In addition to the competition to develop commercial quantum computing, there’s the competition to develop commercial nuclear fusion energy. I have four stories about nuclear fusion, one from Spain, one from Chine, one from the US, and one from Vancouver. There are also a couple of segues into history and the recently (April 2, 2025) announced US tariffs (chaos has since ensued as these have become ‘on again/off again’ tariffs) but the bulk of this posting is focused on the latest (January – early April 2025) in fusion energy.
Fission nuclear energy, where atoms are split, is better known; fusion nuclear energy is released when a star is formed. For anyone unfamiliar with the word tokamak as applied to nuclear fusion (which is mentioned in all the stories), you can find out more in the Tokamak Wikipedia entry.
In a pioneering approach to achieve fusion energy, the SMART device has successfully generated its first tokamak plasma. This step brings the international fusion community closer to achieving sustainable, clean, and virtually limitless energy through controlled fusion reactions.
The SMART tokamak, a state-of-the-art experimental fusion device designed, constructed and operated by the Plasma Science and Fusion Technology Laboratory of the University of Seville, is a worldwide unique spherical tokamak due to its flexible shaping capabilities. SMART has been designed to demonstrate the unique physics and engineering properties of Negative Triangularity shaped plasmas towards compact fusion power plants based on Spherical Tokamaks.
Prof. Manuel García Muñoz, Principal Investigator of the SMART tokamak, stated: “This is an important achievement for the entire team as we are now entering the operational phase of SMART. The SMART approach is a potential game changer with attractive fusion performance and power handling for future compact fusion reactors. We have exciting times ahead! Prof. Eleonora Viezzer, co-PI of the SMART project, adds: “We were all very excited to see the first magnetically confined plasma and are looking forward to exploiting the capabilities of the SMART device together with the international scientific community. SMART has awoken great interest worldwide.
When negative becomes positive and compact
The triangularity describes the shape of the plasma. Most tokamaks operate with positive triangularity, meaning that the plasma shape looks like a D. When the D is mirrored (as shown in the figure on the right), the plasma has negative triangularity.
Negative triangularity plasma shapes feature enhanced performance as it suppresses instabilities that expel particles and energy from the plasma, preventing severe damage to the tokamak wall. Besides offering high fusion performance, negative triangularity also feature attractive power handling solutions, given that it covers a larger divertor area for distributing the heat exhaust. This also facilitates the engineering design for future compact fusion power plants.
Fusion2Grid aimed at developing the foundation for the most compact fusion power plant
SMART is the first step in the Fusion2Grid strategy led by the PSFT team and, in collaboration with the international fusion community, is aimed at the most compact and most efficient magnetically confined fusion power plant based on Negative Triangularity shaped Spherical Tokamaks.
SMART will be the first compact spherical tokamak operating at fusion temperatures with negative triangularity shaped plasmas.
The objective of SMART is to provide the physics and engineering basis for the most compact design of a fusion power plant based on high-field Spherical Tokamaks combined with Negative Triangularity. The solenoid-driven plasma represents a major achievement in the timeline of getting SMART online and advancing towards the most compact fusion device.
The Plasma Science and Fusion Technology Lab of the University of Seville hosts the SMall Aspect Ratio Tokamak (SMART) and leads several worldwide efforts on energetic particles and plasma transport and stability towards the development of magnetically confined fusion energy.
Caption: The Experimental Advanced Superconducting Tokamak achieved a remarkable scientific milestone by maintaining steady-state high-confinement plasma operation for an impressive 1,066 seconds. Credit: Image by HFIPS ( Hefei Institutes of Physical Science at the Chinese Academy of Sciences)
China has made a business announcement and there is no academic paper mentioned in their January 21, 2025 press release on EurekAlert (also available on phys.org as a January 21, 2025 news item), Note: A link has been removed,
The Experimental Advanced Superconducting Tokamak (EAST), commonly known as China’s “artificial sun,” has achieved a remarkable scientific milestone by maintaining steady-state high-confinement plasma operation for an impressive 1,066 seconds. This accomplishment, reached on Monday, sets a new world record and marks a significant breakthrough in the pursuit of fusion power generation.
The duration of 1,066 seconds is a critical advancement in fusion research. This milestone, achieved by the Institute of Plasma Physics (ASIPP) at Hefei Institutes of Physical Scienece [sic] (HFIPS) of the Chinese Academy of Sciences, far surpasses the previous world record of 403 seconds, also set by EAST in 2023.
The ultimate goal of developing an artificial sun is to replicate the nuclear fusion processes that occurr [sci] in the sun, providing humanity with a limitless and clean energy source, and enabling exploration beyond our solar system.
Scientists worldwide have dedicated over 70 years to this ambitious goal. However, generating electricity from a nuclear fusion device involves overcoming key challenges, including reaching temperatures exceeding 100 million degrees Celsius, maintaining stable long-term operation, and ensuring precise control of the fusion process.
“A fusion device must achieve stable operation at high efficiency for thousands of seconds to enable the self-sustaining circulation of plasma, which is essential for the continuous power generation of future fusion plants,” said SONG Yuntao, ASIPP director and also vice president of HFIPS. He said that the recent record is monumental, marking a critical step toward realizing a functional fusion reactor.
According to GONG Xianzu, head of the EAST Physics and Experimental Operations division, several systems of the EAST device have been upgraded since the last round of experiments. For example, the heating system, which previously operated at the equivalent power of nearly 70,000 household microwave ovens, has now doubled its power output while maintaining stability and continuity.
Since its inception in 2006, EAST has served as an open testing platform for both Chinese and international scientists to conduct fusion-related experiments and research.
China officially joined the International Thermonuclear Experimental Reactor (ITER) program in 2006 as its seventh member. Under the agreement, China is responsible for approximately 9 percent of the project’s construction and operation, with ASIPP serving as the primary institution for the Chinese mission.
ITER, currently under construction in southern France, is set to become the world’s largest magnetic confinement plasma physics experiment and the largest experimental tokamak nuclear fusion reactor upon completion.
In recent years, EAST has consistently achieved groundbreaking advancements in high-confinement mode, a fundamental operational mode for experimental fusion reactors like ITER and the future China Fusion Engineering Test Reactor (CFETR). These accomplishments provide invaluable insights and references for the global development of fusion reactors.
“We hope to expand international collaboration via EAST and bring fusion energy into practical use for humanity,” said SONG.
In Hefei, Anhui Province, China, where EAST is loacated [sic], a new generation of experimental fusion research facilities is currently under construction. These facilities aim to further accelerate the development and application of fusion energy.
I always feel a little less confident about the information when there are mistakes. Three typos in the same press release? Maybe someone forgot to give it a final once over?
Successfully harnessing the power of fusion energy could lead to cleaner and safer energy for all – and contribute substantially to combatting [UK spelling] the climate crisis. Towards this goal, Type One Energy has published a comprehensive, self-consistent, and robust physics basis for a practical fusion pilot power plant.
This groundbreaking research is presented in a series of six peer-reviewed scientific papers in a special issue of the prestigious Journal of Plasma Physics (JPP), published by Cambridge University Press.
The articles serve as the foundation for the company’s first fusion power plant project, which Type One Energy is developing with the Tennessee Valley Authority utility in the United States.
Alex Schekochihin, Professor of Theoretical Physics at the University of Oxford and Editor of the JPP, spoke with enthusiasm about this development:
“JPP is very proud to provide a platform for rigorous peer review and publication of the papers presenting the physics basis of the Infinity Two stellarator — an innovative and ground-breaking addition to the expanding family of proposed fusion power plant designs.
“Fusion science and technology are experiencing a period of very rapid development, driven by both public and private enthusiasm for fusion power. In this environment of creative and entrepreneurial ferment, it is crucial that new ideas and designs are both publicly shared and thoroughly scrutinised by the scientific community — Type One Energy and JPP are setting the gold standard for how this is done (as we did with Commonwealth Fusion Systems 5 years ago for their SPARC physics basis).”
The new physics design basis for the pilot power plant is a robust effort to consider realistically the complex relationship between challenging, competing requirements that all need to function together for fusion energy to be possible.
This new physics solution also builds on the operating characteristics of high-performing stellarator fusion technology – a stellarator being a machine that uses complex, helical magnetic fields to confine the plasma, thereby enabling scientists to control it and create suitable conditions for fusion. This technology is already being used with success on the world’s largest research stellarator, the Wendelstein 7-X, located in Germany, but the challenge embraced by Type One Energy’s new design is how to scale it up to a pilot plant.
Building the future of energy
Functional fusion technology could offer limitless clean energy. As global energy demands increase and energy security is front of mind, too, this new physics design basis comes at an excellent time.
Christofer Mowry, CEO of Type One Energy, is cognisant of the landmark nature of his company’s achievement and proud of its strong, real-world foundations.
“The physics basis for our new fusion power plant is grounded in Type One Energy’s expert knowledge about reliable, economic, electrical generation for the power grid. We have an organisation that understands this isn’t only about designing a science project.”
This research was developed collaboratively between Type One Energy and a broad coalition of scientists from national laboratories and universities around the world. Collaborating organisations included the US Department of Energy, for using their supercomputers, such as the exascale Frontier machine at Oak Ridge National Laboratory, to perform its physics simulations.
While commercial fusion energy has yet to move from theory into practice, this new research marks an important and promising milestone. Clean and abundant energy may yet become reality.
This is not directly related to fusion energy, so, you might want to skip this section.
Caption: Type One Energy employees at the Bull Run [emphasis mine] Fossil Plant, soon to be home to the prototype Infinity One. Credit: Type One Energy
I wonder if anyone argued for a change of name given how charged the US history associated with ‘Bull Run’ is, from the the First Battle of Bull Run Wikipedia entry, Note: Links have been removed,
The First Battle of Bull Run, called the Battle of First Manassas[1] by Confederate forces, was the first major battle of the American Civil War. The battle was fought on July 21, 1861, in Prince William County, Virginia, just north of what is now the city of Manassas and about thirty miles west-southwest of Washington, D.C. The Union Army was slow in positioning themselves, allowing Confederate reinforcements time to arrive by rail. Each side had about 18,000 poorly trained and poorly led troops. The battle was a Confederate victory and was followed by a disorganized post-battle retreat of the Union forces.
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A Confederate victory the first time and the second time (Second Battle of Bull Run Wikipedia entry)? For anyone unfamiliar with the history, the US Civil War was fought from 1861 to 1865 between Union and Confederate forces. The Confederate states had seceded from the union (US) and were fighting to retain their slavery-based economy and they lost the war.
Had anyone consulted me I would have advised changing the name from Bull Run to some thing less charged (pun noted) to host your prototype fusion energy pilot plant.
Back to the usual programme.
Type One Energy
Type One Energy issued a March 27, 2025 news release about the special issue of the Journal of Plasma Physics (JPP), Note 1: Some of this redundant; Note 2: Links have been removed,
Type One Energy announced today publication of the world’s first comprehensive, self-consistent, and robust physics basis, with conservative design margins, for a practical fusion pilot power plant. This physics basis is presented in a series of seven peer-reviewed scientific papers in a special issue of the prestigious Journal of Plasma Physics (JPP). They serve as the foundation for the company’s first Infinity Two stellarator fusion power plant project, which Type One Energy is developing for the Tennessee Valley Authority (TVA) utility in the U.S.
The Infinity Two fusion pilot power plant physics design basis realistically considers, for the first time, the complex relationship between competing requirements for plasma performance, power plant startup, construction logistics, reliability, and economics utilizing actual power plant operating experience. This Infinity Two baseline physics solution makes use of the inherently favorable operating characteristics of highly optimized stellarator fusion technology using modular superconducting magnets, as was so successfully proven on the W7-X science machine in Germany.
“Why are we the first private fusion company with an agreement to develop a potential fusion power plant project for an energy utility? Because we have a design anchored in reality,” said Christofer Mowry, CEO of Type One Energy. “The physics basis for Infinity Two is grounded in the knowledge of what is required for application to, and performance in, the demanding environment of reliable electrical generation for the power grid. We have an organization that understands this isn’t about designing a science project.”
Led by Chris Hegna, widely recognized as a leading theorist in modern stellarators, Type One Energy performed high-fidelity computational plasma physics analyses to substantially reduce the risk of meeting Infinity Two power plant functional and performance requirements. This unique and transformational achievement is the result of a global development program led by the Type One Energy plasma physics and stellarator engineering organization, with significant contributions from a broad coalition of scientists from national laboratories and universities around the world. The company made use of a spectrum of high-performance computing facilities, including access to the highest-performance U.S. Department of Energy supercomputers such as the exascale Frontier machine at Oak Ridge National Laboratory (ORNL), to perform its stellarator physics simulations.
“We committed to this ambitious fusion commercialization milestone two years ago and today we delivered,” said John Canik, Chief Science and Engineering Officer for Type One Energy. “The team was able to efficiently develop deep plasma physics insights to inform the design of our Infinity Two stellarator, by taking advantage of our access to high performance computing resources. This enabled the Type One Energy team to demonstrate a realistic, integrated stellarator design that moves far beyond conventional thinking and concepts derived from more limited modeling capabilities.”
The consistent and robust physics solution for Infinity Two results in a deuterium-tritium (D-T) fueled, burning plasma stellarator with 800 MW of fusion power and delivers a nominal 350 MWe to the power grid. It is characterized by fusion plasma with resilient and stable behavior across a broad range of operating conditions, very low heat loss due to turbulent transport, as well as tolerable direct energy losses to the stellarator first wall. The Infinity Two stellarator has sufficient room for both adequately sized island divertors to exhaust helium ash and a blanket which provides appropriate shielding and tritium breeding. Type One Energy has high confidence that this essential physics solution provides a good baseline stellarator configuration for the Infinity Two fusion pilot power plant.
“The articles in this issue [of JPP] represent an important step towards a fusion reactor based on the stellarator concept. Thanks to decades of experiments and theoretical research, much of the latter published in JPP, it has become possible to lay out the physics basis for a stellarator power plant in considerable detail,” said Per Helander, head of Stellarator Theory Division at the Max Planck Institute for Plasma Physics. “JPP is very happy to publish this series of papers from Type One Energy, where this has been accomplished in a way that sets new standards for the fidelity and confidence level in this context.”
Important to successful fusion power plant commercialization, this stellarator configuration has enabled Type One Energy to architect a maintenance solution which supports good power plant Capacity Factors (CF) and associated Levelized Cost of Electricity (LCOE). It also supports favorable regulatory requirements for component manufacturing and power plant construction methods essential to achieving a reasonable Over-Night Cost (ONC) for Infinity Two.
About Type One Energy
Type One Energy Group is mission-driven to provide sustainable, affordable fusion power to the world. Established in 2019 and venture-backed in 2023, the company is led by a team of globally recognized fusion scientists with a strong track record of building state-of-the-art stellarator fusion machines, together with veteran business leaders experienced in scaling companies and commercializing energy technologies. Type One Energy applies proven advanced manufacturing methods, modern computational physics and high-field superconducting magnets to develop its optimized stellarator fusion energy system. Its FusionDirect development program pursues the lowest-risk, shortest-schedule path to a fusion power plant over the coming decade, using a partner-intensive and capital-efficient strategy. Type One Energy is committed to community engagement in the development and deployment of its clean energy technology. For more information, visit www.typeoneenergy.com or follow us on LinkedIn.
While the company is currently headquartered in Knoxville, Tennessee, it was originally a spinoff company from the University of Wisconsin-Madison according to a March 30, 2023 posting on the university’s College of Engineering website,
Type One Energy, a Middleton, Wisconsin-based fusion energy company with roots in the University of Wisconsin-Madison’s College of Engineering, recently announced its first round of seed funding, raising $29 million from investors. The company has also onboarded a new, highly experienced CEO [Christofer Mowry].
Type One, founded in 2019 by a team of globally recognized fusion scientists and business leaders, is hoping to commercialize stellarator technology over the next decade. Stellarators are a type of fusion reactor that uses powerful magnets to confine ultra-hot streams of plasma in order to create the conditions for fusion reactions. Energy from fusion promises to be clean, safe, renewable power. The company is using advanced manufacturing methods, modern computational physics and high-field superconducting magnets to develop its stellarator through an initiative called FusionDirect.
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According to the Type One Energy’s About page, there are four offices with the headquarters in Tennessee,
Madison 316 W Washington Ave. Suite 300 Madison, WI 53703
Boston 299 Washington St. Suites C & E Woburn, MA 01801
Vancouver 1140 West Pender St. Vancouver, BC V6E 4G1
The mention of an office in Vancouver, Canada piqued my curiosity but before getting to that, I’m going to include some informative excerpts about nuclear energy (both fission and fusion) from this August 31, 2023 article written by Tina Tosukhowong on behalf of TDK Ventures, which was posted on Medium,
Fusion power is the key to the energy transformation that humanity needs to drive decarbonization, clean, and baseload energy production that is inherently fail-safe, with no risk of long-lived radioactive waste, while also delivering on ever-growing energy-consumption demands at the global scale. Fusion is hard and requires exceptional conditions for sustained reaction (which is part of what makes it so safe), which has long served as a deterrent for technical maturation and industrial viability. …
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The current reality of our world is monumental fossil-fuel dependence. This, coupled with unprecedented levels of energy demand has resulted in the over 136,700 TWh (that’s 10¹²) of energy consumed via fossil fuels annually [1]. Chief repercussion among the many consequences of this dependence is the now very looming threat of climate catastrophe, which will soon be irreversible if global temperature rise is not abated and held to within 1.5 °C of pre-industrial levels. To do so, the nearly 40 gigatons of CO2 emissions generated each year must be steadily reduced and eventually mitigated entirely [2]. A fundamental shift in how power is generated globally is the only way forward. Humanity needs an energy transformation — the right energy transformation.
Alternative energy-generation techniques, such as wind, solar, geothermal, and hydroelectric approaches have all made excellent strides, and indeed in just the United States electricity generated by renewable methods doubled from 10 to 20% of total between 2010 and 2020 [3–4]. These numbers are incredibly encouraging and give significant credence in the journey to net-zero emission energy generation. However, while these standard renewable approaches should be championed, wind and solar are intermittent and require a large amount of land to deploy, while geothermal and hydroelectric are not available in every geography.
By far the most viable candidates for continuous clean energy generation to replace coal-fired power plants are nuclear-driven technologies, i.e. nuclear fission or nuclear fusion. Nuclear fission has been a proven effective method ever since it was first demonstrated almost 80 years ago underneath the University of Chicago football Stadium by Nobel Laureate Enrico Fermi [5]. Heavier atomic elements, in most cases Uranium-235, are exposed to and bombarded by neutrons. This causes the Uranium to split resulting in two slightly less-heavy elements (like Barium and Krypton). This in turn causes energy to be released and more neutrons to be ejected and bombard other nearby Uranium-235, at which point the process cascades into a chain reaction. The released energy (heat) is utilized in the same way coal is burned in a traditional power plant, being subsequently used to generate electricity usually via the creation of steam to drive a turbine [6]. While already having reached viable commercial maturity, fission carries inherent and nontrivial safety concerns. An unhampered chain reaction can quickly lead to meltdown with disastrous consequences, and, even when properly managed, the end reaction does generate radioactive waste whose half-life can last hundreds of thousands of years.
Figure 1. Breakdown of a nuclear fission reaction [6]. Incident neutron bombards a fissile heavy element, splitting it and release energy and more nuclei setting off a chain reaction.
Especially given modernization efforts and meteoric gains in safety (thanks to advents in material science like ceramic coatings), fission will continue to be a critical piece to better, greener energy transformation. However, in extending our vision to an even brighter future with no such concerns — carbon emissions or safety — nuclear fusion is humanity’s silver bullet. Instead of breaking down atoms leading to a chain reaction, fusion is the combining of atoms (usually isotopes of Hydrogen) into heavier elements which also results in energy release / heat generation [7]. Like fission, fusion can be designed to be a continuous energy source that can serve as a permanent backbone to the power grid. It is extremely energy dense, with 1 kg of fusion fuel producing the same amount of energy as 1,000,000 kg of coal, and it is inherently fail-safe with no long-term radioactive waste.
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As a concept, if fusion is a silver bullet to answer humanity’s energy transformation needs, then why haven’t we done so already? The appeal seems so obvious, what’s the hold up? Simply put, nuclear fusion is hard for the very same reason the process is inherently safe. Atoms in the process must have enough energy to overcome electrostatic repulsive forces between the two positive charges of their nuclei to fuse. The key figure of merit to evaluate fusion is the so-called “Lawson Triple Product.” Essentially, this means in order to generate energy by fusion more than the rate of energy oss to the environment, the nuclei must be very close together (as represented by n — the plasma density), kept at a high enough temperature (as represented by T — temperature), and for long enough time to sustain fusion (as represented by τ — the confinement time). The triple product required to achieve fusion “ignition” (the state where the rate of energy production is higher than the rate of loss) depends on the fuel type and occurs within a plasma state. A deuterium and tritium (D-T) system has the lowest Lawson Triple product requirement, where fusion can achieve a viable threshold for ignition when the density of the fuel atoms, n, multiplied by the fuel temperature, T, multiplied by the confinement time, τ, is greater than 5×10²¹ (nTτ > 5×10²¹ keV-s/m³) [8–9]. For context, the temperature alone in this scenario must be higher than 100-million degrees Celsius.
Figure 2. (Left) Conceptual illustration of a fusion reaction with Deuterium (²H) and Tritium (³H) forming an Alpha particle (⁴He) and free neutron along with energy released as heat (Right). To initiate fusion, repelling electrostatic charge must be overcome via conditions meeting the minimum Lawson Triple Product threshold
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Tosukhowong’s August 31, 2023 article provides a good overview keeping in mind that it is slanted to justify TDK’s investment in Type One Energy.
Why a Vancouver, Canada office?
As for Type One Energy’s Vancouver (British Columbia, Canada) connection, I was reminded of General Fusion, a local fusion energy company while speculating about the connection. First speculative question: could Type One Energy’s presence in Canada allow it to access Canadian government funds for its research? Second speculative question: do they want to have access to people who might hesitate to move to the US or might want to move out of the US but would move to Canada?
The US is currently in an unstable state as suggested in this April 3, 2025 opinion piece by Les Leyne for vancouverisawsome.com
Les Leyne: Trump’s incoherence makes responding to tariff wall tricky
Trump’s announcement was so incoherent that much of the rest of the world had to scramble to grasp even the basic details
B.C. officials were guarded Wednesday [April 2, 2025] about the impact on Canada of the tariff wall U.S. President Donald Trump erected around the U.S., but it appears it could have been worse.
Trump’s announcement was so incoherent that much of the rest of the world had to scramble to grasp even the basic details. So cabinet ministers begged for more time to check the impacts.
“It’s still very uncertain,” said Housing Minister Ravi Kahlon, who chairs the “war room” committee responsible for countering tariff threats. “It’s hard to make sense from President Trump’s speech.” [emphasis mine]
Kahlon said the challenge is that tariff policies change hour by hour, “and anything can happen.”
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On April 2, 2025 US President Donald Trump announced tariffs (then paused some of the tariffs on April 9, 2025) and some of the targets seemed a bit odd, from an April 2, 2025 article by Alex Galbraith for salon.com, Note: Links have been removed,
“Trade war with penguins”: Trump places 10% tariff on uninhabited Antarctic islands
Planned tariffs shared by the White House included a 10% duty on imports from the barren Heard and McDonald Islands
For once in his life, Donald Trump underpromised and over-delivered.
The president announced a 10% duty on all imports on Wednesday [April 2, 2025], along with a raft of reciprocal tariffs on U.S. trading partners. An extensive graphic released by the White House showed how far Trump was willing to take his tit-for-tat trade war, including a shocking levy of 10% on all imports from the Heard and McDonald Islands.
If you haven’t heard of this powerhouse of global trade and territory of Australia, you aren’t alone. Few have outside of Antarctic researchers and seals. These extremely remote islands about 1,000 miles north of Antarctica consist mostly of barren tundra. They’re also entirely uninhabited.
The news that we were starting a trade war with penguins spread quickly after Trump’s announcement. …
U.S. stock futures crumbled following the news of Trump’s widespread tariffs. Dow futures fell by nearly 1,000 points while NASDAQ and S&P futures fell by 3 to 4%. American companies’ stock values rapidly tumbled after the announcement, with large retail importers seeing significant losses. …
No word from the penguins about the ‘pause’. I’m assuming Donald Trump’s next book will be titled, “The art of negotiating trade deals with penguins.” Can’t wait to read it.
(Perhaps someone should tell him there are no penguins in the Arctic so he can’t bypass Canadians or Greenlanders to make a deal.)
Now for the local story.
General Fusion
There’ve been two recent developments at General Fusion. Most recently, an April 2, 2025 General Fusion news release announces a new hire, Note: Links have been removed,
Bob Smith is joining General Fusion as a strategic advisor. Smith brings more than 35 years of experience developing, scaling, and launching world-changing technologies, including spearheading new products and innovation in the aerospace industry at United Space Alliance, Sandia Labs, and Honeywell before serving as CEO of Blue Origin. He joins General Fusion as the company’s Lawson Machine 26 (LM26) fusion demonstration begins operations and progresses toward transformative technical milestones on the path to commercialization.
“I’ve been watching the fusion energy industry closely for my entire career. Fusion is the last energy source humanity will ever need, and I believe its impact as a zero-carbon energy source will transform the global energy supply at the time needed to fight the worst consequences of climate change,” said Smith. “I am thrilled to work with General Fusion. Their novel approach has inherent and distinctive benefits for the generation of commercially competitive fusion power. It’s exciting to join at a time when the team is about to demonstrate the fundamental physics behind their system and move to scaling up to a pilot plant.”
The LM26 program marks a significant step towards commercialization, as the company’s unique Magnetized Target Fusion (MTF) approach makes the path to powering the grid with fusion energy more straightforward than other technologies—because it practically addresses barriers to fusion commercialization, such as neutron material degradation, sustainable fuel production, and efficient energy extraction. As a strategic advisor, Smith will leverage his experience advancing game-changing technologies to help guide General Fusion’s technology development and strategic growth.
“Bob’s insights and experience will be invaluable as we execute the LM26 program and look beyond it to propel our practical technology to powering the grid by the mid-2030s,” said Greg Twinney, CEO, General Fusion. “We are grateful for his commitment of his in-demand time and expertise to our mission and look forward to working together to make fusion power a reality!”
About Bob Smith:
Bob is an experienced business leader in the aerospace and defense industry with extensive technical and operational expertise across the sector. He worked at and managed federal labs, led developments at a large government contractor, grew businesses at a Fortune 100 multinational, and scaled up a launch and space systems startup. Bob also has extensive international experience and has worked with suppliers and OEMs in all the major aerospace regions, including establishing new sites and factories in Europe, India, China, and Puerto Rico.
Bob’s prior leadership roles include Chairman and Chief Executive Officer of Blue Origin, President of Mechanical Systems & Components at Honeywell Aerospace, Chief Technology Officer at Honeywell Aerospace, Chairman of NTESS (Sandia Labs), and Executive Director of Space Shuttle Upgrades at United Space Alliance.
Bob holds a Bachelor of Science degree in aerospace engineering from Texas A&M, a Master of Science degree in engineering/applied mathematics from Brown University, a doctorate from the University of Texas in aerospace engineering, and a business degree from MIT’s Sloan School of Management. Bob is also a Fellow of the Royal Aeronautical Society, a Fellow of the American Institute of Aeronautics and Astronautics, and an Academician in the International Academy of Astronautics.
Quick Facts:
Fusion energy is the ultimate clean energy solution—it is the energy source that powers the sun and stars. Fusion is the process by which two light nuclei merge to form a heavier one, producing a massive amount of energy.
General Fusion’s Magnetized Target Fusion (MTF) technology is designed to scale for cost-efficient power plants. It uses mechanical compression to create fusion conditions in short pulses, eliminating the need for expensive lasers or superconducting magnets. An MTF power plant is designed to produce its own fuel and inherently includes a method to extract the energy and put it to work.
Lawson Machine 26 (LM26) is a world-first Magnetized Target Fusion demonstration. Launched, designed, and assembled in just 16 months, the machine is now forming magnetized plasmas regularly at 50 per cent commercial scale. It is advancing towards a series of results that will demonstrate MTF in a commercially relevant way: 10 million degrees Celsius (1 keV), 100 million degrees Celsius (10 keV), and scientific breakeven equivalent (100% Lawson).
About General Fusion General Fusion is pursuing a fast and practical approach to commercial fusion energy and is headquartered in Richmond, Canada. The company was established in 2002 and is funded by a global syndicate of leading energy venture capital firms, industry leaders, and technology pioneers. Learn more at www.generalfusion.com.
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Bob Smith and Blue Origin: things did not go well
Sometimes you end up in a job and things do not work out well and that seems to have been the case at Blue Origin according to a September 25, 2023 article by Eric Berger for Ars Tecnica,
After six years of running Blue Origin, Bob Smith announced in a company-wide email on Monday that he will be “stepping aside” as chief executive of the space company founded by Jeff Bezos.
“It has been my privilege to be part of this great team, and I am confident that Blue Origin’s greatest achievements are still ahead of us,” Smith wrote in an email. “We’ve rapidly scaled this company from its prototyping and research roots to a large, prominent space business.”
Shortly after Smith’s email, a Blue Origin spokesperson said the company’s new chief executive will be Dave Limp, who stepped down as Amazon’s vice president of devices and services last month.
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To put things politely, Smith has had a rocky tenure as Blue Origin’s chief executive. After being personally vetted and hired by Bezos, Smith took over from Rob Meyerson in 2017. The Honeywell engineer was given a mandate to transform Blue Origin into a large and profitable space business.
He did succeed in growing Blue Origin. The company had about 1,500 employees when Smith arrived, and the company now employs nearly 11,000 people. But he has been significantly late on a number of key programs, including the BE-4 rocket engine and the New Glenn rocket.
As a space reporter, I have spoken with dozens of current and former Blue Origin employees, and virtually none of them have had anything positive to say about Smith’s tenure as chief executive. I asked one current employee about the hiring of Limp on Monday afternoon, and their response was, “Anything is better than Bob.”
Although it is very far from an exact barometer, Smith has received consistently low ratings on Glassdoor for his performance as chief executive of Blue Origin. And two years ago, a group of current and former Blue Origin employees wrote a blistering letter about the company under Smith. “In our experience, Blue Origin’s culture sits on a foundation that ignores the plight of our planet, turns a blind eye to sexism, is not sufficiently attuned to safety concerns, and silences those who seek to correct wrongs,” the essay authors wrote.
With any corporate culture, there will be growing pains, of course. But Smith brought a traditional aerospace mindset into a company that had hitherto been guided by a new space vision, leading to a high turnover rate. And Blue Origin remains significantly underwater, financially. It is likely that Bezos is still providing about $2 billion a year to support the company’s cash needs.
Crucially, as Blue Origin meandered under Smith’s tenure, SpaceX soared, launching hundreds of rockets and thousands of satellites. Smith, clearly, was not the leader Blue Origin needed to make the company more competitive with SpaceX in launch and other spaceflight activities. It became something of a parlor game in the space industry to guess when Bezos would finally get around to firing Smith.
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On the technical front, a March 27, 2025 General Fusion news release announces “Peer-reviewed publication confirms General Fusion achieved plasma energy confinement time required for its LM26 large-scale fusion machine,” Note: Links have been removed,
New results published in Nuclear Fusionconfirm General Fusion successfully created magnetized plasmas that achieved energy confinement times exceeding 10 milliseconds. The published energy confinement time results were achieved on General Fusion’s PI3 plasma injector — the world’s largest and most powerful plasma injector of its kind. Commissioned in 2017, PI3 formed approximately 20,000 plasmas in a machine of 50 per cent commercial scale. The plasma injector is now integrated into General Fusion’s Lawson Machine 26 (LM26) — a world-first Magnetized Target Fusion demonstration tracking toward game-changing technical milestones that will advance the company’s ultimate mission: generating zero-carbon fusion energy for the grid in the next decade.
The 10-millisecond energy confinement time is the duration required to compress plasmas in LM26 to achieve key temperature thresholds of 1 keV, 10 keV, and, ultimately, scientific breakeven equivalent (100% Lawson). These results were imperative to de-risking LM26. The demonstration machine is now forming plasmas regularly, and the company is optimizing its plasma performance in preparation for compressing plasmas to create fusion and heating from compression.
Key Findings:
The plasma injector now integrated into General Fusion’s LM26 achieved energy confinement times exceeding 10 milliseconds, the pre-compression confinement time required for LM26’s targeted technical milestones. These results were achieved without requiring active magnetic stabilization or auxiliary heating. This means the results were achieved without superconducting magnets, demonstrating the company’s cost-effective approach.
The plasma’s energy confinement time improved when the plasma injector vessel was coated with natural lithium. A key differentiator in General Fusion’s commercial approach is its use of a liquid lithium wall to compress plasmas during compression. In addition to the confinement time advantages shown in this paper, the liquid lithium wall will also protect a commercial MTF machine from neutron damage, enable the machine to breed its own fuel, and provide an efficient method for extracting energy from the machine.
The maximum energy confinement time achieved by PI3 was approximately 12 milliseconds. The machine’s maximum plasma density was approximately 6×1019 m-3, and maximum plasma temperatures exceeded 400 eV. These strong pre-compression results support LM26’s transformative targets.
Quotes:
“LM26 is designed to achieve a series of results that will demonstrate MTF in a commercially relevant way. Following LM26’s results, our unique approach makes the path to powering the grid with fusion energy more straightforward than other technologies because we have front-loaded the work to address the barriers to commercialization.”
Dr. Michel Laberge Founder and Chief Science Officer
“For over 16 years, I have worked hand in hand with Michel to advance General Fusion’s practical technology. This company is entrepreneurial at its core. We pride ourselves on building real machines that get results that matter, and I’m thrilled to have the achievements recognized in Nuclear Fusion.”
Mike Donaldson Senior Vice President, Technology Development
For anyone curious about General Fusion, I have a brief overview and history of the company and their particular approach to fusion energy in my February 6, 2024 posting (scroll down to ‘The Canadians’).
Not long after announcing their new work on cartilage and ‘dancing molecules’, Samuel I. Stupp and his team at Northwestern University (Chicago, Illinois) have announced work with a new material that does not have dancing molecules in a study using animal models. It’s here in an August 5, 02024 Northwestern University news release (also on EurekAlert and on SciTechDaily and received by email) by Amanda Morris, Note: Links have been removed,
Northwestern University scientists have developed a new bioactive material that successfully regenerated high-quality cartilage in the knee joints of a large-animal model.
Although it looks like a rubbery goo, the material is actually a complex network of molecular components, which work together to mimic cartilage’s natural environment in the body.
In the new study, the researchers applied the material to damaged cartilage in the animals’ knee joints. Within just six months, the researchers observed evidence of enhanced repair, including the growth of new cartilage containing the natural biopolymers (collagen II and proteoglycans), which enable pain-free mechanical resilience in joints.
With more work, the researchers say the new material someday could potentially be used to prevent full knee replacement surgeries, treat degenerative diseases like osteoarthritis and repair sports-related injuries like ACL [anterior cruciate ligament] tears.
The study will be published during the week of August 5 [2024] in the Proceedings of the National Academy of Sciences.
“Cartilage is a critical component in our joints,” said Northwestern’s Samuel I. Stupp, who led the study. “When cartilage becomes damaged or breaks down over time, it can have a great impact on people’s overall health and mobility. The problem is that, in adult humans, cartilage does not have an inherent ability to heal. Our new therapy can induce repair in a tissue that does not naturally regenerate. We think our treatment could help address a serious, unmet clinical need.”
A pioneer of regenerative nanomedicine, Stupp is Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering at Northwestern, where he is founding director of the Simpson Querrey Institute for BioNanotechnology and its affiliated center, the Center for Regenerative Nanomedicine. Stupp has appointments in the McCormick School of Engineering, Weinberg College of Arts and Sciences and Feinberg School of Medicine. Jacob Lewis, a former Ph.D. student in Stupp’s laboratory, is the paper’s first author.
What’s in the material?
The new study follows recently published work from the Stupp laboratory, in which the team used “dancing molecules” to activate human cartilage cells to boost the production of proteins that build the tissue matrix. Instead of using dancing molecules, the new study evaluates a hybrid biomaterial also developed in Stupp’s lab. The new biomaterial comprises two components: a bioactive peptide that binds to transforming growth factor beta-1 (TGFb-1) — an essential protein for cartilage growth and maintenance — and modified hyaluronic acid, a natural polysaccharide present in cartilage and the lubricating synovial fluid in joints.
“Many people are familiar with hyaluronic acid because it’s a popular ingredient in skincare products,” Stupp said. “It’s also naturally found in many tissues throughout the human body, including the joints and brain. We chose it because it resembles the natural polymers found in cartilage.”
Stupp’s team integrated the bioactive peptide and chemically modified hyaluronic acid particles to drive the self-organization of nanoscale fibers into bundles that mimic the natural architecture of cartilage. The goal was to create an attractive scaffold for the body’s own cells to regenerate cartilage tissue. Using bioactive signals in the nanoscale fibers, the material encourages cartilage repair by the cells, which populate the scaffold.
Clinically relevant to humans
To evaluate the material’s effectiveness in promoting cartilage growth, the researchers tested it in sheep with cartilage defects in the stifle joint, a complex joint in the hind limbs similar to the human knee. This work was carried out in the laboratory of Mark Markel in the School of Veterinary Medicine at the University of Wisconsin–Madison.
According to Stupp, testing in a sheep model was vital. Much like humans, sheep cartilage is stubborn and incredibly difficult to regenerate. Sheep stifles and human knees also have similarities in weight bearing, size and mechanical loads.
“A study on a sheep model is more predictive of how the treatment will work in humans,” Stupp said. “In other smaller animals, cartilage regeneration occurs much more readily.”
In the study, researchers injected the thick, paste-like material into cartilage defects, where it transformed into a rubbery matrix. Not only did new cartilage grow to fill the defect as the scaffold degraded, but the repaired tissue was consistently higher quality compared to the control.
A lasting solution
In the future, Stupp imagines the new material could be applied to joints during open-joint or arthroscopic surgeries. The current standard of care is microfracture surgery, during which surgeons create tiny fractures in the underlying bone to induce new cartilage growth.
“The main issue with the microfracture approach is that it often results in the formation of fibrocartilage — the same cartilage in our ears — as opposed to hyaline cartilage, which is the one we need to have functional joints,” Stupp said. “By regenerating hyaline cartilage, our approach should be more resistant to wear and tear, fixing the problem of poor mobility and joint pain for the long term while also avoiding the need for joint reconstruction with large pieces of hardware.”
The study, “A bioactive supramolecular and covalent polymer scaffold for cartilage repair in a sheep model,” was supported by the Mike and Mary Sue Shannon Family Fund for Bio-Inspired and Bioactive Materials Systems for Musculoskeletal Regeneration.
Here’s a link to and a citation for the paper,
A bioactive supramolecular and covalent polymer scaffold for cartilage repair in a sheep model by Jacob A. Lewis, Brett Nemke, Yan Lu, Nicholas A. Sather, Mark T. McClendon, Michael Mullen, Shelby C. Yuan, Sudheer K. Ravuri, Jason A. Bleedorn, Marc J. Philippon, Johnny Huard, Mark D. Markel, and Samuel I. Stupp. Proceedings ot the National Academy of Sciences (PNAS) 121 (33) e2405454121 DOI: https://doi.org/10.1073/pnas.2405454121 August 6, 2024
I keep telling a friend that noise will be the ‘new smoking’; i.e., there will be more rules and people will demand enforcement. She doesn’t agree, vociferously so. With the mounting research into the effects that noise has on health and on longevity, it doesn’t matter if I win the ‘argument’, I’m just happy to see research dedicated to mitigating noise levels. From a May 7, 2024 news item on ScienceDaily,
We are living in a very noisy world. From the hum of traffic outside your window to the next-door neighbor’s blaring TV to sounds from a co-worker’s cubicle, unwanted noise remains a resounding problem. [nice bit of wordplay]
Caption: The fabric can suppress sound by generating sound waves that interfere with an unwanted noise to cancel it out (as seen in figure C) or by being held still to suppress vibrations that are key to the transmission of sound (as seen in figure D). Credit: Courtesy of Yoel Fink and Grace (Noel) Yang and Massachusetts Institute of Technology (MIT)
To cut through the din, an interdisciplinary collaboration of researchers from MIT and elsewhere developed a sound-suppressing silk fabric that could be used to create quiet spaces.
The fabric, which is barely thicker than a human hair, contains a special fiber that vibrates when a voltage is applied to it. The researchers leveraged those vibrations to suppress sound in two different ways.
In one, the vibrating fabric generates sound waves that interfere with an unwanted noise to cancel it out, similar to noise-canceling headphones, which work well in a small space like your ears but do not work in large enclosures like rooms or planes.
In the other, more surprising technique, the fabric is held still to suppress vibrations that are key to the transmission of sound. This prevents noise from being transmitted through the fabric and quiets the volume beyond. This second approach allows for noise reduction in much larger spaces like rooms or cars.
By using common materials like silk, canvas, and muslin, the researchers created noise-suppressing fabrics which would be practical to implement in real-world spaces. For instance, one could use such a fabric to make dividers in open workspaces or thin fabric walls that prevent sound from getting through.
“Noise is a lot easier to create than quiet. In fact, to keep noise out we dedicate a lot of space to thick walls. [First author] Grace’s work provides a new mechanism for creating quiet spaces with a thin sheet of fabric,” says Yoel Fink, a professor in the departments of Materials Science and Engineering and Electrical Engineering and Computer Science, a Research Laboratory of Electronics principal investigator, and senior author of a paper on the fabric.
The study’s lead author is Grace (Noel) Yang SM ’21, PhD ’24. Co-authors include MIT graduate students Taigyu Joo, Hyunhee Lee, Henry Cheung, and Yongyi Zhao; Zachary Smith, the Robert N. Noyce Career Development Professor of Chemical Engineering at MIT; graduate student Guanchun Rui and professor Lei Zhu of Case Western [Reserve] University; graduate student Jinuan Lin and Assistant Professor Chu Ma of the University of Wisconsin at Madison; and Latika Balachander, a graduate student at the Rhode Island School of Design. The an open-access paper about the research appeared recently in Advanced Materials.
Silky silence
The sound-suppressing silk builds off the group’s prior work to create fabric microphones.
In that research, they sewed a single strand of piezoelectric fiber into fabric. Piezoelectric materials produce an electrical signal when squeezed or bent. When a nearby noise causes the fabric to vibrate, the piezoelectric fiber converts those vibrations into an electrical signal, which can capture the sound.
In the new work, the researchers flipped that idea to create a fabric loudspeaker that can be used to cancel out soundwaves.
“While we can use fabric to create sound, there is already so much noise in our world. We thought creating silence could be even more valuable,” Yang says.
Applying an electrical signal to the piezoelectric fiber causes it to vibrate, which generates sound. The researchers demonstrated this by playing Bach’s “Air” using a 130-micrometer sheet of silk mounted on a circular frame.
To enable direct sound suppression, the researchers use a silk fabric loudspeaker to emit sound waves that destructively interfere with unwanted sound waves. They control the vibrations of the piezoelectric fiber so that sound waves emitted by the fabric are opposite of unwanted sound waves that strike the fabric, which can cancel out the noise.
However, this technique is only effective over a small area. So, the researchers built off this idea to develop a technique that uses fabric vibrations to suppress sound in much larger areas, like a bedroom.
Let’s say your next-door neighbors are playing foosball in the middle of the night. You hear noise in your bedroom because the sound in their apartment causes your shared wall to vibrate, which forms sound waves on your side.
To suppress that sound, the researchers could place the silk fabric onto your side of the shared wall, controlling the vibrations in the fiber to force the fabric to remain still. This vibration-mediated suppression prevents sound from being transmitted through the fabric.
“If we can control those vibrations and stop them from happening, we can stop the noise that is generated, as well,” Yang says.
A mirror for sound
Surprisingly, the researchers found that holding the fabric still causes sound to be reflected by the fabric, resulting in a thin piece of silk that reflects sound like a mirror does with light.
Their experiments also revealed that both the mechanical properties of a fabric and the size of its pores affect the efficiency of sound generation. While silk and muslin have similar mechanical properties, the smaller pore sizes of silk make it a better fabric loudspeaker.
But the effective pore size also depends on the frequency of sound waves. If the frequency is low enough, even a fabric with relatively large pores could function effectively, Yang says.
When they tested the silk fabric in direct suppression mode, the researchers found that it could significantly reduce the volume of sounds up to 65 decibels (about as loud as enthusiastic human conversation). In vibration-mediated suppression mode, the fabric could reduce sound transmission up to 75 percent.
These results were only possible due to a robust group of collaborators, Fink says. Graduate students at the Rhode Island School of Design helped the researchers understand the details of constructing fabrics; scientists at the University of Wisconsin at Madison conducted simulations; researchers at Case Western Reserve University characterized materials; and chemical engineers in the Smith Group at MIT used their expertise in gas membrane separation to measure airflow through the fabric.
Moving forward, the researchers want to explore the use of their fabric to block sound of multiple frequencies. This would likely require complex signal processing and additional electronics.
In addition, they want to further study the architecture of the fabric to see how changing things like the number of piezoelectric fibers, the direction in which they are sewn, or the applied voltages could improve performance.
“There are a lot of knobs we can turn to make this sound-suppressing fabric really effective. We want to get people thinking about controlling structural vibrations to suppress sound. This is just the beginning,” says Yang.
This work is funded, in part, by the National Science Foundation (NSF), the Army Research Office (ARO), the Defense Threat Reduction Agency (DTRA), and the Wisconsin Alumni Research Foundation.
It seems chimeras are of more interest these days. In all likelihood that has something to do with the fellow who received a transplant of a pig’s heart in January 2022 (he died in March 2022).
For those who aren’t familiar with the term, a chimera is an entity with two different DNA (deoxyribonucleic acid) identities. In short, if you get a DNA sample from the heart, it’s different from a DNA sample obtained from a cheek swab. This contrasts with a hybrid such as a mule (donkey/horse) whose DNA samples show a consisted identity throughout its body.
A new report on the ethics of crossing species boundaries by inserting human cells into nonhuman animals – research surrounded by debate – makes recommendations clarifying the ethical issues and calling for improved oversight of this work.
The report, “Creating Chimeric Animals — Seeking Clarity On Ethics and Oversight,” was developed by an interdisciplinary team, with funding from the National Institutes of Health. Principal investigators are Josephine Johnston and Karen Maschke, research scholars at The Hastings Center, and Insoo Hyun, director of the Center for Life Sciences and Public Learning at the Museum of Life Sciences in Boston, formerly of Case Western Reserve University.
Advances in human stem cell science and gene editing enable scientists to insert human cells more extensively and precisely into nonhuman animals, creating “chimeric” animals, embryos, and other organisms that contain a mix of human and nonhuman cells.
Many people hope that this research will yield enormous benefits, including better models of human disease, inexpensive sources of human eggs and embryos for research, and sources of tissues and organs suitable for transplantation into humans.
But there are ethical concerns about this type of research, which raise questions such as whether the moral status of nonhuman animals is altered by the insertion of human stem cells, whether these studies should be subject to additional prohibitions or oversight, and whether this kind of research should be done at all.
The report found that:
Animal welfare is a primary ethical issue and should be a focus of ethical and policy analysis as well as the governance and oversight of chimeric research.
Chimeric studies raise the possibility of unique or novel harms resulting from the insertion and development of human stem cells in nonhuman animals, particularly when those cells develop in the brain or central nervous system.
Oversight and governance of chimeric research are siloed, and public communication is minimal. Public communication should be improved, communication between the different committees involved in oversight at each institution should be enhanced, and a national mechanism created for those involved in oversight of these studies.
Scientists, journalists, bioethicists, and others writing about chimeric research should use precise and accessible language that clarifies rather than obscures the ethical issues at stake. The terms “chimera,” which in Greek mythology refers to a fire-breathing monster, and “humanization” are examples of ethically laden, or overly broad language to be avoided.
The Research Team
The Hastings Center
• Josephine Johnston • Karen J. Maschke • Carolyn P. Neuhaus • Margaret M. Matthews • Isabel Bolo
Case Western Reserve University • Insoo Hyun (now at Museum of Science, Boston) • Patricia Marshall • Kaitlynn P. Craig
The Work Group
• Kara Drolet, Oregon Health & Science University • Henry T. Greely, Stanford University • Lori R. Hill, MD Anderson Cancer Center • Amy Hinterberger, King’s College London • Elisa A. Hurley, Public Responsibility in Medicine and Research • Robert Kesterson, University of Alabama at Birmingham • Jonathan Kimmelman, McGill University • Nancy M. P. King, Wake Forest University School of Medicine • Geoffrey Lomax, California Institute for Regenerative Medicine • Melissa J. Lopes, Harvard University Embryonic Stem Cell Research Oversight Committee • P. Pearl O’Rourke, Harvard Medical School • Brendan Parent, NYU Grossman School of Medicine • Steven Peckman, University of California, Los Angeles • Monika Piotrowska, State University of New York at Albany • May Schwarz, The Salk Institute for Biological Studies • Jeff Sebo, New York University • Chris Stodgell, University of Rochester • Robert Streiffer, University of Wisconsin-Madison • Lorenz Studer, Memorial Sloan Kettering Cancer Center • Amy Wilkerson, The Rockefeller University
Here’s a link to and a citation for the report,
Creating Chimeric Animals: Seeking Clarity on Ethics and Oversight edited by Karen J. Maschke, Margaret M. Matthews, Kaitlynn P. Craig, Carolyn P. Neuhaus, Insoo Hyun, Josephine Johnston, The Hastings Center Report Volume 52, Issue S2 (Special Report), November‐December 2022 First Published: 09 December 2022
Eighteen cartoons have been selected as finalists in the 2023 Ethics Cartooning Competition, an annual contest sponsored by the Morgridge Institute for Research.
Participants from the University of Wisconsin-Madison and affiliated biomedical centers or institutes submitted their work, then a panel of judges selected the final cartoons for display to the public, who is invited to vote and help determine the 2023 winners.
This year’s cartoons depict a variety of research ethics topics, such as the ethics of scientific publishing, research funding and environments, questionable research practices, drug pricing, the ethics of experimenting on animals, social impacts of scientific research, and scientists as responsible members of society.
The Morgridge Ethics Cartooning Competition, developed by Morgridge Bioethics Scholar in Residence Pilar Ossorio, encourages scientists to shed light on timely or recurring issues that arise in scientific research.
“Ethical issues are all around us,” says Ossorio. “An event like the competition encourages people to identify some of those issues, perhaps talk about them with friends and colleagues, and think about how to communicate about those issues with a broader community of people.”
The one above hit home as I commented on a local (Vancouver, Canada) billionaire’s (Chip Wilson of Lululemon) announcement that he was spending $100M on research to treat a rare disease (facio-scapulo-humeral muscular dystrophy [FSHD]) he has. (See my April 5, 2022 posting, scroll down about 80% of the way to the subhead, Money makes the world go around.)
And this too caught my eye,
It reminds me that I’ve been meaning to do a piece on science and racism for the last few years. Maybe this year, eh?
I’ve been wondering when there’d be more ‘public engagement’ discussion in Canada about artificial intelligence, human genome editing, robotics, and other technologies which are rapidly changing status from ’emerging technologies’ to ’embedded technologies’.
In October of 2020, Jennifer Doudna and Emmanuelle Charpentier were awarded the Nobel Prize in chemistry for their discovery of an adaptable, easy way to edit genomes, known as CRISPR [clustered regularly interspaced short palindromic repeats], which has transformed the world of genetic engineering.
CRISPR has been used to fight lung cancer and correct the mutation responsible for sickle cell anemia in stem cells. But the technology was also used by a Chinese scientist to secretly and illegally edit the genomes of twin girls — the first-ever heritable mutation of the human germline made with genetic engineering.
“We’ve moved away from an era of science where we understood the risks that came with new technology and where decision stakes were fairly low,” says Dietram Scheufele, a professor of life sciences communication at the University of Wisconsin-Madison.
Today, Scheufele and his colleagues say, we’re in a world where new technologies have very immediate and sometimes unpredictable but significant impacts on society. In a paper published the week of April 26 [2021] in the Proceedings of the National Academy of Sciences [PNAS], the researchers argue that such advanced tech, especially CRISPR, demands more robust and thoughtful public engagement if it is to be harnessed to benefit the public without crossing ethical lines.
The authors say that being thoughtful and transparent about public engagement goals and using evidence from social science can help facilitate the difficult conversations society must have about scientific issues like CRISPR and their societal implications. Effective public engagement, in turn, lays the groundwork for public ownership of advances that do arise from CRISPR.
Life sciences communication Professor Dominique Brossard and graduate student Nicole Krause, along with University of Vienna research assistant Isabelle Freiling, co-authored the report with Scheufele. The paper stems from a 2019 National Academy of Sciences colloquium on CRISPR.
Since 2012, when the CRISPR system was first described, scientists have understood both its genetic engineering potential and the need for public engagement to discuss the possible uses of the technology. Many scientists wanted to avoid rehashing the controversies surrounding genetically modified organisms, which have been harshly criticized as unnatural and unnecessary by some activists despite broad scientific support for their use.
Yet, Krause says, some scientists who supported using CRISPR began by errantly repeating the public engagement methods employed for GMOs, which “assumes that people just need more knowledge, more of an ability to understand the science.” Instead, Krause adds: “Solutions focused on tailoring communications to people’s values would make more sense.”
This values-based public engagement strategy is supported by social science research into how people form and change their opinions around new technologies. Some public engagement methods engage value systems, and encourage thoughtful conversation, more than others.
For example, what researchers term “public involvement” and “public collaboration” are methods of two-way communication involving the joint exchange of information and values and the identification and design of science-based decisions that adhere to those values. That contrasts with “public communication,” which focuses only on the dissemination of scientific information.
Scheufele and his colleagues say that such collaborative approaches could help scientists widen the representation of voices in debates around science to groups who are often overlooked, such as people with disabilities or racial minorities.
“As the scientific community, we don’t have a long track record of effective engagement mechanism with these communities,” says Scheufele. This failure to reach broader groups stems in part from the low participation rates of most science engagement events, which also attract highly selective audiences.
Another challenge is rewarding scientists for public engagement. “There’s very little incentive in academia to do this kind of work,” says Scheufele.
A recent report by Brossard and others found that a majority of land-grant faculty felt that public engagement was very important, but believed it was less important to their colleagues. That divide suggests scientists feel their engagement efforts won’t be rewarded by their peers, says Brossard.
Now, Brossard, Krause, Scheufele and colleagues have a grant from the National Science Foundation to research how to depolarize debates around CRISPR. Previous studies suggest that making people accountable for their positions helps them think more critically about their underlying reasoning. And when social scientists emphasize the complexity inherent in people’s values, it helps people consider controversial issues with more nuance.
But engaging a diverse society with pluralistic value systems in deliberations on the latest technologies will never be easy.
“The policymaking process involves a lot more than just science. Science will inform how we regulate technologies, and so will religious, political, ethical, regulatory and economic considerations,” says Scheufele. “And so the ability to actually do engagement in this much broader setting where we meaningfully contribute and guide the debate with the best available science is a major challenge.”
This bandage not only heals wounds (on rats) much faster; it’s cheap, according to a November 29, 2018 news item on Nanowerk,
A new, low-cost wound dressing developed by University of Wisconsin-Madison engineers could dramatically speed up healing in a surprising way.
The method leverages energy generated from a patient’s own body motions to apply gentle electrical pulses at the site of an injury.
In rodent tests, the dressings reduced healing times to a mere three days compared to nearly two weeks for the normal healing process.
“We were surprised to see such a fast recovery rate,” says Xudong Wang, a professor of materials science and engineering at UW-Madison. “We suspected that the devices would produce some effect, but the magnitude was much more than we expected.”
Researchers have known for several decades that electricity can be beneficial for skin healing, but most electrotherapy units in use today require bulky electrical equipment and complicated wiring to deliver powerful jolts of electricity.
“Acute and chronic wounds represent a substantial burden in healthcare worldwide,” says collaborator Angela Gibson, professor of surgery at UW-Madison and a burn surgeon and director of wound healing services at UW Health. “The use of electrical stimulation in wound healing is uncommon.”
In contrast with existing methods, the new dressing is much more straightforward.
“Our device is as convenient as a bandage you put on your skin,” says Wang.
The new dressings consist of small electrodes for the injury site that are linked to a band holding energy-harvesting units called nanogenerators, which are looped around a wearer’s torso. The natural expansion and contraction of the wearer’s ribcage during breathing powers the nanogenerators, which deliver low-intensity electric pulses.
“The nature of these electrical pulses is similar to the way the body generates an internal electric field,” says Wang.
And, those low-power pulses won’t harm healthy tissue like traditional, high-power electrotherapy devices might.
In fact, the researchers showed that exposing cells to high-energy electrical pulses caused them to produce almost five times more reactive oxygen species — major risk factors for cancer and cellular aging — than did cells that were exposed to the nanogenerators.
Also a boon to healing: They determined that the low-power pulses boosted viability for a type of skin cell called fibroblasts, and exposure to the nanogenerator’s pulses encouraged fibroblasts to line up (a crucial step in wound healing) and produce more biochemical substances that promote tissue growth.
“These findings are very exciting,” says collaborator Weibo Cai, a professor of radiology at UW-Madison. “The detailed mechanisms will still need to be elucidated in future work.”
In that vein, the researchers aim to tease out precisely how the gentle pulses aid in healing. The scientists also plan to test the devices on pig skin, which closely mimics human tissue.
And, they are working to give the nanogenerators additional capabilities–tweaking their structure to allow for energy harvesting from small imperceptible twitches in the skin or the thrumming pulse of a heartbeat.
“The impressive results in this study represent an exciting new spin on electrical stimulation for many different wound types, given the simplicity of the design,” says Gibson, who will collaborate with the team to confirm the reproducibility of these results in human skin models.
If the team is successful, the devices could help solve a major challenge for modern medicine.
“We think our nanogenerator could be the most effective electrical stimulation approach for many therapeutic purposes,” says Wang.
And because the nanogenerators consist of relatively common materials, price won’t be an issue.
“I don’t think the cost will be much more than a regular bandage,” says Wang. “The device in itself is very simple and convenient to fabricate.”
Michael Berger has written a May 24, 2018 Nanowerk Spotlight article about some of the latest research on transparent graphene electrode technology and the brain (Note: A link has been removed),
…
In new work, scientists from the labs of Kuzum [Duygu Kuzum, an Assistant Professor of Electrical and Computer Engineering at the University of California, San Diego {UCSD}] and Anna Devor report a transparent graphene microelectrode neural implant that eliminates light-induced artifacts to enable crosstalk-free integration of 2-photon microscopy, optogenetic stimulation, and cortical recordings in the same in vivo experiment. The new class of transparent brain implant is based on monolayer graphene. It offers a practical pathway to investigate neuronal activity over multiple spatial scales extending from single neurons to large neuronal populations.
…
Conventional metal-based microelectrodes cannot be used for simultaneous measurements of multiple optical and electrical parameters, which are essential for comprehensive investigation of brain function across spatio-temporal scales. Since they are opaque, they block the field of view of the microscopes and generate optical shadows impeding imaging.
More importantly, they cause light induced artifacts in electrical recordings, which can significantly interfere with neural signals. Transparent graphene electrode technology presented in this paper addresses these problems and allow seamless and crosstalk-free integration of optical and electrical sensing and manipulation technologies.
In their work, the scientists demonstrate that by careful design of key steps in the fabrication process for transparent graphene electrodes, the light-induced artifact problem can be mitigated and virtually artifact-free local field potential (LFP) recordings can be achieved within operating light intensities.
“Optical transparency of graphene enables seamless integration of imaging, optogenetic stimulation and electrical recording of brain activity in the same experiment with animal models,” Kuzum explains. “Different from conventional implants based on metal electrodes, graphene-based electrodes do not generate any electrical artifacts upon interacting with light used for imaging or optogenetics. That enables crosstalk free integration of three modalities: imaging, stimulation and recording to investigate brain activity over multiple spatial scales extending from single neurons to large populations of neurons in the same experiment.”
The team’s new fabrication process avoids any crack formation in the transfer process, resulting in a 95-100% yield for the electrode arrays. This fabrication quality is important for expanding this technology to high-density large area transparent arrays to monitor brain-scale cortical activity in large animal models or humans.
…
“Our technology is also well-suited for neurovascular and neurometabolic studies, providing a ‘gold standard’ neuronal correlate for optical measurements of vascular, hemodynamic, and metabolic activity,” Kuzum points out. “It will find application in multiple areas, advancing our understanding of how microscopic neural activity at the cellular scale translates into macroscopic activity of large neuron populations.”
“Combining optical techniques with electrical recordings using graphene electrodes will allow to connect the large body of neuroscience knowledge obtained from animal models to human studies mainly relying on electrophysiological recordings of brain-scale activity,” she adds.
Next steps for the team involve employing this technology to investigate coupling and information transfer between different brain regions.
…
This work is part of the US BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative and there’s more than one team working with transparent graphene electrodes. John Hewitt in an Oct. 21, 2014 posting on ExtremeTech describes two other teams’ work (Note: Links have been removed),
…
The solution [to the problems with metal electrodes], now emerging from multiple labs throughout the universe is to build flexible, transparent electrode arrays from graphene. Two studies in the latest issue of Nature Communications, one from the University of Wisconsin-Madison and the other from Penn [University of Pennsylvania], describe how to build these devices.
The University of Wisconsin researchers are either a little bit smarter or just a little bit richer, because they published their work open access. It’s a no-brainer then that we will focus on their methods first, and also in more detail. To make the arrays, these guys first deposited the parylene (polymer) substrate on a silicon wafer, metalized it with gold, and then patterned it with an electron beam to create small contact pads. The magic was to then apply four stacked single-atom-thick graphene layers using a wet transfer technique. These layers were then protected with a silicon dioxide layer, another parylene layer, and finally molded into brain signal recording goodness with reactive ion etching.
The researchers went with four graphene layers because that provided optimal mechanical integrity and conductivity while maintaining sufficient transparency. They tested the device in opto-enhanced mice whose neurons expressed proteins that react to blue light. When they hit the neurons with a laser fired in through the implant, the protein channels opened and fired the cell beneath. The masterstroke that remained was then to successfully record the electrical signals from this firing, sit back, and wait for the Nobel prize office to call.
The Penn State group [Note: Every reearcher mentioned in the paper Hewitt linked to is from the University of Pennsylvania] in the used a similar 16-spot electrode array (pictured above right), and proceeded — we presume — in much the same fashion. Their angle was to perform high-resolution optical imaging, in particular calcium imaging, right out through the transparent electrode arrays which simultaneously recorded in high-temporal-resolution signals. They did this in slices of the hippocampus where they could bring to bear the complex and multifarious hardware needed to perform confocal and two-photon microscopy. These latter techniques provide a boost in spatial resolution by zeroing in over narrow planes inside the specimen, and limiting the background by the requirement of two photons to generate an optical signal. We should mention that there are voltage sensitive dyes available, in addition to standard calcium dyes, which can almost record the fastest single spikes, but electrical recording still reigns supreme for speed.
What a mouse looks like with an optogenetics system plugged in
One concern of both groups in making these kinds of simultaneous electro-optic measurements was the generation of light-induced artifacts in the electrical recordings. This potential complication, called the Becqueral photovoltaic effect, has been known to exist since it was first demonstrated back in 1839. When light hits a conventional metal electrode, a photoelectrochemical (or more simply, a photovoltaic) effect occurs. If present in these recordings, the different signals could be highly disambiguatable. The Penn researchers reported that they saw no significant artifact, while the Wisconsin researchers saw some small effects with their device. In particular, when compared with platinum electrodes put into the opposite side cortical hemisphere, the Wisconsin researchers found that the artifact from graphene was similar to that obtained from platinum electrodes.
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Here’s a link to and a citation for the latest research from UCSD,
Deep 2-photon imaging and artifact-free optogenetics through transparent graphene microelectrode arrays by Martin Thunemann, Yichen Lu, Xin Liu, Kıvılcım Kılıç, Michèle Desjardins, Matthieu Vandenberghe, Sanaz Sadegh, Payam A. Saisan, Qun Cheng, Kimberly L. Weldy, Hongming Lyu, Srdjan Djurovic, Ole A. Andreassen, Anders M. Dale, Anna Devor, & Duygu Kuzum. Nature Communicationsvolume 9, Article number: 2035 (2018) doi:10.1038/s41467-018-04457-5 Published: 23 May 2018
This paper is open access.
You can find out more about the US BRAIN initiative here and if you’re curious, you can find out more about the project at UCSD here. Duygu Kuzum (now at UCSD) was at the University of Pennsylvania in 2014 and participated in the work mentioned in Hewitt’s 2014 posting.
After giving a basic explanation of the technology and some of the controversies in part 1 and offering more detail about the technology and about the possibility of designer babies in part 2; this part covers public discussion, a call for one and the suggestion that one is taking place in popular culture.
But a discussion does need to happen
In a move that is either an exquisite coincidence or has been carefully orchestrated (I vote for the latter), researchers from the University of Wisconsin-Madison have released a study about attitudes in the US to human genome editing. From an Aug. 11, 2017 University of Wisconsin-Madison news release (also on EurekAllert),
In early August 2017, an international team of scientists announced they had successfully edited the DNA of human embryos. As people process the political, moral and regulatory issues of the technology — which nudges us closer to nonfiction than science fiction — researchers at the University of Wisconsin-Madison and Temple University show the time is now to involve the American public in discussions about human genome editing.
In a study published Aug. 11 in the journal Science, the researchers assessed what people in the United States think about the uses of human genome editing and how their attitudes may drive public discussion. They found a public divided on its uses but united in the importance of moving conversations forward.
“There are several pathways we can go down with gene editing,” says UW-Madison’s Dietram Scheufele, lead author of the study and member of a National Academy of Sciences committee that compiled a report focused on human gene editing earlier this year. “Our study takes an exhaustive look at all of those possible pathways forward and asks where the public stands on each one of them.”
Compared to previous studies on public attitudes about the technology, the new study takes a more nuanced approach, examining public opinion about the use of gene editing for disease therapy versus for human enhancement, and about editing that becomes hereditary versus editing that does not.
The research team, which included Scheufele and Dominique Brossard — both professors of life sciences communication — along with Michael Xenos, professor of communication arts, first surveyed study participants about the use of editing to treat disease (therapy) versus for enhancement (creating so-called “designer babies”). While about two-thirds of respondents expressed at least some support for therapeutic editing, only one-third expressed support for using the technology for enhancement.
Diving even deeper, researchers looked into public attitudes about gene editing on specific cell types — somatic or germline — either for therapy or enhancement. Somatic cells are non-reproductive, so edits made in those cells do not affect future generations. Germline cells, however, are heritable, and changes made in these cells would be passed on to children.
Public support of therapeutic editing was high both in cells that would be inherited and those that would not, with 65 percent of respondents supporting therapy in germline cells and 64 percent supporting therapy in somatic cells. When considering enhancement editing, however, support depended more upon whether the changes would affect future generations. Only 26 percent of people surveyed supported enhancement editing in heritable germline cells and 39 percent supported enhancement of somatic cells that would not be passed on to children.
“A majority of people are saying that germline enhancement is where the technology crosses that invisible line and becomes unacceptable,” says Scheufele. “When it comes to therapy, the public is more open, and that may partly be reflective of how severe some of those genetically inherited diseases are. The potential treatments for those diseases are something the public at least is willing to consider.”
Beyond questions of support, researchers also wanted to understand what was driving public opinions. They found that two factors were related to respondents’ attitudes toward gene editing as well as their attitudes toward the public’s role in its emergence: the level of religious guidance in their lives, and factual knowledge about the technology.
Those with a high level of religious guidance in their daily lives had lower support for human genome editing than those with low religious guidance. Additionally, those with high knowledge of the technology were more supportive of it than those with less knowledge.
While respondents with high religious guidance and those with high knowledge differed on their support for the technology, both groups highly supported public engagement in its development and use. These results suggest broad agreement that the public should be involved in questions of political, regulatory and moral aspects of human genome editing.
“The public may be split along lines of religiosity or knowledge with regard to what they think about the technology and scientific community, but they are united in the idea that this is an issue that requires public involvement,” says Scheufele. “Our findings show very nicely that the public is ready for these discussions and that the time to have the discussions is now, before the science is fully ready and while we have time to carefully think through different options regarding how we want to move forward.”
Here’s a link to and a citation for the paper,
U.S. attitudes on human genome editing by Dietram A. Scheufele, Michael A. Xenos, Emily L. Howell, Kathleen M. Rose, Dominique Brossard1, and Bruce W. Hardy. Science 11 Aug 2017: Vol. 357, Issue 6351, pp. 553-554 DOI: 10.1126/science.aan3708
This paper is behind a paywall.
A couple of final comments
Briefly, I notice that there’s no mention of the ethics of patenting this technology in the news release about the study.
Moving on, it seems surprising that the first team to engage in germline editing in the US is in Oregon; I would have expected the work to come from Massachusetts, California, or Illinois where a lot of bleeding edge medical research is performed. However, given the dearth of financial support from federal funding institutions, it seems likely that only an outsider would dare to engage i the research. Given the timing, Mitalipov’s work was already well underway before the recent about-face from the US National Academy of Sciences (Note: Kaiser’s Feb. 14, 2017 article does note that for some the recent recommendations do not represent any change).
As for discussion on issues such as editing of the germline, I’ve often noted here that popular culture (including advertising with the science fiction and other dramas laid in various media) often provides an informal forum for discussion. Joelle Renstrom in an Aug. 13, 2017 article for slate.com writes that Orphan Black (a BBC America series featuring clones) opened up a series of questions about science and ethics in the guise of a thriller about clones. She offers a précis of the first four seasons (Note: A link has been removed),
If you stopped watching a few seasons back, here’s a brief synopsis of how the mysteries wrap up. Neolution, an organization that seeks to control human evolution through genetic modification, began Project Leda, the cloning program, for two primary reasons: to see whether they could and to experiment with mutations that might allow people (i.e., themselves) to live longer. Neolution partnered with biotech companies such as Dyad, using its big pharma reach and deep pockets to harvest people’s genetic information and to conduct individual and germline (that is, genetic alterations passed down through generations) experiments, including infertility treatments that result in horrifying birth defects and body modification, such as tail-growing.
She then provides the article’s thesis (Note: Links have been removed),
Orphan Black demonstrates Carl Sagan’s warning of a time when “awesome technological powers are in the hands of a very few.” Neolutionists do whatever they want, pausing only to consider whether they’re missing an opportunity to exploit. Their hubris is straight out of Victor Frankenstein’s playbook. Frankenstein wonders whether he ought to first reanimate something “of simpler organisation” than a human, but starting small means waiting for glory. Orphan Black’s evil scientists embody this belief: if they’re going to play God, then they’ll control not just their own destinies, but the clones’ and, ultimately, all of humanity’s. Any sacrifices along the way are for the greater good—reasoning that culminates in Westmoreland’s eugenics fantasy to genetically sterilize 99 percent of the population he doesn’t enhance.
Orphan Black uses sci-fi tropes to explore real-world plausibility. Neolution shares similarities with transhumanism, the belief that humans should use science and technology to take control of their own evolution. While some transhumanists dabble in body modifications, such as microchip implants or night-vision eye drops, others seek to end suffering by curing human illness and aging. But even these goals can be seen as selfish, as access to disease-eradicating or life-extending technologies would be limited to the wealthy. Westmoreland’s goal to “sell Neolution to the 1 percent” seems frighteningly plausible—transhumanists, who statistically tend to be white, well-educated, and male, and their associated organizations raise and spend massive sums of money to help fulfill their goals. …
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On Orphan Black, denial of choice is tantamount to imprisonment. That the clones have to earn autonomy underscores the need for ethics in science, especially when it comes to genetics. The show’s message here is timely given the rise of gene-editing techniques such as CRISPR. Recently, the National Academy of Sciences gave germline gene editing the green light, just one year after academy scientists from around the world argued it would be “irresponsible to proceed” without further exploring the implications. Scientists in the United Kingdom and China have already begun human genetic engineering and American scientists recently genetically engineered a human embryo for the first time. The possibility of Project Leda isn’t farfetched. Orphan Black warns us that money, power, and fear of death can corrupt both people and science. Once that happens, loss of humanity—of both the scientists and the subjects—is inevitable.
In Carl Sagan’s dark vision of the future, “people have lost the ability to set their own agendas or knowledgeably question those in authority.” This describes the plight of the clones at the outset of Orphan Black, but as the series continues, they challenge this paradigm by approaching science and scientists with skepticism, ingenuity, and grit. …
I hope there are discussions such as those Scheufele and Brossard are advocating but it might be worth considering that there is already some discussion underway, as informal as it is.
Having included an explanation of CRISPR-CAS9 technology along with the news about the first US team to edit the germline and bits and pieces about ethics and a patent fight (part 1), this part hones in on the details of the work and worries about ‘designer babies’.
The interest flurry
I found three articles addressing the research and all three concur that despite some of the early reporting, this is not the beginning of a ‘designer baby’ generation.
MIT Technology Review reported Thursday that a team of researchers from Portland, Oregon were the first team of U.S.-based scientists to successfully create a genetically modified human embryo. The researchers, led by Shoukhrat Mitalipov of Oregon Health and Science University, changed the DNA of—in MIT Technology Review’s words—“many tens” of genetically-diseased embryos by injecting the host egg with CRISPR, a DNA-based gene editing tool first discovered in bacteria, at the time of fertilization. CRISPR-Cas9, as the full editing system is called, allows scientists to change genes accurately and efficiently. As has happened with research elsewhere, the CRISPR-edited embryos weren’t implanted—they were kept sustained for only a couple of days.
In addition to being the first American team to complete this feat, the researchers also improved upon the work of the three Chinese research teams that beat them to editing embryos with CRISPR: Mitalipov’s team increased the proportion of embryonic cells that received the intended genetic changes, addressing an issue called “mosaicism,” which is when an embryo is comprised of cells with different genetic makeups. Increasing that proportion is essential to CRISPR work in eliminating inherited diseases, to ensure that the CRISPR therapy has the intended result. The Oregon team also reduced the number of genetic errors introduced by CRISPR, reducing the likelihood that a patient would develop cancer elsewhere in the body.
Separate from the scientific advancements, it’s a big deal that this work happened in a country with such intense politicization of embryo research. …
But there are a great number of obstacles between the current research and the future of genetically editing all children to be 12-foot-tall Einsteins.
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Ed Yong in an Aug. 2, 2017 article for The Atlantic offered a comprehensive overview of the research and its implications (unusually for Yong, there seems to be mildly condescending note but it’s worth ignoring for the wealth of information in the article; Note: Links have been removed),
… the full details of the experiment, which are released today, show that the study is scientifically important but much less of a social inflection point than has been suggested. “This has been widely reported as the dawn of the era of the designer baby, making it probably the fifth or sixth time people have reported that dawn,” says Alta Charo, an expert on law and bioethics at the University of Wisconsin-Madison. “And it’s not.”
Given the persistent confusion around CRISPR and its implications, I’ve laid out exactly what the team did, and what it means.
Who did the experiments?
Shoukhrat Mitalipov is a Kazakhstani-born cell biologist with a history of breakthroughs—and controversy—in the stem cell field. He was the scientist to clone monkeys. He was the first to create human embryos by cloning adult cells—a move that could provide patients with an easy supply of personalized stem cells. He also pioneered a technique for creating embryos with genetic material from three biological parents, as a way of preventing a group of debilitating inherited diseases.
Although MIT Tech Review name-checked Mitalipov alone, the paper splits credit for the research between five collaborating teams—four based in the United States, and one in South Korea.
What did they actually do?
The project effectively began with an elevator conversation between Mitalipov and his colleague Sanjiv Kaul. Mitalipov explained that he wanted to use CRISPR to correct a disease-causing gene in human embryos, and was trying to figure out which disease to focus on. Kaul, a cardiologist, told him about hypertrophic cardiomyopathy (HCM)—an inherited heart disease that’s commonly caused by mutations in a gene called MYBPC3. HCM is surprisingly common, affecting 1 in 500 adults. Many of them lead normal lives, but in some, the walls of their hearts can thicken and suddenly fail. For that reason, HCM is the commonest cause of sudden death in athletes. “There really is no treatment,” says Kaul. “A number of drugs are being evaluated but they are all experimental,” and they merely treat the symptoms. The team wanted to prevent HCM entirely by removing the underlying mutation.
They collected sperm from a man with HCM and used CRISPR to change his mutant gene into its normal healthy version, while simultaneously using the sperm to fertilize eggs that had been donated by female volunteers. In this way, they created embryos that were completely free of the mutation. The procedure was effective, and avoided some of the critical problems that have plagued past attempts to use CRISPR in human embryos.
Wait, other human embryos have been edited before?
There have been three attempts in China. The first two—in 2015 and 2016—used non-viable embryos that could never have resulted in a live birth. The third—announced this March—was the first to use viable embryos that could theoretically have been implanted in a womb. All of these studies showed that CRISPR gene-editing, for all its hype, is still in its infancy.
The editing was imprecise. CRISPR is heralded for its precision, allowing scientists to edit particular genes of choice. But in practice, some of the Chinese researchers found worrying levels of off-target mutations, where CRISPR mistakenly cut other parts of the genome.
The editing was inefficient. The first Chinese team only managed to successfully edit a disease gene in 4 out of 86 embryos, and the second team fared even worse.
The editing was incomplete. Even in the successful cases, each embryo had a mix of modified and unmodified cells. This pattern, known as mosaicism, poses serious safety problems if gene-editing were ever to be used in practice. Doctors could end up implanting women with embryos that they thought were free of a disease-causing mutation, but were only partially free. The resulting person would still have many tissues and organs that carry those mutations, and might go on to develop symptoms.
What did the American team do differently?
The Chinese teams all used CRISPR to edit embryos at early stages of their development. By contrast, the Oregon researchers delivered the CRISPR components at the earliest possible point—minutes before fertilization. That neatly avoids the problem of mosaicism by ensuring that an embryo is edited from the very moment it is created. The team did this with 54 embryos and successfully edited the mutant MYBPC3 gene in 72 percent of them. In the other 28 percent, the editing didn’t work—a high failure rate, but far lower than in previous attempts. Better still, the team found no evidence of off-target mutations.
This is a big deal. Many scientists assumed that they’d have to do something more convoluted to avoid mosaicism. They’d have to collect a patient’s cells, which they’d revert into stem cells, which they’d use to make sperm or eggs, which they’d edit using CRISPR. “That’s a lot of extra steps, with more risks,” says Alta Charo. “If it’s possible to edit the embryo itself, that’s a real advance.” Perhaps for that reason, this is the first study to edit human embryos that was published in a top-tier scientific journal—Nature, which rejected some of the earlier Chinese papers.
Is this kind of research even legal?
Yes. In Western Europe, 15 countries out of 22 ban any attempts to change the human germ line—a term referring to sperm, eggs, and other cells that can transmit genetic information to future generations. No such stance exists in the United States but Congress has banned the Food and Drug Administration from considering research applications that make such modifications. Separately, federal agencies like the National Institutes of Health are banned from funding research that ultimately destroys human embryos. But the Oregon team used non-federal money from their institutions, and donations from several small non-profits. No taxpayer money went into their work. [emphasis mine]
Why would you want to edit embryos at all?
Partly to learn more about ourselves. By using CRISPR to manipulate the genes of embryos, scientists can learn more about the earliest stages of human development, and about problems like infertility and miscarriages. That’s why biologist Kathy Niakan from the Crick Institute in London recently secured a license from a British regulator to use CRISPR on human embryos.
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Isn’t this a slippery slope toward making designer babies?
In terms of avoiding genetic diseases, it’s not conceptually different from PGD, which is already widely used. The bigger worry is that gene-editing could be used to make people stronger, smarter, or taller, paving the way for a new eugenics, and widening the already substantial gaps between the wealthy and poor. But many geneticists believe that such a future is fundamentally unlikely because complex traits like height and intelligence are the work of hundreds or thousands of genes, each of which have a tiny effect. The prospect of editing them all is implausible. And since genes are so thoroughly interconnected, it may be impossible to edit one particular trait without also affecting many others.
“There’s the worry that this could be used for enhancement, so society has to draw a line,” says Mitalipov. “But this is pretty complex technology and it wouldn’t be hard to regulate it.”
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Does this discovery have any social importance at all?
“It’s not so much about designer babies as it is about geographical location,” says Charo. “It’s happening in the United States, and everything here around embryo research has high sensitivity.” She and others worry that the early report about the study, before the actual details were available for scrutiny, could lead to unnecessary panic. “Panic reactions often lead to panic-driven policy … which is usually bad policy,” wrote Greely [bioethicist Hank Greely].
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As I understand it, despite the change in stance, there is no federal funding available for the research performed by Mitalipov and his team.
Finally, University College London (UCL) scientists Joyce Harper and Helen O’Neill wrote about CRISPR, the Oregon team’s work, and the possibilities in an Aug. 3, 2017 essay for The Conversation (Note: Links have been removed),
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The genome editing tool used, CRISPR-Cas9, has transformed the field of biology in the short time since its discovery in that it not only promises, but delivers. CRISPR has surpassed all previous efforts to engineer cells and alter genomes at a fraction of the time and cost.
The technology, which works like molecular scissors to cut and paste DNA, is a natural defence system that bacteria use to fend off harmful infections. This system has the ability to recognise invading virus DNA, cut it and integrate this cut sequence into its own genome – allowing the bacterium to render itself immune to future infections of viruses with similar DNA. It is this ability to recognise and cut DNA that has allowed scientists to use it to target and edit specific DNA regions.
When this technology is applied to “germ cells” – the sperm and eggs – or embryos, it changes the germline. That means that any alterations made would be permanent and passed down to future generations. This makes it more ethically complex, but there are strict regulations around human germline genome editing, which is predominantly illegal. The UK received a licence in 2016 to carry out CRISPR on human embryos for research into early development. But edited embryos are not allowed to be inserted into the uterus and develop into a fetus in any country.
Germline genome editing came into the global spotlight when Chinese scientists announced in 2015 that they had used CRISPR to edit non-viable human embryos – cells that could never result in a live birth. They did this to modify the gene responsible for the blood disorder β-thalassaemia. While it was met with some success, it received a lot of criticism because of the premature use of this technology in human embryos. The results showed a high number of potentially dangerous, off-target mutations created in the procedure.
Impressive results
The new study, published in Nature, is different because it deals with viable human embryos and shows that the genome editing can be carried out safely – without creating harmful mutations. The team used CRISPR to correct a mutation in the gene MYBPC3, which accounts for approximately 40% of the myocardial disease hypertrophic cardiomyopathy. This is a dominant disease, so an affected individual only needs one abnormal copy of the gene to be affected.
The researchers used sperm from a patient carrying one copy of the MYBPC3 mutation to create 54 embryos. They edited them using CRISPR-Cas9 to correct the mutation. Without genome editing, approximately 50% of the embryos would carry the patients’ normal gene and 50% would carry his abnormal gene.
After genome editing, the aim would be for 100% of embryos to be normal. In the first round of the experiments, they found that 66.7% of embryos – 36 out of 54 – were normal after being injected with CRIPSR. Of the remaining 18 embryos, five had remained unchanged, suggesting editing had not worked. In 13 embryos, only a portion of cells had been edited.
The level of efficiency is affected by the type of CRISPR machinery used and, critically, the timing in which it is put into the embryo. The researchers therefore also tried injecting the sperm and the CRISPR-Cas9 complex into the egg at the same time, which resulted in more promising results. This was done for 75 mature donated human eggs using a common IVF technique called intracytoplasmic sperm injection. This time, impressively, 72.4% of embryos were normal as a result. The approach also lowered the number of embryos containing a mixture of edited and unedited cells (these embryos are called mosaics).
Finally, the team injected a further 22 embryos which were grown into blastocyst – a later stage of embryo development. These were sequenced and the researchers found that the editing had indeed worked. Importantly, they could show that the level of off-target mutations was low.
A brave new world?
So does this mean we finally have a cure for debilitating, heritable diseases? It’s important to remember that the study did not achieve a 100% success rate. Even the researchers themselves stress that further research is needed in order to fully understand the potential and limitations of the technique.
In our view, it is unlikely that genome editing would be used to treat the majority of inherited conditions anytime soon. We still can’t be sure how a child with a genetically altered genome will develop over a lifetime, so it seems unlikely that couples carrying a genetic disease would embark on gene editing rather than undergoing already available tests – such as preimplantation genetic diagnosis or prenatal diagnosis – where the embryos or fetus are tested for genetic faults.
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As might be expected there is now a call for public discussion about the ethics about this kind of work. See Part 3.
For anyone who started in the middle of this series, here’s Part 1 featuring an introduction to the technology and some of the issues.
