-staffed hotels, the country has played a major role in advancing
more than USD $250 million in this field in the past 15 years, and Japanese technological progress on the world stage. Now its next performance is about to
industry is matching these amounts. Moreover, in 2018, the government debut, with a new star—quantum computing.

1118Product.indd 684 11/10/22 8:21 AM

 Produced by the Science

  

Director of the Quantum ICT Forum Akihisa Tomita is helping to usher in quantum technology.

Gathering the best minds in quantum technology

The strength of Japan’s research in quantum information and communication Bringing more people to quantum ICT
technology (ICT) can be seen all across the country. In terms of R&D, Japan’s Officially, the Quantum ICT Forum was founded in 2019, but its history can be
universities are at the top of the field and its companies are at the forefront of traced to 2001, when Japanese researchers were rapidly making several major
developing key technologies such as superconducting qubits, quantum annealing, discoveries in the field. Since then, the Forum has undergone a number of
and optical lattice clocks. However, so long as this progress remains scattered, changes to reflect how quantum ICT has progressed, and it now comprises more
its benefits to society will be limited. It was in response to this problem that the than 100 members, including both individuals and companies, who lead the
Quantum ICT Forum was founded, to quicken Japan’s adoption of quantum ICT. quantum-related R&D. The Forum hopes to increase its membership, and many
History has shown that societies have gone through four great transformations, of its activities—from its regular public seminars to interviews with leaders in the
beginning with the hunter-gatherer society and moving through the agricultural, field—are dedicated to doing so.
industrial, and most recently, information societies. Japan is now preparing for The Forum is an ideal organization for people with creative ideas seeking
Society 5.0, which aims to connect cyberspace with physical space. This will networking opportunities in Japan, looking for research partners, and pursuing
only happen through a new generation of ICT, one that will depend heavily on funding for their ventures. It also provides an opportunity to have real influence
quantum-based technologies. on the direction of quantum ICT. For example, the Forum’s input is requested at
“Our goal is to bring researchers and industry together so that we can use the task force meeting on the Cross-Ministerial Strategic Innovation Promotion
quantum technologies for a healthier, more productive society,” says Akihisa Program, a Japanese government initiative that has identified key technology
Tomita, director of the Quantum ICT Forum. fields—such as quantum ICT—that have a strong potential to grow the economy.
However, unlike academic societies, the Forum does more than invite Tomita stresses that although the Forum is focused currently on Japan, it
researchers to present their studies. It is designed to promote commercialization also provides a place for international partners to understand the talent and
so that Japan stays at the forefront of ICT. dedication that Japan has to offer to quantum ICT.
In particular, the Forum has identified three sectors—high-speed “It is important for Japan not only to have a strong environment for quantum
computers, highly sensitive and accurate sensors, and faster and more secure ICT; we also want the world to know how much investment the country is making
communications—as having the biggest impact on ICT in the near future. Thus, it in this field and how dedicated we are to it,” he says.
has formed three committees: one on quantum computing, another on quantum
Sponsored by
sensing, and the last on quantum key distribution.
These committees serve many purposes that benefit academic, industrial,
PHOTO: PROVIDED BY QUANTUM ICT FORUM

and public interests. First and foremost, they promote collaborative research.
Second, they bring consensus to standards and provide guidance on government
policy. Finally, they promote public awareness through information dissemination,
whether in the form of exhibitions, seminars, newsletters, or other mediums.
“Each committee is looking at best practices to keep Japan at the leading
edge of quantum ICT. The most important efforts involve translating research
into valuable customer products and assisting with policy making so that society
benefits,” says Tomita.

1118Product.indd 685 11/10/22 8:21 AM

 Advertorial

Scientific discoveries for technological advances

Throughout its history, Toshiba technology has been found everywhere, of parallel processing distinguishes simulated bifurcation machines from other
ranging from everyday items in the home to social infrastructure to protect simulated annealers used to solve optimization problems.
entire nations. This diversity reflects not only the high quality of its products, “In simulated annealers, we have to update variables one by one. But with
but also the commitment and excellence of its research, which pushes for this algorithm we can update the variables in parallel, which is a tremendous
discovery in both applied technology and pure science. Now, Toshiba’s scientific advantage,” he added. Indeed, his algorithm has set world records for
breakthroughs are impacting computer science, setting the stage for faster, computation times, and problems that would take more than a year to solve
more accurate computational solutions to businesses’ most difficult problems. using standard central processing unit (CPU)-based simulated annealers can be
completed in less than an hour if using the simulated bifurcation algorithm.7
Protecting data Thus, industries anticipating the benefits of quantum computing—including
Toshiba is a global company driving innovation in its many research centers finance, logistics, and pharmaceuticals—no longer need to wait when working
across the world, including its Cambridge Research Laboratory in the United with Toshiba.
Kingdom, founded more than 30 years ago. It was there that Toshiba made its QKD and the simulated bifurcation algorithm are just two examples of
first significant innovation in quantum cryptography.1 With quantum computing Toshiba’s efforts in quantum computing and another reminder of how its
becoming a reality and the protection of data becoming more urgent, Toshiba research breaks new ground in science and technology. The drive for this
is leveraging its initial investment in the field to generate estimated revenue progress, however, comes because Toshiba is committed to people and to the
exceeding USD 3 billion by 2030. future.
“Data vulnerability is a major concern in many sectors. Our quantum key
distribution [QKD] platform is being used by governments, health care centers, References
and financial companies to protect data,” says Yoshimichi Tanizawa, chief 1. Z. Yuan et al., Science 295, 102–105, https://www.science.org/doi/full/10.1126/
science.1066790.
research scientist at Toshiba.
2. https://www.global.toshiba/ww/technology/corporate/rdc/rd/topics/21/2108-02.html
Using its QKD, Toshiba has repeatedly set world records for the fastest 3. https://news.toshiba.com/press-releases/press-release-details/2022/JPMorgan-Chase-
data transmission time over long distances, drawing attention from many Toshiba-and-Ciena-Build-the-First-Quantum-Key-Distribution-Network-Used-to-Secure-
organizations for data encryption. Mission-Critical-Blockchain-Application/default.aspx
4. https://www.global.toshiba/ww/news/corporate/2022/04/news-20220427-01.html
In Japan, Toshiba, Tohoku University, and NICT demonstrated a secure genome
5. https://www.global.toshiba/ww/company/digitalsolution/news/2022/0328.html
analysis data backup to multiple sites with Toshiba’s QKD system. 2 In the United 6. H. Goto, K. Tatsumura, A. R. Dixon, Sci. Adv. 5, eaav2372 (2019), https://doi.org/10.1126/
States, JPMorgan Chase, Toshiba and Ciena demonstrated QKD system securing sciadv.aav2372
a peer-to-peer blockchain network.3 In London, BT and Toshiba, along with EY, 7. H. Goto et al., Sci. Adv. 7, eabe7953 (2021), https://doi.org/10.1126/sciadv.abe7953
launched the trial of world first commercial quantum-secured metro network,
Sponsored by
helping secure information transmission across the city’s data networks.4 And
in South Korea, Toshiba group and KT is developing a long
distance hybrid QKD network, enabling the safe transfer of data
between the country’s biggest cities, Seoul and Busan.5
Sponsored by
Changing science and technology
While Toshiba research is designed to push new frontiers in
technologies, it is also changing our understanding of the
science behind these technologies. Such is the case with its
simulated bifurcation machine. In their efforts to develop a
quantum annealer, which is considered the gold standard
for solving combinatorics optimization problems, Toshiba
scientists discovered that the principle of quantum annealing
called “adiabatic evolution” could be applied to classical
nonlinear Hamiltonian systems. The result was the simulated
bifurcation algorithm,6 which incorporates bifurcation
phenomena, adiabatic evolution, and chaos theory, allowing
PHOTO: PROVIDED BY TOSHIBA

digital computers to quickly solve the same complex problems

thought exclusive to the domain of quantum computing.
“This is a new idea in computer science. This algorithm can
be used by classical computers to achieve high performance
from parallel processing,” said Toshiba chief research scientist
Hayato Goto, who discovered the algorithm. The incorporation
Simulated bifurcation machine

1118Product.indd 686 11/10/22 8:21 AM

 Produced by the Science

  

A company of firsts in quantum technology

Throughout its history, NEC—originally founded as the Nippon Electric The next critical step for quantum technology is quantum computing. In
Company more than 100 years ago—has proudly accomplished a number 1999, NEC succeeded in demonstrating the basic operation of the world’s first
of firsts in science and engineering. While its initial innovations were in superconducting-based quantum bits suitable for integration, and has continued
telecommunication technologies, its R&D has positioned the company as a to research and develop quantum computers for more than 20 years. 2 Currently,
global leader in communications, with developments in semiconductors, mobile we are developing a quantum annealing machine dedicated to combinatorial
communications, and now the next great frontier—quantum technology. optimization problems using Josephson parametric oscillators, as well as a
Despite being a multinational company with more than 100,000 employees, fault-tolerant quantum computer that no one has been able to produce yet. Since
NEC conducts research with an academic approach in which curiosity and 2019, we have advanced quantum technology by starting to verify the application
exploration are paramount. It is this attitude that has led NEC to numerous of solving customers’ combinatorial optimization problems with simulated
quantum-computing firsts—most notably, in 1999, being the first in the world to annealing using vector machines, which are supercomputers that NEC has
report a solid-state qubit. accumulated over many years.

The evolution of quantum technology at NEC Great gains through great ambition
Progress in quantum technology is happening in stages. The first is quantum NEC’s work demonstrates the incremental process required to achieve true
key distribution (QKD), which will revolutionize cryptography, securing data quantum technology. Its competence is on par with those who are developing
that implements this technology while enabling safety guaranteed by quantum the “quantum internet.” However, as with many of the grander problems in
mechanics and information theory. science today, no one organization can solve them all. While NEC is at the
NEC’s quantum cryptography efforts have been dedicated on the forefront of the evolution of quantum technology, the company is therefore
commercialization and social implementation of the BB84 system, which partnering with many university laboratories and companies, building a wide
excels in medium-to-long-distance communication, and currently center on network of quantum technology experts who are dedicated to realizing this great
researching the continuous variable QKD (CV-QKD) system for widespread use, leap in quantum ability.
with the aim of further expanding its applications. NEC has been conducting This strategy, Nakamura explains, is in place because NEC’s ultimate goal
demonstration experiments in various fields, such as health care and finance, goes beyond individual applications such as QKD or quantum computing. “Few
with a secure encryption method that will not be deciphered even when companies have the diversity in quantum technology that we have. And few
quantum computers eventually appear. Many enterprises with a long-term companies have the partners we have,” he says. “Ultimately, our technology
perspective on their business have been interested in NEC’s quantum aims to solve today’s most difficult challenges and meet society’s most pressing
cryptography technology as a powerful measure to protect their critical needs. Quantum technology definitely has such potential.”
information in the future.
“As a company with strong research and development, we are committed to References
innovation and translating that innovation into customer solutions,” says Yuichi 1. K. Matsumoto et al., Phys Rev. A 105, 023110 (2022).
Nakamura, an NEC executive professional and former vice president. 2. Y. Nakamura, Y. A. Pashkin, J. S. Tsai, Nature 398, 786–788, https://www.nature.com/
Another essential step toward quantum technology is to control quantum articles/19718.
states with accurate clock timing despite environmental disturbances. This PHOTO: PROVIDED BY POSTECH
PHOTO: PROVIDED BY NEC

requires quantum clocks that operate accurately against external turbulence.

Researching the construction of these clocks, NEC has reported specific Sponsored by
coherent-population-trapping resonances.1 Advances in this technology will
have profound effects on the robustness of our communications systems by
protecting them against natural disasters and malicious attacks.

1118Product.indd 687 11/10/22 8:21 AM

 Advertorial

The complete array of advanced computing

Since its founding, the Tokyo-based information company Fujitsu has been using Operational at room temperature and using traditional racks, Fujitsu’s Digital
communications technologies to build a more sustainable world. Critical to this Annealer is already being employed in multiple industries, bringing radical
aim is staying at the forefront of computing. In the past 20 years, this has meant solutions and great savings. Successful use cases include new drug design that
putting intensive efforts into high-performance computing (HPC) and quantum reduces the delivery of candidate molecules from several months to several
computing in order to offer the most comprehensive toolkit available for problems weeks, warehouse management that reduces the distances travelled for parts by
demanding computational solutions. 45%, and traffic optimization that reduces car congestion by 40%.
Its versatility has also been demonstrated
Collaboration is key in response to COVID-19. A critical problem in
Fujitsu recognizes that progress comes faster by managing the pandemic has been the effective
working with partners who hold complementary distribution of personal protective equipment,
strengths. Its supercomputer Fugaku—which it such as masks and N95 respirators, which
completed last year in collaboration with RIKEN, were suddenly in major demand throughout
Japan’s largest research institute—held the top the world when the pandemic started, leading
spot in HPC rankings for four consecutive terms. to huge supply shortfalls. It was validated
Several groups in Japan are using Fujitsu’s by a CRADA report that the Digital Annealer
supercomputing technologies to interpret optimized resource allocation and minimized
tsunami data for evacuation responses and the time data traveled to emerging hotspots
protein bindings for drug design. in the United States in mere seconds, as
In the promising field of quantum computing, compared to the days or weeks required by
Fujitsu has teamed with RIKEN to establish traditional computing algorithms. It was also
the RIKEN RQC-Fujitsu Collaboration Center, used to maximize the number of people who
which aims to develop quantum computers could attend professional football matches
using superconducting qubits to solve even in Germany while respecting social distance
more difficult societal problems. Parallel to policies, allowing communities to return to
Superconducting 64-qubit chip IMAGE: © RIKEN CENTER FOR QUANTUM COMPUTING
this, a collaboration with Delft University of normal life faster.
Technology in the Netherlands is looking at the advantages of diamond-spin
qubits.1 Where superconducting qubits have excellent scalability so far, diamond- The future of computing
spin qubits can hold quantum information relatively long. A major concern in Quantum computing will have profound effects that resonate throughout society.
quantum computing is the sensitivity of qubits to environmental interference, However, as powerful as this technology may one day become, it will not solve all
including noise. Fujitsu’s collaboration with Delft University also recently revealed the problems by itself. In other words, quantum computing will not replace HPC,
a solution to this problem by demonstrating a fault-tolerant qubit operation using but as a very important new tool, work with other computing technologies to solve
a quantum processor based on spin qubits in diamond. 2 difficult societal problems in the future.
While its projects with RIKEN and Delft are focused on hardware, Fujitsu is “Quantum computing is just one type of computing at which we excel. Our
teaming with Osaka University in Japan to develop software for fault-tolerant research is motivated by society’s needs. In the future, our offerings will include
quantum computing in combination with Fujitsu hardware for higher-level supercomputing, quantum-inspired computing, and quantum computing,”
quantum computers. The collaboration will take the form of a new research says Sato.
division on the university campus.
While working on superconducting and diamond-spin quantum computers, References
Fujitsu also developed the world’s fastest 36-qubit quantum computer simulator 1. R. Ishihara et al, 2021 IEEE International Electron Devices Meeting (IEDM),
using its supercomputing technologies. https://ieeexplore.ieee.org/document/9720552
“In quantum computing, there is no best technology. Fujitsu believes it must 2. M. H. Abobeih et al., Nature 606, 884–889 (2022), https://www.nature.com/articles/19718.
explore multiple channels to reach the fullest potential,” says Shintaro Sato, head
of the Quantum Laboratory at Fujitsu. Sponsored by

Quantum-inspired computers
Fujitsu surveys have found that a large majority of businesses are eager to
benefit from quantum computing. However, many experts predict that the first
commercially practical quantum computers are still years away. As an alternative,
researchers are developing quantum-inspired computing technologies. The best
example at Fujitsu is its Digital Annealer.

1118Product.indd 688 11/10/22 8:21 AM

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 NEWS
IN BRIEF
Edited by
Jeffrey Brainard

CLIMATE POLICY

Carbon emissions increase—as do ways to track them

C
arbon dioxide emissions from burning fossil track, verify, and regulate greenhouse gases. One tool,
fuels are on track to rise 1% this year from the developed by the Climate TRACE coalition, uses satel-
2021 level, making it harder for many nations lite imagery and machine-learning algorithms to detect
to reach their goal of achieving net-zero emis- and measure emissions from 72,000 sources, including
sions by 2050, scientists from the Global Carbon power plants. Separately, the United Nations unveiled
Project said last week. They cited an easing of the Methane Alert and Response System, which will use
pandemic precautions, including increased air data from new satellites capable of spotting large leaks
travel, as one reason for the rise. Most researchers say of methane, a powerful greenhouse gas. The announce-
the world is unlikely to meet the net-zero ments came as politicians at the U.N. climate
Transmission lines carry
goals and limit global warming to 1.5°C by electricity from
conference in Egypt debated whether and
2050. But two new tools announced last week a coal-fired power plant how wealthy countries should pay for climate-
will aid efforts by improving the ability to in Weisweiler, Germany. related damages to low-income nations.

PHOTO: INA FASSBENDER/AFP/GETTY IMAGES

database on U.S. water management and on administrative leave starting in 2018. Her
Wrongful dismissal case is settled providing information to a Chinese govern- case mobilized the Chinese American com-
RESEARCH SECURITY | The U.S. govern- ment official while working at the National munity, which saw it as racial profiling years
ment has agreed to pay hydrologist Xiafen Weather Service. Chen denied acting before former President Donald Trump’s
“Sherry” Chen $1.8 million to settle a wrong- improperly, and the government dropped administration’s China Initiative against
ful dismissal lawsuit that stemmed from a the charges in 2015. The Department of Chinese espionage drew similar criti-
failed federal prosecution alleging threats to Commerce, which includes the weather cism. In the 10 November settlement, the
national security. In 2014, the government service, fired her in 2016, but after a review Department of Commerce does not admit
accused her of tapping into a restricted board ruled the termination illegal, put her any wrongdoing but agrees to meet with

690 18 NOVEMBER 2022 • VOL 378 ISSUE 6621 science.org SCIENCE

1118NewsInBrief_16210255.indd 690 11/15/22 5:23 PM

 Chen to discuss how she was treated and DEMOGRAPHY
to issue a letter praising her work. Chen
agreed to retire by the end of this year. Her World population hits 8 billion as growth slows
legal team called the settlement “a great

E
arth’s population has reached a milestone by surpassing 8 billion people, the United
blow … against bigotry and for the rights Nations said this week. But the rate of increase is falling, and global population may
of Asian Americans.” begin to decline late in the century after topping out at about 10.4 billion, according to
the U.N. Population Division. Its World Population Prospects 2022 report notes that two-
thirds of the global population already lives in a country or area where lifetime fertility
China trims some COVID-19 rules is below 2.1 births per woman, roughly the level required for zero growth for a population
| China last week
P U B L I C H E A LT H with low mortality. More than half of the projected increase in global population between
announced 20 revisions of pandemic control now and 2050 will be concentrated in just eight countries: the Democratic Republic of the
and prevention measures that somewhat Congo, Egypt, Ethiopia, India, Nigeria, Pakistan, the Philippines, and Tanzania.
ease the burden on its weary, frustrated pop-
ulation. Changes include cutting required 2.5 %
stays in designated quarantine facilities from
Predicted 95% prediction range
7 days to 5 days for international travelers

Annual rate of population change

2
and close contacts of infected people, end-
ing tracing of contacts of patients’ contacts,
and restricting mass testing to situations 1.5
where the source of infection is unclear.
Local governments retain responsibility for 1
setting the timing, location, and duration of
lockdowns, which have disrupted industry
0.5
and sparked increasingly angry protests;
on 14 November, residents of Guangzhou
defied a lockdown by crashing barriers and 0
marching through the streets. The policy
changes come as COVID-19 is surging again –0.5
in China: The National Health Commission 1950 1975 2000 2025 2050 2075 2100
reported 17,909 new cases on 14 November,
the most since the spring. Most of the new 2.5 billion 4 billion 6 billion 8 billion 10 billion 10.4 billion
cases were asymptomatic.

each $150,000 to further develop the protec- adhesive to make a tight fit on differently
Roche Alzheimer’s drug flops tive wear. The Mask Innovation Challenge, shaped faces. Both masks are already on the
| An antibody that
C L I N I CA L R E S E A R C H bankrolled by the Biomedical Advanced market. Despite the wins, BARDA says it has
pharmaceutical giant Roche designed to Research and Development Authority no plans to purchase either to stockpile for
treat Alzheimer’s disease by targeting beta (BARDA), tested the masks for ability to health emergencies.
amyloid, a protein that builds up in patients’ filter out airborne particles as small as
brains, has failed in two large, phase 3 viruses and for breathability, comfort, and
clinical trials. Compared with a placebo, looks. The contest began in March 2021 and Big satellite vexes astronomers
injections of gantenerumab slowed cogni- attracted 1448 entrants. One first-place win- | Scientists are alarmed that
S PAC E P O L I C Y
tive decline on standard tests by just 6% or ner, called Airgami and made by Air99, uses the glow from the largest commercial com-
8% in trials enrolling nearly 2000 people an origami shape that provides a big breath- munications satellite could interfere with
CREDITS: (GRAPHIC) C. BICKEL/SCIENCE; (DATA) UNITED NATIONS, DEPARTMENT OF ECONOMIC

with mild dementia due to Alzheimer’s, ing space, making it comfortable to wear ground-based observations. The satellite,
Roche announced on 13 November. That for long periods. The other, ReadiMask, by BlueWalker 3, unfurled its 64-square-
AND SOCIAL AFFAIRS, POPULATION DIVISION, WORLD POPULATION PROSPECTS 2022

reduction was not statistically significant. Global Safety First, has no straps and uses meter antenna this week, which made it
The drug removed less beta amyloid than among the brightest satellites in the sky.
expected, which some scientists suggest BlueWalker 3 is a prototype for the world’s
explains its failure. The setback follows THEY SAID IT first space-based broadband network,
positive results earlier this year for an anti- planned by the company AST SpaceMobile,
It just tells us how terrible
“
amyloid antibody called lecanemab, made which would deploy a constellation of 168
by Biogen and Eisai. More detailed results even larger satellites. Astronomers worry
on several antibody drugs are expected at our culture is becoming, it could blot out objects such as explod-
the Clinical Trials on Alzheimer’s Disease that we can’t have an honest ing stars or Earth-bound asteroids. Radio
meeting later this month. astronomers are also troubled because the
scientific debate.
Improved masks win U.S. contest
| Two small companies that
PA N D E M I C S
Georges Benjamin, executive director of
the American Public Health Association, in MedPage
Today, on the decision by public health specialist
” satellites will operate at radio frequencies
that could infringe on parts of the spectrum
traditionally reserved for the ground-based
observatories. Astronomers were already
make innovative face masks designed to and commentator Leana Wen not to speak anxious that communications satellites
thwart the spread of pathogens tied for at its annual meeting about harassment of public launched by the corporation SpaceX, which
first place this week in a U.S. government– health officials, after she received criticism plans a network of thousands, are obstruct-
sponsored competition that awarded them and threats over her views about COVID-19. ing observations.

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 IN DEP TH

U.S. ELECTIONS

Science community braces for divided government

Split control of Congress could produce fiery hearings and limit new funding

By Jeffrey Mervis with China’s push to become a technological see NIH’s budget keep pace with inflation—
superpower, how the National Institutes of or exceed it. Several higher education lob-

T
he U.S. Congress returned this week Health (NIH) responded to the COVID-19 byists think the Democrats’ stronger-than-
after tumultuous midterm elections pandemic, and whether a laboratory leak in expected showing at the polls will result
that left the Republicans likely to China led to the catastrophe. They will also in 2023 budgets for research agencies
retake control of the House of Repre- likely challenge the Biden administration’s that are close to the generous requests the
sentatives and the Democrats beating efforts to curb climate change by moving White House submitted to Congress earlier
expectations by retaining the Senate. away from fossil fuels. Although such hear- this year.
A divided Congress could mean a bumpy ings will allow Republicans to showcase Some research advocates fear those
ride for the U.S. research community over political arguments that resonate with their numbers could represent a high-water
the next 2 years. In the short run, however, supporters, they are unlikely to lead to sub- mark, however. Under one scenario, if the
science advocates hope the looming pros- stantive policy changes. Democrat-led Senate and the Republican
pect of gridlock could propel legislators to Science advocates are hopeful the parti- House fail to agree on new spending levels
approve bigger research budgets before the san battles and gridlock won’t undermine in 2024 and 2025, budgets could end up es-
current session ends next month. Once the the traditional bipartisan support for re- sentially frozen at or near the 2023 levels.
new Congress begins its 2-year session in search funding. An early test began this “Many Republicans, and some Demo-
January 2023, funding increases could be- week as the current Congress took up a crats, view the massive expansion of the
come more difficult to secure. massive piece of legislation that would set national debt in the last 3 years as un-
“I believe that the days of generous sci- spending levels for all federal agencies in sustainable,” Atkinson says. Those lawmak-
ence funding increases are over,” says Robert fiscal year 2023, which began on 1 October. ers “will likely try to limit the growth of
Atkinson, president of the Information (Federal agencies are now under a spending nonentitlement, nondefense spending to at
Technology and Innovation Foundation. freeze that expires on 16 December, raising most the rate of inflation.”

PHOTO: MICHAEL CIAGLO/GETTY IMAGES

The 8 November elections didn’t gener- the prospect of a government shutdown un- The fate of future research budgets will
ate a “red wave” that would have given Re- less the freeze is extended or replaced with be partly in the hands of the lawmakers who
publicans the sheer numbers to roll back a yearlong appropriation.) end up leading the appropriations panels in
large parts of President Joe Biden’s agenda. A new law, the CHIPS and Science Act, both chambers. Senator Patty Murray (D–
Instead, neither party will likely be able to calls for double-digit annual funding boosts WA) is expected to succeed retiring Senator
advance major new policy initiatives. for several research agencies, including the Patrick Leahy (D–VT) atop the full Senate
House Republicans have said they will ag- National Science Foundation (NSF), and spending panel, with subcommittee chairs
gressively investigate whether the Biden ad- science advocates hope lawmakers will fol- still in flux. A Republican House is expected
ministration is doing enough to keep pace low through on that plan. They’d also like to to elevate Representative Kay Granger

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 NE WS

(R–TX) to lead the spending panel, re- CANCER RESEARCH

placing Representative Rosa DeLauro
(D–CT). Representative Robert Aderholt
(R–AL) is in line to lead the panel oversee-
ing NSF, NASA, and several other research
Tumors can teem with microbes.
agencies, while Representative Tom Cole
(R–OK) would get the appropriations sub-
committee overseeing NIH.
But what are they doing there?
Cole has been a reliable advocate for New study suggests microbiomes can promote cancer
biomedical research spending. And one re-
tired Republican congressman thinks his
by suppressing immune response and seeding metastases
former colleagues will continue to back
hefty budgets for NIH. “Who wants to fight By Gunjan Sinha antibiotics. And because each type of can-
with their constituents when they come to cer appears to come with a unique micro-

O
Washington to demand the government do ur bodies harbor countless biome, researchers are exploring whether
more to find a cure for this or that disease?” microbes—and so do our tumors, it microbes could be used as a diagnostic tool
says Charlie Dent, who now serves on the turns out. Over the past 5 years, re- to detect cancer early in a blood sample.
board of Research!America, an advocacy searchers have shown cancer tissue Until recently, most cancer researchers
group for biomedical research. At the same contains entire communities of bac- believed tumors were sterile, says Ravid
time, Dent says, the retirement of Senator teria and fungi. Now, it appears some Straussman, a cancer researcher at the
Roy Blunt (R–MO) means NIH needs a new of the bacteria may be cancer’s accomplices. Weizmann Institute of Science. But about
champion in the Senate. In a paper in Nature this week, a team a decade ago, as a postdoc at the Broad
The House science committee, which led by Susan Bullman of the Fred Hutchin- Institute, Straussman accidentally dis-
helps set policy at major nonhealth research son Cancer Center reports that in oral covered that human pancreatic and colo-
agencies, would also get a new leader: Rep- and colorectal tumors, bacteria live inside rectal cancer cells grown in the lab stopped
resentative Frank Lucas (OK). Currently the cancer cells and boost their production of responding to a cancer drug named gem-
panel’s top Republican, Lucas worked closely proteins known to suppress immune re- citabine when Mycoplasma bacteria
with the committee’s outgoing chair, Repre- sponses. The microbial interlopers may set were present in the culture. The bacteria,
sentative Eddie Bernice Johnson (D–TX), to off a chain reaction that prevents the im- he discovered, “protected” the cells by
craft broadly bipartisan bills. That includes mune system from killing cancerous cells, producing an enzyme that breaks down
CHIPS, although Lucas reluctantly voted and they may also help cancer metastasize gemcitabine.
against it after Republican leaders decided to to other parts of the body. Straussman found he could render gem-
enforce party discipline for political reasons. The study doesn’t entirely clinch the citabine ineffective in mice with colon
The science committee is expected to case for a bacterial role in cancer, but it cancer by injecting the animals with other
look at how the Biden administration is is very suggestive, says Laurence Zitvogel, types of bacteria, including an Escherichia
implementing several popular provisions in a tumor immunologist at the Gustave coli strain, and that treating them with
CHIPS, notably programs to spread federal Roussy Institute. “It shows that bacteria antibiotics restored the drug’s effective-
research spending to regions of the country in colorectal and oral tumors can actively ness. When he studied 113 human pan-
that traditionally receive little of it and to disturb the immune equilibrium,” she says. creatic cancer samples, he found bacteria
accelerate the commercialization of basic Confirmation that microbes can cause tu- that produced the drug-chewing enzymes
research discoveries, creating new indus- mors to grow or spread could open up new in 76% of them—raising the question of
tries and lots of well-paying jobs. Issues ways to make cancer treatment more effec- whether they contributed to drug resis-
important to Lucas’s rural district are also tive, for instance by killing bacteria with tance in human cancers. Straussman and
high on his agenda, including reauthoriza-
tion of a major bill governing U.S. agricul-
tural research policy, weather programs,
and the regulation of drones.
Given the economic and fiscal strug-
gles facing the nation, U.S. research-
ers shouldn’t expect to get everything
they want from the new Congress, says
John Culberson, a Texas Republican who
chaired the House spending panel that
oversees NSF and NASA before losing his
IMAGE: JORGE GALEANO NINO/BULLMAN LAB

House seat as part of a Democratic wave

in 2018. But Culberson, now a lobbyist for
Federal Science Partners, believes Republi-
cans who are likely to occupy key positions
in the next Congress “understand that in-
creased support for basic science and space
exploration are good for the economy and
important to the nation. And they will
fund as much science as the country—and Researchers cultured cancer spheroids without bacteria (left) and with Fusobacterium nucleatum (shown
taxpayers—can afford.” j in pink, right). After 20 hours, individual cancer cells containing bacteria migrated away from the spheroid.

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 NEWS | I N D E P T H

his colleagues are now planning a clinical outcome. Now, Bullman and her colleagues SCIENTIFIC INTEGRITY
trial to test whether antibiotics can im- have addressed the question by studying
prove pancreatic cancer treatment.
Soon afterward, Gregory Sepich-Poore, a
doctoral student in the lab of microbiome
eight tumors removed from patients with
oral cancer and 19 others from colorectal
cancer patients. Mapping the distribution
Whistleblower
researcher Rob Knight at the University of
California, San Diego (UCSD), was hunting
for ways to diagnose pancreatic cancers
of the microbes showed they only colonized
specific areas of the tumors. These infected
regions had high levels of proteins known
finds possible
early. He was motivated by his grandmother’s
death from the cancer, which is often di-
agnosed too late for treatment to be effec-
to suppress cancer-fighting T cells or fuel
cancer growth. T cells amassed outside
these regions, the researchers found, but
misconduct in
tive. Inspired by Straussman’s 2017 paper,
Sepich-Poore began to scour the Cancer
few were found inside. (Instead, the regions
contained neutrophils—a type of immune
his own papers
Genome Atlas, a large DNA database of hu- cell that fights infections, among other
man cancers, for snippets of genetic material jobs.) “It’s conceivable that the bacteria are Matthew Schrag confronts
from microbes. somehow causing the T cells to move away a mentor after their
In March 2020, he, Knight, and colleagues from the tumor,” Blaser says.
reported that microbial RNA and DNA was Using a technique called single cell se- joint work is flagged on
present in each of the 33 types of cancers quencing, the researchers found bacte- the PubPeer website
they studied, and that each cancer type had ria preferentially infect cancer epithelial
a unique microbiome. The team also found cells—which line the inside surface of
those distinct microbial signatures in blood organs—and that only cells in which Fuso- By Charles Piller
samples from cancer patients. Based on bacterium and Treponema bacteria were

W
their findings, Sepich-Poore and dominant tended to show both hen Vanderbilt University neuro-
Knight co-founded San Diego– immunosuppressive and can- scientist and physician Matthew
based Micronoma, a startup “This paper cer promoting characteristics. Schrag went public earlier this
that aims to identify early-stage
cancer in blood samples—a so-
has taken the “This paper fills a critical
gap” by showing that bacteria
year with concerns about appar-
ently doctored images in scores
called liquid biopsy. field a big inside cancer cells may alter of Alzheimer’s papers—including
Later in 2020, Straussman the cells’ behavior, says George seminal research underpinning one aspect
and his colleagues confirmed step forward.” Miller, a cancer doctor and re- of the dominant amyloid hypothesis of the
that many tumors have distinc- Ravid Straussman, searcher at Trinity Health of disease—he anticipated that his motives and
tive populations of microbes Weizmann New England. analyses would be dissected. “I also expected
and found they mostly reside Institute of Science Bullman and her colleagues every project that I ever participated in to
inside cancer and immune also co-cultured Fusobacterium be carefully scrutinized, and that my work
cells, rather than between those cells. species with colon cancer spheroids—small would stand up to that scrutiny,” he says.
Fungi often take up residence in tumors models of human cancers—embedded in a So Schrag assumed there would be an
as well. In a study of 17,000 tumors, pub- matrix that contained neutrophils, and innocent explanation when, a few weeks
lished in Cell in September, the UCSD and compared them with bacteria-free spher- after a Science investigation reported
Weizmann groups found fungal species re- oids. With the bacteria present, neutro- his disturbing findings of apparent mis-
siding in each of 35 cancer types. Again, phils tended to move toward the cancer conduct, he received automated emails
each cancer type was associated with a dis- cells, just as they did in the patient tumor from PubPeer, a web forum where scien-
tinct combination of species, which could samples. And the researchers saw infected tific wrongdoing charges are often leveled.
help refine Micronoma’s diagnostic tools. cancer cells breaking off the spheroids and They notified him that two of his own arti-
(Straussman now sits on the company’s sci- migrating, which Bullman thinks may be a cles from more than 15 years ago had been
entific advisory board.) sign that they are metastasizing. flagged as containing dubious images.
The paper reported another striking Zitvogel says the paper paints a plausi- On close examination, Schrag had to
finding: Certain combinations of fun- ble picture of how microbes could hamper confront an unnerving prospect: that a
gal species correlated with lower odds of the body’s defenses against cancer. Still, co-author, neuropharmacologist Othman
survival in several types of cancers, most the spheroid model “is a reductionist ap- Ghribi, Schrag’s first mentor and still a
strongly in ovarian and breast cancer. In proach,” she cautions; the human body, trusted friend, might have also engaged
October, another group reported some- which has a varied arsenal of immune cells in misconduct. The papers, published in
thing similar in Cancer Cell: The presence and a diverse and largely beneficial micro- 2006 when Schrag was an undergraduate
of a particular bacterial signature seemed biome, may have other mechanisms that working in Ghribi’s lab at the University
to hasten death in pancreatic cancer. The keep cancers from metastasizing. of North Dakota (UND), covered research
probability of surviving 2 years after treat- The study was small and only included on several factors related to amyloid pro-
ment doubled in patients that did not have two types of cancers, Straussman adds, teins in rabbit brains. (Many Alzheimer’s
the signature. “That’s an eyebrow-raising which leaves plenty of work to do. But, researchers believe the disease is caused by
finding,” says co-author Martin Blaser, a “Bullman’s research has shown us how we amyloid’s effects on brain cells.)
cancer microbiome researcher at Rutgers should be exploring the tumor microbiome,” Schrag soon discovered that the suspect
University, Piscataway, who also sits on he says. “This paper has taken the field a big work in the two papers fit a large pattern
Micronoma’s scientific advisory board. step forward.” j of questionable research spanning much of
But none of these findings showed just Ghribi’s career, both before and after they
how fungi or bacteria might lead to a worse Gunjan Sinha is a science journalist in Berlin. worked together.

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 According to Schrag, in a phone con-
versation the senior scientist emotion-
ally acknowledged “problems” in many of
his papers, including those two flagged
on PubPeer, and accepted responsibility.
During their discussion, which Schrag re-
counted to Science, Ghribi maintained to
his former student that the underlying
findings were correct but admitted to ex-
aggerating data. “I’m nauseated talking
about it,” Schrag says.
After initially agreeing to an in-person
interview with Science, Ghribi backed out
a few days before the appointment, cit-
ing a pending UND investigation. He did
not respond to a request to verify Schrag’s
account of their talk or to comment on a
dossier of suspect images in his papers
that Schrag has compiled with other foren-
sic experts. But Ghribi told Science via a
5 October email that he wanted to “exoner-
ate [Schrag] of any wrongdoing with the
manuscripts he co-authored in my lab.”
Back in August, Schrag contacted a UND
official to see whether any of the original
images for the two suspect papers could be
found. The official said he could not iden- Matthew Schrag (left) and Othman Ghribi enjoying better times at Schrag’s Ph.D. graduation ceremony.
tify any relevant documents. But the uni-
versity found that Schrag’s concerns about prepared by Ghribi for a third joint paper, the matter, but in an email to Schrag it said
the papers, along with PubPeer comments which appeared in 2008 in the journal it would look into the concerns.)
on those and other publications by Ghribi, Hippocampus, also warrant a retraction or The three found possible scientific mis-
warranted the inquiry, according to a 10 Oc- correction; he has contacted the journal to conduct in five other Ghribi papers in the
tober email to Ghribi, obtained by Science. share his concerns. Journal of Neurochemistry. Lawrence and
“We are taking all reasonable steps to After reviewing additional comments Prado said those cases “will be also care-
secure records related to the research in posted to PubPeer about other Ghribi pa- fully evaluated in a timely way.” Four pa-
question,” John Mihelich, a UND vice pres- pers, Schrag says he recently resolved to pers with suspect images, co-authored
ident, told Science in an email. “We are in take a deeper look at his mentor’s work, by Ghribi, appeared in the Journal of Al-
communication with the appropriate fed- including all their joint papers. He enlisted zheimer’s Disease. UT San Antonio pro-
eral research offices and sponsors.” help from microbiologist and forensic im- fessor George Perry, chief editor of the
Resolving the matter might prove chal- age analyst Elisabeth Bik and another im- journal, reviewed the full dossier and says
lenging. Ghribi has moved to the Univer- age sleuth—a nonscientist who uses the he was surprised to find many images “sus-
sity of Texas (UT), Rio Grande Valley. And pseudonym Cheshire, in part to minimize picious,” although he emphasizes that he
Schrag says during the recent phone call legal risks. (Science confirmed Cheshire’s has no expertise in forensic image analysis.
Ghribi said that, out of remorse, he had identity and agreed to keep it confidential.) He describes Ghribi as a “likeable,” rela-
discarded his scholarly awards and purged In recent years, Bik and Cheshire have iden- tively established researcher whom he has
his computers and files of raw experimen- tified thousands of apparently manipulated always considered “a person of integrity.”
tal data. If so, a review of Ghribi’s papers or duplicated images in many papers, often Perry says he contacted Ghribi to ask for
could be hampered, because proof of im- leading to retractions or corrections. more information on the suspect papers
age manipulation sometimes requires un- In their assessment of Ghribi’s work and discuss Ghribi’s role as a member of
cropped original images for comparison from 2001 through 2019, the three found the journal’s editorial board. The journal
with published images. suspect images in 33 papers, including the will assess the claims, he adds, and issue
Schrag recently asked two journals to three co-authored with Schrag. Ghribi was errata or retractions if warranted.
retract his suspect papers with Ghribi. the only author shared by all the papers, Schrag acknowledges Ghribi’s early in-
The publisher of Experimental Neurology and he was usually in a prominent posi- fluence in his career and feels sad about
said via email he was awaiting comment tion as either first or last author. The prob- his former mentor’s apparent misdeeds.
from Ghribi. Andrew Lawrence and Marco lematic images included Western blots (a But Schrag says he faced an imperative
Prado, editors of the Journal of Neuro- common method for displaying proteins in to correct the scientific record, including
chemistry, said in an email to Science tissue samples) and micrographs of brain work he played a part in. “You have to have
PHOTO: MATTHEW SCHRAG

they “applied forensic analysis and con- tissue. Their joint 67-page dossier, which a near-religious commitment to research
cluded there are issues with the pub- Schrag provided to Science, shows more integrity. If the rules apply to others they
lication.” They added that all authors, than 100 apparently problematic images, have to apply to [all of ] us,” he says. j
including Ghribi, agreed the paper should many from work funded by grants from
be retracted, which will occur soon. Schrag the National Institutes of Health. (The This story was supported by the Science Fund for
says he’s also evaluating whether images agency declined to comment to Science on Investigative Reporting.

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 CONSERVATION Woolly mammoth tusks, such as these from Wrangel
Island in Russia, may be sustaining

Booming trade in mammoth ivory the global market for illegal elephant ivory.

ephant ivory, Huynh said. “In order to

may be bad news for elephants make up for decreasing supply, organized
crime has turned to using mammoth ivory.”
According to Huynh, criminal organiza-
Paleontologists are urged to take a stand against a market tions in Russia pay good money for private
that may provide cover for continued poaching tusk hunters to find and extract mammoth
ivory from the melting permafrost. “The
rest of the skeleton is either destroyed on
By Michael Price, in Toronto living elephants. He urged paleontologists the spot or lost to erosion,” he said.
to raise their voices against the fossil ivory He noted a 2014 report from wildlife

I
n 2015, Andy Huynh was accompany- trade—and avoid dealing with unscrupu- conservation researchers Lucy Vigne of
ing wildlife guards in Kenya’s Maasai lous collectors who might be involved in it. Oxford Brookes University and Esmond
Mara National Reserve to help ward off Some researchers question whether there Bradley Martin, which found that since
poachers. Fresh off a decade of service are enough data to prove ancient ivory really 2002, sales of mammoth ivory had grown
in the Middle East with U.S. Special Op- is buoying the demand for elephant tusks, from almost nothing to about 40% of all
erations Forces, he thought there was but others at the meeting welcomed his call ivory items sold in Beijing and nearly 70%
little that could faze him. But when he saw to action. “Andy did a great job of making in Shanghai. Huynh also presented more
his first poached rhinoceros, with half of its his case,” says Thomas Holtz, a paleonto- recent, unpublished data from a 2018–19
face sawed away for the horn, he turned and logist at the University of Maryland, College joint operation conducted by Interpol
threw up. “I knew then and there I wanted Park. “Plenty of SVP talks address mass ex- and the United Nations Office on Drug
to dedicate my life to stopping wildlife tinction or even the death of an individual, and Crime that suggested both elephant
crime,” Huynh said. but those are separated from us by an im- and mammoth ivory are continuing to
He began to work with various wildlife mensity of time. This dealt with death and enter Vietnamese and Chinese markets,
protection nonprofits, then joined a series suffering happening right now.” primarily on Russian shipping contain-
of U.N. and Interpol undercover operations Ivory from African and Asian elephants ers that at times also contain illicit drugs
in China and Vietnam to bust up the il- commands up to $3000 per kilogram on and weapons.

PHOTO: SERGEY GORSHKOV/MINDEN PICTURES

legal trade in elephant ivory. Now, he has the black market, primarily in South- The Convention on International Trade
extended his definition of wildlife to the east Asia, where it is mixed into tradi- in Endangered Species of Wild Fauna and
distant past: the great, tusked mammoths tional medicine as a powder and carved Flora monitors and regulates the trade of
and mastodons of the ice age. into status-signifying statues and other items such as elephant ivory and rhinoceros
At the annual meeting of the Society of trinkets. About 55 African elephants are horn, but it has no explicit protections for ex-
Vertebrate Paleontology (SVP) here last killed every day for their tusks. But stricter tinct animals such as mammoths or woolly
week, Huynh argued that the growing trade poaching laws and China’s closing of le- rhinos. “So, the trade for mammoth ivory is
in ivory from the ancient carcasses found gal ivory carving facilities in 2018 have left unchecked and growing … and the global
in thawing Arctic permafrost is sustaining made it harder for suppliers—sometimes criminal network has clearly taken advan-
a global market that leads to the death of tied to criminal syndicates—to source el- tage of this loophole,” Huynh said.

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The harm extends to today’s elephants, PHILANTHROPY

he argued. He noted that although mam-
moth ivory has surged into the market, the
overall demand for elephant ivory appears
to have remained constant or even grown.
Billionaire’s crypto company
His conclusion: Ancient ivory isn’t replac-
ing elephant ivory, but is instead sustaining
the market’s appetite for it. Some traffickers
collapse strands scientists
may even be passing off elephant ivory as As FTX files for bankruptcy, the grantees its foundations
legal mammoth ivory, he says, noting that
it can be hard to distinguish between the
supported may not see all of their pledged money
materials in smaller worked pieces, such as
trinkets and beads. By Robert F. Service avoiding use of its Future Fund grant
Vigne, who did not attend the conference money for now, except to pay the salaries

L
but watched a recording of Huynh’s talk, ast week’s collapse of the crypto- of the three newly hired people.
says it’s unclear just how mammoth ivory currency exchange FTX is sending “We don’t think it is right that anyone
is affecting demand for elephant ivory in aftershocks through the scientific should lose their jobs over a financial ca-
mainland China. Some research hints that community. An undergraduate phys- lamity totally unrelated to the excellent
the rise in mammoth ivory has led to less ics major at the Massachusetts In- work they are doing,” Esvelt says.
elephant poaching. Vigne’s own visits to stitute of Technology (MIT) who SecureBio is now scrambling to secure
mainland Chinese ivory markets suggest founded FTX and quickly became a bil- emergency funding. The organization just
“mammoth ivory has certainly helped re- lionaire, 30-year-old Sam Bankman-Fried last week released a white paper that re-
duce elephant ivory, but it has also pro- backed philanthropic organizations that views new technologies, such as improved
vided a route to [continue to sell] elephant supported a wide variety of science- personal protective equipment and germi-
ivory,” she says. “So, it’s a tricky one.” related causes designed to improve human cidal lights, that could cope with or halt
What is needed, Vigne says, is more infor- well-being. pandemics. “The events of last week put
mation on just how much worked elephant Now, with FTX in bankruptcy and un- this critical work in jeopardy,” Esvelt says.
ivory is being trafficked under the guise of der investigation for misuse of investors’ FTX’s collapse was unthinkable just
legal mammoth ivory. Victoria Herridge, a money, his formerly flush foundations are days earlier. The company, which serves
paleontologist at the Natural History Mu- suddenly strapped for cash and much of as an online trading platform for crypto-
seum in London, agrees. “You need passion- that work is at risk. currency, had assets between $10 billion
ate, activist voices [like Huynh’s], but you One foundation, the Future Fund, was and $50 billion, according to bankruptcy
also need data.” just launched in February. But by the end documents. But it was brought to its knees
Thomas Carr, a paleontologist at Car- of June, its officials reported awarding by an old-style run on the bank, as inves-
thage College and Huynh’s undergraduate 262 grants and “investments” totaling tors tried to withdraw their money after
mentor, notes that paleontology also has a $132 million. It’s unclear how much of that doubts were raised about FTX’s financial
stake in limiting the trade: The sale of fos- money has been distributed. But on 10 No- health. The company declared bankruptcy
sil ivory reduces the number of mammoth vember, five senior Future Fund officials re- on 11 November, and just hours later more
carcasses available for study. “If fossils are signed and announced in a statement, “We than $500 million was reportedly stolen
being destroyed for tusks, you lose so much are devastated to say that it looks likely that from it by hackers.
data,” he says. “It’s a loss for science and it’s there are many committed grants that the Just what will happen to awards the Fu-
a loss for society.” Future Fund will be unable to honor.” ture Fund and the similar FTX Foundation
SVP and the broader paleontological “It’s definitely a mess,” says Josh have already made remains unclear. FTX
community can help, Huynh says, by issu- Morrison, who heads 1Day Sooner, a pan- owes billions of dollars to creditors and is
ing public statements and putting pressure demic preparedness research and advocacy now being investigated by the U.S. Securi-
on elected officials and international regu- organization that received $375,000 from ties and Exchange Commission and the De-
lating bodies. Scientists should also avoid the Future Fund and the FTX Foundation. partment of Justice, according to The Wall
obtaining samples from unscrupulous tusk During the pandemic, 1Day Sooner became Street Journal.
hunters, he says, as they might be collabo- known for advocating so-called human chal- Writing in an online forum hosted by the
rating with collectors who are employed lenge trials, which deliberately infected vol- Center for Effective Altruism, to which the
by criminal organizations. Holtz agrees unteers with SARS-CoV-2 to test vaccines. Future Fund pledged nearly $14 million,
paleontologists should do more, saying, “I Other notable science recipients of the Molly Kovite, legal operations manager for
don’t think most of us understood that fos- Future Fund’s money include Sherlock Bio- the Open Philanthropy foundation, noted
sils were being run in the same shipments sciences, which was awarded $2 million that FTX’s creditors could try to “claw
as, for example, heroin.” for CRISPR-based infectious disease diag- back” their investments during bankruptcy
Jessica Theodor, a paleontologist at the nostics; HelixNano, which was awarded proceedings. If grantees received awards
University of Calgary and SVP’s outgoing $10 million for research on a vaccine effec- after 11 August, which is 90 days prior to
president, says SVP has for decades issued tive against all different coronaviruses; and the bankruptcy filing, “the bankruptcy pro-
statements decrying the loss of scientifi- SecureBio, which was given $1.2 million to cess will probably ask you, at some point,
cally significant fossils to commercial trade. develop better pandemic defenses, such as to pay all or part of that money back,”
In the wake of Huynh’s talk, though, she an early warning system that screens waste- she predicts.
says the society will establish a task force to water for pathogen genetic material. That has grantees wondering how they
investigate what more it can do to protect SecureBio’s co-founder, Kevin Esvelt, will pay the bills. “Everyone is obviously
mammoth ivory. j a biologist at MIT, says the nonprofit is really worried,” Morrison says. j

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 NEWS

FEATURES

PHOTO: CREDIT GOES HERE AS SHOWN; CREDIT GOES HERE AS SHOWN

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 NE WS

SHELTER FROM THE STORM

A plan to wall off Houston and nearby industry from flooding
caused by hurricanes will cost tens of billions of dollars. Will it be enough?

P
lans for one of the world’s biggest By Warren Cornwall, in Galveston, Texas government. In the process, each country or
and most expensive flood barriers city is confronting similar trade-offs: between
were born in a second-floor apart- the U.S. Army Corps of Engineers, the na- protecting people and preserving ecosystems,
ment here in this city on the Gulf tion’s builder of mammoth water infrastruc- between technically sensible designs and aes-
of Mexico, as water 4 meters deep ture. The state of Texas has embraced the thetically acceptable ones, between maximal
filled the street below. In Septem- idea, creating a taxing district to help pay its protection and what’s affordable.
ber 2008, Bill Merrell, an oceano- share. In July, Congress authorized the Corps In Galveston, Merrell and some other
grapher at Texas A&M University, to proceed—though it has yet to appropriate scientists think the Corps hasn’t struck
Galveston, was trapped with his money for construction. the right balance. Merrell warns that its
wife, daughter, grandson, and “two annoy- The project would be the costliest ever built plan—a scaled-down version of his original
ing chihuahuas” in the historic building he by the agency. By some measures it would blueprint—is destined to fail, perhaps cata-
owns. Outside, 180-kilometer- strophically. “It’s too weak—[the
per-hour winds generated by defenses] would only stand up
Hurricane Ike rattled windows to like a 30-year storm,” he says.
and drove water from the gulf “Essentially you don’t have any
and Galveston Bay into the city. protection” against the more ex-
As saltwater swirled through treme storms that have already
the shops and restaurants left deep scars on Galveston—
downstairs, Merrell sat in his and are likely, as climate change
office and sketched plans for a advances, to leave more.
project he hoped would put an
end to the storm-driven flood- LIKE A GYMNAST on a balance
ing that had repeatedly devas- beam, Galveston perches on a
tated this part of Texas. slender ridge of sand, precari-
It was an ambitious vision: ous and exposed. To the north,
Seventy kilometers of seawalls behind that barrier island, lies
rising 5 meters above sea level Galveston Bay, an estuary half
would stretch the length of the size of Rhode Island, teem-
Galveston Island and beyond. ing with shrimp and birds. The
Enormous gates would span Oceanographer Bill Merrell, next to a statue memorializing a deadly hurricane that hit bay is so shallow, locals joke that
PHOTOS: MELISSA PHILLIP/© HOUSTON CHRONICLE; (OPPOSITE PAGE) SMILEY N. POOL/AP PHOTO

the 3-kilometer-wide channel Galveston, Texas, in 1900, developed a plan for protecting the region from storms. if you fall out of a boat, just stand
through which ships pass in up. To the south, Galveston faces
and out of Galveston Bay. The defensive pe- dwarf anything else in the world. The sea the Gulf of Mexico, whose warm waters fuel
rimeter would seal off not just Galveston, gates meant to block gulf waters from Galves- hurricanes nearly every year.
but the whole bay, with Houston at its far ton Bay would span a gap bigger than the Merrell’s 1870 building in the Strand
end, protecting more than 6 million people famous pivoting Maeslant barriers that hold Historic District has survived a number of
and the country’s largest collection of chem- back the North Sea near Rotterdam, Nether- them, including the all-time worst. In Sep-
ical plants and oil refineries. lands. “Everything is bigger in Texas,” quips tember 1900, a monster Category 4 hurri-
Though Merrell had spent decades study- Bas Jonkman, a civil engineer and water- cane with gusts topping 210 kilometers per
ing ocean currents and storm surges, he control expert at the Delft University of Tech- hour blasted the area. Driven by the wind,
had no engineering experience. But as he nology (TU Delft). flood waters nearly 5 meters deep surged
watched the murky waters soak the city, Dutch experts like Jonkman are in high into the city from both the bay and the gulf,
including his own carefully restored 19th demand these days. Around the world, from crushing thousands of buildings. More than
century landmark, he New York City to Singapore, governments 8000 people died. It’s still the deadliest natu-
In 2008, winds decided there had to be are planning massive seawalls and other ral disaster in U.S. history.
and flooding from a better way. “The Dutch measures to ward off the rising seas and In the aftermath, local leaders and the fed-
Hurricane Ike would never put up with intensifying storms expected from climate eral government erected a 6-kilometer-long,
leveled shorefront this,” he said to his wife. change. “A lot of countries are really think- 5-meter-high seawall along the gulf, filling
homes along Today, that first brain- ing through now: ‘How should we defend the space behind it with a deep sand layer
the Gulf of Mexico storm has morphed into ourselves?’” says Marc Walraven, a senior that sloped gently toward the bay. On that
in Texas. a $31 billion plan from adviser on storm surge barriers to the Dutch raised ground, they rebuilt their city.

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 NEWS | F E AT U R E S

When Hurricane Ike made landfall a cen-

Houston tury later, Galveston’s seawall held. But bay
waters flooded central Galveston, including
Trinity the Strand, from the less protected north-
Defensive measures Bay ern side. Low-lying neighborhoods nearby
Deadly flooding from wind-driven storm washed away. Storm surge inside Galveston
surges has repeatedly devastated Texas Bay drenched towns dozens of kilometers
coastal communities around Galveston 2 from the gulf. When the water receded, it left
Galveston
and Houston. To reduce the threat, the U.S. Bay Bolivar behind $37.5 billion in damage and 74 dead.
Army Corps of Engineers has proposed Texas Peninsula Galveston got lucky. At the last minute,
building a network of walls, gates, and sand City 1 the storm veered east, sending the eye over
dunes. The $31 billion plan would be the the city and up the bay. In the Northern
largest single project ever for the Corps, Galveston Gulf of Hemisphere, where cyclones rotate counter-
Mexico
and has drawn extensive criticism. clockwise, the most destructive winds blow
on the eastern side, known as the “dirty side.”
Sam Brody, a coastal planner at Texas A&M
San Luis Galveston, calls Ike a “near miss.”
Pass
A MONTH AFTER the storm, in a small online
Galveston seawall Bolivar Roads gate
Texas newsletter, Merrell wrote a column unveiling
Extended seawall Path of Hurricane
Houston his idea for a wall that would barricade the
0 20 Dune surge barriers Ike (2008)
barrier islands and Galveston Bay during a
At right km Houston ship channel Petrochemical facility storm. He called it the “Ike Dike.”
Although the name caught on, the idea
Flood sector
didn’t at first. Some derided it as a monu-
1 Bolivar Roads gate mental overreach in a place that had relied
The centerpiece of the project, a system of gates, gates
would span the 3-kilometer-wide channel that To prevent storm- for years on more modest seawalls to pro-
is the main connection between the Gulf of Mexico driven waters tect towns like Galveston, and on perching
from surging into Water
and Galveston Bay. houses on stilts. But eventually the Corps,
Bolivar Peninsula the bay, huge flow
gates would close which has a regional office on the outskirts
channels that of Galveston, agreed to study the matter. In
allow freighters 2021, it signed off on the current plan, which
New Panamax ship Gulff of
Gul of and tankers to Congress authorized this summer.
3 km M ic
Me
Mex ico
ico reach Houston’s
port and many The blueprint has key features in com-
chemical plants. mon with the original Ike Dike. At Boli-
Surge blocked
var Roads, the chief waterway joining the
gulf and the bay, four swinging gates, each
Vertical lift more than 100 meters long, would guard
Galves
Galves
vve
eston
t n gates two openings big enough to fit some of the
Bay
ay Barriers flanking world’s largest freighters, including Pana-
the channels Gate
max ships (see graphic, left). In Galveston,
would remain
open except the existing seawall would be extended and
during a storm, improved to encircle much of the city. Over-
to allow regular Gates all, analysts at the Corps forecast that the
Shipping channel tidal currents lowered system could reduce storm surge damage to
openings are to flow back
the region by $62 billion over 50 years, or
Galveston 200 meters wide and forth.
and 18 meters deep. twice its estimated cost.
But the plan’s flood-stopping powers are
less than what the Corps—and Merrell—first
envisioned. In 2018, the agency had proposed
2 Dune system New beach Seawall (5.2 meters above sea level) a more conventional concrete seawall along
The Corps has proposed profile the beaches and highways at the gulf’s edge,
protecting the coastline
by constructing a double the length of Galveston Island and the Boli-
Dunes Surge water
row of dunes with tops (4.2 meters
var Peninsula, much like Merrell’s Ike Dike.
level
up to 4.25 meters above sea That proposal did not fare well with island
above sea level. Some level) residents. People living near the beaches ob-
critics fear the dunes
won’t be tall or strong
jected that the wall would be an eyesore,
enough to withstand even as it left many homes unprotected. GRAPHIC: C. BICKEL/SCIENCE

large storm surges, and “The public went ballistic,” says Kelly Burks-
would prefer a taller Copes, an ecologist who led the crafting of
concrete seawall or taller Sea level the plan. “We had some really harsh, really
dunes built over a
hardened rock core. confrontational public meetings.”
Recently, standing on a 50-meter-wide
Old beach profile beach in front of the houses that crowd

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 Galveston Island’s gulf shore, Burks-Copes tropical cyclones. But there is broad agree- Michel Bechtel, mayor of Morgan’s Point, a
explained how the Corps adapted to the crit- ment that the most severe storms—such as town on the northwestern shore of Galves-
icisms. In its final plan, the agency replaced Category 4 and 5 hurricanes—will become ton Bay. Bechtel is president of the board for
much of the seawall with two parallel dunes more intense, says Gabriel Vecchi, a Princ- the Gulf Coast Protection District, which the
built from sand dredged offshore, each eton University climate scientist. And an state created to collect taxes to help pay for
roughly 2.5 meters tall. One dune would increasing number of storms in the Gulf the project. Bechtel questions why any bar-
crest at 3.7 meters above sea level, and a of Mexico will be Category 3 or bigger, pre- rier on the islands would be built lower than
second, farther up the sloping beach, at dicted a 2017 study by scientists at the Na- the nearby Galveston city seawall and the
4.25 meters—almost 1 meter shorter than tional Center for Atmospheric Research. gates spanning the water channel.
the earlier proposed wall. The Corps has understated the risks “Why are we spending billions of dollars
The new plan didn’t trigger an outcry from posed by such storms, Merrell and his col- to do that and have it overtopped?” he says.
locals, but it also doesn’t offer them as much laborators warn, because it overstates the “Let’s look at it with common sense.”
protection. The dunes are sized to withstand protection the new dunes will offer. “I know
the kind of storm that, in the historic record, from my own experience that those dunes THERE IS AN ARGUMENT for spending many
has come along every 50 years on average. will be completely obliterated by any signif- billions more than the Corps has proposed
The surge from a storm like Ike (which an icant hurricane,” says Bruce Ebersole, a civil on protecting Galveston Bay. It rests on a
agency engineer pegged at about an 80-year engineer who until 2011 oversaw storm and worst-case scenario that envisions hurricane-
storm) would flood over the embankments, flood protection research at the agency’s driven floodwaters battering Houston, the
the Corps acknowledges. laboratory in Vicksburg, Mississippi. nation’s fourth largest city, some 80 kilo-
meters away. Modeling by both Ebersole
and Clint Dawson, who studies coastal
ocean dynamics at the University of Texas,
Austin, shows a Category 4 hurricane could
drive a storm surge topping 7 meters into
the northern tendrils of the bay, where the
shore is lined with sprawling oil refineries
and chemical plants.
That’s Jim Blackburn’s nightmare. Earlier
this year, the veteran environmental attorney,
co-director of Rice University’s Severe Storm
Prediction, Education, & Evacuation from
Disasters Center (SSPEED), pictured that sce-
nario as he stood on a bluff looking across the
placid waters of the bay near Buffalo Bayou.
At his back, a concrete tower topped by a sin-
gle enormous star marked the site of the 1836
Battle of San Jacinto, which paved the way for
Texas’s independence from Mexico. Ahead,
Blackburn faced an industrial landscape of
metal towers and white tanks that sprouted
like giant mushrooms along the waterfront.
After Hurricane Ike, officials moved quickly to shore up dunes and seawalls damaged by the storm. “Every one of these tanks could be hit.
That’s what I’m horrified about,” he said.
But Burks-Copes said the agency will be Ebersole, who recently retired from a re- “This complex is incredibly vulnerable.”
able to blunt some of the flooding by clos- search position at Jackson State University, About 30% of the country’s crude oil and
ing the Bolivar Road gates at low tide be- worked with Merrell to craft the Ike Dike 25% of its natural gas are processed in coastal
fore a big storm arrives, leaving room in plan and to vet the proposal from the Corps. Texas, much of it around Galveston Bay. The
the estuary for some of the overflow. Most He says agency modelers assume the dunes region’s refineries can churn out 2.5 million
beachfront homes, meanwhile, are now less will act like a solid 3.5-meter wall during a barrels a day, nearly 15% of the U.S. capacity.
vulnerable than when Ike arrived, Burks- storm. But in a major hurricane, “They’re go- Oil is stored in more than 4600 huge tanks,
Copes noted, because they’ve been elevated ing to be eroded and destroyed quite early,” many near Houston.
PHOTO: NICK DE LA TORRE/HOUSTON CHRONICLE/AP PHOTO

on pilings. “Unless the surge is over the first he says. “Their effect on storm surge,” he If a 500-year storm hit, Rice scientists
floor,” she said, “they’re not impacted.” suspects, will be “negligible.” have found, the surge and winds could dam-
To stand up to a 100-year storm, col- age some 700 tanks, spilling as much as
EVEN UNDER ITS PLAN, the Corps estimates leagues calculated the dunes would need 470 million liters of oil—almost as much as
that damages from multiple storms over to be far more massive: nearly 7 meters tall the 2010 Deepwater Horizon spill in the Gulf
50 years could still reach $30 billion or more in with a crest 45 meters across, almost as wide of Mexico, the largest in U.S. history. The wa-
the Galveston Bay region. The agency’s esti- as a U.S. football field. A more realistic solu- ters could also inundate Houston neighbor-
mate of how often a storm of a certain size is tion, Ebersole and Merrell argue, would be hoods kilometers upstream of the tanks. “The
likely to strike is based, however, on historical building the original Ike Dike seawall, or an toxic goo that might be produced could set
patterns. It does not take into account how a artificial dune made of sand spread over a back not only the region, but the country, for
warmer future might alter that equation. hardened core of rocks or concrete. decades,” says Houston City Council Member
Debate and uncertainty surround the Their view has won support from some David Robinson, an architect who chairs the
many ways a warmer planet could influence important local political leaders, such as council’s infrastructure committee.

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 NEWS | F E AT U R E S

For Robinson, some version of the Ike York Harbor to fend off a repeat of 2012’s There’s no reason different regions should
Dike is the cornerstone of preventing that Hurricane Sandy. That option beat an ear- adopt the same standard, says engineer
nightmare. But he worries it’s not enough. lier proposal for a single gated wall guarding Gregory Baecher of the University of Mary-
That’s because, even if the defenses succeed the whole harbor, which earned widespread land, College Park, who served on a National
in reducing a storm surge originating from criticism in part for its $119 billion price tag. Academy of Sciences panel in the 2010s that
the gulf, a major hurricane could still gener- Also in September, the agency said it would studied how the Corps evaluates risks. In the
ate a surge inside the bay. reconsider its proposal to build 10 kilo- Netherlands, he notes, surges from a 1000-
Houston, surrounding Harris County, the meters of seawalls and gates, 6 meters high year storm aren’t much deeper than those
Port of Houston, and a local entrepreneur in some places, around downtown Miami. caused by a 100-year storm, because even
have committed $1 million to SSPEED for Local officials and environmental groups very rare storms there aren’t much more
studies. Blackburn and his colleagues have had strongly objected to the plan, fearing it severe. Gulf Coast hurricanes, however, can
already touted one solution. They propose could further degrade Biscayne Bay and ruin dwarf European storms. By one estimate,
building a string of artificial islands in the the city’s famous shoreline. the surge from a 100-year storm in the gulf
bay—in effect a second wall guarding its In Singapore, officials announced plans is roughly equal to a once-in-a-millennium
northwestern reaches, including Houston. earlier this year to study the feasibility of storm in the Netherlands. So, building to
“The Dutch talk about multiple lines of de- storm barriers. Indonesia is considering a the more conservative Dutch-level standard
fense,” Blackburn says. “That’s what we’re re- giant sea wall to protect Jakarta, its sinking along the gulf would be an enormous task.
ally talking about here.” capital, even as it builds a new capital city “Everybody loves the Dutch,” Baecher says.
One obstacle is cost: Blackburn estimates elsewhere. In 2020, Venice, Italy, after de- But, “They’ve got an easier problem.”
building the islands would add $3 billion to cades of debate and delay, finally inaugurated Merrell says the split also reflects a dif-
$6 billion to the price of the plan advanced a system of 72 mobile walls to seal off its la- ferent attitude. The Dutch build to prevent
by the Corps. Another issue is the potential goon and protect the flood-prone city from flooding, whereas the United States is more
environmental damage caused by yet an- rising seas and extreme high tides. The sys- willing to accept flood damage and then
other huge engineering scheme. rebuild. But allowing another
Regulators “are just not going to Ike-scale flood to hit the Texas
let some massive island be built coast, Merrell says, would be
in the middle of Galveston Bay,” “insane. … We have to protect
says Bob Stokes, president of the it. We can’t recover it anymore.
Galveston Bay Foundation, an It’s just too expensive.”
environmental group. The Corps says federal law re-
Environmental concerns have quires it to build projects that,
already prompted the Corps over 50 years, will produce ben-
to ditch one part of the Ike efits greater than the cost. If a
Dike—a proposed gate system region wants something more
across the shallow San Luis robust, it must be willing to pay
Pass, a smaller channel join- the higher price—but it might
ing the gulf to the bay’s west- be a lot higher, warns agency
ern end. Putting a barrier there engineer Mike Braden. “How
would “cause irreparable envi- close to 100% [protection] are
ronmental impacts” by inter- we trying to get?” he asked ear-
fering with ecologically rich lier this year as he stood on the
tidelands, Burks-Copes says. beach next to Burks-Copes. “As
Stokes fears that even the Hurricane Harvey’s intense rains flooded this chemical facility in 2017. we try to approach that 99%,
remaining gates on the deeper A wind-driven storm surge could be more destructive. 100% solution, the costs expo-
Bolivar Roads channel could nentially go up.”
meddle with tidal currents and wildlife— tem is working—but environmentalists say it Braden, who arrived in Galveston earlier
including commercially valuable shrimp. threatens to destroy salt marshes. this year, has a title out of a Marvel super-
As a result, his group has withheld judg- Underlying many of the debates about the hero movie: He’s chief of the Mega Project
ment on the agency’s plan. “It’s hard to say costs and impacts of flood barriers are deeper Division at the Corps. That means he’s in
we’re for or against it,” Stokes says, “until questions: How much risk is tolerable, and charge of shepherding the Texas project
we actually have a deeper level of environ- what is worth preserving? Do you build for a through the remainder of the planning
mental analysis.” once-in-a-lifetime or a once-in-a-millennium process and breaking ground. If everything
All these protection plans come an impor- storm? And how do you account for the un- goes smoothly—if Congress appropriates the
tant caveat: They would do little to prevent certain effect climate change will have on money, and the project survives challenges
the destruction caused by storms like 2017’s those odds? from opponents—it will take decades to com-
Hurricane Harvey, which brought record in- In the Netherlands, key coastal defenses plete. The Corps now predicts the system

PHOTO: CHARLIE RIEDEL/AP PHOTO

land rains—not a wind-driven storm surge— are built to withstand freakishly rare could be finished by 2043.
that flooded Houston neighborhoods. 10,000-year storms. That partly reflects Braden is open to tweaking the design.
the existential threat of flooding to a na- But he also hears the clock ticking. His big-
OTHER CITIES in the United States and else- tion in which one-third of the land is below gest fear is that a massive storm rivaling
where are wrestling with similar issues as sea level, including much of Rotterdam. In Hurricane Ike or the 1900 disaster will arrive
they consider new defenses against storm the United States, by contrast, the Corps before the work is done. If we don’t want to
surges. In September, the Corps issued plans frequently designs projects for a storm ex- repeat those catastrophes, he said, “We need
for a $52 billion network of barriers in New pected to hit once in a century. to go, go, go, go.” j

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 CALL FOR PAPE RS

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A R T I C L E P R O C E S S I N G C H A R G E S WA I V E D U N T I L J U LY 2 0 2 3

1118Product.indd 703 11/14/22 10:10 AM

 INSIGHTS

Various studies show that

COVID-19 vaccination
temporarily alters
menstrual cycles, but the
PERSPECTIVES underlying mechanisms
require more research.

VIEWPOINT: COVID-19

COVID-19 vaccination and menstruation

COVID-19 vaccination causes small changes to menstruation that quickly resolve

By Victoria Male been reported in association with a variety However, these systems are not designed to
of vaccines, including those against patho- detect increased rates of nonserious events

T
he rapid development of safe and ef- gens other than severe acute respiratory that occur commonly. Because menstrual
fective vaccines against COVID-19 has syndrome coronavirus 2 (SARS-CoV-2), so a cycles vary naturally, a particular challenge
been a triumph of medical science, secondary aim of this work is to understand was determining the extent (if any) to which
but vaccines only work if people take the mechanisms by which vaccine-associated the changes reported could be attributed
them. Although there is extensive menstrual changes could occur. to COVID-19 vaccination rather than back-
evidence that COVID-19 vaccination By April 2022, the Vaccine Adverse Event ground variation.
does not affect fertility, misinformation that Reporting System (VAERS) in the United Recent studies illustrate the extent to
it could has been a major source of vaccine States had received more than 11,000 reports which menstrual cycles vary in the absence
hesitancy among young women. As the vac- of menstrual changes and unexpected vagi- of vaccination. The Norwegian Institute of
cination program was rolled out to younger nal bleeding after COVID-19 vaccination (1). Public Health (NIPH) studied a cohort of
age groups, some people noticed menstrual Yellow Card, the equivalent scheme in the 5688 females aged 18 to 30 years who had
changes after COVID-19 vaccination, and United Kingdom, had received more than been recruited to examine other side effects

PHOTO: LUKAS BARTH/REUTERS PICTURES

many members of the public found these 50,000 reports (1). These schemes are effec- of COVID-19 vaccination. Participants were
reports concerning. Research was needed to tive at detecting patterns of serious, but rare, asked to recall their prevaccination and
generate robust data to inform health care adverse events associated with vaccination: postvaccination menstrual cycles: 37.8% de-
professionals and the public about these po- Yellow Card detected the rare clotting dis- scribed at least one aspect as different from
tential side effects. Menstrual changes have order vaccine-induced immune thrombotic their usual experience, even in prevaccina-
thrombocytopenia (VITT) that is associated tion cycles (2). Further, a US study that exam-
with adenovirus-vectored vaccines, and ined changes to cycle length using data from
Department of Metabolism, Digestion
and Reproduction, Imperial College London, VAERS identified myocarditis as a rare ad- a menstrual cycle tracking app reported a
London, UK. Email: [email protected] verse event associated with mRNA vaccines. within-individual standard deviation in cycle

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 length of 4.2 days in unvaccinated individu- this resolved in subsequent follow-ups (6). extent of side effects and changes to cycle
als (1). This underlines the need for formal The NIPH study found that heavi- length or flow (5). Conversely, a survey of
approaches, including unvaccinated compar- er-than-normal bleeding was most com- 27,143 menstruating individuals found that
ison groups, to identify vaccine-associated monly associated with vaccination, with those who experienced fever or fatigue post-
cycle changes. 13.6% of participants reporting this for the vaccination were more likely to experience a
The findings of these formal approaches period after they were vaccinated compared heavier-than-usual period (8). Each of these
have been remarkably consistent: COVID-19 with 7.6% for the period before vaccination approaches has weaknesses: The UK cohort
vaccination is associated with a small in- (2). The UK study of 79 participants was un- is potentially underpowered to detect an as-
crease in menstrual cycle length, but this rap- able to detect an increase in menstrual flow sociation, whereas the survey relies on partic-
idly resolves. In a study of data from 3959 US- associated with vaccination (5), although ipants accurately recalling their experiences
resident users of the menstrual cycle tracking this could be a result of the smaller cohort and is potentially influenced by respondents
app Natural Cycles, of whom 2403 were vac- size. These conflicting results could also re- being more likely to recall other side effects if
cinated and 1556 were unvaccinated, there flect the increased risk of recall bias in the they noticed a menstrual change.
was no effect of the first vaccine dose, the sec- NIPH study. Approaches that combine large Two biologically plausible mechanisms
ond dose was associated with an increase in cohorts and data collection in real time are by which immune stimulation might cause
cycle length of 0.45 days, and administration needed to resolve this. menstrual changes have been proposed:
of both doses of vaccine in the same cycle was Given this evidence that COVID-19 vac- Innate immune responses could transiently
associated with an increase of 2.32 days (3). cination does alter menstrual cycles, albeit interfere with the hormones that drive the
A follow-up study using the same approach temporarily, the obvious question is how? menstrual cycle, or they could affect mac-
in a global cohort of 19,622 people, of whom The type of vaccine does not affect the chance rophages and natural killer cells in the lining
14,936 were vaccinated, reported similar that an individual will experience a change of the uterus, which control the breakdown
results (4). Notably, in both studies, cycle to menstrual timing (1, 5–7) or flow (5, 7, 8), and regeneration of this tissue through the
length returned to normal within two cycles. suggesting that the effect is a result of the cycle (see the figure). In support of the hy-
Consistently, data from 9652 US residents immune response to vaccination rather than pothesis that the effects are hormonally
who tracked their cycles as part of the Apple a specific vaccine component. In support mediated, individuals in whom the ovarian
Women’s Health Study identified an increase of this, menstrual changes have previously hormones estrogen and progesterone are
in cycle length of 0.5 days after the first vac- been reported with typhoid (9), hepatitis B supplied exogenously by combined hormo-
cine dose and 0.39 days after the second (10), and human papillomavirus (HPV) (11) nal contraception are less likely to experi-
dose, with cycle length returning to normal vaccines. Indeed, as early as 1549, the doc- ence menstrual changes after vaccination (5,
the next cycle (1). In the UK, a prospectively tor Wan Chhüan observed that inoculation 7). Furthermore, the timing of vaccination
recruited cohort of 79 people who recorded against smallpox could bring on menstru- within the menstrual cycle affects whether
their cycles in real time also found a small, ation unexpectedly (12). Two studies have cycle length increases. The menstrual cycle
but significant, increase in cycle length only addressed the hypothesis that menstrual is divided into two phases: the follicular
in cycles in which a vaccine dose was given changes after COVID-19 vaccination are as- phase, which occurs before ovulation and
(5). Among 3858 North American nurses tak- sociated with activation of the immune re- can be prolonged by hormonal alterations,
ing part in the Nurses’ Health Study 3, which sponse, but with conflicting results. The 79 and the luteal phase, which occurs after ovu-
collects data from its participants biannually, participants in the prospectively recruited lation and is more consistent in length. If
vaccination was associated with increased UK cohort recorded their experience of com- menstrual changes are mediated by immune
odds (1.48) of reporting a longer menstrual mon immune-mediated vaccine side effects, effects on the control of ovarian hormones,
cycle in the next follow-up questionnaire, but and no association was found between the vaccination would be expected to prolong

Possible mechanisms by which vaccines affect menstrual cycles

Cytokines produced in response to COVID-19 vaccination could affect the hormonal dialogue between the hypothalamus, pituitary gland, and ovaries (HPO), lengthening
the cycle. Cytokines could also affect macrophages and natural killer cells in the lining of the uterus, which mediate tissue repair, resulting in heavier menstrual flow.

Effects on the HPO axis

Menstruation Follicular phase Luteal phase
Hypothalamus
Pituitary gland

FSH Estrogen Typical After Increased

LH Progesterone 28-day cycle vaccination cycle length

Ovary

Effects on immune cells in the endometrium

GRAPHIC: A. MASTIN/SCIENCE

Macrophages and Increased

natural killer cells menstrual flow
control regeneration
Uterus of the endometrium
FSH, follicle-stimulating hormone;
LH, luteinizing hormone.

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 INSIGHTS | P E R S P E C T I V E S

the follicular phase, but this can only occur if menstruate at some time in their lives, yet GEOLOGY
vaccines are administered during this phase. data about effects on menstruation are
Indeed, the Apple Women’s Health Study
found that cycle-length increases are only
associated with vaccination in the follicular
rarely collected in vaccine trials. This must
change—not least to offer reassurance that
this area of public health is also taken seri-
Defining the
phase of the cycle (2).
In support of the possibility that COVID-19
vaccination affects immune cells in the
ously by vaccine developers. Furthermore,
some information can only be collected in
randomized controlled trials. Approaches
onset of the
uterine lining, the survey of 27,143 men-
struating individuals found that increasing
age was associated with an increased risk of
using menstrual cycle tracking apps have
proved powerful because large volumes of
data are available and data collection in real
Anthropocene
heavier bleeding (8). This could suggest that time mitigates recall and recruitment bias. Twelve sites are
altered tissue repair, which is mediated by
immune cells in the uterus and may be less
However, app users are not representative
of the global population because they live
considered for defining
effective in older people, is the mechanism mainly in high-income countries and young, the Anthropocene
by which COVID-19 vaccination increases
menstrual flow.
white, educated individuals are overrepre-
sented (1, 3, 4). App users are also aware of
geological epoch
The evidence for the underlying mecha- being vaccinated, and this may affect their
nism is therefore mixed and could be con- perceptions of aspects of menstruation that By Colin N. Waters1 and Simon D. Turner2
sistent with effects mediated are partially or wholly subjec-

E
by both ovarian hormones (af- tive, such as menstrual flow, arth’s geological history is divided into
fecting cycle length) and endo- “...data about pain, and premenstrual syn- chronostratigraphic units that distin-
metrial repair (affecting men- drome (PMS) symptoms. The guish phases in the planet’s evolution
strual flow). Further research effects on inclusion of a blinded control by summarizing complex biotic, geo-
is required to definitively iden-
tify the pathways involved, but
menstruation group, as in vaccine trials, pre-
cludes these problems.
chemical, and climatic changes. Over
the past century, many components
now that there is evidence that are rarely But there are also opportu- of the Earth system have changed so much
COVID-19 vaccination is asso- nities. The recent advances in that they no longer occur within the ranges
ciated with menstrual changes, collected in defining vaccine effects on the evident during the Holocene—the geologi-
more-involved studies that
track blood hormone levels
vaccine trials.” menstrual cycle open several
avenues of inquiry. Vaccination
cal epoch that represents the past ~11,700
years. There are also distinct geological traces
before and after vaccination is planned and occurs at a sin- that warrant recognition as a new geologic
and studies of immune cells isolated from gle point in time, and thus, importantly, epoch: the Anthropocene. The Anthropocene
endometrial biopsies or menstrual fluid individuals who are already planning to re- Working Group (AWG), a task group of the
are justified. ceive a vaccine dose can be recruited, which Subcommission on Quaternary Stratigraphy
Does SARS-CoV-2 infection affect men- circumvents the ethical challenges of giving (SQS) of the International Commission on
struation? The nature of COVID-19 vaccina- participants an immune stimulus purely Stratigraphy (ICS), have been working to de-
tion makes it amenable to studies that track for experimental reasons. These individuals cide precisely when the Anthropocene began,
menstrual cycle parameters before and after can participate in studies not only to fully with a focus around the mid-20th century.
exposure, but this is harder for infection define how immune stimulation affects The definition will need to identify specific
because it is unpredictable, it may last for female reproductive parameters but also physical properties in sediment layers, or
days or weeks, and many people may be un- to address the converse question: How do strata, that capture the effects of recent in-
aware that they have been infected, making menstrual cycle phase and the use of hor- creases in human population; unprecedented
it more difficult to define an uninfected con- monal contraception affect the immune re- industrialization and globalization; and
trol group. In studies early in the pandemic, sponse? There is an opportunity, finally, to changes imposed on the landscape, climate,
between 15 and 25% of individuals reported start making real progress in an area that and biosphere (1–7).
changes to their periods after SARS-CoV-2 has historically been understudied. j The definitions of chronostratigraphic
infection, although one study was on individ- units form the basis of the International
R EF ERENCES AND NOTES
uals who were hospitalized with COVID-19, Chronostratigraphic Chart (ICC) (8) and
1. E. A. Gibson et al., medRxiv 2022.07.07.22277371 (2022).
one was on individuals with Long Covid, and 2. L. Trogstad, SSRN ssrn.3998180 (2022). standardize the geological time scale—e.g.,
none included an uninfected control group, 3. A. Edelman et al., Obstet. Gynecol. 139, 481 (2022). when specific periods, epochs, and ages be-
so these are likely to be overestimates (13– 4. A. Edelman et al., BMJ Med. 1, e000297 (2022). gin and end and how they can be identified
5. A. Alvergne et al., Front. Reprod. Health 4, 952976 (2022).
15). More recently, the Nurses’ Health Study 6. S. Wang et al., Am. J. Obstet. Gynecol. 227, 739.e1 (2022). in strata. Protocols established by the ICS to
3, which compared menstrual cycle length 7. A. Alvergne et al., medRxiv 2021.11.23.21266709 (2022). formalize chronostratigraphic units require
and regularity self-reported in 2011 to 2016 8. K. M. N. Lee et al., Sci. Adv. 8, eabm7201 (2022). the definition of a global boundary strato-
9. A. R. Lamb, Arch. Intern. Med. XII, 565 (1913).
to that self-reported in 2021 found no effect 10. T. Shingu et al., Kurume Med. J. 29, 123 (1982). type section and point (GSSP). This requires
of SARS-CoV-2 infection, although the tim- 11. S. Suzuki, A. Hosono, Papillomavirus Res. 5, 96 (2018). the selection of a single reference point for
ing of the questionnaires (not immediately 12. J. Needham, East. Horiz. 19, 6 (1980). defining the base (the lowermost part) of a
13. K. Li et al., Reprod. Biomed. Online 42, 260 (2021).
pre- and post-exposure) and the relatively 14. S. M. Khan et al., Am. J. Obstet. Gynecol. 226, 270 (2022).
chronostratigraphic unit, from which cor-
coarse detail in which participants could 15. H. E. Davis et al., EClinicalMedicine 38, 101019 (2021). relation of an isochronous boundary (i.e.,
respond limit the ability of this approach to
ACKNOWL EDGMENTS 1
School of Geography, Geology and the Environment,
detect small or temporary effects (6).
The author receives financial support from Borne, University of Leicester, Leicester, UK. 2Department
There are important lessons to be learned. a charity that funds preterm-birth research. of Geography, University College London, London, UK.
More than half of the world’s population 10.1126/science.ade1051 Email: [email protected]

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 one that is the same age everywhere) for Candidate sites for defining the Anthropocene
the Anthropocene can be achieved globally Core samples from the 12 candidate sites contain various markers of geochemical change and anthropogenic
(9). Given the diversity of geological modi- influence. Globally important stratigraphic markers from each core sample include spheroidal carbonaceous
fication that has occurred in different envi- particles (SCPs), plutonium isotopes, carbon-14 (14C), and d15N [based on the ratio of nitrogen-14 (14N)/15N
ronments, it is challenging to find a single isotopes]. Lines show the full range of each marker’s presence in the core. The point of rapid change of multiple
GSSP that can best represent a global refer- markers provides chronological correlation between the sites.
ence for the Anthropocene.
A candidate Anthropocene GSSP site
must have at least one primary stratigraphic 1
marker to be used as a reference to corre- 11
late the boundary at the selected GSSP site 7 6 12 8
9 10
to other locations across the planet (see the 2
Lake 3
figure). These markers include those that
Coral
indicate a geochemical change—e.g., plu-
Estuary or coastal
tonium isotopes, carbon-14 (14C), and d15N
Anthropogenic
[based on the ratio of nitrogen-14 (14N)/15N
Speleothem (stalagmite) 4
isotopes]—or the appearance of anthropo-
genic particles—e.g., spheroidal carbona- Anoxic marine basin
ceous particles (SCPs), which are a type of Peat
fly ash only produced by high-temperature Ice sheet
combustion of coal or fuel oil (see the photo).
5
Ideally, the site should have precisely dat-
able strata with enough resolution to fix the
onset of the Anthropocene to a specific year Markers: SCPs Plutonium isotopes 14
C d15N Rapid change Peak
(10). The strata, mainly extracted as cores
East Gotland Basin 1
at the sites, must represent a complete time
record, with no gaps or disturbances in the Beppu Bay 2
critical Holocene-Anthropocene boundary West Flower Garden Bank 3
interval. A continuous part of the entire
Flinders Reef 4
core will need to be conserved (for future
reference), and the site should preferably be Palmer Ice Sheet 5
sufficiently accessible that additional cores Ernesto Cave 6
can be extracted if needed.
Building on many years of previous re- Crawford Lake 7
search (10), 12 candidate sites have been pro- Sihailongwan Maar 8
posed for consideration by the AWG. In ad-
Searsville Lake 9
dition to the globally important stratigraphic
markers (plutonium isotopes, 14C, d15N, and San Francisco Bay 10
SCPs), numerous regional markers have been Śnieżka, Sudetes 11
analyzed, including microplastics, heavy met-
als, and even biological proxies such as the Vienna 12
population trends of introduced species (neo- 1830 1850 1870 1890 1910 1930 1950 1970 1990 2010
biota). AWG voting members are tasked with
selecting one candidate GSSP site. several other Anthropocene markers, includ- ter lake with a seasonally stratified water
Two of the candidate sites are in ma- ing d13C (based on the ratio of 13C/12C), d15N, column with a lowermost anoxic layer; and
rine sediments—one in the Baltic Sea and SCPs, microplastics, and pesticides. Searsville Lake in the US, created by a dam
one in the coastal Beppu Bay of Japan. For Two candidate sites are from coral reefs— built in 1892. The Crawford Lake core indi-
the Anthropocene, suitable marine sedi- the West Flower Garden Bank (Gulf of cates ecological effects from indigenous oc-
ments should exhibit sufficient accumula- Mexico) and the Flinders Reef (Coral Sea, cupation followed by European colonization
tion rates, be in contact with anoxic bottom Australia). Here, the skeletons of long-lived and shows major ecological changes in its
waters to limit bioturbation (disturbance corals preserve visible seasonal growth bands microfossils from the 1950s onward, with
by living organisms), and be unaffected by that contain geochemical markers of envi- carbon and nitrogen cycle perturbations
“anthroturbation”—i.e., disturbance by hu- ronmental change, which can be resolved and SCP influx. Sihailongwan Lake is more
man activities, such as trawler fishing (10). precisely back to the 1750s and 1700s, respec- remote and lacks obvious anthropogenic sig-
Both the Baltic Sea and Beppu Bay sites con- tively, allowing for suitable comparison of nals during the Holocene but shows the in-
tain dark, carbon-rich silts and clays tens of Anthropocene and late Holocene successions. creased concentrations of soot (particulates
centimeters thick, with the Beppu Bay site Both sites show clear effects of increased formed as a high-temperature condensate),
GRAPHIC: K. FRANKLIN/SCIENCE

also showing seasonal layering. At both sites, global fossil fuel combustion driving d13C to SCPs, heavy metals, and polycyclic aromatic
these strata lie above the paler, weakly lami- more negative values and proxies indicating hydrocarbons resulting from fossil fuel burn-
nated Holocene sediments, and human activ- warming sea surface temperatures. ing and industrial emissions. Searsville Lake
ity–driven eutrophication (i.e., nutrient en- Three lake sites have been proposed— has silts impounded through seasonal storm
richment causing phytoplanktonic blooms) is Crawford Lake in Canada, which is meromic- events with a layer-count chronology tied to
reflected in the prominent textural and com- tic (i.e., its water layers do not intermix); local pollution and two earthquake events. At
positional changes in the strata along with Sihailongwan Lake in China, which is a cra- Searsville Lake, SCPs, polychlorinated biphe-

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 INSIGHTS | P E R S P E C T I V E S

nyls, and pesticides mark the Anthropocene.

The Palmer ice core from the Antarctic
Peninsula has also been proposed. Ice cores
have previously been selected to define a
GSSP for two Holocene subdivisions (11). The
length of the core from the Palmer site that
corresponds to the Anthropocene is by far the
longest among the candidates, at ~32 m. This
provides more material to analyze per year,
which is important given the low concentra-
tions of some markers in this very remote set-
ting. The core displays seasonally resolvable
laminae and records snowfall extremes dur-
ing the Anthropocene, acceleration of atmo-
spheric methane concentrations, and even
small amounts of SCPs.
A core from a raised ombrotrophic peat
bog—i.e., one that receives nutrients and wa-
ter from the atmosphere for growth—near
the Śnieżka peak in the Sudetes Mountains,
Poland, has been proposed. The peat from 5mm
the site shows an increase of fly ash from
thermal power stations, coinciding with A scanning electron microscopy image shows an ~40-µm-diameter spheroidal carbonaceous particle (SCP)
the appearance of pollen from introduced from Crawford Lake, Canada.
plants and perturbations in d13C and d15N,
respectively, that align with the 1950s. signals from industrial and agricultural the ICC. Each of these votes is required
Three proposals have proved less favor- processes with decade-scale variations in to pass by a 60% majority and may fail at
able as the GSSP site: the Ernesto Cave in timing, global signals provide clear in- any stage, in which case it cannot be sub-
Italy, the San Francisco Bay estuary, and a stances of time that can be linked between sequently modified for at least 10 years.
section in anthropogenic deposits in cen- the sites. Hence, the base of strata mark- If approved, the Anthropocene will have
tral Vienna. The Ernesto Cave site, based on ing the beginning of the Anthropocene can a fixed scientific definition with a precise
a core of a stalagmite only 4 mm thick that be recognized and correlated between all of start date that is characterized by a section
accumulated during the Anthropocene, the sites, whether on land, in ice, or beneath in the strata with well-defined markers.
has 14C and sulfur records that lag behind the sea. For instance, one such marker is This will help focus studies on the scale
monitored atmospheric records by 1 to 2 the acute influx of plutonium isotopes cre- and effect of recent human activity on the
decades as a result of vegetation and soil ated by a series of aboveground hydrogen planet, contrasting with the relative stabil-
delaying atmospheric signals reaching the bomb test detonations commencing in late ity of the preceding Holocene. j
cave. The site was discounted because of 1952 (12). The plutonium provides a sharper
REF ERENCES AND NOTES
this delay. The San Francisco Bay estuary global marker than those produced by
1. W. Steffen, W. Broadgate, L. Deutsch, O. Gaffney,
was originally proposed because it has one larger and longer-lasting drivers of Earth C. Ludwig, Anthr. Rev. 2, 81 (2015).
of the best-resolved historical records of system change—e.g., increased burning of 2. M. J. Head et al., Episodes 10.18814/epiiugs/2021/021031
(2021).
neobiotic species, more than half of which fossil fuels and expansion of agriculture— 3. C. N. Waters et al., Science 351, eaad2622 (2016).
were introduced after 1960. The core re- and consequently has been selected by 4. J. Zalasiewicz, C. N. Waters, M. Williams, C. P.
cords increases in mercury and SCPs in the many of the sites as the primary marker. Summerhayes, Eds., The Anthropocene as a Geological
Time Unit: A Guide to the Scientific Evidence and Current
1960s and a paleontological succession of The AWG will select their preferred can- Debate (Cambridge Univ. Press, 2019).
five neobiotic species in the 1980s, with didate GSSP site based on comparison of 5. J. Syvitski et al., Commun. Earth Environ. 1, 32 (2020).
6. J. Zalasiewicz, C. Waters, M. Williams, in A Geologic Time
their stratigraphic appearances mirroring the robustness of the core chronology and Scale 2020, F. M. Gradstein, J. G. Ogg, M. D. Schmitz, G. M.
their known arrival dates. However, be- clarity of physical markers around the on- Ogg, Eds. (Elsevier, 2020), pp. 1257–1280.
cause the age of the succession is relatively set of the Anthropocene. The chosen site 7. M. Williams et al., Palaeontology 65, e12618 (2022).
8. K. M. Cohen, S. C. Finney, P. L. Gibbard, J.-X. Fan,
poorly constrained and the core stopped will be used to compose the age name. For The ICS International Chronostratigraphic Chart
before reaching the key interval at the example, if the Crawford Lake is chosen, (IUGS, 2022); https://stratigraphy.org/ICSchart/
ChronostratChart2022-02.pdf.
base of the Anthropocene, this site was then the current age may be named the 9. A. Salvador, International Stratigraphic Guide: A Guide to
also discounted as a GSSP. Finally, a sec- Crawfordian Age, which would be the first Stratigraphic Classification, Terminology, and Procedure
tion of anthropogenic deposits in central age of the Anthropocene epoch. The chosen (IUGS and Geological Society of America, 1994).
10. C. N. Waters et al., Earth Sci. Rev. 178, 379 (2018).
Vienna reflects the city’s development and GSSP level at the site will be used to set the 11. M. Walker et al., Episodes 41, 213 (2018).
can be dated by artifacts, including debris precise beginning of the Anthropocene. 12. C. N. Waters et al., Bull. At. Sci. 71, 46 (2015).
from World War II. It provides a near-200- The AWG will vote on the site in late ACKNOWL EDGMENTS
year history of pronounced urban changes. 2022, which is only the initial stage in a C.N.W. and S.D.T. are, respectively, the Chair and Secretary
However, because of notable gaps during process. It will be followed by a proposal of the AWG. The authors thank J. Zalasiewicz and M. Head for
PHOTO: SARAH ROBERTS

this time interval, the Vienna site is also to be voted on by the SQS, then voted their comments; the Haus der Kulturen der Welt, Berlin, for
its support and collaboration with the AWG and for the many
not suitable as a GSSP. on by the ICS, and finally ratified by the teams involved in compiling the results for the 12 sites; and
Together, the 12 sites provide a diverse International Union of Geological Sciences S. Roberts for supplying the SCP image.
perspective on the geological reality of the (IUGS). Only then will the Anthropocene
Anthropocene. Although showing regional be formally approved as a component of 10.1126/science.ade2310

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 GENETICS

Potential bias in genetic correlations

Mating patterns across two traits can inflate estimates of genetic overlap

By Andrew D. Grotzinger1,2 and both traits. If this were the only issue, the the true sense of the term: The inflation of rg
Matthew C. Keller1,2 interpretation of rg as strictly an index of is a statistical artifact that distorts the corre-
shared biology would require updating, but lation between polygenic scores. Somewhat

G
enome-wide association studies rg would still be a valuable metric with etio- reassuringly, the first effect of xAM on rg will
(GWASs) identify genetic variants as- logical and clinical implications for under- typically be greater than the influence of the
sociated with a trait. Most traits are standing risk for trait Y given trait Z. second effect, particularly when genomic
associated with thousands of vari- The second effect that xAM has on rg is REML is used.
ants, and many variants are pleiotro- potentially more problematic. Commonly In the worst-case scenario, xAM for two
pic, meaning they are associated with used methods for estimating rg, such as link- traits with no overlapping causal variants
multiple traits. Pervasive pleiotropy makes it age disequilibrium (LD) score regression will produce rg estimates that are not due to
impractical to assess genetic overlap between (5), Haseman-Elston regression (6), and ge- pleiotropy and are upwardly biased. Border
two traits by tallying the shared variants. For nomic residual maximum likelihood (REML) et al. use simulation findings and empirical
example, traits such as major depression and (7), assume that there is no long-range cor- rg and cross-mate, cross-trait correlation esti-
anxiety are likely associated with a shared set relation across causal variants. Border et al. mates to show that, for example, rg estimates
of thousands of variants. Genetic correlation find that xAM violates this assumption by between alcohol use disorder–schizophrenia
(rg) estimated from GWASs of a pair of traits inducing long-range correlations between or height–educational attainment may fall
is typically interpreted as an overall measure causal variants that are on average positive into this worst-case scenario. However, for
of genetic overlap, providing a useful met- or negative (i.e., sign-consistent). This causes other pairs of traits, the rg estimates are too
ric for quantifying shared biology between an upward bias in rg estimates after even high relative to the estimated levels of xAM
traits. On page 754 of this issue, Border et a single generation of xAM. Unlike in the to realistically reflect a by-product of xAM
al. (1) report simulation-based and empirical first case where only the interpretation of rg alone. Within psychiatric phenotypes, these
findings that challenge this interpretation. would shift, this second issue causes bias in trait pairs with large rg estimates include
Border et al. investigate the ef- bipolar disorder–schizophrenia and
fect on rg of cross-trait assortative major depressive disorder–anxiety.
mating (xAM), which occurs when Measuring genetic correlations In addition, estimates of rg between
individuals scoring highly for trait Y Cross-trait assortative mating could result in genetic correlations traits that show little or no xAM,
mate with partners who score high with certain traits that are explained by three scenarios, two of such as certain diseases or late-
(or low) for a separate trait, Z. The which inflate the score, rg, upward even in the absence of pleiotropy. onset disorders, are still likely to re-
level of xAM will vary depending on flect pleiotropy. Even for traits that
the pair of traits being considered Cross-trait
Cro
oss-trait do show evidence for xAM, rg will
and is quantified in their study us- assortative
assortati
ative mating typically reflect some combination
ing cross-trait correlations across of three alternative contributions—
spouses. They show that xAM can in- pleiotropy, correlated polygenic
crease rg in two ways (see the figure). scores not due to pleiotropy, and
Trait Y Trait Z
They demonstrate that xAM will in- bias due to long-range correlation.
crease rg due to genetic variants for Therefore, the findings of Border et
trait Y being coinherited with the Child inherit
inherits two
al. should not be interpreted as im-
variants for trait Z (and vice versa). copies of shared plying that rg estimates are wholly
This first potential effect of xAM on causal variant for unrelated to pleiotropy.
rg estimates has been understood for traits Y and Z Their results for case-control
decades as an interpretive caveat in along with variant traits, which compare individuals
family-based studies (2–4), although for trait Y and with a disorder (a case) to those who
variant for trait Z.
it is perhaps not widely discussed. do not have the disorder (a control),
The authors point out that this first should also be interpreted with cau-
If assortative mating occurs in the population,
population the measure
effect of xAM does not cause an ac- of genetic correlation, rg, would reflect three scenarios: tion. As is standard, Border et al.
tual bias in rg estimates because the quantify xAM between case-control
polygenic scores—the cumulative set traits using tetrachoric correlations,
of genetic variants that affect each which estimate the correlation be-
trait—are legitimately correlated. tween the continuous risk scores
GRAPHIC: V. ALTOUNIAN/SCIENCE

This is despite there being no pleio- assumed to underlie two disorders.

tropic genetic variants that affect Because patterns of xAM across all
levels of genetic risk affect rg, this
Shared causal Separate causal variants Upward bias in
1
Institute for Behavioral Genetics, University approach assumes that the same
of Colorado at Boulder, Boulder, CO, USA. variant reflects are inherited together. rg score owing
2 typical pleiotropy rg increases owing to to long-range degree of xAM inferred from mat-
Department of Psychology and Neuroscience,
University of Colorado at Boulder, Boulder, CO, interpretation of r g
. correlated genetic scores correlation ing patterns for cases with extreme
USA. Email: [email protected] but not pleiotropy. between variants. risk holds across all levels of risk,

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 INSIGHTS | P E R S P E C T I V E S

including for mates who are “subthreshold” ORGANIC CHEMISTRY

for a disorder. However, increased mating
between individuals who receive a diagnosis
may occur for reasons, such as an elevated
chance of meeting a partner in a clinical set-
Adding functions to pyridines
ting, that have no bearing on mating that oc- Chemical reactions break a pyridine ring
curs between individuals with subthreshold
risk. Thus, tetrachoric correlations between
to allow its modification
disorders, and perhaps especially between
psychiatric disorders, may overstate the in- By Jung Min Joo oms themselves are electron poor and thus
fluence of xAM on rg estimates. do not react easily with electrophiles. Fur-

P
The findings of Border et al. make it clear yridine (C5H5N) is a launch point for thermore, the nitrogen atom reacts prefer-
that more realistic models for why mates creating a wide range of chemicals, entially with electrophilic reagents to form
correlate within and between multiple traits including those used in drug discov- the corresponding pyridinium salts, which
need to be developed and tested. It may be ery, catalysis, and materials science are more electron poor than pyridines and
that xAM occurs only on a few traits of cen- (1). It consists of a hexagonal ring of thereby less likely to react with electrophilic
tral importance to mating and that most five carbon-hydrogen (C–H) pairs and halogen species. As a result, halogenation
other mate correlations are consequences one nitrogen (N) atom. The synthesis of pyr- requires harsh reaction conditions, usually
of the phenotypic and genetic correlations idine derivatives bearing substituents other involving strong acids and elevated temper-
between those central traits and the traits than hydrogen requires custom-designed atures, to generate very strong electrophiles
that are actually measured (indirect AM). processes. Among them, substitutions of that can enable the reaction. This limits the
It is also possible that some xAM estimates one substituent for another are frequently range of reactants that can be used and the
are due to mates becoming more similar performed while maintaining the integrity products that can be created.
over time (convergence). Assortment can of the ring. However, the efficiency of these Positional selectivity is another impor-
also reflect social homogamy, which oc- methods and the diversity of pyridine com- tant consideration in preparing pyridine
curs when mate choice is based on envi- pounds that they yield derivatives. Although the
ronmental components of the trait that are need improvement (2). most relatively electron-
not due to genetics. This could occur, for On pages 773 and 779 of “...new pathways... rich positions on the
example, if mates are chosen on the basis
of religious beliefs and religion is both due
this issue, Boyle et al. (3)
and Cao et al. (4), respec- generate a wider variety ring (positions 3 and 5)
allow electrophilic sub-
to the environment and affects the traits
being studied. Convergence and social ho-
tively, report different
approaches to breaking
of agrochemicals, stitution, it is difficult to
control which of these
mogamy are not expected to affect rg esti- a pyridine ring, replac- pharmaceuticals, positions is substituted
mates. Deriving more complete models of ing the hydrogens, and or whether one or both of
the mechanisms through which observed then restoring the ring. and material compounds.” the positions are substi-
levels of xAM manifest will be important These techniques present tuted. In addition, some
for obtaining a better understanding of possible new pathways to generate a wider substituents could alter the electronic and
downstream effects on rg. variety of agrochemicals, pharmaceuticals, structural characteristics of the pyridine
Border et al. demonstrate that xAM is and material compounds. ring in ways that enable chemical functions
likely to be pervasive and affect many rg The effects of substituents that replace but may decrease the positional selectivity
estimates to some degree. This bias will in- the hydrogens in a pyridine is an important of the reaction on the ring (7). There are also
herently carry forward to results from any topic in organic chemistry. Halogenation— certain products that require the pyridine
methods that use genetic correlations as the replacement of these hydrogens with to react while positioned alongside other
input, such as Mendelian randomization a halogen atom—is useful as an interme- aromatic rings (such as those with delocal-
(8) or genomic structural equation model- diate step for making pyridine derivatives ized electrons) that would compete with the
ing (9). Therefore, complex trait genetics because the installed halogen can be much aromatic pyridine ring for halogenation.
ignores these problems at its peril. These more readily substituted by another atom or Different strategies addressing the halo-
issues can be addressed by increased care group of atoms as compared with hydrogen genation of pyridines present advantages
in interpreting rg as well as through the de- (5). In addition, the halogen substituents and disadvantages. For example, the use
velopment of methods that can disentangle can facilitate intermolecular interactions of bases instead of acids to mediate halo-
the various contributions to rg estimates. j that are essential for certain desired func- genation tends to generate more reactive
tions such as binding to target proteins (6). intermediates (8). Some indirect methods
REFERENCES AND NOTES
Halogenation of pyridines can be accom- use more reactive and accessible intermedi-
1. R. Border et al., Science 378, 754 (2022).
2. L. J. Eaves, A. C. Heath, N. G. Martin, Behav. Genet. 14, plished through their reaction with elec- ates to avoid the use of strong electrophiles
371 (1984). trophilic chemicals (7). These electrophiles (9, 10). However, the requirements of these
3. M. C. Keller et al., PLOS Genet. 9, e1003451 (2013). are electron poor and can form chemical other strategies can limit the range of pos-
4. G. P. Vogler, J. C. DeFries, Behav. Genet. 15, 111 (1985).
5. B. Bulik-Sullivan et al., Nat. Genet. 47, 1236 (2015). bonds by accepting an electron pair from sible substituents. Thus, more versatile
6. J. K. Haseman, R. C. Elston, Behav. Genet. 2, 3 (1972). electron-rich chemicals. However, because means are needed to prepare halogenated
7. J. Yang, S. H. Lee, M. E. Goddard, P. M. Visscher, Am. J. the nitrogen atom attracts electrons from pyridines from simple pyridines or complex
Hum. Genet. 88, 76 (2011).
8. F. P. Hartwig, N. M. Davies, G. Davey Smith, Genet. carbon atoms of the ring, the carbon at- substituted pyridines.
Epidemiol. 42, 608 (2018). Boyle et al. developed a strategy that
9. A. D. Grotzinger et al., Nat. Hum. Behav. 3, 513 (2019). transforms the electron-deficient pyridine
Department of Chemistry and Chemistry Institute for
Functional Materials, Pusan National University, Busan into an electron-rich molecule, enabling
10.1126/science.ade8002 46241, South Korea. Email: [email protected] it to react with electrophilic halogenat-

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 ing reagents with high site selectivity (see A sequence of open and closed rings
the figure). The authors were inspired by Generating halogen derivatives of pyridine is typically a slow and inefficient process. However, two approaches
a century-old method that creates reac- that break open the pyridine ring allow it to readily react with a reagent and with high positional selectivity on
tive intermediates by opening the pyridine the ring. The ring can then be restored. Both pathways allow halogenation, and it may be possible to explore
ring. The process, called a Zincke reaction, other ring modifications. C3 and C5 are positions on the ring.
was originally devised to convert pyridines
to pyridinium salts by substituting at the Existing substituent E Electrophile X Electrophilic halogen
nitrogen site (11). The intermediate com-
1 Nitrogen (N) reacts with an
pound during this reaction, known as the C5 C3 E X
X electrophile (E), which hampers
Zincke imine intermediate, has one of the further reactions with an
N Slow
carbon-nitrogen (C–N) bonds broken, thus N additional electrophile (X) such
E N
opening the ring. Boyle et al. adopted the Pyridine as a halogen.
Zincke reaction for installing substituents Pyridinium salt
at carbon atoms of pyridines by using an
electrophilic reagent, trifluoromethanesul-
fonic anhydride [(CF3SO2)2O], and an amine X
additive, dibenzylamine [(C6H5CH2)2NH)], X 2 The pyridine ring can be broken
R R to allow modification with an
to produce electron-rich Zincke imine inter- N N N N electrophilic halogenating reagent.
mediates. The resultant intermediates are R E R E
even more electron rich than conventional
Zincke imine
electron-rich aromatic rings and can out-
compete the latter for electrophilic haloge-
X
nation. Subsequent ring closure to regener- X
ate the pyridine ring was also unexpectedly 3 The aromaticity of the pyridine
O N O N ring can also be broken by
easy and did not cause the highly reactive R" R" attaching a readily removable
Zincke imine intermediates to decompose R' R' R' R' oxazino ring. This allows
through undesirable side reactions. This re- R' R' modification with an electrophilic
action sequence of ring-opening, halogena- Oxazino pyridine halogen.
tion, and ring-closing allowed the authors to
synthesize several different C3-halogenated bromine, and iodine), nitro (NO2), sulfanyl to produce pyridine derivatives with vary-
pyridine derivatives. (SC6H5), and selenyl (SeC6H5) group do- ing substituents. Apart from electrophilic
Cao et al. took a different path to produce nors. After the substitutions, the attached halogenating reagents, other electrophiles
the same result by transforming pyridines oxazino ring was removed by means of acid that are not typically amenable to pyridine
to electron-rich oxazino (C4N1O1) pyridine treatment to yield the final product. functionalization may now be considered.
intermediates. The oxazino pyridine can The approaches developed by Boyle et al. The ease of producing reactive intermedi-
react with radical species (compounds with and Cao et al. can be performed in a “one- ates with a wide range of installable substit-
at least one unpaired electron) as well as pot” process that only requires the sequen- uents should optimize the creation of drug
with electrophilic reagents to substitute hy- tial addition of reagents without changing candidates and organic functional materi-
drogen with another atom or group of at- the reaction vessel. Both methods exhibit als that were not achievable in the past. j
oms. Similar to the intermediates described high selectivity for the pyridine ring, which
REF ERENCES AND NOTES
by Boyle et al., the formation of oxazino allows the selective halogenation of the ring
1. C. H. McAteer, R. Murugan, J. H. Yamamoto, in
pyridine intermediates is well studied (12), without halogenating other aromatic rings. Comprehensive Heterocyclic Chemistry IV, D. S. Black, J.
but the potential for their use in pyridine They also have high selectivity for the C3 Cossy, C. V. Stevens, Eds. (Elsevier, 2022), pp. 217.
functionalization has not been explored. position within the pyridine ring. Although 2. K. Murakami, S. Yamada, T. Kaneda, K. Itami, Chem. Rev.
117, 9302 (2017).
Cao et al. used inexpensive reagents, in- the two electron-rich positions, C3 and C5, 3. B. T. Boyle, J. N. Levy, L. de Lescure, R. S. Paton, A.
cluding dimethyl acetylenedicarboxylate exist in the intermediates of both synthe- McNally, Science 378, 773 (2022).
(CH3OCOC≡CCO2CH3) and methyl pyruvate ses, C3 is preferentially substituted over 4. H. Cao, Q. Cheng, A. Studer, Science 378, 779 (2022).
5. I. J. S. Fairlamb, Chem. Soc. Rev. 36, 1036 (2007).
(CH3COCO2CH3), to break the aromatic- C5 except in a few cases, such as when a 6. G. Cavallo et al., Chem. Rev. 116, 2478 (2016).
ity of the pyridine ring and make it more substituent is already present at C3. Both 7. M. R. Grimmett, in Advances in Heterocyclic Chemistry,
reactive. This approach is similar to other approaches also allow sequential haloge- A. R. Katritzky, Ed. (Academic Press, 1993), vol. 58,
pp. 271.
known reactions that break the aromatic- nation, which produces pyridines with two 8. M. Balkenhohl, P. Knochel, SynOpen 2, 78 (2018).
ity of the pyridine ring (13). However, these halogen atoms in the ring—first at C3 and 9. S. P. Zucker, F. Wossidlo, M. Weber, D. Lentz, C. C.
other pathways tend to generate intermedi- then at C5. Tzschucke, J. Org. Chem. 82, 5616 (2017).
10. J. S. Wright, P. J. H. Scott, P. G. Steel, Angew. Chem. Int.
ates that are either too stable and do not The techniques of Boyle et al. and Cao et
GRAPHIC: N. CARY/SCIENCE BASED ON J. M. JOO

Ed. 60, 2796 (2021).

allow restoration of the pyridine ring after al. offer opportunities to explore pyridine 11. T. Zincke, G. Heuser, W. Möller, Justus Liebigs Ann. Chem.
substitution or are too unstable and restore functionalization. The preferential haloge- 333, 296 (1904).
the ring before the desired substitutions nation of pyridines over other electron-rich 12. R. Huisgen, M. Morikawa, K. Herbig, E. Brunn, Chem. Ber.
100, 1094 (1967).
can happen. By attaching a readily remov- aromatic rings, with high positional selec- 13. X.-Y. Zhou, M. Zhang, Z. Liu, J.-H. He, X.-C. Wang, J. Am.
able oxazino ring, Boyle et al. created stable tivity, removes the constraints of having to Chem. Soc. 144, 14463 (2022).
intermediates compared with these other generate halogen-containing pyridines at an
ACKNOWL EDGMENTS
approaches. They demonstrated the com- early stage of synthesis to prevent halogena-
The National Research Foundation of Korea (NRF-
patibility of their method using a range of tion of all aromatic rings. Furthermore, se- 2022R1A2C2008629) is gratefully acknowledged.
reagents, including trifluoromethyl (CF3), lective halogenation can be combined with
perfluoroalkyl (CnF2n+1), halogen (chlorine, the diversification of carbon-halogen bonds 10.1126/science.ade5501

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 INSIGHTS | P E R S P E C T I V E S

POLARITON CHEMISTRY

Using mirrors to control molecular dynamics

An optical cavity mixes molecular vibrations with light and changes chemical reactivity

By Lev Chuntonov and intermediates affect reactions, identify- ments for all the molecules in solution. The
ing the corresponding mechanisms in detail authors observed that vibrational dynamics

P
olariton chemistry is an emerging is difficult. Learning how coupling to the were different only when the polariton state
field that explores whether the prod- cavity changes the way vibrational energy was excited, whereas upon excitation of the
ucts and rates of chemical reactions is dissipated can help in developing cavity- reservoir, the molecules behaved the same in
can be controlled by placing a reac- catalyzed chemistry for other reactions. the cavity as outside the cavity.
tion mixture between a pair of mir- Highly symmetrical Fe(CO)5 undergoes an Chemists quantify the likelihood of reac-
rors (an optical cavity), allowing light ultrafast process of pseudo-rotation in which tions by the associated change in enthalpy
to interact with the molecules through mo- the CO moieties slightly change their angles and entropy. Synchronous vibrations of the
lecular vibrational excitation. In this setup, in such a way that the molecule appears to polariton states presumably reduce the en-
molecules absorb energy from the light and have rotated by 90°, even though it did not tropy of reactants with a potentially large
release it back to the cavity many times over. rotate at all (8). Chen et al. measured the impact on the reaction rate compared with
Despite recent demonstrations (1–3), the de- directional change of the C–O stretching vi- relatively small changes in molecular vibra-
tails of this phenomenon are poorly under- bration using infrared spectroscopy (9) and tions caused by coupling to the cavity (12).
stood (4). On page 790 of this issue, Chen et found that the strong coupling between the However, in contrast to other reported reac-
al. (5) describe the molecular dynamics of C–O vibrations and the cavity slowed down tions (1–3), Chen et al. did not observe sub-
iron pentacarbonyl [Fe(CO)5] in an optical the pseudo-rotation rate by about one-fourth stantial changes in the entropy and enthalpy
cavity. By using ultrafast infrared spectros- of the corresponding value for reactions that of the pseudo-rotation and IVR upon cou-
copy with subpicosecond time resolution, occur outside the cavity. At the same time, the pling of Fe(CO)5 to the cavity. It is not clear
the authors observed how the cavity affects rate of energy redistribution between differ- how these traditional chemical concepts can
the intramolecular energy dissipation and ent C–O vibrations nearly doubled at room be used to interpret polariton chemistry.
rearrangement of CO moieties around the Fe Chen et al. simultaneously excited mole-
atom. The findings add to our understanding cules to the first excited vibrational state and
of how polariton chemistry might be used to “...polariton chemistry from the first to the second excited state. To
perform molecular transformations that are
intractable by conventional synthesis.
might be used to perform simplify the theoretical treatment, research-
ers frequently make approximations by con-
Chemical reactions depend on how a mol-
ecule shares energy between different vibra-
molecular transformations sidering only the two lowest-energy quantum
states of the molecule. This leads to a theo-
tions (imagine a molecule changing the way that are intractable retical model where the coupling strength be-
it vibrates from stretching a chemical bond to tween the molecules and the cavity depends
bending) (6). Such intramolecular vibrational by conventional synthesis.” on the number of molecules being excited
relaxation (IVR) can be important when (13). Such an approach, however, cannot de-
considering polariton chemistry (7). When temperature (25°C) and increased fourfold at scribe experiments where dynamics of higher
the vibrations of many molecules interact 80°C. These findings apparently contradict a excited states must be considered (14). More
with light trapped inside an optical cavity, recent conclusion that the pseudo-rotation fundamental research is needed to bridge be-
the molecules and the cavity are said to be reaction coordinate and the C-O stretching tween different interpretations of the experi-
strongly coupled because the energy excess vibrations do not interact strongly (10), and mental observations.
in one component can be readily distributed emphasize the need for tools that measure Polariton chemistry is in its infancy, and
to the other. This coupling can be described internal vibrational coupling in molecules. the fundamental principles driving uncharac-
by a quantum-mechanical state shared by the When molecules are strongly coupled to terized phenomena are yet to be understood.
combined system (the molecules and the cav- the cavity, each contributes a small vibrational The work of Chen et al. is a step toward a bet-
ity) known as a vibrational polariton. amplitude to the collective polariton state in ter understanding of such principles. j
Reaction coordinates describe the path- which all the molecules vibrate in sync. The
REF ERENCES AND NOTES
ways that reactants take as they transform remaining vibrational amplitude contributes
1. A. Thomas et al., Science 363, 615 (2019).
into products. Vibrations and the reaction to the so-called reservoir states, whose prop- 2. J. Lather et al., Chem. Sci. 13, 195 (2022).
coordinate may interact directly, for example, erties are not entirely understood. When all 3. A. Sau et al., Angew. Chem. Int. Ed. 60, 5712 (2021).
when the strong vibration of a chemical bond the molecules in solution are surrounded by 4. B. S. Simpkins et al., J. Phys. Chem. C 125, 19081 (2021).
5. T.-T. Chen et al., Science 378, 790 (2022).
leads to its cleavage (1), or indirectly, when similar microscopic environments, reservoir 6. S. Karmakar, S. Keshavamurthy, Phys. Chem. Chem. Phys.
the vibrational energy in one bond is trans- states involve unsynchronized vibrations of 22, 11139 (2020).
ferred through other bonds to the one that is individual molecules, akin to molecules out- 7. D. S. Wang et al., J. Phys. Chem. Lett. 13, 3317 (2022).
8. J. F. Cahoon et al., Science 319, 1820 (2008).
cleaved (3). Although such intramolecular vi- side the cavity. However, when the environ- 9. M. C. Thielges, M. D. Fayer, Acc. Chem. Res. 45, 1866 (2012).
brational couplings in the reagents, products, ments slightly differ from one molecule to 10. P. Portius et al., Organometallics 38, 4288 (2019).
another, reservoir states can involve synchro- 11. B. Cohn et al., J. Phys. Chem. Lett. 13, 8369 (2022).
12. G. D. Scholes et al., J. Phys. Chem. Lett. 11, 6389 (2020).
nized vibrations of multiple molecules (11). 13. R. Houdré et al., Phys. Rev. B 52, 7810 (1995).
Schulich Faculty of Chemistry and Solid-State
Institute, Technion–Israel Institute of Technology, Chen et al. used laser pulses to excite Fe(CO)5 14. C. A. DelPo et al., J. Phys. Chem. Lett. 11, 2667 (2020).
Haifa, Israel. Email: [email protected] in solvents, which creates similar environ- 10.1126/science.ade9815

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 P OLICY FORUM

DATA REGULATION

Research under China’s personal information law

The new law may present obstacles to some kinds of research

By Xiaojie Li1,2, Yali Cong1,3, Ruishuang Liu1,3 freedom in data processing (1). We provide We suggest a few potential explanations
here a general overview of the effect of the for why, unlike under GDPR, the PIPL does

T
he Personal Information Protection PIPL on ongoing and future transnational not adequately address the needs of con-
Law (PIPL) that came into effect in scientific research through a legal analysis temporary scientific research. Most legis-
the Peoples Republic of China (PRC) of its provisions, and we suggest feasible lators believed that China was particularly
in November 2021 is in line with many solutions for challenges brought by the insufficient in personal information protec-
international standards because it PIPL to transnational scientific research. tion, including in scientific research; thus,
was designed by referring to jurisdic- The PIPL covers personal information of they felt that much stricter provisions were
tions of other nations, especially the provi- people in China, regardless of the location needed to protect personal information
sions of the European Union (EU) General of the processing of information. In the re- rights (2). Also, legislators did not fully con-
Data Protection Regulation (GDPR). Thus, search context, its provisions apply across sider the issues and implications around
the fundamental principles of the PIPL— the entire span of research processing, from scientific research in the big data era, espe-
such as lawfulness, fairness, transparency, the moment of data or biospecimens collec- cially when the secondary use of personal
accuracy, and purpose limitation—are now tion until the disclosure of research results. information can be quite important. In part,
broadly in line with the GDPR. However, All personal information, except through this is because there was a relative lack of
China has not used “academic derogation” anonymization processing that does not re- voices from the scientific community dur-
ILLUSTRATION: DAVIDE BONAZZI/SALZMAN ART

or “academic exemptions” as have been late to an identified or identifiable person, ing the legislation process, a result of the
used in European nations, the United States, is included in the regulation scope of the legislation system in China.
and Australia to reconcile the protection of PIPL, no matter whether it was processed With the law having taken effect only a
personal data rights with scientific research by scientific researchers, government agen- year ago, there has not yet been a great deal of
cies, companies, or others and no matter systematic monitoring and analysis of the im-
1
Department of Medical Ethics and Law, Peking University whether it was provided knowingly by peo- plementation and impacts. Anecdotally, how-
Health Science Center, Beijing, China. 2Department of ple or collected without the knowledge of ever, there is an impression that many ethical
Situation and Policy, University of International Business those whose information was collected (for review boards and researchers are still in con-
and Economics, Beijing, China. 3National Institute of Health
Data Science, Peking University, Beijing, China. example, by cameras in public spaces and fusion or unclear about what is considered
Email: [email protected] cookies on web browsers). legal under the PIPL. Many researchers may

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 INSIGHTS | P O L I C Y F O RU M

still be using broad consent in their research SEPARATE CONSENT which consent is sought, the corresponding
and may not know how PIPL lacks space for Like the GDPR, the PIPL requires “specific types of information should be listed under
this. Some researchers may be eager to con- consent,” which means obtaining consent each processing item, and consent should be
sider ways by which broad consent for big for a specific purpose, such as developing obtained separately for each option.
data research may be made compatible with a drug for diabetes. But unlike the GDPR,
the PIPL. PIPL also requires “separate consent,” SPECIMENS AND DATA TRANSPORT
meaning that the authorization of multiple ACROSS BOUNDARIES
PURPOSE LIMITATION general types or features of processing (for Compared with the relatively low limita-
The PIPL requires that personal informa- example, processing of genetic information, tion on free transfer of data and specimens
tion shall be processed for explicit and rea- processing of health care information, or under the GDPR, transport of data and
sonable purposes and be directly related to change of information processors) cannot be specimens across boundaries in China is
the purpose of processing in a manner that bundled together to fall under a single um- subject to stricter requirements under the
has a minimum impact on the rights and brella authorization of individual consent. PIPL. Personal information, reaching up to
interests of individuals (article 6). If there Instead, if there are multiple general types a specified quantity collected and generated
is any change in the purpose or method of or features of sensitive personal informa- within PRC territory by critical information
the processing of personal information, or tion processing for which consent is sought, infrastructure (CII) operators and personal
the category of processed personal infor- consent options should be set separately for information processors must be stored do-
mation, the individual is to be informed each (4). The PIPL stipulates five scenarios mestically (article 40) (for example, trans-
and their consent obtained again. The PIPL in which obtaining separate consent is re- port abroad of genetic information on 500
expects researchers to gain consent from quired, three of which are particularly rel- people or more needs administrative permis-
the participant even if they have been dei- evant for transnational scientific research: sion). If scientific researchers require trans-
dentified, except by using “anonymization (i) when processing sensitive personal in- fer of personal information beyond the PRC,
processing” (article 4). This severely limits formation, such as biometric identification, they must obtain separate consent from the
the conditions of processing sensitive infor- participants and also meet one of the follow-
mation without specific consent from the ing conditions: (i) pass a security assessment
participant. Primary investigators (the pro- “A repeated informed-consent organized by the Cyberspace Administra-
cessors) are required to seek voluntary and
explicit consent from participants for the
process…may dilute tion of China (CAC) in accordance with the
provisions of article 40; (ii) be awarded per-
use of data or samples obtained from them the purpose of research and sonal information protection certification
by specified groups for a specific purpose by a professional institution in accordance
that is necessary for the original study. For what it can achieve…” with provisions of the CAC; (iii) enter into a
example, medical research institutions are contract with the foreign recipient in accor-
typically not allowed to collect genetic in- health care, specific identification, financial dance with the standard contract formulated
formation for research use unless they have accounts, religious beliefs, personal loca- by the CAC, stipulating the rights and obliga-
a specific purpose (such as a multinational tions, and personal information of minors tions of both parties; or (iv) adhere to other
clinical trial) and sufficient necessity and under the age of fourteen (articles 28 and conditions stipulated by laws, administrative
take strict protective measures (article 28). 29); (ii) when personal information is pro- regulations, or the CAC (article 38).
The process of scientific research and inno- vided to any processor outside the territory The presence of article 38(2) offers
vation in this era of big data is dynamic, full of of the PRC (article 39); and (iii) when the prospects for the free flow of data across
uncertainties and possibilities. Determining information processors change (article 22). boundaries under international treaties
all potential future specific purposes of data Draft regulations on the management of and agreements concluded or acceded to by
processing at the time of data collection is online data security define separate consent China that stipulate the conditions for pro-
often not possible. If specific and explicit con- as “the data processor obtains individual viding personal information outside China
sent is required before the scientific research consent for each item of personal informa- (for example, if China acceded to an agree-
process begins, it may be almost impossible tion when carrying out specific data pro- ment with other countries similar to the
for many researchers to lawfully process the cessing activities, excluding the consent for EU-US and Swiss-US Privacy Shield for com-
information. It may hinder advances in sci- multiple personal information and multiple mercial purposes). Furthermore, scientific
ence and technology and the free flow of data. processing activities at one time” (5). We be- researchers are to take necessary measures
Furthermore, obtaining specific and explicit lieve that separate consent refers to obtain- to ensure that the processing of personal
consent for secondary research often needs a ing personal consent for each type—such as information by foreign recipients meets the
disproportionate amount of effort, and find- biometric identification, financial accounts, personal information protection standards
ing the sources of data and specimens could and personal information of minors under stipulated in the PIPL under article 38(3). No
be difficult or impossible. Such specification the age of 14—rather than obtaining personal specifications are available for determining
and identification of each type of process- consent for each item. To define the scope of whether the foreign receptions have met the
ing without any derogation of personal data “separate,” look to three points from article PIPL’s standard, which leads to uncertainty
rights can substantially burden scientific re- 23 of the PIPL: (i) The data processor has to and requires the CAC to publish a standard
searchers with additional bureaucratic work. perform specific data processing behavior contract for that purpose (6).
A repeated informed-consent process that or collect a specific type of data, (ii) the data
protects participants may dilute the purpose processor has to inform each participant in- INDIVIDUAL RIGHTS AND DEROGATIONS
of research and what it can achieve while dividually, and (iii) the process of obtaining FOR TRANSNATIONAL SCIENTIFIC
bringing unnecessary disturbances to par- informed consent has to be independent of RESEARCH
ticipants (3). An exception from the purpose other authorizations or should not be con- One key tenet of the PIPL, outlined in article
limitation principle may promote the use of founded with the provision of other services. 1, is that it prioritizes the rights of the data
data under many research scenarios. If multiple types of information are used for subjects (2). Accordingly, to ensure legiti-

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 macy and to comply with PIPL, researchers medical Research Involving Human Subjects To ensure that research is considered legal
should ensure that subjects understand sev- allow the donated sample and related infor- under the PIPL, we suggest some key steps.
eral rights when obtaining consent: the rights mation to be used for all kinds of medical re- First and foremost, awareness of the require-
to be informed, to make decisions about the search once the biological sample donor has ments of PIPL must be increased, and the
processing of their personal information, to signed the informed consent form (7). In the law enforced, in transnational scientific re-
access their information, to copy their in- absence of restrictions, this kind of “blanket search efforts. Institutions such as the Peking
formation, to correct and supplement their consent” allows samples and data to be used University Health Science Center–Michigan
information, as well as the right to erasure in future studies that may conflict with the Medicine (PKUHSC-MM) Joint Institute for
(to be forgotten), and the right to portability individual’s fundamental values. However, Translational and Clinical Research should
(to move data from A to B). Procedures for according to article 88 of the Legislation Law update informed consent forms and process
realizing these rights are elaborated, and re- (8), this provision became invalid after the personal information within the process-
quirements for processing sensitive personal Regulations on the Administration of Hu- ing purpose and scope. Institutional review
information such as genetic data are stricter: man Genetic Resources (HGR regulation) boards must be in place to ensure that the
“Only when there is a specific purpose, suffi- and the PIPL took effect. Draft Ethical Re- PIPL has been followed through training,
cient necessity and strict protection measures view Measures for Life Sciences and Medical guidance, and ethical review. Additionally,
are taken, the processor can handle sensitive Research Involving Human Subjects clearly foreign researchers can promote the formu-
personal information” (article 28). support broad consent by allowing second- lation of a treaty with China on transnational
However, there are legal bases for a certain ary research to be carried out without recon- research or join a common international
degree of derogation from the data subject’s sent under a wide range of circumstances (9). convention in accordance with article 38(2).
right to be informed and make decisions However, these provisions are contradictory Research experts should work toward con-
(article 44: otherwise provided by laws and to the PIPL, and the draft finally did not pass. sensus and provide proposals to the National
administrative regulation), the right to delete Under PIPL, scientific researchers may be People’s Congress to characterize what con-
(article 47: the circumstances specified in granted exceptions from the requirement stitutes scientific research and to legitimize
article 18, paragraph 1, and article 35), and to collect consent when (i) performing legal exemption from portions of the PIPL for sci-
the right to access and copy (article 45: if the duties or legal obligations; (ii) responding entific research exemptions, such as the der-
retention period stipulated by laws and ad- to public health emergencies or providing ogation of rights, the substitution of broad
ministrative regulations has not expired, or protection to the life, health, and property of consent for specific consent under specific
it is technically difficult to delete personal individuals in emergencies; (iii) conducting conditions, and the relaxation of purpose lim-
information), although these derogations are news reports, public opinion supervision, and itation. The advantages and disadvantages of
not as detailed as those in the GDPR. other acts for the public interest and process- applying PIPL should be evaluated as this law
ing personal information within a reasonable is being implemented. We believe that legis-
LACK OF SPACE FOR BROAD CONSENT scope; (iv) processing personal information lative adjustments should be made to ensure
Broad consent is an alternative to specific that has been disclosed by individuals them- better balance among the rights and interests
consent only in cases in which it is not fea- selves or that has been legally disclosed in of data subjects, the wellness of the human-
sible to obtain specific consent for scientific accordance with the provisions of this law, kind, and the interests of researchers. j
research (such as the situation in which the within a reasonable scope; or (v) there are
REF ERENCES AND NOTES
purpose of future research is uncertain and other circumstances stipulated by laws and
1. M. Mourby et al., Int. Data Priv. Law 9, 192 (2019).
the secondary use of personal information is administrative regulations (article 13). In the 2. C. Xiao, Understanding and Application of Personal Infor-
required in the future). Unlike blanket con- above scenario, the PIPL allows processing mation Protection Law (China Legal Publishing House,
2021).
sent or general consent, broad consent must of personal information without consent but 3. D. Nicol et al., Science 364, 445 (2019).
inform potential research subjects of certain does not deprive individuals of their right to 4. X. Zhang, Interpretation of “China Personal Information
matters concerning the long-term storage their personal information. But these scenar- Protection Law” (People’s Press, (2021), p. 245.
5. CAC,“Regulations on the management of online data
of biological samples or future studies with ios would not likely apply to most transna- security (draft for comments),” November 2021; http://
uncertain purposes: risks, benefits, confiden- tional scientific research, which means that www.cac.gov.cn/2021-11/14/c_1638501991577898.htm.
6. A. Lee et al.,“Seven major changes in China’s finalized
tiality, right to refuse participation without the PIPL lack space for broad consent. Fortu- personal information protection law” (Brookings, 2021);
reason, right to withdraw at any time, per- nately, article 13(7) points out the direction of https://www.brookings.edu/articles/seven-major-
sonal information processor information, efforts in relation to scientific research: new changes-in-chinas-finalized-personal-information-
protection-law.
whether biological samples are used for com- laws and administrative regulations can be 7. The National Health Commission of the People’s Republic
mercial benefit-sharing or whole-genome se- put forward in the future to support the legit- of China (NHC),“The ethical review measures for biomedi-
cal research involving human beings (October 2016);
quencing, a brief description of the field or imacy and utility of broad consent. http://www.nhc.gov.cn/cms-search/xxgk/getManuscrip-
type of research involved, storage duration, tXxgk.htm?id=84b33b81d8e747eaaf048f68b174f829.
and research contacts and contact informa- SUGGESTIONS FOR THE FUTURE 8. The Ninth National People’s Congress, The Legislation Law
of the People’s Republic of China (March,2000); http://
tion. It is worth emphasizing that if specific Although PIPL emphasizes personal infor- www.gov.cn/xinwen/2015-03/18/content_2835648.
consent is feasible after the purpose of future mation rights and interests, it does not fully htm.
9. NHC, The National Science and Technology Ethics Com-
research is determined, then specific consent consider the special circumstances of trans- mittee Measures for ethical review of life sciences and
should still be preferred. national scientific research in the big data medical research involving human beings (March 2021);
Unlike the GDPR, which includes provi- era. It does not recognize how processing of http://www.nhc.gov.cn/qjjys/s7946/202103/beb-
66b1525e64472b1a9b8921ed1aedf.shtml.
sions that seem to offer clear support for personal data for research is different from 10. J. Bovenberg et al., Science 370, 40 (2020).
broad consent in scientific research, the PIPL other uses such as commercial purposes,
ACKNOWL EDGMENTS
requires specific consent for secondary use of neither do they notice that transnational
All authors contributed equally to this work. Partial support
personal information and specimens, which scientific research can benefit society while came from the PKUHSC-MM Joint Institute for Translational
is inconsistent with research traditions and balancing data subjects’ rights (10). These and Clinical Research.
current ethical review guidelines. For ex- concerns have been raised in the scientific
ample, the Ethical Review Measures for Bio- research community. 10.1126/science.abq7402

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 B O OKS et al .
HISTORY OF SCIENCE

The Gaia letters

Contextualized correspondence traces the emergence of a provocative hypothesis

By Paul Falkowski 1970, when Margulis, on the advice of James Lovelock and Lynn Margulis grappled with
her ex-husband Carl Sagan, first wrote to the possibility that Earth’s life and its geosphere are

W
riting Gaia, edited by Bruce Clarke Lovelock, seeking his assistance in fleshing intertwined in a single, synergistic system.
and Sébastien Dutreuil, is a fasci- out research questions related to the contri-
nating read that reproduces and bution of biological entities to the planetary neers in a field that would become geobiol-
contextualizes a four-decade-long atmosphere. (That letter, unfortunately, is ogy. Vernadsky published Biosfera in Russian
conversation between environ- not included in this collection.) in 1926, which was informally translated into
mental scientist James Lovelock The first letter in the book, dated English in the 1980s but not formally pub-
and evolutionary biologist Lynn Margulis 11 September 1970, from Lovelock states, lished in English until 1998.
from which emerged the provocative Gaia “I am in the course of writing a paper on the In the foreword of the 1998 edition,
hypothesis, which posits that Earth and Earth’s atmosphere as a biological cybernetic Margulis wrote, “[Vernadsky] illuminates the
all its inhabitants can be thought system.” The editors explain that difference between an inanimate, mineralog-
of as a single, synergistic, self- by 1969, Lovelock had begun to ical view of Earth’s history, and an endlessly
regulating system. think about Earth as a planetary dynamic picture of Earth as the domain and
The book opens with a foreword ecosystem, and the term “biologi- product of life, to a degree not yet well under-
by the late Lovelock, in which he cal cybernetic system” became a stood.” Lovelock disagreed; to him, Gaia was
discusses a conversation he had “shorthand trademark” for Gaia. original. In June 1986, he wrote of Vernadsky
in 1967 with William Golding— Although much of the cor- to Margulis, saying, “he was a middle weight
the Nobel Prize–winning author respondence is relatively trivial, expressing his ideas in a vague and all-
of Lord of the Flies—about Erwin Writing Gaia detailing, for example, when and inclusive manner and with the support of
Schrödinger’s book What Is Life? Bruce Clarke and where they would meet, the editors little or no testable evidence.”
“According to this book,” observes Sébastien Dutreuil, Eds. did an exceptional job of culling Regardless of its originality, Lovelock per-
Lovelock, “life was a process that Cambridge University the myriad letters and—with help sisted in developing Gaia as a theory and, to
Press, 2022.
reduced the entropy of a system 510 pp.
from students and colleagues—in- his death, defended the notion of a positive
while excreting entropy to the en- terpreting the correspondence and feedback between the biosphere and geo-
vironment.” Lovelock wanted to understand revealing how the Gaia hypothesis evolved. sphere. He and Margulis thought the concept
how Mars, with an atmosphere composed By the early 1970s, we learn, Margulis had was as seminal as Darwin’s theory of evolu-
almost entirely of carbon dioxide, is of “high become a major force for developing the idea tion. Indeed, in 1995, Lovelock wrote, “Where
entropy” and therefore probably lifeless, that Earth systems function through feed- organisms affected their personal environ-
whereas Earth, containing both methane backs between life and the geosphere and ment then the tendency could be inherited
and oxygen, is of “low entropy” and sustains gave Lovelock increasing confidence in the and could become extensive, even global.”
life. “If you intend to put forward an idea like notion that “Gaia has the equivalent of a cen- At almost 500 pages, Writing Gaia is a
that,” Golding replied, “you had better give tral nervous system.” This notion would even- weighty read. The more casual reader can
the low-entropy system that is our planet a tually lead to heated debates among many skim the correspondence and read the edi-

PHOTO: TUI DE ROY/MINDEN PICTURES

proper name, and I suggest the name Gaia.” scientists, and the concept was, and still is, tors’ excellent summaries. Others will find
The book goes on to document the challenged, if not downright dismissed as an the details of the correspondence a fascinat-
four-decade-long correspondence between untestable hypothesis. ing illustration of how ideas between scien-
Lovelock and Margulis, which began in Arguably, one of the key questions sur- tists evolve. I am sure this tome will be used
rounding the Gaia hypothesis is how original by many students and scholars to under-
The reviewer is at the Department of Earth and Planetary it was. The editors address this issue, discuss- stand the history of geobiology, writ large,
Sciences and the Department of Marine and Coastal
Sciences, Rutgers University, New Brunswick, NJ, USA. ing the contributions of Vladimir Vernadsky, in the 20th century. j
Email: [email protected] a Soviet scientist who was one of the pio- 10.1126/science.ade8916

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 INSI GHTS

SCIENCE AND SOCIETY How Far the

Light Reaches:

Aquatic life and its parallels A Life in Ten

Sea Creatures
Sabrina Imbler
Little, Brown, 2022.
Blurring the personal and the scientific, an author probes 320 pp.

the beauty, terror, and richness of the natural world

where, along hydrothermal vents, the yeti
By Juli Berwald death of a relationship with a lover. crab dances with its claws in the air, bring-
As a writer, Imbler is a terrific talent, ing sulfur-laden water to the chemosynthetic

I
n 1996, Scientific American staff writer at once commanding and questioning, un- bacteria that sustain it. In the dark nights and
John Horgan published The End of flinching and vulnerable, factual and po- gay bars of Seattle, Imbler, too, learns what
Science, which posited that all the great etic, polished and raw, specific and general. it means to dance to be alive, finally among
discoveries had been made and science The book opens with the words “The truth a community of people who make them feel
was reaching its twilight (1). But from is,” which the reader should take seriously. seen and known.
within those pages, a loophole emerged. Imbler bares their soul and leaves no room The theme that pulls these essays to-
In one chapter, physicist David Bohm pointed for platitudes. gether is that the distinctive characteristics
out that art and science, now separate pur- Some of the book’s most powerful essays that make the author who they are, which
suits, have not always been so. During the revolve around Imbler’s growing under- are often framed as outliers and differences,
Renaissance, for example, the two intermin- standing and recognition of their queerness. are all reflected throughout the natural
gled, and great progress was made. They contemplate the biology of a goldfish, world. Nature’s greatest gift is its creativity
But as science became more objective, confined to a bowl growing ever more pol- and diversity.
it also became more erudite and less relat-
able. Facts, although powerful, eventually
cave under the weight of emotion. Vaccine
hesitancy and climate denial, to name two
big examples, suggest the limits of sci-
ence, which is constrained not by all pos-
sible discoveries having been made but by
the fact that humans tend to comprehend
ideas yet act on feelings.
What would happen if art, whose main
purpose is to make us feel, again merged
with science? Writer and science journalist
Sabrina Imbler’s second book, How Far the
Light Reaches, points toward an answer. The
book’s 10 essays, each musing on a different
aquatic creature, upend paradigms of culture
and history and force readers to confront
their assumptions about society.
Imbler’s pieces often start in one place
and end up somewhere else entirely. “Beware
the Sand Striker” describes what it means
to be preyed upon, bringing together pain-
ful stories of Imbler’s sexual encounters with Like a goldfish in a bowl, we can survive in stifling environments, but we thrive when our needs are fully met.
men and the whip-fast strike of a polychaete
worm that hides in the sandy seafloor, invis- luted. The same chapter tells of Imbler’s But there is something else going on in
ible to the fish and crabs above. It also tells struggle as an overachieving rule-follower Imbler’s work. Like Horgan did in 1996,
the true story of Lorena Bobbitt, whose mar- in high school. And then, years later, their Imbler may make readers uncomfortable.
ried surname has been exploited as a nick- first gay encounter with someone unex- Not because they portend a dismal future,
name for the same worm. pectedly from their hometown. “Release a but because, with brutal candor and elegant
In a chapter called “Hybrids,” Imbler goldfish, and it will never look back,” Imbler metaphor, How Far the Light Reaches reveals
explores “The Question” of being biracial, writes. “Nothing fully lives in a bowl; it only the gap between where we are today and a
intertwining it with the story of a hybrid learns to survive it.” truly inclusive and connected world. In so
PHOTO: MATT LEE/ALAMY STOCK PHOTO

butterflyfish collected in Australia in the In another essay, contemplating the seem- doing, it also threads the loophole, weaving
1970s, in the process turning a searing eye ingly boundless morphing of a cuttlefish’s the outlines of a future where art and science
on a celebrated ichthyologist. In “How to color and texture to avoid predation, Imbler amplify one other. j
Draw a Sperm Whale,” Imbler describes asks, “But once the danger passes, you may
REF ERENCES AND NOTES
whale necropsy—the animal equivalent of feel tempted to seize this metamorphic power
1. J. Horgan, The End of Science: Facing the Limits
an autopsy—and then uses it to dissect the for means beyond escape. When you are not of Knowledge in the Twilight of the Scientific Age
fleeing, what will you become?” (Broadway Books, 1996).
The reviewer is the author of Life on the Rocks:
Building a Future for Coral Reefs (Riverhead Books, Part of a solution is discovered in the es-
2022). Contact: www.juliberwald.com say “Pure Life,” which looks into the deep sea 10.1126/science.ade9267

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 INSIGHTS

infrastructure. The legislation designates never in the public interest to destroy

LET TERS Permanent Protection Areas around water Permanent Protection Areas and risk pro-
bodies to guarantee the health of riparian voking disasters.
areas that can buffer floods. According William E. Magnusson
Edited by Jennifer Sills to the law, construction is forbidden in Instituto Nacional de Pesquisas da Amazônia,
Manaus, Amazonas, Brazil.
these important ecosystems. The law also
Email: [email protected]
Editorial Retraction protects riparian systems in the Amazon,
which has heavy rainfall, fragile soils, and REF ERENCES AND NOTES
On 21 July 2017, Science published the often superficial water tables. 1. H. Cristaldo, “Amazonas registra segundo desabamento
de ponte na BR-319,” Agência Brasil (2022); https://
Report “Chiral Majorana fermion modes Earth-moving companies are the pri-
agenciabrasil.ebc.com.br/geral/noticia/2022-10/
in a quantum anomalous Hall insula- mary beneficiaries of the law’s loophole. amazonas-registra-segundo-desabamento-de-ponte-
tor–superconductor structure” by Q. L. The companies argue that the cost sav- na-br-319 [in Portuguese].
He et al. (1). Readers who failed to repro- ings of bulldozing earthen access ramps 2. C. Rosa et al., Aquat. Conserv. Mar. Freshw. Ecosys. 31,
1548 (2021).
duce the findings requested raw data files across protected riparian areas justifies 3. “Queda de pontes e viadutos no Brasil,” Folha de São
from the authors, which they provided. the added risks. However, the embank- Paulo (2018); https://fotografia.folha.uol.com.br/
Subsequently, the provenance of the raw ments they build funnel the main flow galerias/1617195713692955-queda-de-pontes-e-
viadutos [in Portuguese].
data came into question; additionally, an of flood waters around the pylons of 4. Câmara dos Deputados, “Legislação Informatizado
analysis of the raw and published data bridges, increasing the pressure and the – Lei n° 12.651, de 25 de maio de 2012 – publicação
revealed serious irregularities and dis- likelihood of collapse. In some cases, the original” (2012); https://www2.camara.leg.br/legin/
fed/lei/2012/lei-12651-25-maio-2012-613076-publica-
crepancies. These issues have caused the bridge holds up and only the access ramps caooriginal-136199-pl.html [in Portuguese].
editors at Science to lose all confidence in are washed away, after which the earth-
the conclusions of the paper, and we are moving companies are paid to restore 10.1126/science.adf2868
therefore proceeding with an Editorial the road. The companies benefit, perhaps
Retraction. Authors A. L. Stern, J. Wang, unwittingly, but the economy and local
and B. Lian agree with this decision.
Authors Q. L. He, L. Pan, X. Che, G. Yin, E.
population suffer.
The Forest Code is good, evidence-based
Welcoming Taiwan’s
S. Choi, K. Murata, X. Kou, Z. Chen, T. Nie,
Q. Shao, Y. Fan, K. Liu, J. Xia, and K. L.
policy, but it must be enforced wisely to
maximize its impact. The loophole was
diaspora scientists
Wang disagree with this decision. Authors included so that infrastructure truly in the Academia Sinica, the highest research
E. C. Burks and Q. Zhou did not respond. public good, such as bridges required for academy in Taiwan, recently announced
Author S.-C. Zhang is deceased. access, could be constructed in the ripar- 19 newly elected Members and 3 Honorary
This Retraction replaces the Editorial ian zone. The policy was not designed Members (1) after a 2-year pandemic delay.
Expression of Concern posted on 16 to license the wholesale destruction of Because in 2020, the Taiwanese authority
December 2021 (2). protected areas, along with their essential declared that only Taiwanese citizens could
H. Holden Thorp ecosystem functions in flood mitigation. be nominated as Members of Academia
Editor-in-Chief Brazil must acknowledge that it is almost Sinica (2), another five candidates remain
REFERENCES AND NOTES
1. Q. L. He et al., Science 357, 294 (2017).
2. H. H. Thorp, Science 374, 1454 (2021).

10.1126/science.adf7575

Brazil’s preventable
bridge disasters
In October, a second bridge collapsed
within 10 days on Brazil’s controversial
BR 319 highway (1), as biologists predicted
could happen (2). Bridges collapse regu-
larly in Brazil, and the events are often
associated with flooding (3). Brazil’s envi-
ronmental legislation theoretically protects
locations that are likely to flood from
development, but a legal loophole allows
infrastructure projects to proceed if they
PHOTO: BRUNO KELLY/REUTERS
are considered to be in the public interest.
If Brazil’s government does not take action
to restrict use of the loophole, preventable
disasters will continue to occur.
Brazilian Law 12,651, known as the
Forest Code (4), was enacted to pre-
vent natural disasters and protect A loophole has allowed construction in Brazil’s protected areas, contributing to multiple bridge collapses.

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 pending (1). This decision undermines the
inclusiveness of Academia Sinica and the
scientific community in Taiwan.
Many small countries and territories—
including Taiwan—have suffered from
“brain drain” (3) as scientists leave to
study and work elsewhere. Elections of
diaspora scientists into the academies
of their home countries and territories
provide an opportunity to keep them
connected to their homelands, in some
cases even influencing their decision to
return (4–6). The Hungarian Academy of
Sciences has External Memberships for
diaspora Hungarians, as well as Honorary
Memberships for non-Hungarian foreign-
ers. In Colombia (7), Israel (8), mainland
China (9), and African countries (10), The Asian elephant’s
efforts to connect with diaspora scien- anatomy could hold the
tists include research scholarships and key to questions in a
cooperation initiatives that facilitate posi- variety of scientific fields.
tive interactions between overseas scien-
tists and scientific developments in their
native countries.
LIFE IN SCIENCE
A small homeland like Taiwan can ben-
efit from enhancing the local influence
of scientists who have left (11). The new The elephant in the inbox
citizenship requirement for member elec- “We’ll need to get you some boots,” the veterinarian said to me, pointing toward
tions at Academia Sinica in Taiwan could my clean, shiny dress shoes. “Excuse me?” I replied naively, beginning to regret my
instead decrease the engagement of sci- decision to check my emails at 5 p.m. on a Friday. I had come to work dressed for an
entists abroad (12). Given the challenges after-work dinner date, not for what I was about to experience.
Taiwan faces, the Taiwanese authority An hour before, I had been shutting down the microscope and finishing up
should adapt its policy to be more wel- what had been a normal week as a postdoc in a muscular metabolism lab here
coming of its diaspora scientists. In in Copenhagen. Looking forward to what I thought would be a romantic evening, I
addition to piloting an External Member scanned my inbox one last time. Seven new emails caught my attention, all sharing a
system, similar to those in Hungary and title: Re: Elephant.
Columbia, Taiwan should counter brain Copenhagen Zoo houses more than 3000 animals, and despite receiving excellent
drain by increasing the opportunities care, one of them occasionally requires euthanasia. The tragic death of such a unique
available to overseas scientists and animal can provide a valuable opportunity for scientists. The Asian elephant (Elephas
adopting more flexible citizenship maximus) is one of the largest existing land mammals, and
requirements. powerful animals require powerful muscles. By studying how
Call for submissions an elephant’s muscles function, we may be able to better
Jianan Huang
Nanyang Centre for Public Administration, Life in Science is
an occasional feature understand how our own muscles work.
Nanyang Technological University, 639798
Singapore and National Institute of Education,
highlighting some In my career, I have worked with mice, rats, and worms. Yet
of the humorous or when I clicked on the emails, I found a request to cycle to the
Nanyang Technological University, 639798
unusual day-to-day
Singapore. Email: [email protected] local zoo immediately with some ice and collect a sample of
realities that face
REFERENCES AND NOTES
our readers. Can you elephant muscle from the front gate.
top this? Submit So there I was, in my best shoes, clutching my box of ice and
1. Academia Sinica, Academia Sinica Newsletter (Eng. Ver.) your story to www.
1769 (2022). submit2science.org. suddenly realizing why boots were going to be required. There
2. Legislative Yuan of ROC, Legislative Yuan Bulletin 72, 109 would be no quick handoff at the zoo entrance as the emails
(2020) [in Chinese].
3. M. U. M. Anas, S. I. Wickremasinghe, Sci. Public Pol. 5, 37
had implied. Over the next 4 hours, I assisted a team of veterinarians in the post-
(2010). mortem of this gigantic animal, as a forklift and heavy machinery harvested organs
4. Y. Wang et al., Bull. Chin. Acad. Sci. (Chin. Ver.) 1, 34 to send to teams of researchers across Europe. I learned that tissue would be used in
(2019) [in Chinese]. research for vaccines, cardiac disease, diabetes, and infectious disease, as well as for
PHOTO: WPHIL MCLEAN/FLPA/SCIENCE SOURCE

5. C. Cao, China’s Scientific Elite (Routledge, 2004).

6. C. Cao, Science 278, 785 (1997). my lab’s research into muscular weakness.
7. J.-B. Meyer et al., Sci. Technol. Soc. 2, 285 (1997). It was dark by the time I stored the tissue. Five hours late for my dinner, I left the
8. O. Rabinowitz, Y. Abramson, Soc. Stud. Sci. 2, 52 (2022). boots behind and went to beg forgiveness. Fortunately, my date forgave me. We now
9. D. Zweig, S. F. Chung, D. Han, Sci. Technol. Soc. 1, 13
(2008). live together, and we have a no-email rule for Friday nights.
10. H. Pellerin, B. Mullings, Rev. Int. Polit. Econ. 20, 89
(2013). Christopher T. A. Lewis
11. Y. Shain, A. Barth, Int. Org. 57, 449 (2003). Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical
12. Legislative Yuan of ROC, Legislative Yuan Bulletin 83, 111 Sciences, University of Copenhagen, Copenhagen, Denmark.
(2022) [in Chinese].
10.1126/science.adf5850
10.1126/science.adf3523

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11/11/22 4:32 PM
 SPECIAL SECTION

PERSPECTIVES
Moore’s law: The journey ahead p. 722

Toward gallium oxide power

electronics p. 724

REVIEWS
Carbon nanotube transistors: Making
electronics from molecules p. 726
Toward attojoule switching energy in
logic transistors p. 733

RELATED ITEM
EDITORIAL p. 683

FROM ONE
TRANSISTOR…
By Phil Szuromi

F
or most of 1947, the count of transis- transformed communications but also made com-
tors made was…zero. It is now estimated puters widely available. In science and technology,
that at least 3 sextillion transistors have high-power electronics enable gel electrophoresis
been made and shipped since then. What of DNA and extensive computational and software
started as a fundamental experiment prob- resources enable genomic sequencing. The transis-
ing the nature of electronic structure at tor-based Apollo mission guidance computers ex-
semiconductor surfaces ended up contain- ecuted complex control tasks in real time, with the
ing a seed for applied science—it was soon help of reliable software to operate them.
recognized that the three-electrode device The discovery of transistors speaks to the
could amplify signals and replace vacuum-tube importance of asking fundamental questions
amplifiers. The development of integrated circuits and being aware of potential applications that
spawned the ongoing race to continually increase could be hidden in the answers. The develop-
the number of transistors on a chip and lower the ment of transistors into modern integrated
cost and energy use per transistor. This special is- circuits over the past 75 years was the result
sue recaps some of this history and of the efforts of huge teams of re-
offers glimpses into how transistor Margaret Hamilton presents the searchers and engineers. If used
listings of the software
technology may move forward. she and her team developed for
wisely by the rest of us, transistors
The reach of transistors is difficult the transistor-based can continue to extend our scien-
to overestimate. Transistors not only Apollo guidance computer. tific and technological reach.

721

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 SPECIAL SEC TION T RA N S I S T O R S

DEVICE TECHNOLOGY

Moore’s law: The journey ahead

High-performance electronics will focus on increasing the rate of computation

By Mark S. Lundstrom and off current ratio to allow practical opera- The number of transistors on a chip
Muhammad A. Alam tion and suppress leakage current to reduce is still increasing, but the rate of scaling
wasted power. In 2003, strained silicon has slowed because smaller transistors

T
he transistor was invented 75 years was introduced as channel material, and do not function very well. Specifically, the
ago, and the integrated circuit (IC) it increased the on-current by increasing length of the channel (the region between
soon thereafter. The progress in the velocity of electrons (3), and in 2004, the source and drain electrode where the
making transistors smaller also led gate insulators with a high dielectric con- gate acts as a switch) is now ~10 nm. At
to them becoming cheaper, which stant decreased the off-state gate-leakage shorter channel lengths, excessive quan-
was famously noted as Moore’s law current. In 2011, the FinFET, a nonplanar tum-mechanical tunneling degrades tran-
(1). Today’s sophisticated processor chips transistor structure that increases the elec- sistor action. Key performance metrics,
contain more than 100 billion transistors, trostatic control of the energy barrier by such as on-current (which should be high
but the pace of downsizing (“scaling”) the gate electrode (and thereby improves for high-speed operation), off-current
has slowed and it is no longer the only or the on-off current ratio), was introduced (which should be low to minimize standby
even main design goal for improv- power), and power supply voltage
ing performance in particular ap- (which should be low to minimize
plications. How can Moore’s law Three platforms forward the power consumed), all degrade
continue on a path forward? New Two-dimensional (2D) nanoelectonics, three-dimensional (3D) terascale simultaneously. Silicon MOSFETS
approaches include three-dimen- integration, and functional integration can all extend Moore’s law, but all are now about as small as they can
sional (3D) integration that will face substantial challenges and fundamental limits. get, and the 2D chips are about as
focus on increasing the rate of in- large as they can be made, so new
formation processing, rather than Platforms Challenges Limits ways to advance performance must
on increasing the density of tran- be found.
2D nanoelectronics • Heat
sistors on a chip. dissipation
Performance is being enhanced
Although Moore’s law predicted Although other design challenges
• Process
Electron by moving from general-purpose,
a rate for the decrease in cost per can be met, smaller transistors, even integration tunneling “commodity chips” to ones that
ones enabled by advanced surround-
transistor, it is popularly viewed gate design, will eventually hit the • Lithography accelerate specific functions. For
in terms of transistor size, which electron tunneling limit. example, hardware acceleration
for two-dimensional (2D) chip ar- offloads specific tasks to spe-
rays translates into an areal size or 3D terascale integration • Process cialized chips such as graphics
“footprint.” During the last 75 years, integration processing units or an application-
Transistor count can increase • 3D design Heat
as the footprint has decreased from through 3D monolithic integration dissipation specific IC. Companies such as Ap-
micrometer to nanometer scales, or stacking of logic, memory, and
• Reliability ple now design their own chips to
issues with implementing new fab- power chips. The approach, however, • Lab-to-Fab meet their specific requirements,
rication technologies have raised faces several design challenges and as will all of the major automobile
heat dissipation limits.
concerns several times about the manufacturers. Computing is the
“end of Moore’s Law.” Twenty years Functional integration • Application- limiting factor for machine learn-
ago, a pessimistic outlook pre- specific design ing, and companies such as Google
vailed regarding the development Integrating intelligent sensing, Unknown now design their own artificial in-
• Developing
actuation, and data analytics sensors and
of several difficult technologies for would improve functional perform- telligence (AI) accelerator chips.
edge analytics
scaling to continue. In this con- ance by sending information Custom chip designs can increase
text, one of the authors (M.S.L.) instead of raw data. performance by orders of magni-
predicted that instead of slowing tude, but just as the cost of chip
down, the scaling of metal-oxide-semicon- in commercial ICs. Gate all-around transis- manufacturing facilities (“fabs”) has mul-
ductor field-effect transistors (MOSFETs) tors that further improve the electrostatic tiplied (from ~$1 billion in 2000 to ~ $20
below the so-called 65-nm node, which was control of the gate are now in development billion for a leading-edge fab), so has the
state-of-the-art in 2003, would continue (4). The size of transistors that can be fabri- cost of leading-edge design. The design of a
unabated for at least a decade before the cated is limited by patterning and etching. leading-edge chip can cost $0.5 billion and
scaling limit was reached (2). Patterning is done by a process known as require a team of ~1000 engineers. Lower-
Scaling indeed continued from about photolithography, in which a photoreactive ing the cost of leading-edge, custom-chip
100 million transistors per chip in 2003 to polymer creates a mask on the chip for etch- design (possibly by using machine learning GRAPHIC: K. HOLOSKI/SCIENCE

as many as 100 billion transistors per chip ing steps. The minimum size of the pattern techniques) will be a key challenge for the
today. One approach was to improve the on- is determined by the wavelength of the light next era of electronics.
used. The recent emergence of extreme ul- Continued progress will also require
traviolet lithography (EUV) made it possi- advances in the underlying technology.
School of Electrical and Computer Engineering, Purdue
University, West Lafayette, IN 47907-1971, USA. ble for Moore’s law to continue beyond the Despite the sharp increase in the number
Email: [email protected] 7-nm node (5). of transistors on chips (both by decreasing

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 their size and increasing the 2D chip area), developed. Stacking already-processed 2D experimental loops that maximize learning
until recently one aspect of the design had chips to achieve 3D systems has its own are needed.
remained largely unchanged. Individual set of material and processing challenges, Thermal issues will define the limits of
chips are packaged and combined with such as maintaining interconnect align- 3D terascale integration, just as tunnel-
other chips and other components (such ment over distances of ~1 to 5 mm. Hetero- ing limits have stymied 2D scaling. This
as inductors) laterally on printed circuit geneous integration of components such as requirement need not herald an end of
boards. Sending signals on- and off-chip Si high- and low-voltage logic and memory Moore’s law. The goal of computing is not
increases delays and power consumption. transistors, and compound semiconduc- operations per second but information per
An emerging design theme is to exploit tor-based power and high-frequency tran- second. In that regard, biology offers a
the third (vertical) dimension to enable sistors, presents another set of complex guide. Human senses process information
terascale integration (TSI), with trillions integration challenges. locally before forwarding it to the brain.
of transistors integrated into monolithic or Transistors generate heat when they op- Empowering the sensors at the edge that
stacked chips and terabits per second per erate, and removing the heat is a serious interfaces the analog world, supported by
millimeter communication speed for elec- issue in electronics today (7, 10). Indeed, local memory and data processing (edge
trical or optical interconnections (“per mil- thermal cross-talk among logic, memory, analytics), could prevent the data deluge
limeter” refers to the communication link power transistors, and inductors in a het- from overwhelming the computer.
distance between the chips). For example, a erogeneous IC creates unprecedented de- Electronics is at an inflection point. For
3D NAND flash memory (which is based on sign challenges. New ways to remove heat, 75 years, it has been possible to make tran-
NAND logic gates and retains its states with perhaps mimicking the thermoregulation sistors smaller, but that will not be the driv-
the power off ) can have nearly 200 layers of organisms, and thermally aware design ing force for progress in the decades ahead.
of devices and half a trillion memory tran- will be critical when trillions of transistors If Moore’s law is understood to refer to the
sistors (6). Emerging logic transistors with are placed in close proximity. increasing number of transistors per inte-
new channel materials (such as transition The reliability of electronic systems must grated system (not necessarily per chip),
metal dichalcogenides and indium oxide) be guaranteed for a minimum time, typi- then the end of Moore’s law is not in sight
that can be processed at low temperatures cally 10 years, but decades for some applica- (see the figure). The increasing number of
and embedded within the interconnect tions. Ensuring a failure rate between 1 and transistors will not come by making them
stacks offer further opportunities. 10 parts per million for ICs with 100 billion smaller, but by stacking them vertically or
The third dimension also opens up the transistors each requires predicting the reli- combining them laterally in sophisticated
possibility of vertical heterogeneous in- ability of quintillion (~1018) transistors. In packages, and eventually in monolithic 3D
tegration of logic, memory, and power practice, reliability is determined through chips and adding functionality.
transistors. With “through-Si vias,” metal short-term accelerated testing of no more Shifting from nanoelectronics (focused
wires that connect vertically from the chip, than a few thousand transistors. Thus, the on reducing the transistor dimension) to
already-processed chips can be stacked to reliability physics of the wear-out and cata- terascale electronics (driven by increas-
put them in close physical proximity to strophic failure modes of these new systems ing transistor count and related function-
minimize signal delays and reduce power need to be understood with unprecedented ality) defines the paradigm shift and core
consumption (7). Vertically stacked logic precision. When so many devices are inter- research challenges of the future. It will
and memory chips also enable new com- connected and placed in close proximity, require fundamental advances in materi-
puting paradigms, such as “compute-in- new phenomena will emerge, and these als, devices, processing, and the design and
memory.” Monolithic 3D ICs would consist must be managed or exploited. manufacture of the most complex systems
of layers of active devices, such as 2D logic Future terascale systems will be funda- humans have ever built. Someday the elec-
transistors, magnetoresistive and resistive mentally different from today’s gigascale trical tunneling and thermal bottleneck will
random-access memories, and ferroelectric systems in that understanding the building define the limits of 3D integration. Until
FETs, along with the metal lines that inter- blocks of a system do not inform how these then, Moore’s law will likely continue as re-
connect them (8). blocks interact and lead to new phenom- searchers address the challenges of these ex-
Recent packaging innovations, such as ena (11). Chip design is already complex traordinarily complex electronic systems. j
silicon-interposer and multi-die silicon and expensive, but algorithms or tools to
REF ERENCES AND NOTES
bridges, inserted between the 3D chips place devices for 3D design and routing the
1. G. E. Moore, Electronics (Basel) no. 8 (19 April 1965)
and the substrate, create denser lateral interconnections among them are not yet (1965).
interconnection and faster communica- available. These design tools must model 2. M. Lundstrom, Science 299, 210 (2003).
tion among the chips. Advanced packaging the complexity of the process and package 3. K. Mistry et al., in IEEE International Electron Devices
brings together logic, memory, power man- integration, thermal cross-talk among 3D Meeting, pp. 247250 (2007).
4. D. Jang et al., IEEE Trans. Electron Dev. 64, 2707 (2017).
agement, communications, and photon- ICs, and operation-specific variability and 5. WIRED, “The $150 million machine keeping Moore’s law
ics through side-by-side integration. The reliability of the packaged system. alive,” 30 August 2021; https://www.wired.com/story/
proximity of integration now rivals that in When new materials and processing asml-extreme-ultraviolet-lithography-chips-moores-
stacked and monolithic 3D ICs (8, 9). techniques are developed in research, they law/.
6. A. Goda, Electronics 10, 3156 (2021).
Monolithic 3D integration will require must be translated to large-scale manufac-
7. R. W. Keyes, Proc. IEEE 60, 225 (1972).
that the growth or deposition steps do not turing. Translating advances achieved with 8. S. Iyer, IEEE Trans. Compon. Packaging Manuf. Technol. 6,
affect the already-processed layers. For ex- research-grade equipment to large-scale 973 (2016).
ample, the transistors embedded within manufacturing with different and more so- 9. C. H. Douglas et al., in 2021 IEEE International Electron
Devices Meeting, pp. 3–7.
the interconnect stack must be deposited phisticated state-of-the-art manufacturing
10. M. A. Alam et al., IEEE Trans. Electron Dev. 66, 4556
at a low-enough temperature not to disturb equipment presents a serious “lab to fab” (2019).
the dopant profiles of the Si transistors un- challenge. The research community will 11. P. W. Anderson, Science 177, 393 (1972).
derneath. The needed materials are often need access to advanced processing facili-
incompatible unless special processes are ties, and short “conceive-conduct-analyze” 10.1126/science.ade2191

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 SPECIAL SEC TION T RA N S I S T O R S

DEVICE TECHNOLOGY

Toward gallium oxide power electronics

Ultrawide-bandgap semiconductors show promise for high-power transistors

By Marko J. Tadjer device would also reduce switching losses into their development cycle, UWBG de-
(proportional to capacitance) and provide vice architectures are still actively ex-

E
fficient, ultrahigh-voltage power- a platform for higher-speed electronics plored by researchers. A vertical field-ef-
conversion electronics (with voltages without sacrificing output power. Such fect transistor (FET), such as the FinFET
>20 kV) require semiconductors with high-speed power transistors would be dis- (see the figure, left), can in theory block
an energy gap much larger than that ruptive in the power electronics industry very high fields but is more susceptible to
of silicon. The wide-bandgap (WBG) because system volume is inversely propor- extended defects in the epitaxial layer. A
semiconductor silicon carbide (SiC) tional to frequency. lateral transistor, such as the heterojunc-
has matured into a commercial techno- Out of the six crystalline Ga2O3 phases, tion FET (see the figure, right), could po-
logical platform for power electronics (1), the low-symmetry monoclinic b-Ga2O3 is tentially switch faster and more efficiently
but ultrawide-bandgap (UWBG) (band- furthest along in its development cycle because of its smaller capacitances and
gaps >4.5 eV) semiconductor devices could because of its thermal stability at high shorter transit times, and it could also
potentially enable substantially higher- temperatures (>650°C) (3), and the dis- use ternary alloys of Ga2O3, in this case
voltage electronics. Candidate UWBG cussion below refers to this phase. Unlike b-(AlxGa1-x)2O3, to boost power performance
semiconductors include aluminum nitride any other WBG or UWBG semiconductor, even further.
(AlN), cubic boron nitride, and diamond, melt growth methods originally developed The existence of shallow energy donors
but during the past decade, the greatest in- for silicon substrates have been adapted and acceptors (charged impurities) has
crease in research activity has likely been
directed at gallium oxide (Ga2O3). This in-
terest is driven in part by its large bandgap Gallium oxide (b-Ga2O3) devices
of ~4.85 eV and breakthroughs in crystal The availability of wafer substrates and growth processes enables fabrication of devices for power electronics.
growth that led to the first Ga2O3 transis-
tor demonstration in 2012 (2). Ga2O3 has High-field operation Thermal management
promise as a platform for power electron- Schematic of a vertical b-Ga2O3 Schematic of near-junction integration of
ics, but there are challenges in bringing fin field-effect transistor (FinFET) nanocrystalline diamond with b-Ga2O3
with 4.2-kV breakdown voltage. transistor for top-side heat extraction.
this UWBG semiconductor into commer-
cial use within the next decade. Source n+ layer Gate metal Gate oxide
The electrification process that has
captured the attention of many indus- Heat Heat
tries could be disruptively accelerated if Field oxide Gate oxide
ultrahigh-voltage electronics penetrate Gate metal Source
Diamond
Drain
into applications such as next-generation Dielectric
power-grid control and protection, ultra- (Al0.21Ga0.79)2O3
n+ layer n+ layer
fast electric vehicle chargers, or efficient Silicon-doped layer
point-of-load converters with size, weight, Unintentionally doped b-Ga2O3 buffer
and power advantages. Although SiC de-
vices are higher in cost compared with b-Ga2O3 drift layer
conventional silicon power electronics, at n+ b-Ga2O3 substrate
Drain Semi-insulating (010) b-Ga2O3 substrate
the system level, those costs are expected
to be offset by savings given simpler cir-

GRAPHIC: A. FISHER/SCIENCE BASED ON NOVEL CRYSTAL TECHNOLOGY, INC.

cuitry requirements. to commercialize Ga2O3 substrates (4). plagued all UWBG semiconductors be-
Power conversion at very high voltages b-Ga2O3 wafers have reached the 4-inch cause an increasingly wider energy gap
and high switching speeds may become at- (100-mm) commercial milestone and are typically leaves an extrinsic impurity to
tainable beyond 20 kV if a viable UWBG on track to become available at the 6-inch reside farther from the conduction (or va-
technological platform emerges. Even at (150-mm) size by 2027 (5). In parallel, the lence) band. However, for Ga2O3, silicon is
10 kV, it is difficult to increase the switch- infrastructure for high-quality epitaxy is an excellent extrinsic shallow donor that
ing frequency of a power converter beyond being scaled to keep up with the increasing has enabled a very wide range of con-
~10 kHz without sacrificing circuit effi- Ga2O3 substrate size. Methods for Ga2O3 trolled conductivities, from below 1014 cm-3
ciency. UWBG semiconductors inherently epitaxial growth, such as chemical vapor to above 1020 cm-3. The controllable n-type
require thinner device layers that lead to deposition (CVD), molecular beam epitaxy, conductivity extends even to the ternary
reduced conduction losses (proportional and halide vapor phase epitaxy among alloy (AlxGa1-x)2O3, which has an even wider
to channel resistance). The reduced car- others, are being extensively researched bandgap that is also tunable depending
rier transit time through a smaller UWBG with the goal of producing the highest- on phase and Al concentration (6). Also,
quality material. CVD-grown homoepitaxial b-Ga2O3 has a
United States Naval Research Laboratory, Washington, DC Although the basic infrastructure build- purity surpassed only by silicon. Recently,
20375, USA. Email: [email protected] ing blocks for UWBG technology are well extremely high low-temperature mobility

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 (23,000 cm2 V-1 s-1) in homoepitaxial CVD in device fabrication processes to pattern portance of this new technology. The recently
Ga2O3 was enabled by ultralow levels of conducting and insulating surface regions. enacted US CHIPS and Science Act will not
background donor compensation by unin- Dry etching—a common processing step for only fund chip fabrication facilities but will
tentional acceptors (2 × 1013 cm-3, ~0.06% creating such patterns, which can introduce also direct $13 billion to the US Department
donor compensation), likely originating surface defects that affect device reliability— of Commerce and the US Department of
from unintentional formation of point de- could potentially be eliminated altogether Defense toward semiconductor and micro-
fects in the lattice (7). if patterning could be implemented solely electronics research and development. These
However, achieving growth of very thick through ion implantation. Unlike any other investments should spur additional funding
(>30 µm) epitaxial b-Ga2O3 at this level of UWBG material, Ga2O3 can even be wet of research into UWBG semiconductors and
purity is extremely challenging, and its de- etched in phosphoric acid and etched using related materials in the coming years, with
velopment is required to be competitive with gas-phase Ga, both of which eliminate chemi- the expectation that a diverse portfolio of
SiC for the ultrahigh-power switching appli- cal and mechanical damage from plasma heterogeneously integrated semiconductor
cations space. The understanding of defects etching that always introduces defects at the modules will overcome the drawbacks of
in Ga2O3 epitaxy will have to advance over etched surface (10, 11). Developing Ga2O3- chips made using one particular semicon-
the next several years before high-voltage specific fabrication processes in parallel with ductor. Furthermore, a higher-frequency
Ga2O3 devices could become commercially high-quality thick epilayers could speed up device will be beneficial at the system level
viable. Point defects, such as vacancies and Ga2O3 device commercialization during the only if the passive components can keep up.
their related complexes (such as vacancy-in- next decade, at least at the scale of a two- Advances in magnetic materials could also
terstitial defects) as well as extended defects terminal device (such as a diode) (5). help prevent components such as inductors
in thick epitaxial layers, currently inhibit The extremely low thermal conductivity and transformers from becoming too lossy at
Ga2O3 device dimensions. In general, defect of Ga2O3 (11 to 27 W m-1 K-1) must be care- higher frequencies.
characterization in Ga2O3 promises to be a fully considered (5). Cooling of Ga2O3 tran- Exploratory research into Ga2O3 as well as
rich research field that will also enable any sistors will be even more critical than that of other UWBG semiconductors will likely con-
Ga2O3 power electronics commercial enter- GaN transistors, which also suffer from self- tinue given that fundamental questions are
prise hoping to break the 20-kV barrier with heating effects (12). Although Ga2O3 devices still being resolved (15). For Ga2O3, the larg-
a useful device size to do so. still output about an order of magnitude less est hurdles, such as scaling epilayer thick-
For power electronics, the development of power during operation compared with their ness without sacrificing material quality and
p-type (hole-carrier) materials is necessary GaN counterparts, the top- and substrate- managing ultralow thermal conductivity
because holes in Ga2O3 form localized polar- side cooling approaches developed for GaN and unipolar conductivity, will require new
ons that lead to a self-trapping phenomenon could be applied to Ga2O3 (12). Indeed, cap- physics to be solved as well as the develop-
that limits their conduction (8). The absence ping a lateral transistor with AlN or nano- ment of new or modified materials. The
of p-type conductivity in Ga2O3 presents a crystalline diamond has allowed for the continued pace of innovative engineering
challenge for high–electric field management achievement of 5– to 6–W mm-1 DC output of Ga2O3 could bring commercialization of
regardless of device geometry, and any practi- power with Ga2O3, which is similar to early GaO3 power diodes within the next decade,
cal solution will require innovation in hetero- results from GaN high–electron mobility but only if substantial investments in this in-
geneous integration not faced for previously transistors in the 1990s. Heterogeneous in- teresting semiconductor continue. j
developed semiconductors. tegration with high–thermal conductivity,
REF ERENCES AND NOTES
Unlike p-type semiconductors, such as SiC, WBG p-type semiconductors, such as SiC,
1. C. R. Eddy Jr., D. K. Gaskill, Science 324, 1398 (2009).
gallium nitride (GaN), or diamond, WBG p- GaN, and even diamond, is of particular 2. M. Higashiwaki, K. Sasaki, A. Kuramata, T. Masui, S.
type nickel oxide (NiO) can be sputtered at interest for p-n and junction barrier Yamakoshi, Appl. Phys. Lett. 100, 013504 (2012).
room temperature and is thus benign for in- Schottky rectifiers. 3. S. J. Pearton et al., Appl. Phys. Rev. 5, 011301 (2018).
4. Novel Crystal Technology, Inc., Current commercial
tegration with Ga2O3 devices. Recent studies, Looking to early commercialization efforts β-Ga2O3 wafer suppliers; www.novelcrystal.co.jp/.
such as the 8-kV NiO/Ga2O3 p-n diode dem- of WBG semiconductors, the success of SiC 5. A. J. Green et al., APL Mater. 10, 029201 (2022).
onstration by Zhang et al. (9), have shown was driven in part by substantial government 6. J. A. Spencer et al., Appl. Phys. Rev. 9, 011315 (2022).
7. G. Seryogin et al., Appl. Phys. Lett. 117, 262101 (2020).
that the lack of p-type conductivity in Ga2O3 investment and scientific research efforts 8. J. B. Varley, A. Janotti, C. Franchini, C. G. Van de Walle,
could potentially be managed by integrat- that continue its innovation. Solving the is- Phys. Rev. B 85, 081109 (2012).
ing heterojunctions with the purpose of field sues of micropipe and basal plane dislocation 9. J. Zhang et al., Nat. Commun. 13, 3900 (2022).
10. H.-C. Huang, Z. Ren, C. Chan, X. Li, J. Mater. Res. 36, 4756
management and charge balance in these de- defects in SiC relied on advanced character- (2021).
vices. The prospects of Ga2O3 as a power elec- ization techniques, such as ultraviolet pho- 11. N. K. Kalarickal et al., Appl. Phys. Lett. 119, 123503
tronics material would be greatly enhanced if toluminescence imaging and spectroscopy. (2021).
12. M. J. Tadjer, T. J. Anderson, Eds., Thermal Management of
robust heterogeneous integration with p-type Material scientists have continued to develop
Gallium Nitride Electronics (Elsevier, 2022).
WBG semiconductors (such as GaN or AlN) their understanding of defects in the ever- 13. N. A. Mahadik, R. E. Stahlbush, W. Sung, J. Appl. Phys.
are developed. Such development could lead larger-diameter SiC wafers (13). 131, 225702 (2022).
to a reliable junction barrier Schottky recti- Similar efforts will be needed to under- 14. M. D. McCluskey, J. Appl. Phys. 127, 101101 (2020).
15. J. Y. Tsao et al., Adv. Electron. Mater. 4, 1600501 (2018).
fier being commercialized, as was the case stand and control both point and extended
for SiC. defects in thick (>30 µm) Ga2O3 epitaxial lay- ACKNOWL EDGMENTS
Effective electric field termination at sur- ers (14). Government funding would be cru- The views expressed in this article do not necessarily rep-
faces is a key requirement for the use of cial in the early support of such efforts. The resent the views of the US Department of Defense or the
United States. Research at the Naval Research Laboratory
UWBG materials in practical high-voltage small-business technology transfer program
was supported by the Office of Naval Research. K. Hobart, C.
electronic devices. The nitrogen deep ac- initiated by the US Office of Naval Research Eddy Jr., R. Stahlbush, A. Jacobs, H. Masten, J. S. Lundh, and
ceptor has been effective in rendering Ga2O3 in 2017 with the purpose of initiating the de- T. Anderson; epitaxial growth by Novel Crystal Technology
nearly insulating and creating an effective di- velopment of b-Ga2O3 CVD has resulted in (Sayama, Japan); and Agnitron Technology (Chanhassen,
MN) are gratefully acknowledged.
electric layer that can reduce electric fields. the commercialization of this capability be-
Selective ion implantation could be useful fore the program’s end and highlights the im- 10.1126/science.add2713

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1118Perspectives_Special_Issue_16126706.indd 725 11/11/22 5:00 PM

 T R A N S I S T O RS

REVIEW Advances in materials for CNT transistors

Carbon nanotube transistors:

Exploiting the advantages of semiconducting
CNTs requires overcoming several materials

Making electronics from molecules

science hurdles. Just as silicon must be pu-
rified and doped to be a useful channel mate-
rial, as-synthesized CNTs can be either metallic
Aaron D. Franklin1,2*, Mark C. Hersam3,4,5, H.-S. Philip Wong6,7 or semiconducting and must be purified into
semiconducting-only for use in transistors.
Semiconducting carbon nanotubes are robust molecules with nanometer-scale diameters that can be Whether CNTs are metallic or semiconducting
used in field-effect transistors, from larger thin-film implementation to devices that work in depends on how the hexagonal lattice wraps
conjunction with silicon electronics, and can potentially be used as a platform for high-performance into a tube. This structure is most easily vis-
digital electronics as well as radio-frequency and sensing applications. Recent progress in the ualized by rolling a rectangular section of the
materials, devices, and technologies related to carbon nanotube transistors is briefly reviewed. sp2-bonded hexagonal carbon lattice of atom-
Emphasis is placed on the most broadly impactful advancements that have evolved from ically thin graphene into a 1D cylinder, where
single-nanotube devices to implementations with aligned nanotubes and even nanotube thin the resulting diameter is ~1 nm and the length
films. There are obstacles that remain to be addressed, including material synthesis and processing is 102 to 108 nm. The vector that defines the
control, device structure design and transport considerations, and further integration demonstrations width of the rectangular section with respect
with improved reproducibility and reliability; however, the integration of more than 10,000 devices to the graphene lattice is commonly referred
in single functional chips has already been realized. to as the chiral vector and ultimately deter-
mines the diameter, helicity, and conductiv-

T
ity properties of the CNT (5).
ransistors are electronic switching devices thus have limited utility as transistor channels In addition to specifying the physical struc-
that enable digital computation based (5). Throughout this review, CNTs will imply ture of the CNT, the chiral vector also imposes
on their on-state (binary 1) and off-state single-walled nanotubes. Semiconducting well-defined quantum-mechanical boundary
(binary 0) operation. In the earliest days CNTs are composed of a cylindrical shell of conditions on the electronic band structure,
of integrated circuits, it became clear hexagonally arranged carbon with a diameter which implies that for random tube closure,
that scaling down the size of the transistors of ~1 nm. Electrons travel only forward or back- ~33% of CNT chiralities are metallic and ~67%
would drive better chip-level performance, ward with a wave function wrapping around are semiconducting. Moreover, among the
which is now known as Moore’s law. One of the the nanotube to create a one-dimensional (1D) semiconducting chiralities, the bandgap is
most important dimensions for such scaling semiconductor with an energy bandgap of a approximately inversely proportional to the
is the semiconducting channel length, which few hundred milli–electron volts (5). These ma- CNT diameter. Because CNT transistors re-
is the distance that electrical current flows terials are stable in air and can be manipulated quire semiconducting channels, preferably
or is controlled by a gate electric field to turn the through a variety of processing methods that with a well-defined and uniform bandgap, the
device on and off. Although the initial channel are commonly used in the semiconductor in- ability to scalably synthesize and isolate CNTs
lengths were many microns in size, proposals dustry. The early demonstrations of field-effect with atomically precise chiral vector control is
to scale the semiconducting channel to the transistors (FETs) by draping a semiconducting the ultimate goal for high-performance CNT
ultimate limit of molecular dimensions (frac- CNT over metal electrodes (3, 4) have led to integrated circuits.
tions of a nanometer) date to the mid-1970s (1). continued research activity with the goal of
Decades of study on the transfer of electrons creating reproducible, scalable, and high- Controlled synthesis of CNTs
through conjugated organic molecules, con- performance devices integrated into dense cir- CNTs can be synthesized by introducing a
sidered to replace the silicon channel, high- cuitry using processing steps similar to those carbonaceous feedstock with a metal catalyst
lighted several important challenges for such used to create silicon electronics. (usually Fe or Ni) into a growth chamber,
molecular transistors. The foremost issues in- The widespread interest in semiconducting where energy is added through heat, light, or
cluded low stability and the difficulty of effec- CNTs has also inspired intense and ongoing plasma excitation. Because CNT growth typ-
tively gating, and making reliable electrical exploration of other nanomaterials, including ically occurs at temperatures at which these
contact to, the molecules (2). semiconducting nanowires (6), 2D graphene catalysts undergo substantial restructuring,
To meet or exceed the performance of silicon (7), transition metal dichalcogenides (8), and it is difficult to control the chiral vector, and a
electronics, it became clear that new channel Xenes (9). Despite the growing number of range of CNT diameters and both electronic
materials must have similar stability. Among nanomaterial options, CNTs stand out in offer- types are produced; much effort has been ex-
the molecular options, semiconducting single- ing stability, bandgap, and superb electrical pended to gain control over CNT chirality (10).
walled carbon nanotubes (CNTs) have several and thermal properties that are unmatched These approaches include the use of refrac-
advantages (3, 4). Nested multiwalled CNTs are by other candidates. Here, we review recent tory catalyst particles such as W-Co alloys with
effectively metallic at room temperature and material, device, and technology advances for well-defined size and shape that remain struc-
CNT transistors, establishing both the sub- turally invariant at the growth temperature
stantial promise and the remaining challenges and thus can drive predictable nucleation of
1
Department of Electrical and Computer Engineering, Duke
for this molecular transistor. Progress in the targeted CNT chiralities (Fig. 2A) (11), the
University, Durham, NC, USA. 2Department of Chemistry, field will be related to the foremost potential addition of molecular seeds that have a struc-
Duke University, Durham, NC, USA. 3Department of Materials applications for CNT transistors, highlighted ture that closely matches the targeted CNT
Science and Engineering, Northwestern University, Evanston,
in Fig. 1. Two of the most prominent potential chirality (12), or the deployment of CNTs them-
IL, USA. 4Department of Chemistry, Northwestern University,
Evanston, IL, USA. 5Department of Electrical and Computer applications are high-performance (HP) com- selves as seeds in “CNT cloning” (13). Although
Engineering, Northwestern University, Evanston, IL, USA. puting chips and thin-film transistors (TFTs) for tailored catalysts or seeds help control synthetic
6
Department of Electrical Engineering, Stanford University, display backplanes and the internet of things outcomes, many other growth parameters also
Stanford, CA, USA. 7Stanford SystemX Alliance, Stanford
University, Stanford, CA, USA. (IoT); a few of the target performance metrics play a role—including temperature, pressure,
*Corresponding author. Email: [email protected] for these applications are summarized in Table 1. flow rates, and applied electric fields (14)—and

726 18 NOVEMBER 2022 • VOL 378 ISSUE 6621 science.org SCIENCE

thus growth optimization entails the search of
L ch < 100 nm L ch < 10 nm
a broad parameter space. In an effort to accel- Source Gate
erate this exploration, autonomous growth 3D Drain
using closed-loop iterative experimentation Memory
is showing promise for rapid identification
of synthesis conditions that minimize CNT L ch > 10 µm 3D logic
structural polydispersity (15). Scaled, HP FETs
CMOS
Separation of semiconducting CNTs
Because the most-optimized CNT growth pro- 3D integration

Performance
cedures still lack sufficient monodispersity
for wafer-scale transistor applications, post-
synthetic separation methods are required
to sort as-grown CNTs by diameter, chirality, Low-voltage VLSI
Thin-film devices
and electronic type. Fortunately, CNTs have RF transistors for telecom
sizes and shapes that are comparable to those
of biological macromolecules, which has al- Heterogeneous 3D chips
lowed many CNT separation methods to be Chemical and biomedical sensors
adapted from ones that have already been
developed for biochemistry. In density gra- Paper-based printed electronics
dient ultracentrifugation (DGU), CNTs are
first dispersed and encapsulated with mix-
Cost and complexity
tures of surfactants that show selectivity for
different CNT separation targets (including Fig. 1. Broad range of potential applications for CNT transistors. Illustration of device performance
chiral vector, chiral handedness, electronic versus cost and complexity for some of the foremost potential applications of CNT transistors. Applications
type, and diameter) and then separated by range from microscale thin-film devices (e.g., printed electronics, biosensors) to three-dimensionally
buoyant density in aqueous density gradients integrated BEOL devices (such as heterogeneous 3D layers integrated onto silicon CMOS) and scaled
(16). Although DGU has sufficient scalability high-performance (HP) FETs [such as low-voltage very-large-scale integration (VLSI)], with increasing
to be viable commercially, other strategies performance corresponding with increased cost and complexity of integration. Lch, channel length.
from biochemistry have also been heavily
developed, including gel chromatography
(17) and dielectrophoresis. The latter method Table 1. A few of the target metrics for two prominent CNT transistor applications. Values are
has the added benefit of enabling aligned as- approximations based on achieving optimal performance. Notably, although some of these targets
sembly of CNTs between prepatterned elec- have been achieved, one of the foremost challenges is to achieve them simultaneously (e.g., high
trodes (18). on-state current with low subthreshold swing, which is a measure of how much gate voltage is
Methods from polymer chemistry have required to modulate the current by one decade). High-performance FETs are used in applications
also been used for CNT separations, includ- such as central processing units (CPUs) for servers, and TFTs are thin-film transistors such as those
ing aqueous two-phase extraction (19) and used in the backplane electronics of displays.
selective dispersion of targeted CNT chiralities
with structure-discriminating polymers that Target for
Metric Target for TFTs
wrap the nanotubes (Fig. 2B) (20). In all cases, high-performance FETs
purities of semiconducting CNTs have reached CNT semiconducting purity >99.9999% >99.9%
.....................................................................................................................................................................................................................
the detectable limits of optical spectroscopic Parallel CNTs, Thin-film CNTs in an
characterization (~99.9%) and begun to pro- CNT array alignment
consistent pitch unaligned network
.....................................................................................................................................................................................................................
vide sufficient monodispersity for many CNT >200 CNTs per micrometer >50 CNTs per square
transistor applications. The ultimate goal for CNT array density
(linear density) micrometer (aerial density)
.....................................................................................................................................................................................................................
high-performance digital transistors is to Channel length <12 nm >10 μm
.....................................................................................................................................................................................................................
achieve >99.9999% pure semiconducting CNTs Contact length <10 nm >1 μm
.....................................................................................................................................................................................................................
(see Table 1)—the higher the purity, the bet- On-state current > 0.5 mA μm−1 at 0.6 V >100 μA mm−1 at 3 V
.....................................................................................................................................................................................................................
ter the corresponding performance. In addi- Contact resistance <50 ohm·μm per side <20 kilohm·μm per side
.....................................................................................................................................................................................................................
tion, any molecular wrapper (e.g., surfactant or <200 mV per decade
polymer) should ideally be completely removed Subthreshold swing <70 mV per decade
(application dependent)
.....................................................................................................................................................................................................................
after deposition of the CNTs because this pre-
sents an unwanted residue that can hamper
electrical contact, gating efficiency, and trans-
port in the CNT transistor. transistors (21). However, the requirement based on metal work function, such as Pd for
for complementary p-type and n-type transis- p-type injection and Sc for n-type injection,
Other material considerations tors in digital circuits implies that controlled also enable complementary CNT transistors
A transistor also requires electrical contacts, n-type injection and/or doping is required. (24, 25). Beyond the metal selection, interfacial
doping, and dielectrics. Because contacts from Electron-donating adsorbates, such as organo- material considerations and overall contact struc-
commonly used metals (e.g., Au, Pd) tend to rhodium compounds (22), coupled with atomic ture also play a role (see Fig. 2D for an exemplary
yield Fermi-level alignment near the valence layer–deposited encapsulation layers (23), en- end-bonded contact structure using Mo). Ex-
band of CNTs, p-type behavior from the in- able the fabrication of highly stable n-type CNT tension regions of a metal-oxide-semiconductor
jection of holes is readily achieved for CNT transistors (Fig. 2C). Charge-selective contacts FET (MOSFET), which are between the source

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 T R A N S I S T O RS

A B Initial SFM 1st

Templated growth
3 Recycling
tion
struc

Absorbance (cm–1)
Ethanol CVD 1st
Recon
, ( H2
2) 2nd E11
(1) O 2
2 3rd

Nanocrystal
1 E22

Molecular cluster
Interface 0
500 1000 1500
W Co C (n,m) SWNT Wavelength (nm)

C D Mo
Ni
SiO2

Al2O3 SiNx
Au

SiO2 Lch
Lc
Nanotube
Si
Silicon

Fig. 2. Examples of materials for high-performance CNT transistors, on the right. E11 and E22, absorption peaks; SFM, shear force mixing. [Adapted
including synthesized CNTs, purified CNT mixtures, doping strategies, and from (20) with permission from Elsevier]. (C) Electron-donating organorhodium
contact metals. (A) Templated CNT growth of targeted chiralities using compounds encapsulated with atomic layerÐdeposited alumina enabling stable
refractory W-Co nanocrystal catalysts. CVD, chemical vapor deposition; SWNT, n-type CNT transistors. Black is the CNT layer, orange is the dopant layer,
single-walled nanotube. [Adapted by permission from Springer Nature Customer and red is a seeding layer for dielectric growth. [Adapted with permission
Service Center GmbH, Springer Nature (11), copyright (2014)]. (B) Selective from (22). Copyright 2016 American Chemical Society]. (D) When reacted to
polymer dispersion enabling scalable isolation of targeted CNT chiralities form end-bonded carbides, molybdenum contacts to CNT transistors can be
from as-grown polydisperse mixtures as verified by absorption spectrum is scaled down to sub-10-nm dimensions in contact length (Lc) while retaining
shown on the left; a photo of the resultant bottle of sorted CNTs is shown efficient charge injection. [Adapted with permission from (54)].

or drain and the gated semiconducting chan- ity (29). Although devices with an individual Recent progress is encouraging, including a
nel, require stable doping with well-controlled nanotube channel are still of interest for sensing small-scale demonstration with a controlled CNT
doping levels that are optimized for the trade- applications, they are no longer considered suit- pitch of ~10 nm using DNA-directed assembly
off between series resistance and parasitic able for digital or radio-frequency (RF) electron- (34). There are also wafer-scale, high-throughput
capacitances (26)—a feat yet to be reliably ac- ics based on the need for higher current flow strategies that use various forms of solution-
complished for CNT transistors. For the gate than a single CNT can deliver. Although the phase assembly (also referred to as dimension-
dielectric layer, specific materials such as current-carrying capacity for CNTs is astonish- limited self-alignment or liquid crystalline
Y2O3 have exhibited nearly ideal properties ing [~109 A cm−2 (30)], they are only ~1 nm in interfacial assembly), which achieved a ~20-nm
with a high dielectric constant κ and conformal diameter, which yields only ~10 mA per CNT. pitch (Fig. 3, C and D) in one report (35) and a
dielectric coating on CNTs after oxidation of Hence, recent work has predominantly focused 5- to 10-nm pitch in another (36). The primary
deposited yttrium (27). A more conventional on having multiple CNTs in the channel. differences in the two studies were the polymer
approach that uses atomic layer deposition of used to wrap the CNTs and the solution-phase
Al3O3 and HfO2 bilayer dielectrics has enabled Aligned arrays of CNTs technique of depositing the CNTs into arrays
transistors that have a 10-nm gate length with Ideally, the CNTs in a transistor channel would on the substrate. Nevertheless, these ap-
a gate leakage current commensurate with be perfectly aligned in a parallel array with a proaches still require further work to remove
state-of-the-art Si transistors (28). Upon inte- controlled pitch of ~2 to 5 nm (31), similar to unwanted residue from the solution-phase pro-
gration of all these optimized materials, CNT how fins of silicon are arranged in modern cessing along with more consistent, controlled
transistors have been shown to exceed the transistor technologies (FinFETs). Realizing alignment (without bundling) in all directions
performance of incumbent silicon integrated such arrays continues to be a challenge. If the with uniform spacing.
circuit technology, as will be discussed in the CNTs are too close (or bundled), it can create
subsequent sections. cross-talk (electric field screening) and effective Thin films of CNTs
gating issues (32). If the CNTs are too far apart, The difficulty of achieving aligned arrays with
CNT transistor design current density (current per transistor width) controlled pitch has led some researchers to
The initial focus for CNT transistor research will be insufficient. For digital systems with a use unaligned CNT networks or thin films
was on the use of a single CNT as the channel high density of CNT transistors, variations in the (Fig. 3, E to H). Although these unaligned films
(see Fig. 3, A and B) and demonstration of bal- pitch between CNTs also deleteriously affects are less favorable for carrier transport, as well
listic transport (21) and digital circuit operabil- the overall energy, delay, and noise margin (33). as for contacting and gating the nanotubes,

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unaligned CNT networks have achieved high thin-film channel are not long enough to trans- ness and permittivity of both the gate dielectric
performance in nanoscale transistors (37, 38). verse the channel and instead operate as perco- and the semiconducting channel. A generally
Moreover, CNT thin films can be deposited by lating networks in which electrons travel from accepted approximation is that a channel length
using printing techniques, including roll-to- CNT to CNT in transit from source to drain greater than 3λ will ensure that deleterious
roll (39) and direct-write (40, 41) approaches (Fig. 3G) (44, 45). Compared with long-studied short-channel effects are avoided.
(Fig. 3H), which makes them attractive for organic semiconductor TFTs (46), CNT-TFTs Given their intrinsically small size, CNTs
TFTs. The application space for these larger have considerably higher mobilities (10 to offer advantages for aggressively scaled de-
(approximately tens of micrometers) TFTs is 100 cm2 V−1 s−1) and stability under bias, in air, vices. Although it is ideal for an FET to have
distinct from high-performance nanoscale or both. a gate-all-around geometry to minimize λ,
FETs and includes sensors, flexible electron- and demonstrations of such gate structures
ics, IoT, and display backplanes (42). For TFT Advanced gating structures for CNTs have been reported (48, 49), studies
applications, CNT thin films compete well In addition to the density and arrangement of have shown that channel lengths that are
against incumbent semiconductor options such nanotubes in the channel, the gate configura- much less than 10 nm (as short as 5 nm) can
as organics and polymers, metal oxides, and tion in a CNT transistor has advanced in many be achieved in either bottom-gate (50, 51)
low-temperature polysilicon (LTPS) (43). ways. For nanoscale FETs, the primary goal is or top-gate (51, 52) geometries. Although gate
When CNT thin films are used in FETs with to maximize the gate control of the CNT energy geometry does vary for TFTs, it is less critical
nanoscale channel lengths (<100 nm), most of bands in the channel, which is achieved through and mostly limited by the gate dielectric mate-
the nanotubes bridge the entire channel, even if strong gate coupling that is typically expressed rial and the application needs.
they are not perfectly aligned (Fig. 3F). In the as a small scale length, λ (47). The scale length
microscale lengths of TFTs, nanotubes in the depends on the gate geometry and on the thick- Source-drain contact structures
For highly scaled CNT transistors with small
A Single CNT B footprints, not only does the channel length
Pt SIO2 Pt SIO2 Pt need to be at the nanometer scale but the
source and drain contacts also need to have
minimal dimensions while still providing
efficient ohmic charge injection. Palladium
contacts have achieved the quantum limit of
C D 6.5 kilohm per CNT at a 10-nm contact length
CNT array
for a p-type side contact, where the metal rests
on top of a CNT without any chemical bond-
Source ing (53), though this needs to be realized with
higher yield and reproducibility. Alternatively,
Drain an edge-contact structure would offer ideal
scalability and has been demonstrated by re-
E CNT network F Pad CNT film
acting Mo with CNTs to yield a carbide end-
500 nm Wch
V 1 = 4.987 µm bonded contact with sub-10-nm contact lengths
Source H 1 = 208.4 nm (Fig. 2D) (54). Regardless of the geometry,
Gate

Drain L ch contacts to CNTs are a leading factor in deter-

1 µm
mining overall performance, and the combi-
nation of material, structure, and processing
must be further refined to yield contacts for
H
G CNT thin film both p- and n-type carrier injection with high
consistency and low resistance.

Technology demonstrations
5 mm High-performance, energy-efficient digital logic
Although many applications can benefit from
Fig. 3. Variations in CNT transistor structures. (A) Illustration of a single CNT channel with metallic source the properties of CNTs, digital logic applica-
and drain contacts. (B) Atomic force microscopy image of the first-reported CNT transistor, which had a single tions have received the greatest attention
nanotube. [Reprinted by permission from Springer Nature Customer Service Center GmbH, Springer Nature (Fig. 4) because they have the potential to sur-
(3), copyright (1998)]. (C and D) Illustration of an aligned array of CNTs as the channel (C) and a corresponding pass incumbent Si technology in performance
recent example of a transistor with such an array (D), including a scanning electron microscopy (SEM) image and energy efficiency. Such exemplary high-
of the aligned CNTs (left) and schematic of the solution-phase assembly process (right). [(D) is reprinted with performance devices from aligned arrays of
permission from (35); Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). CNTs can achieve high on-state currents at rel-
https://creativecommons.org/licenses/by-nc/4.0/]. (E and F) Illustration of a CNT network (not aligned) atively low voltages (Fig. 4, A to C). As shown
used as channel for nanoscale FET (E) with a corresponding recent example of a high-performance transistor (F), in Fig. 4D, gate-all-around CNT transistors
including a SEM image of the high-density film (left) and a top-view schematic of the device structure (right). with doped extensions and multiple layers of
Note that most nanotubes directly bridge the source and drain in this nanoscale configuration. H1 and V1, measurement high-density CNTs are projected to show up to
markers of CNT film area height and channel length, respectively; Wch, width of CNT channel region. [(F) is adapted seven times the energy-delay product (EDP)
by permission from Springer Nature Customer Service Center GmbH, Springer Nature (38), copyright (2018)]. benefits compared with Si nanosheets at the
(G and H) Illustration of a CNT thin film used in a thin-film transistor (dimensions of tens of micrometers) (G) with a 2-nm technology node (the EDP, or switching
corresponding recent example of an aerosol-jet printed CNT-TFT on a flexible plastic substrate (H), including a energy, is the product of the time and the
SEM image of the printed thin film (left) and a picture of the printed CNT-TFTs with a schematic of the printing power consumption for an on-off cycle, and
technique (right). [(H) is reprinted with permission from (41). Copyright 2019 American Chemical Society]. a measure of energy efficiency) (26). As noted

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 T R A N S I S T O RS

A 10–3 B 1.4
Vgs from –2.5 V to 1 V C Source D 3
Gate Drain
1.2 (0.5-V step)

Total energy (aJ/cycle)

10–4 Si nanosheet
10–5 1.0

Ids (A/µm)

Ids (A/µm)
10–6 190 0.8
mV/dec 7 x EDP benefits
10–7 0.6
Vds =–0.1 V
Si nanosheet Source Gate
10–8 Vds =–0.3 V 0.4 Drain
Vds =–0.5 V
10–9 Vds =–0.8 V 0.2 CNT aligned array
Vds =–1 V Preferred corner
10–10 0.0 0
–2 –1 0 1 2 –1.2 –0.8 –0.4 0.0 0 600
Vgs (V) Vds (V) CNT aligned array Frequency (GHz)

Fig. 4. High-performance CNT transistors for digital logic applications. schematics for a Si nanosheet transistor with two stacked channels
(A and B) Subthreshold (A) and output characteristics (B) of CNT transistors and a CNT aligned array transistor. (D) Projected energy versus frequency
fabricated with aligned arrays of ~150 CNTs per micrometer that achieve pareto curves for Si nanosheet and CNT transistors at the 2-nm technology
an on-state current of >1 mA μm−1. Ids, drain current; Vds, drain-source voltage; node for an inverter ring oscillator. [© 2021. Adapted, with permission,
Vgs, gate-source voltage. [Adapted with permission from (36)]. (C) Device from (26)].

earlier, because of their ultrathin body (~1 nm), resistance of 6.5 kilohm per CNT (53), sub- RF electronics
CNT transistors offer excellent electrostatic 10-nm gate length (52), multiple stacked CNT Although digital electronics remains the dom-
control even at aggressively scaled gate lengths, channel layers (61), and doped source or drain inant focus in the field, CNT transistors also
limited only by direct source-to-drain tunnel- extensions (62). This MOSFET-like CNT struc- hold great promise for high-frequency RF
ing. Parasitic capacitance, a key detractor of ture with 35-nm contacted gate pitch and 20-nm transistors, which are relevant to telecommu-
speed and energy efficiency, accounts for >70% active width is projected to have a performance nications applications (68, 69). Many of the
of the total capacitance of modern Si tran- that far exceeds that of Si transistors for a 2-nm material and device needs for digital CNT
sistors. Because of the ultrathin body, CNT node logic technology. transistors also apply to RF electronics, with
transistors have substantially lower parasitic some relaxing of the semiconducting purity
gate-to-source or gate-to-drain capacitance. These 3D integration needs and an enhanced need for high trans-
two key attributes of CNTs, along with the Future semiconductor chips will go beyond 2D conductance and linearity, which translates
high transport and injection velocities, are the device miniaturization and instead will have to low distortion when amplifying a signal.
physical basis for high-performance, energy- 3D layers of active devices (63). Because logic Recent progress on RF CNT transistors from
efficient digital logic. device layers in 3D must be thin and fabricated aligned arrays of nanotubes shows the abil-
As noted earlier, many fundamental build- at temperatures that are compatible with back- ity to operate at frequencies up to hundreds
ing blocks of a CNT transistor technology have end-of-line (BEOL) wiring layers (typically of gigahertz with attractively low power con-
already been demonstrated. At the circuit or <400°C), CNT transistors are particularly well- sumption and high versatility for integration
system level, a fully functional static random- suited for 3D integration because of the low in system-on-chip applications (70).
access memory (SRAM) array (55), a monolithic device-fabrication temperature and thin device
3D imager (56), and a 16-bit RISC-V (where layer. Starting from the first demonstration of Printed electronics
RISC is reduced instruction set computer) an all-CNT transistor computer almost a decade The ability to purify a solution-phase dispersion
processor with >14,000 transistors (Fig. 5B) ago (64), progress has occurred not only in the of semiconducting CNTs also enables printing
(57) have been fabricated entirely from CNT level of integration but also in the variety of into thin-film devices (Fig. 2H). Many reports
transistors. What’s more, wafer-scale fabrica- devices as well as maturation of the technology have shown that fully printed CNT-TFTs can
tion of CNT transistors has been demonstrated from university laboratories to industry. be used in digital logic circuitry to illustrate the
in an industrial foundry using 200-mm wafer A four-layer monolithically integrated chip ability of these devices to deliver computational
processing techniques (Fig. 5A) (58). The fab- comprising a silicon transistor layer, a CNT functionality (71–73). However, given the low
rication and design of CNT transistors with transistor memory read-out circuit layer, a cost of legacy-node silicon transistor technol-
the same tools and infrastructure as commer- resistive switching metal-oxide random-access ogies, the likelihood that printed CNT-TFT
cial semiconductor technologies helps lower memory (RRAM) layer, and a CNT transistor circuitry will be of widespread use is low. More
the barrier for the introduction of CNT devices sensor layer on the top illustrates the benefits encouraging is the use of printed CNT-TFTs
into mass production. of monolithic integration (Fig. 5, C to E) (65). for the backplane control of displays (74) or
At the individual device level, recent work This 3D chip can process information from the for custom biosensing systems (75). Recent
shows short gate length (10 nm), complemen- sensors to the memory cells to the transistors studies also reveal the recyclability of CNT
tary p- and n-channel devices with near ideal in parallel at rates of terabytes per second. An- thin films (76), which shows promise for en-
subthreshold swing for single-CNT transis- other example is an end-to-end brain-inspired abling a fully printed, paper-based electronic
tors (59), and high on-state current per width hyperdimensional computing nanosystem that system in which all core materials are able to
for aligned CNTs with a density of 50 CNTs is effective for cognitive tasks such as language be recaptured and reused (77).
per micrometer (60). In the near future, it recognition, which was realized with monolithic
will be possible to integrate the following ele- 3D integration of CNT transistors and RRAM, Future developments and perspectives
ments (already shown separately) in a single enabling fine-grained and dense vertical con- Materials outlook
device demonstration: gate-all-around geom- nections between computation and storage Advances in materials are anticipated to be
etry (48, 49), >250 CNTs per micrometer in layers using BEOL interlayer vias (66). The CNT central to future advances in CNT transistors.
highly aligned arrays (36), 3-nm oxide dielectric transistor fabrication process not only has been Improving the purity of semiconducting CNTs
(target oxide capacitance = 2.94 × 10−10 F m−1) shown on full 200-mm wafers (58) but also is critical for all device use cases. In this regard,
(28), sub-10-nm p-type contacts with a contact has 3D integration with RRAM (67). one of the largest impediments to minimizing

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metallic CNT impurities down to concentra- Ultimately, growth conditions encompass mentary metal-oxide-semiconductor (CMOS)
tions of parts per million or billion is the lack of such a vast parameter space that methods for fabs. Most metal-contact formation processes
high-throughput analytical methods for detect- efficiently searching for and identifying opti- rely on liftoff, which is not considered a scala-
ing ultralow concentrations of metallic CNTs. mal growth conditions are needed. Emerging ble process, and the liftoff-free alternatives also
Most high-throughput optical detection meth- artificial intelligence and machine-learning tend to rely on slow patterning processes (78).
ods for CNTs (such as photoluminescence optimization approaches coupled with high- The scalability of the contact length, which
spectroscopy) are less sensitive, if not com- throughput experimental screening hold prom- is an equally important parameter as the gate
pletely insensitive, to metallic species. Indeed, ise for next-generation synthetic efforts (15). length for overall transistor scaling, needs fur-
the only established method for quantifying Similarly, the discovery, optimization, and in- ther consideration. Some studies show severe
ultralow concentrations of metallic CNTs is tegration of the many other materials in a CNT degradation at sub-30-nm contact lengths (52),
to fabricate massive arrays of individual CNT transistor (including dopants, contacts, gate whereas others have shown less degradation at
transistors and then electrically probe them electrodes, and dielectrics) can also likely be scaled lengths but have not yet realized them at
one by one in search of short circuits. This accelerated by machine learning coupled with high yield (53). Such contact-length scaling chal-
approach is extremely time consuming and high-throughput experimental screening. lenges are common to all transistors (79), but
only gets worse as the semiconducting purity discovering a solution that allows for aggressively
increases. Thus, most CNT separation meth- Device outlook scaled contacts without degrading the device
ods have only been optimized to the detection Although much has been learned about es- would be a critical advance. End-bonded or edge
limits of optical spectroscopy (~99.9%). tablishing interfaces to CNTs, including gate contacts present one such possibility (54), al-
Another unresolved issue for semiconducting structure and contacts, challenges remain. The though further work is required to reduce the
CNTs is the need for a scalable and sustainable roles of material selection and purification processing temperature and to understand trans-
manufacturing approach to produce sufficient (discussed earlier), methods of fabrication, port and performance limits. In addition, realiz-
quantities of ultrahigh-purity semiconducting and doping control continue to be elucidated in ing an equally high-quality and scalable contact to
CNTs to meet the potentially large market rep- an expansive volume of reports. Indeed, one of n-type CNT transistors remains to be addressed.
resented not only by high-performance inte- the foremost challenges moving forward is de- Regarding TFTs from CNTs, much of the
grated circuits but also by high-volume printed termining what combination of materials and knowledge gained from nanoscale FET devices
electronics. Most solution-based separation processes (of the thousands reported) is most is applicable. The foremost exceptions are that
methods do not possess fundamental barriers appropriate to use. More systematic studies are a TFT technology should ideally be compatible
to scalability, but the yields of these processes needed that explore certain contact and gate- with large substrate sizes and have exception-
are ultimately limited by the quality of the input stack material configurations for their impact ally low cost. Because one of the primary appli-
raw material. Improvements in synthesis that on device performance, yield, reproducibility, cations for TFTs is in display backplanes, the
minimize impurities and maximize semicon- and stability. For example, it is clear that CNT materials and processes should be scalable to
ducting purity with narrow CNT diameter dis- channels are scalable to sub-10-nm lengths in large panels. Although device-level performance
tributions are needed to improve the yield of a variety of configurations, but it is not clear and size matter, TFTs have relaxed constraints,
downstream separation. An enticing option which device structure is superior (e.g., top-gate with more emphasis given to fabrication cost
would be to refine cloning (13) to the point that versus gate-all-around, side contact versus edge because these devices will be used in com-
iterative separation and amplification could be contact) and whether top-performing options modity applications (such as backplanes) or
achieved in a manner analogous to the poly- also have fabrication processes that are com- disposable applications (such as IoT). The
merase chain reaction (PCR) in biochemistry. patible with relevant manufacturing in comple- recent demonstration of recyclable printed

A B C
CNT logic and
CNT transistor RV16X-NANO

200-mm Si wafer sensors

of CNT RRAM
transistors
CNT logic
Silicon logic

CNTs
D E

S D
High-k G
20 µm 1 µm

Fig. 5. Wafer-scale and 3D integration of CNT transistors. (A) A 200-mm Si [Adapted by permission from Springer Nature Customer Service Center GmbH,
wafer with CNT transistors processed in a commercial silicon foundry. An image of a Springer Nature (57), copyright (2019)]. (C to E) Image and schematic of a 3D N3XT
single die or chip from the wafer is shown at the bottom left, and a schematic of the chip with monolithic integration of CNT transistors and RRAM memory layers on top of
CNT transistor structure is shown at the bottom right. D, drain; G, gate; k, relative silicon logic (C); cross-sectional TEM image showing the bottom Si logic layer, the
permittivity; S, source. [Adapted by permission from Springer Nature Customer RRAM memory layer, and the two CNT transistor layers [carbon nanotube field-effect
Service Center GmbH, Springer Nature (58), copyright (2020)]. (B) Optical image transistor (CNFET), logic, and sensors] (D); and scanning electron microscopy
of a RISC-V processor realized with CMOS CNT transistors (RV16X-NANO), including images of a CNT circuit and devices in the top layer of the 3D N3XT chip (E) (scale bar,
higher magnification images showing details of CNT circuits (false colors represent 500 nm). [Adapted by permission by Springer Nature Customer Service Center
different metal layers) and a single CNT device (CNTs are highlighted in yellow). GmbH, Springer Nature (65), copyright (2017)].

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 T R A N S I S T O RS

CNT-TFTs on paper substrates suggests sus- and surfaces without dangling bonds), it also 39. P. H. Lau et al., Nano Lett. 13, 3864–3869 (2013).
tainable implementations (77). Improvements retains all the benefits of an FET, which in- 40. P. Chen et al., Nano Lett. 11, 5301–5308 (2011).
41. S. Lu et al., ACS Nano 13, 11263–11272 (2019).
in CNT-TFT yield and stability will be critical, clude a well-developed circuit or system design 42. A. D. Franklin, Science 349, aab2750 (2015).
particularly the role of tube-tube contacts in ecosystem and a mature manufacturing tech- 43. J. A. Cardenas, J. B. Andrews, S. G. Noyce, A. D. Franklin, Nano
percolating networks. nology, with the further potential to integrate Futures 4, 012001 (2020).
44. N. F. Zorn, J. Zaumseil, Appl. Phys. Rev. 8, 041318 (2021).
in three dimensions for chips with increasing 45. Q. Cao et al., Nature 454, 495–500 (2008).
Technology outlook device count and connectivity. These benefits 46. S. Park, S. H. Kim, H. H. Choi, B. Kang, K. Cho, Adv. Funct.
The realization of a CNT transistor technology are projected to eventually outweigh all the Mater. 30, 1904590 (2020).
47. R. Yan, A. Ourmazd, K. F. Lee, IEEE Trans. Electron Dev. 39,
that meets high-volume manufacturing needs limitations because the power of incumbency 704–710 (1992).
has many remaining hurdles that require a and scalability in three dimensions cannot be 48. Z. H. Chen et al., IEEE Electron Device Lett. 29, 183–185
concerted effort from academia and industry understated. Between the opportunities in high- (2008).
49. A. D. Franklin et al., Nano Lett. 13, 2490–2495 (2013).
to surmount. Regarding semiconducting CNT performance digital logic with the potential for
50. A. D. Franklin et al., Nano Lett. 12, 758–762 (2012).
purity, although the highest possible purity 3D integration and the possibilities for printed 51. Q. Cao, J. Tersoff, D. B. Farmer, Y. Zhu, S. J. Han, Science 356,
remains ideal for EDP, logic design techniques and even recyclable thin-film electronics, CNT 1369–1372 (2017).
can be used to relax the requirement for cer- transistors warrant a renewed and even re- 52. C. Qiu et al., Science 355, 271–276 (2017).
53. G. Pitner et al., Nano Lett. 19, 1083–1089 (2019).
tain applications by about 100 times (from doubled effort from academic, government, and 54. Q. Cao et al., Science 350, 68–72 (2015).
99.9999 to 99.99%), without imposing addi- industry contributors. These molecular transis- 55. P. S. Kanhaiya, C. Lau, G. Hills, M. D. Bishop, M. M. Shulaker,
tional processing steps or redundancy (65). tor technologies are within reach, but only if the IEEE Trans. Electron Dev. 66, 5375–5380 (2019).
56. T. Srimani, G. Hills, C. Lau, M. Shulaker, in 2019 Symposium on
For high-performance digital systems, device remaining challenges are surmounted by the VLSI Technology (TEL, 2019), pp. T24–T25.
variations play an important role in determin- scientific and engineering communities. 57. G. Hills et al., Nature 572, 595–602 (2019).
ing the overall EDP and noise margin of the 58. M. D. Bishop et al., Nat. Electron. 3, 492–501 (2020).
59. L. Peng, Z. Zhang, C. Qiu, Nat. Electron. 2, 499–505 (2019).
system. CNT-specific sources of variation in- RE FERENCES AND NOTES
60. G. J. Brady et al., Sci. Adv. 2, e1601240 (2016).
clude CNT density and pitch (distance between 1. A. Aviram, M. A. Ratner, Chem. Phys. Lett. 29, 277–283 (1974). 61. Y. Xie, Z. Zhang, D. Zhong, L. Peng, Nano Res. 12, 1810–1816
2. M. Ratner, Nat. Nanotechnol. 8, 378–381 (2013). (2019).
CNTs in a multi-CNT transistor), CNT band- 3. S. J. Tans, A. R. M. Verschueren, C. Dekker, Nature 393, 49–52 62. C. Lau, T. Srimani, M. D. Bishop, G. Hills, M. M. Shulaker, ACS
gap (determined by the chirality and diame- (1998). Nano 12, 10924–10931 (2018).
ter), and extreme sensitivity to random fixed 4. R. Martel, T. Schmidt, H. Shea, T. Hertel, P. Avouris, Appl. 63. S. Salahuddin, K. Ni, S. Datta, Nat. Electron. 1, 442–450
Phys. Lett. 73, 2447–2449 (1998). (2018).
charges in the surroundings (which is also the
5. M. S. Dresselhaus, G. Dresselhaus, P. Avouris, Carbon 64. M. M. Shulaker et al., Nature 501, 526–530 (2013).
reason why CNTs are ultrasensitive sensors). Nanotubes: Synthesis, Structure, Properties, and Applications 65. M. M. Shulaker et al., Nature 547, 74–78 (2017).
The transistor width (perpendicular to the di- (Springer, 2001). 66. T. F. Wu et al., in 2018 IEEE International Solid - State Circuits
6. C. Jia, Z. Lin, Y. Huang, X. Duan, Chem. Rev. 119, 9074–9135 Conference (ISSCC) (IEEE, 2018), pp. 492–494.
rection of current flow) of logic technologies is 67. T. Srimani et al., in 2020 IEEE Symposium on VLSI Technology
(2019).
on the order of 20 to 40 nm. For a CNT density 7. D. Akinwande et al., Nature 573, 507–518 (2019). (IEEE, 2020), pp. 1–2.
of 250 CNTs per micrometer, there will only be 8. S. Das et al., Nat. Electron. 4, 786–799 (2021). 68. Y. Cao et al., ACS Nano 10, 6782–6790 (2016).
69. M. Schroter, M. Claus, P. Sakalas, M. Haferlach, W. Dawei,
5 to 10 CNTs in the channel; hence, variations 9. L. Zhang et al., Adv. Funct. Mater. 31, 2005471 (2021).
Electron Devices Soc. IEEE J. 1, 9–20 (2013).
10. R. Rao et al., ACS Nano 12, 11756–11784 (2018).
of the CNT density and the CNT pitch will lead 70. H. Shi et al., Nat. Electron. 4, 405–415 (2021).
11. F. Yang et al., Nature 510, 522–524 (2014).
71. M. Ha et al., ACS Nano 4, 4388–4395 (2010).
to substantial variations in the current drive. 12. J. R. Sanchez-Valencia et al., Nature 512, 61–64 (2014). 72. S. Lu, A. D. Franklin, Nanoscale 12, 23371–23390 (2020).
Design solutions that mitigate such varia- 13. B. Liu et al., Nano Lett. 13, 4416–4421 (2013). 73. K. Hong et al., Adv. Mater. 26, 7032–7037 (2014).
14. J. Wang et al., Nat. Catal. 1, 326–331 (2018). 74. K. Schnittker, M. Tursunniyaz, J. B. Andrews, J. Inf. Disp. 22,
tions are essential as part of a co-design process 15. P. Nikolaev et al., npj Comput. Mater. 2, 16031 (2016). 193–209 (2021).
for technology development (80). For example, 16. M. S. Arnold, A. A. Green, J. F. Hulvat, S. I. Stupp, 75. Z. Lin, G. Wu, L. Zhao, K. W. C. Lai, IEEE Nanotechnol. Mag. 13,
CNT bandgap variation directly translates into M. C. Hersam, Nat. Nanotechnol. 1, 60–65 (2006). 4–14 (2019).
17. H. Liu, D. Nishide, T. Tanaka, H. Kataura, Nat. Commun. 2, 309 76. S. Wang, J. Zhao, Q. Wang, D. Zhang, ACS Sustain. Chem. Eng.
variation in off-state leakage current through (2011). 10, 3851–3861 (2022).
the threshold voltage and band-to-band tun- 18. Q. Cao, S. J. Han, G. S. Tulevski, Nat. Commun. 5, 5071 77. N. X. Williams, G. Bullard, N. Brooke, M. J. Therien,
neling at the drain. Band-to-band tunneling (2014). A. D. Franklin, Nat. Electron. 4, 261–268 (2021).
19. J. A. Fagan et al., Adv. Mater. 26, 2800–2804 (2014). 78. A. J. M. Mackus et al., Appl. Phys. Lett. 110, 013101 (2017).
leakage varies exponentially with bandgap 79. S. K. Su et al., in 2022 IEEE Symposium On VLSI Technology
20. A. Graf et al., Carbon 105, 593–599 (2016).
and sets a minimum achievable leakage cur- 21. A. Javey, J. Guo, Q. Wang, M. Lundstrom, H. Dai, Nature 424, and Circuits (IEEE, 2022), pp. 403–404.
rent (81)—a boundary for trading on-state cur- 654–657 (2003). 80. G. Hills et al., IEEE Trans. Comput. Aided Des. Integrated Circ.
22. M. L. Geier, K. Moudgil, S. Barlow, S. R. Marder, M. C. Hersam, Syst. 34, 1082–1095 (2015).
rent with off-state leakage current by tuning 81. Q. Lin et al., IEEE Electron Device Lett. 43, 490–493 (2022).
Nano Lett. 16, 4329–4334 (2016).
the threshold voltage. Direct source-to-drain 82. G. Hills et al., IEEE Trans. NanoTechnol. 17, 1259–1269
23. M. L. Geier et al., Nat. Nanotechnol. 10, 944–948 (2015).
(2018).
tunneling current also depends exponentially 24. Z. Chen, J. Appenzeller, J. Knoch, Y. Lin, P. Avouris, Nano Lett.
on the bandgap and sets the limit for gate- 5, 1497–1502 (2005).
AC KNOWLED GME NTS
25. C. Wang, K. Ryu, A. Badmaev, J. Zhang, C. Zhou, ACS Nano 5,
length scaling. The choice of the CNT diameter 1147–1153 (2011). Funding: A.D.F. acknowledges support from the National Science
(bandgap) is faced with the same trade-off as 26. C. Gilardi et al., in 2021 IEEE International Electron Devices Foundation (NSF) (NSF ECCS-1915814). M.C.H. acknowledges
Meeting (IEDM) (IEEE, 2021), pp. 27.3.1–27.3.4. support from the NSF Materials Research Science and Engineering
other FETs. Small-bandgap CNTs have lower
27. Z. Wang et al., Nano Lett. 10, 2024–2030 (2010). Center at Northwestern University (NSF DMR-1720139). H.-S.P.W.
effective masses and higher on-state currents, 28. G. Pitner et al., in 2020 IEEE International Electron Devices acknowledges support in part from the Defense Advanced Research
and large-bandgap CNTs have lower tunneling Meeting (IEDM) (IEEE, 2020), pp. 3.5.1–3.5.4. Projects Agency (DARPA) Electronics Resurgence Initiative (ERI)
off-state leakage currents and can scale down 29. Z. Chen et al., Science 311, 1735 (2006). Three Dimensional Monolithic System on a Chip (3DSoC), the NSF
30. B. Q. Wei, R. Vajtai, P. M. Ajayan, Appl. Phys. Lett. 79, (award 1640060), and the Stanford SystemX Alliance, as well as
further in gate length and maintain higher 1172–1174 (2001). collaboration and discussion with G. Pitner and colleagues at Taiwan
operating voltages for high speed. The optimal 31. A. D. Franklin, Nature 498, 443–444 (2013). Semiconductor Manufacturing Company (TSMC), M. Shulaker at
choice is necessarily application-dependent and 32. F. Léonard, Nanotechnology 17, 2381–2385 (2006). MIT, and S. Mitra at Stanford. Competing interests: The authors
33. J. Zhang, N. P. Patil, A. Hazeghi, H.-S. P. Wong, S. Mitra, IEEE declare no competing interests. License information: Copyright ©
must be co-designed, given the target comput-
Trans. Comput. Aided Des. Integrated Circ. Syst. 30, 1103–1113 2022 the authors, some rights reserved; exclusive licensee
ing workloads (82). (2011). American Association for the Advancement of Science. No claim to
Although the CNT transistor inherits all the 34. W. Sun et al., Science 368, 874–877 (2020). original US government works. https://www.science.org/about/
limitations of a MOSFET (electrostatics and 35. K. R. Jinkins et al., Sci. Adv. 7, eabh0640 (2021). science-licenses-journal-article-reuse
36. L. Liu et al., Science 368, 850–856 (2020).
transport physics) and has all the challenges of 37. C. Zhao et al., Adv. Funct. Mater. 29, 1808574 (2019). Submitted 15 June 2022; accepted 7 September 2022
a low-dimensional channel material (contacts 38. D. Zhong et al., Nat. Electron. 1, 40–45 (2018). 10.1126/science.abp8278

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REVIEW power while in a stable logical state, as it dis-
sipated power only during state transition (2).
Toward attoJoule switching energy In its infancy CMOS was viewed by circuit
designers as too slow compared with bipolar
in logic transistors transistors for use in high-performance pro-
cessors and was relegated to low-power and
Suman Datta1,2*, Wriddhi Chakraborty2, Marko Radosavljevic3 lightweight processing engines meant for data
terminals, calculators, and avionics. Advances
Advances in the theory of semiconductors in the 1930s in addition to the purification of germanium and silicon in high-resolution lithography techniques for
crystals in the 1940s enabled the point-contact junction transistor in 1947 and initiated the era of transferring fine patterns to the integrated
semiconductor electronics. Gordon Moore postulated 18 years later that the number of components in an circuit and in ion implantation and dopant
integrated circuit would double every 1 to 2 years with associated reductions in cost per transistor. Transistor activation techniques for forming shallow
density doubling through scaling—the decrease of component sizes—with each new process node continues source-drain junctions and tailoring channel
today, albeit at a slower pace compared with historical rates of scaling. Transistor scaling has resulted in doping profiles led to the design of highly scaled
exponential gain in performance and energy efficiency of integrated circuits, which transformed computing and fast-switching metal-oxide-silicon field-
from mainframes to personal computers and from mobile computing to cloud computing. Innovations in effect transistors (MOSFETs), which can have
new materials, transistor structures, and lithographic technologies will enable further scaling. Monolithic 3D p- or n-type channels (PMOS and NMOS, re-
integration, design technology co-optimization, alternative switching mechanisms, and cryogenic operation spectively), CMOS used complementary and
could enable further transistor scaling and improved energy efficiency in the foreseeable future. symmetrical pairs of these transistors. During
the next four decades, transistor scaling would

I
provide steady metronomic improvement for
n electronics, new inventions that reduce logic (1) to deliver two billion floating point CMOS circuit performance. Gordon Moore’s
energy consumption and enhance integra- operations per second (gigaFLOPs) of peak prediction that transistor count would double
tion capacity tend to become the dominant performance. The fast clock speed and dense every 2 years (3) proved true (Fig. 1). Demon-
device platform. For example, the triode in packaging led to such high heat dissipation strating clear advantages in energy efficien-
a vacuum tube was used to amplify signals that the machine had to be continuously cooled cy and device density over bipolar transistors,
for almost half a century but engineers recog- through circulation of Fluorinert liquid (sup- MOSFET would become the primary choice
nized drawbacks such as high power consump- plied by 3M) through the processor circuits. The for high-performance digital circuits for a broad
tion resulting in high heat dissipation as well as visible heat exchange water tank that came with range of technologies from general-purpose
overall lack of robustness. Energy consumption the liquid cooling system earned the Cray-2 the processors to domain-specific accelerators for
issues in telephone signal transmission drove nickname “Bubbles.” cloud-enabled data centers and from desktop
researchers at Bell Laboratories to invent a During the late 1980s, there was a wide- and mobile client computers to low-power em-
solid-state semiconductor device as a more re- spread design transition from bipolar to com- bedded processors for wearable and internet-of-
liable and energy-efficient replacement for the plementary metal oxide semiconductor (CMOS) things applications.
vacuum tube amplifier. The bipolar point-contact transistor technology. CMOS, which had been The operating voltage of the MOSFETs de-
was made from two isolated strips of gold foil on in development since the 1960s and was fa- creased progressively as the lithographic di-
a plastic wedge, and these strips were pushed vored by Japanese manufacturers, allowed for mensions shrank, leading to improved energy
down to make contact with a slab of n-doped a much-needed reprieve from power challenges. efficiency, faster speed, and lower cost per
germanium. This was dubbed the transistor and Unlike bipolar transistors, complementary pull transistor. The lower energy consumption per
was commercialized by their Western Electric up and pull down transistor configuration of switching event per transistor meant that the
subsidiary for radio transmission applications, CMOS technology consumed negligible standby integrated circuit could accommodate more
although this configuration was eventually re-
placed by the easier-to-manufacture and more Geometrical scaling
reliable silicon bipolar junction transistor. Equivalent scaling 103
10 Å
For three decades, the silicon bipolar tran- 10 9 Hyper scaling 14 Å
sistor would remain the device of choice in the 2 nm
design of both discrete and integrated circuits. FinFET 6T, 2 Fins
Number of transistors (mm–2 )

3 nm

Switching energy (attoJoule)

The performance of the bipolar transistor im- 8 7.5T, 3 Fins 5 nm Stacked
10 nano 102
proved with scaling but also led to increased 9T, 4 Fins 7 nm
sheet
self-heating and lower breakdown voltage. In
10 nm Gate all
the early 1980s, the increasing count of bipolar
transistors on the integrated circuit reached 10 7 High k/ 14 nm
around (GAA)
Metal gate nano sheet
an unacceptable level of power density. Man- 22 nm 101
aging power delivery and heat dissipation be- Strain 32 nm
came a formidable challenge. For example, the 106 45 nm
65 nm
iconic Cray-2 supercomputer of this era used 90 nm
dense packaging of multiple processors and fast 130 nm
180 nm
100
bipolar transistor logic called emitter-coupled 105
1999 2001 2003 2005 2007 2009 2011 2013 2015 2017 2019 2021 2023 2025 2027 2029
1
School of Electrical and Computer Engineering, Georgia Year
Institute of Technology, Atlanta, GA, USA. 2Department of
Electrical Engineering, University of Notre Dame, Notre Fig. 1. Metronomic progress in CMOS transistor density and switching energy. Improvements in
Dame, IN, USA. 3Components Research, Logic Technology
Development, Intel Corporation, Hillsboro, OR, USA. transistor density and switching energy are shown for geometrical, equivalent, and hyperscaling approaches.
*Corresponding author. Email: [email protected] Examples for each approach are illustrated in Fig. 2.

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logic gates that switched faster while main- millimeter, and the switching energy per tran- degenerate conduction band valleys, whereas
taining the same operating power budget. The sistor fell below 1 picojoule (note that terms the hole mobility increases with compressive
power dissipated is energy consumed per switch- such as “90 nm process” refer to the design strain as a result of the lifting of degeneracy
ing event divided by the temporal duration of goals of the International Technology Road- between the light and heavy hole bands. A
the switching event. In theory, it is conceivable map for Semiconductors that assessed the transistor structure with epitaxial source-drain
to keep the power consumption of the chip research challenges for each size reduction). regions can be designed to impart strain of
constant but in reality the power budget is Operating voltage scaling was responsible for both types to the channel (Fig. 2A). After the
often exceeded to meet the performance spe- the reduction in the switching energy, whereas formation of gate stack and sidewall spacers as
cification, especially for high-performance com- gate length scaling increased switching speed. well as a silicon recess etch, selective hetero-
puting applications. During the era of geometric scaling, the pro- epitaxy can be performed to regrow a strained
Complicating the matter further, modern cessor clock frequency rose three orders of material in the source-drain regions adjacent
processor chips use a heterogenous structure in magnitude from 2 MHz in the case of the Intel to the channel. If the lattice spacing of this
which diverse functional blocks work with vary- 8008 processor (used to control traffic light sig- material is larger (or smaller) than silicon, uni-
ing activity factors (activity factors refer to how nals) to 3 GHz in the case of the Intel Pentium D axial compressive (or tensile) strain is induced
often the transistors undergo state transitions), 64-bit dual-core processor (used to power client in the channel. The transistor designers at Intel
resulting in non-uniform dissipation of power desktop computers). engineered uniaxial compressive strain in the
on the chip. This spatial nonuniformity is ac- It is implicit in Dennard’s scaling law that channel of PMOS transistors using selective
companied by temporal nonuniformity as circ- the threshold voltage of the transistor, VT, will silicon-germanium heteroepitaxy in the source-
uit blocks switch modes from idle to fully active scale proportionally with the operating voltage drain regions to boost hole mobility, and in-
at different points in time. Modern power- to ensure that there is sufficient voltage over- troduced uniaxial tensile strain in the channel
aware design techniques (e.g., power-down drive to provide high drive current. After three of the NMOS transistors using a tensile silicon
sleep modes, clock gating, dynamic voltage, decades of transistor downsizing, VT dropped nitride capping layer to increase electron mo-
and frequency scaling) exacerbate the spatio- so low that the subthreshold leakage current bility (4). The widespread use of strained chan-
temporal nonuniformity, creating “hot spots” (the current that flows through the transistor nel CMOS transistors in volume production at
on the chip. Failure to remove these hot spots even in its standby or off state) was now high the 90 nm and 65 nm nodes heralded the era of
in an expeditious manner not only affects chip enough to make standby power impose a con- equivalent scaling.
performance but also causes errors in logic straint in addition to the dissipated dynamic
states, accelerates aging of the transistors, and power. A second implicit assumption in Dennard’s Gate dielectrics
in extreme cases results in premature failure scaling law is the continued scaling of the phys- Toward the end of the geometric scaling era,
of the integrated circuit. ical gate oxide thickness, which provides electri- the gate dielectric SiO2 layers were so thin that
Reflecting on the innovations that have en- cal insulation of the gate electrode from the further decreases would effectively run out of
abled CMOS transistor scaling and elucidated current carrying transistor channel. After three atomic layers. There were two critical challenges
ongoing efforts to improve energy efficiency, decades of scaling, the thickness of the gate to replacing the polycrystalline silicon (polySi)
performance, and density of transistors in the dielectric—which used a nitrogen-containing gate electrode and SiO2 with polySi and higher
future, this Review revisits past innovations silicon dioxide—was reduced to 1.2 nm (4 mono- permittivity dielectrics such as hafnium diox-
and highlights future advances required for layers thick) at the 90 nm node. With such a thin ide (HfO2). First, HfO2 and polySi were incom-
the transistor to continue its scaling trajectory dielectric, the gate leakage current caused by patible because charge sharing between the
and approach the milestone of attoJoule (aJ) direct quantum mechanical tunneling became polySi and defect states within the HfO2 created
energy consumption per switching event and a noticeable fraction of the standby power. undesirable interface dipoles that led to un-
density of over three billion transistors per These unacceptable levels of subthreshold and acceptably high VT in the transistors. Second,
square millimeter of silicon. gate leakage current finally ended the era of polySi/HfO2 transistors exhibited severely de-
geometric scaling and began that of equivalent graded channel mobility caused by scattering
Geometric Scaling of Transistors following scaling of transistors. of the carriers in the channel by the soft op-
DennardÕs Law tical (SO) phonons arising from the polariza-
Robert Dennard and his colleagues at IBM Equivalent Scaling of transistors tion of the HfO2.
T. J. Watson Research Center established the The era of equivalent scaling of transistors is Metal gate electrodes proved effective in
MOSFET scaling rules that result in simul- defined by innovations in new materials and screening the high-κ SO phonons from coupling
taneous improvement in transistor density, transistor structures in addition to dimen- to the channel electrons and holes, whereas
switching speed, and power dissipation (2). sional scaling. In the absence of physical scaling strain engineering in the channel provided fur-
Each new generation of CMOS process tech- of the SiO2 gate oxide, transistor researchers ther boosts in both electron and hole mobility
nology was expected to reduce the minimum pioneered three complementary approaches to (5, 6). Transistor researchers successfully engi-
transistor dimension from X in the current improving transistor performance, energy effi- neered the gate metal electrodes to exhibit the
generation to 0.7X in the next, which then ciency, and scalability. Channel mobility was correct work functions (4.1 eV for NMOS and
led to a 0.49X reduction in transistor area enhanced through the introduction of strain. 5.1 eV for PMOS) using a replacement metal
and thus a 2X increase in transistor density. The electrical gate oxide thickness was scaled gate process flow. Also called the gate-last flow,
The industry embraced Dennard’s scaling and by replacing SiO2 with an alternative dielectric the gate metal electrode and the high-κ dielec-
between 1974 (when the idea was introduced) with high electrical permittivity κ. Planar, single- tric are deposited after the high-temperature
and 2003 (when the 90 nm process, also called gate architectures were replaced with nonplanar, activation anneal associated with source-drain
the 90 nm node, was introduced), the physical multigate structures to improve electrostatic dopant activation. This sequence preserves
gate length of the transistor was successfully integrity. the targeted threshold voltage, mobility, and
scaled from 1 mm to 35 nm. Additionally, the reliability at scaled electrical oxide thicknesses.
operating voltage was lowered from 4 V to Strain engineering High-performance high-κ/metal gate CMOS
1.2 V, the transistor density increased from a Electron mobility in silicon increases with ten- with negligible gate leakage, targeted thresh-
few hundred to 6 × 105 transistors per square sile strain as a result of splitting of the sixfold old voltages, low electrical oxide thickness, and

734 18 NOVEMBER 2022 • VOL 378 ISSUE 6621 science.org SCIENCE

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