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Creating Baby Geniuses to Thwart the AI Threat? (Yes, Really.)

The new wave of Silicon Valley–backed gene-editing startups is straight out of “Brave New World.”

Abby VesoulisMay+June 2026 Issue

Additional reporting by Anna Rogers

Two years ago, we devoted an entire issue to the rise of the American oligarchy. Since then, our oligarchic system has become more entrenched and pervasive, revolving around a small crew of tech titans whose quest for wealth and power—in all of its forms—is destabilizing our democracy and reshaping our society. In the May + June 2026 issue, we investigate our new AI overlords and the world they are striving to create, whether we like it or not. Read the rest of the package here.

Mathematician Tsvi Benson-Tilsen once worked at the Peter Thiel–funded Machine Intelligence Research Institute, where he was one of many experts tasked with figuring out how to ensure AI doesn’t eventually destroy humankind. After seven years, he concluded that he’s not smart enough to figure it out. As of today, he doesn’t think anybody is.

The 33-year-old is racing against a threat known as “the singularity,” the moment when superintelligent machines, having surpassed the feeble cognitive abilities of humans, begin to act in ways contrary to the interests of humanity. “If it’s smarter than you, you cannot tell what’s dangerous necessarily, and you cannot tell what it’s thinking, because it could hide its thoughts,” Benson-Tilsen explains.

Even the sector’s leading thinkers don’t really comprehend how their systems work and thus cannot guarantee their models won’t try to deceive, overthrow, or even kill us. “Our inability to understand models’ internal mechanisms means that we cannot meaningfully predict such behaviors and therefore struggle to rule them out,” Anthropic CEO Dario Amodei wrote in April 2025, citing the possibility of AI-contrived cyber and biological weapons.

The report released a couple months later by Amodei’s firm—the $380 billion behemoth behind Claude—didn’t exactly quell these concerns. Anthropic had presented the leading AI systems, including Claude, Gemini, ChatGPT, and DeepSeek, with an extreme stress test: What would they do if a hypothetical corporate executive made a business decision the models didn’t like? In more than 75 percent of simulations across five of the tested models, they attempted to blackmail or trick the executive. Occasionally, they even trapped their imaginary boss, Kyle, in a control room with insufficient oxygen and extreme temperatures. That is, they killed him.

Such scenarios may seem remote to the roughly 50 percent of Americans who say they use large language models, a subset of the broader category of “generative AI” designed for content creation, and tasks like composing grocery lists or designing birthday party invites. But the industry’s momentum is toward “agentic AI,” which lets the machines conceive and execute plans without human input. Useful for booking a multidestination vacation, perhaps. But a fully autonomous AI system with a generalized, non-task-specific mission—a.k.a. artificial general intelligence (AGI)—might simply decide humans are in the way.

Benson-Tilsen is optimistic about how long it will take AGI to reach that conclusion—he puts the odds at around 20 percent by 2050, a timeline he believes gives humanity time to come up with a solution: namely, advancing technologies that enable parents to optimize their offspring, including for superior intelligence, with the hope that some of these smarter humans will understand the logic of AGI and ensure that its goals do not interfere with the continuance of, well, us. And this notion of creating superbabies to stop the rise of something akin to Skynet from The Terminator is capturing the fancy—and the wallets—of the same billionaires who bankrolled the AI revolution.

In late 2024, Benson-Tilsen founded the Berkeley Genomics Project—no relation to the University of California, Berkeley, where he was a PhD candidate—to build a case for editing the genes of human embryos. This is prohibited or highly restricted in every developed country, hence Benson-Tilsen’s effort to spur dialogue about how it could theoretically be done safely and ethically.

Scientists have tinkered plenty with nonreproductive, or somatic, cells. The first successful use of gene therapy—two young girls were injected with modified cells to treat a rare genetic disorder—occurred in the early 1990s, and the first attempt to edit a patient’s genes inside their body happened in 2017. No approved genetic therapy to date has involved germline editing (that is, modifying reproductive cells). But screening embryos for genetic traits prior to implantation has grown increasingly popular—even among couples who lack any of the genetic variance known to cause disorders like cystic fibrosis, Huntington’s disease, or sickle cell disease. And now a host of startups is working toward genetically optimizing children, including for intelligence, with at least one that said it was committed to using germline editing to get there.

The primary argument for genetic optimization is that it could revolutionize disease prevention. Based on the capital flowing into these startups—$36.5 billion in 2024, according to Astute Analytica—investors are bullish on the industry’s future. Backers include Thiel; Coinbase co-founder Brian Armstrong; OpenAI’s Sam Altman and his husband, Oliver Mulherin; venture capitalist Marc Andreessen; and Ethereum founder Vitalik Buterin, all of whom are heavily invested in AI, too.

Investors follow the money, of course, but part of the dual appeal of genetic optimization and AI is that both are central to transhumanism. This futurist philosophy, popular among the tech elite, aims to marry advancements in biology and technology to accomplish things today’s humans cannot—like extending our lives (perhaps forever!) or circumventing climate change (by colonizing other planets). While it may seem odd that these billionaires are constructing one technology some of them admit could bring about human extinction, even as they back another one to save us from what they’re building, there is, in fact, a unifying theme: “the rejection of limitation,” explains Alexander Thomas, author of The Politics and Ethics of Transhumanism. “That colonial impulse of ‘I want more.’”

Sure, there are less extreme ways to extend life expectancy and clean up the planet. But those solutions—like expanding health care access and slashing carbon emissions—would force the AI moguls to acknowledge their culpability and perhaps commit some of their vast financial resources to the cause. And putting the brakes on AI would leave too many trillions on the table, so instead they fantasize about a future in which they are celebrated for building the ark that saves humanity from the next great flood. Never mind that they opened the floodgates.

If you’ve ridden the New York subway lately, you’ve seen the signs: “Have your best baby.” The ads direct people to the website PickYourBaby.com, which belongs to a startup called Nucleus that caters to couples undergoing in vitro fertilization. In 44 percent of IVF cycles, patients screen their viable embryos for extra chromosomes and easily detectable disorders, such as Tay-Sachs and Huntington’s, which are caused by single genes. But Nucleus will screen pre-implantation embryos for hundreds of traits, many of which are controlled by multiple genes in a delicate, poorly understood balancing act.

How important is IQ or hair color? Is a marginally lower risk of developing Alzheimer’s worth giving up a few inches in height? These are some of the questions Nucleus asks prospective parents to consider as it claims to give them a better-than-winging-it chance at having babies with or without certain features. The pitch is that these so-called polygenic risk scores increase the likelihood of passing down dad’s blue eyes and mom’s smarts, should the parents choose to, or decrease the chance of having a child who develops cancer.

When I spoke with 26-year-old Nucleus founder Kian Sadeghi in February, his demeanor was gentler than his company’s brash marketing tactics suggest. Sadeghi, who dropped out of college before launching his startup, explained that a family tragedy had propelled his interest in genetic optimization: His cousin died in her sleep at age 15 from complications that doctors suspected were related to long QT syndrome, a serious but generally treatable heart disorder nobody knew she had. “How does this happen?” Sadeghi, then a second grader, recalls asking. “Bad genetics,” answered his dad, a physician.

He would later have an epiphany when his biology professor at the University of Pennsylvania presented a chart depicting the plummeting cost of gene sequencing. In 2003, when an international team of scientists completed the Human Genome Project, decoding a genome cost $3 billion and took 13 years. By 2019, when Sadeghi was a college freshman, a person’s full DNA could be sequenced for about $1,000 in just a few days. “Obviously, the price is going to keep decreasing,” he remembers thinking. “Someone needs to build the kind of interpretation layer to stop what happened to my cousin from happening to anybody.”

Elon Musk, who revels in controversy, has said he personally avoided working in the field of genetic optimization because of what he called “the Hitler problem.”

When Covid hit, he unenrolled from school and began scouring for investors to create such a company, eventually landing $3.5 million in a seed funding round led by Thiel’s Founders Fund. Five years and thousands of embryo analyses later, Sadeghi says Nucleus can screen embryos for IQ and hundreds of possible health conditions for a few thousand dollars on top of the cost of IVF. Simulations published by the company, which have not been peer-reviewed, report to lower the risk of several common conditions by 27 to 67 percent.

Had his aunt and uncle had access to the tool, they may have known to treat their daughter. Or, had she been conceived via IVF, they might have simply chosen a different embryo. Sadeghi emphasizes these are personal choices that only prospective parents can make. “There’s no universal ideal, because the way parents define that is so different,” he says.

Still, the concept of establishing preferences for heritable traits makes many people uneasy. The United States has a dark history of eugenics, justifying racism on the basis of perceived genetic differences and forcing the sterilization of mentally disabled people. It was less than a century ago that Nazi Germany predicated the murder of millions on ethnic and physical characteristics. Even Elon Musk, who revels in controversy, has said he personally avoided working in the field of genetic optimization because of what he called “the Hitler problem.”

Fans of genetic optimization are quick to point out that Hitler’s atrocities were state directed, whereas nobody is forcing parents to screen their embryos. Israel even covers the costs of IVF and genetic testing for up to two live births per family, largely to prevent Tay-Sachs, a fatal genetic mutation prevalent among people of Ashkenazi Jewish descent. “Whereas in Nazi Germany Jewish life was systematically destroyed in the name of eugenics, Zionists in the Land of Israel conceived of eugenics as part of their mission to restore the Jewish people,” Raphael Falk, a Jewish geneticist, wrote in 2010.

But the argument—and the science—becomes hazier when couples seek to optimize embryos around complex traits. Take mental illness. Conditions like schizophrenia and bipolar disorder run in some families, though other risk factors, such as prenatal exposure to viruses and childhood trauma, make it impractical to predict whether a baby will ultimately face either diagnosis. “Calculating a ‘polygenic risk score’ for, say, schizophrenia is near impossible,” says Fyodor Urnov, director of therapeutic R&D at UC Berkeley’s Innovative Genomics Institute. If vendors of genetic screening promise otherwise, “they are lying.”

The genetic basis for intelligence is similarly elusive, “confounded by environmental factors” including nutrition, family stability, and primary school quality, according to a 2024 meta-analysis. There’s also the scale issue: Polygenic risk scores are based on tens of thousands of genomes. But there’s far less variability when parents are choosing from a small collection of their own embryos. One 2019 research article in the journal Cell calculated that the average IQ gain parents could expect from screening five embryos was just 2.5 points. (A typical IQ score is around 100.) “We’re talking about a very minimal gain,” says Sophie von Stumm, a University of York psychology professor and cognitive development expert. “I know companies are selling this…but right now, selecting embryos for polygenic scores to get smart kids is pretty impossible.”

Kaitlyn Gallacher, communications director at Nucleus, says the science has “advanced significantly,” particularly regarding IQ, but she notes: “No genetic model determines a child’s life…Environment, upbringing, education, and many other factors shape outcomes. That nuance is built directly into how we present genetic insights.”

Nucleus isn’t alone in qualifying the usefulness of its IQ predictions. Looking at an embryo’s predicted score in a vacuum is “borderline nonsense,” says Jonathan Anomaly, communications director for the embryo selection company Herasight. After clients review their embryo options for serious health risks, particularly hereditary conditions, “then, fine,” he says. “If you care about IQ, maybe you kind of look at it.”

“Some don’t care about it at all and some care a lot,” adds Anomaly, who seems to be among the latter. A former Duke University philosophy lecturer, he wrote in a 2018 paper, titled “Defending Eugenics,” that he was concerned about successful, well-educated women “substituting cats for kids,” which would result in “bad effects on the gene pool” over time. “The current demographics of Western countries are troubling,” he wrote, “as people with a higher IQ, more education, and greater income reproduce at relatively low levels.”

Musk shares a similar perspective, which helps explain why he’s had at least 14 children, including four with Shivon Zilis, an executive at his company Neuralink. “He really wants smart people to have kids,” Zilis, a Yale-educated AI specialist, told Musk biographer Walter Isaacson.

Especially him. “To reach legion-level before the apocalypse we will need to use surrogates,” Musk told the mother of one of his children in a text reviewed by the Wall Street Journal. The Washington Post, meanwhile, reported that Musk has been a client of Orchid, an embryo screening company founded by Noor Siddiqui, whose career was kickstarted via a fellowship funded by Thiel. (Orchid says it does not screen embryos for IQ, though it does screen for “intellectual disabilities” and autism.)

Embryo selection is just the start of what some tech billionaires envision. At the “IVF clinic of the future,” Coinbase’s Armstrong mused in a post on X, multiple technologies will be combined for absolute offspring optimization. Using in vitro gametogenesis, he wrote, technicians will be able to generate thousands of eggs from a client’s blood or skin cells. Once those eggs are fertilized, the client will be able to screen the embryos and pick a favorite, whose DNA can then be edited as desired. Even surrogacy won’t be necessary, Armstrong predicted, because artificial wombs will allow fetuses to develop without “the risk/burden of pregnancy.” He dubbed this medley the “Gattaca stack,” perhaps forgetting that the protagonist of the 1997 dystopian classic was a nongenetically optimized “in-valid,” gestated in his mother’s womb.

A GIF illustration in red, black, and white of a figure evocative of a baby in a womb, made up of 0's and 1's, representing binary code, and the letters A, T, G, and C, representing the four-letter genetic code. The baby rotates clockwise.

Outlanders Design

Twenty-month-old KJ Muldoon of eastern Pennsylvania represents the marvel of gene editing. Without it, he probably wouldn’t be alive. Born without functional copies of CPS1, a gene needed to produce a protein that enables the liver to clear out ammonia, he spent most of his first year of life in the hospital.

Doctors and scientists at Children’s Hospital of Philadelphia and the University of Pennsylvania developed a custom gene-editing protocol for KJ. It was the first use of a new form of CRISPR, a biological tool that allows scientists to modify DNA with great accuracy. In the absence of other options, the decision to move forward was easy for KJ’s mother, Nicole. “We would do anything for our kids,” she said at the time. Proponents of embryonic gene editing have long used that same rationale: What good parent wouldn’t?

But to look at KJ’s case and conclude we’re ready to program pre-implantation embryos is like declaring you’re fluent in a new language because you’ve tried Duolingo. His treatment, in early 2025, required altering just two DNA base pairs among the 6 billion that make up a person’s genome. And the mutated CPS1 gene that caused his condition was no mystery—it had been thoroughly researched since the 1970s.

That’s not the case for the vast majority of the 20,000 or so genes within our chromosomes. And even those genes, the little blueprints our bodies use to make specific proteins, are far better understood than the remaining 98 percent of our genetic material, which scientists refer to as our cells’ “dark matter.” That’s because research suggests it serves important biological functions we haven’t quite grasped yet.

Tweaking a single well-known gene is one thing. But trying to edit an embryo for more complex traits or conditions would mean meddling with dozens to thousands of sequences scattered widely throughout our chromosomes. It’s a bit like playing with the dials on an unlabeled control panel, a level of unknown that gives many scientists and bioethicists pause.

KJ’s therapy was not particularly controversial because he was already born, so his treatment targeted only the cells of his liver. But embryos are clumps of cells that haven’t decided what they are yet. Some will give rise to the liver and the brain, while others will spawn sperm or egg cells, passing any genetic changes along to future generations. The consequences of embryonic gene editing are impossible to predict, which is why Australia, the European Union, the United Kingdom, and the United States all prohibit doing it for reproductive purposes.

“I cannot imagine…figuring out how to raise a newborn without ChatGPT.” —Sam Altman, CEO of OpenAI

China too. Yet Chinese biophysicist He Jiankui defied the prohibition and shocked the world in 2018, announcing that twin girls had been born from embryos he’d edited pre-implantation. By deleting part of the CCR5 gene, which produces a protein docking site for HIV, he claimed he made the twins immune to the virus, though there’s been no independent confirmation of his work.

In his 2021 book, CRISPR People, Stanford University law professor Henry Greely described He’s experiment as “criminally reckless” and “deeply unethical.” The Chinese government agreed, sentencing He to three years in prison. But after his release in 2022, He returned to work on embryo-editing research, now at a private lab with secretive financing. Then, in 2025, the Chinese government issued new regulations opening the door to “manipulating human reproductive cells” under the oversight of the State Council health department. He says his work is aimed solely at curing disease, and he predicts embryonic gene editing will soon be legal for reproductive purposes in both China and the United States.

He’s ex-wife, Cathy Tie, a Chinese-born Canadian, says she is pursuing the same goal of editing embryos for heritable conditions. She, like Orchid’s Siddiqui, was awarded a large grant from Thiel, which enabled her to drop out of college at 18 and build a company geared toward analyzing rare mutations and common cancer genes. Last year, Tie launched Manhattan Genomics, which has not disclosed its investors. It is part of a wave of embryo-editing startups that includes Preventive, launched in 2025 with $30 million from techies including Armstrong and Altman and his husband.

Both Manhattan Genomics and Preventive stress that their goal isn’t optimizing babies for brilliance. “We draw the line at disease prevention,” Tie told NPR. But it might not be entirely up to them. Federal funds cannot be used for research on embryo editing—Congress has seen to that—which leaves private investors in charge of the direction of the science. “I wouldn’t take them at their word,” Jennifer Denbow, a California Polytechnic State University professor who researches reproductive technologies, says of the entrepreneurs. “There’s some very powerful influences and a lot of money that is interested, ultimately, in intelligence.”

Berkeley’s Urnov is also pessimistic. In his opinion, he said via email, “The ‘embryo editors’ are deceiving themselves and the public when they speak of using this technology to address the public health challenge of genetic disease.” According to him, “their sole purpose is ‘baby improvement.’”

Altman has previously said that some form of genetic engineering is inevitable. “Superhuman AI is going to happen, genetic enhancement is going to happen, and brain-machine interfaces are going to happen. It is a failure of human imagination and human arrogance to assume that we will never build things smarter than ourselves,” he wrote in 2017. “My guess is that we can either be the biological bootloader for digital intelligence and then fade into an evolutionary tree branch, or we can figure out what a successful merge looks like.”

That was effectively the mission a company called Bootstrap Bio touted openly. “Of particular interest to me is whether we could modify intelligence,” co-founders Chase Denecke and Ben Korpan noted in a viral 2023 essay.

Like Benson-Tilsen, they framed the concept as an imperative, noting there’s currently a “very limited number of people” who have the intellect required to protect the world from a dangerously capable AGI. “It is not an exaggeration to say that the lives of literally everyone depend on whether a few hundred engineers and mathematicians can figure out how to control the machines built by the mad scientists in the office next door,” Denecke and Korpan wrote.

When I emailed Denecke, he told me Bootstrap Bio had ceased operations due to lack of funding. (The company’s former chief science officer, Qichen Yuan, was indicted for attempted sex trafficking of a child in September 2025. His case is ongoing.) But before the company unraveled, its early investors included Malcolm and Simone Collins, whom you may have heard of. They’re the media-hungry face of the pronatalist movement, which contends the world is headed for population collapse if birth rates don’t rise substantially.

Malcolm, a quirky, fast-talking former venture capitalist, envisions two possibilities: Either the cognitive capabilities of humans improve significantly or we’re all goners. “For a long time, humanity has had a synthetic component to it that has evolved alongside our organic component,” he told me. “We finally reached a stage where the synthetic component is sort of turning around and putting a gun to the organic component and saying, ‘Okay, now prove your worth.’”

Malcolm laments that the people he considers the most brilliant are prioritizing careers over child-rearing, ceding ground to those he finds genetically lacking and thus risking a future in which there are not enough smart people to save us. “The dumb ones,” he said during a 2024 episode of Based Camp, the podcast he hosts with Simone, “are going to be more and more of the general population as time goes on. And so they will be electing and building bureaucracies that make it harder and harder for the geniuses to do their jobs.”

The couple’s message contains echoes of The Bell Curve, the controversial 1994 book that claimed people with less “cognitive capital” were having more children. It also theorized that white people had higher IQs than Black people on account of genetic differences. Right-wing nationalists use the same thoroughly debunked theory, which they call dysgenics, to rationalize racism and xenophobia. Malcolm does not say any race is inherently smarter than another but he emphasizes that genetic differences matter. “Noticing genes exist and caring about them in terms of future populations is not eugenics,” he says, “but it is definitely playing in a spicy territory.”

While it would be tempting to discount the Collinses’ views as fringe, their worldview extends far beyond their farmhouse. They have a growing online platform and run in powerful circles. Malcolm says he’s attended meetings focused on fertility at the White House, whose gene-obsessed occupant, Donald Trump, routinely disparages people of color (including literally all Somalis) as “low IQ.” The Collinses reportedly have spent time, too, with Musk, who also links intelligence to race, having endorsed statements theorizing that students from predominantly Black universities have IQs approaching “borderline intellectual impairment” and shouldn’t be allowed to become pilots.

The obsession with intelligence and its genetic components suggests an inherent sense of superiority, Cal Poly’s Denbow says. The notion that IQ can be genetically optimized only reinforces the false notion that some people are “more worthwhile.”

Among the numerous ethical questions raised by genetic engineering is whether its use will effectively create a new hereditary caste system, not unlike the dystopian pecking order in Aldous Huxley’s Brave New World, where “Alpha” elites rule over the lesser classes. The future that Malcolm Collins describes sounds very much like a society stratified by genetic haves and have-nots: “I think it will be both dramatically less equitable, but dramatically better for the poor individuals in the same way that the United States right now might be less equitable than it would have been at the time of the Revolution,” he says. “But right now, the poorest Americans still have cellphones and computers and refrigerators, right? They’re not dying of cholera in the streets.”

In Benson-Tilsen’s ideal tomorrow, there would be no genotocracy—some of the wunderkinds optimized for superior intelligence will have quashed the threat of advanced AI, and the technology needed to have healthier and smarter babies will be widely accessible and affordable. But current trends—a small group of Silicon Valley titans holding a vast amount of our nation’s technological, political, and financial power—don’t seem to point in that direction. What, I ask him, will stop billionaire investors from hijacking the tech of even the most well-intentioned embryo-editing entrepreneur? After a long pause, he concedes he doesn’t have a great answer: “It’s an interesting question I haven’t thought that much about.”

Well, perhaps the superhumans will figure it out.

Read more of our coverage of the roots and rise of the American oligarchy.

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https://theintercept.com/2022/09/28/cia-extinction-woolly-mammoth-dna/

AS A RAPIDLY ADVANCING climate emergency turns the planet ever hotter, the Dallas-based biotechnology company Colossal Biosciences has a vision: “To see the Woolly Mammoth thunder upon the tundra once again.” Founders George Church and Ben Lamm have already racked up an impressive list of high-profile funders and investors, includingPeter Thiel, Tony Robbins, Paris Hilton, Winklevoss Capital — and, according to the public portfolio its venture capital arm released this month, the CIA.

Colossal says it hopes to use advanced genetic sequencing to resurrect two extinct mammals — not just the giant, ice age mammoth, but also a mid-sized marsupial known as the thylacine, or Tasmanian tiger, that died out less than a century ago. On its website, the company vows: “Combining the science of genetics with the business of discovery, we endeavor to jumpstart nature’s ancestral heartbeat.”

In-Q-Tel, its new investor, is registered as a nonprofit venture capital firm funded by the CIA. On its surface, the group funds technology startups with the potential to safeguard national security. In addition to its long-standing pursuit of intelligence and weapons technologies, the CIA outfit has lately displayed an increased interest in biotechnology and particularly DNA sequencing.

“Why the interest in a company like Colossal, which was founded with a mission to “de-extinct” the wooly mammoth and other species?” reads an In-Q-Tel blog post published on September 22. “Strategically, it’s less about the mammoths and more about the capability.”

“Biotechnology and the broader bioeconomy are critical for humanity to further develop. It is important for all facets of our government to develop them and have an understanding of what is possible,” Colossal co-founder Ben Lamm wrote in an email to The Intercept. (A spokesperson for Lamm stressed that while Thiel provided Church with $100,000 in funding to launch the woolly mammoth project that became Colossal, he is not a stakeholder like Robbins, Hilton, Winklevoss Capital, and In-Q-Tel.)

Colossal uses CRISPR gene editing, a method of genetic engineering based on a naturally occurring type of DNA sequence. CRISPR sequences present on their own in some bacterial cells and act as an immune defense system, allowing the cell to detect and excise viral material that tries to invade. The eponymous gene editing technique was developed to function the same way, allowing users to snip unwanted genes and program a more ideal version of the genetic code.

“CRISPR is the use of genetic scissors,” Robert Klitzman, a bioethicist at Columbia University and a prominent voice of caution on genetic engineering, told The Intercept. “You’re going into DNA, which is a 3-billion-molecule-long chain, and clipping some of it out and replacing it. You can clip out bad mutations and put in good genes, but these editing scissors can also take out too much.”

The embrace of this technology, according to In-Q-Tel’s blog post, will help allow U.S. government agencies to read, write, and edit genetic material, and, importantly, to steer global biological phenomena that impact “nation-to-nation competition” while enabling the United States “to help set the ethical, as well as the technological, standards” for its use.

In-Q-Tel did not respond to The Intercept’s requests for comment

https://en.wikipedia.org/wiki/CRISPR_Therapeutics

CRISPR Therapeutics AG is a Swiss–American biotechnology company headquartered in Zug, Switzerland. In fiscal year 2019, the company had revenues of $289.59 million, with net income of $66.86 million. In the same year, the number of employees stood at 304.^[1] As of early 2021, the company had a market capitalization of over $13 billion.^[2] CRISPR Therapeutics' investors include German chemical company Bayer. The company operates R&D in Cambridge, Massachusetts.^[3]

History

CRISPR Therapeutics was founded in 2012. One of the co-founders Emmanuelle Charpentier later shared the Nobel Prize in Chemistry in 2020 with Jennifer Doudna. As part of a working group, she provided the first scientific documentation on the development and use of CRISPR gene editing. This allows DNA to be specifically modified and exchanged, which can for example prevent diseases. The company CRISPR Therapeutics is to apply this new technology commercially and advance research.^[4]

In 2016, the company went public on NASDAQ.^[5]In August 2016 the company started to operate Casebia Therapeutics, as a joint venture with Bayer. In 2019, Casebia Therapeutics came directly under the control of CRISPR Therapeutics.^[6]

Products

The company has several drugs in development. These include the drug CTX001 for the treatment of the rare blood disorders Beta thalassemia and sickle cell disease, which is being developed jointly with Vertex Pharmaceuticals.^[4] In May 2020, CTX001 received Orphan drug Designation from the U.S. Food and Drug Administration for transfusion-dependent beta thalassemia and from the European Medicines Agency for sickle cell disease and transfusion-dependent beta thalassemia.^[7] Early clinical trial results support the safety and efficacy of this treatment.^[8][9][10]

References

^ "CRISPR THERAPEUTICS Bilanz GuV | Kennzahlen | Umsatz | Gewinn". finanzen.net (in German). Retrieved 8 January 2021.
^ "CRISPR Therapeutics AG (CRSP) Stock Price, News, Quote & History – Yahoo Finance". finance.yahoo.com. Retrieved 8 January 2021.
^ "Mission". CRISPR. Retrieved 15 April 2021.
^ :{Jump up to::(style="user-select:none;top:-99999px;clip:rect(1px, 1px, 1px, 1px);overflow:hidden;position:absolute !important;padding:0px !important;border:0px !important;height:1px !important;width:1px !important"):}:^a ^b(https://en.wikipedia.org/wiki/CRISPR_Therapeutics#cite_ref-:0_4-1) "CRISPR Therapeutics: Ist diese Aktie nobelpreiswürdig?". GodmodeTrader (in German). Retrieved 8 January 2021.
^ "Börsengang von CRISPR Therapeutics an der NASDAQ". VISCHER (in German). Retrieved 8 January2021.
^ "Bayer backs off running Casebia JV as CRISPR Tx takes over management". FierceBiotech. Retrieved 8 January2021.
^ CRISPR Therapeutics and Vertex Pharmaceuticals Announce FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to CTX001™ for the Treatment of Severe Hemoglobinopathies, PM Vertex 11 May 2020; retrieved 11 May 2020
^ Frangoul, Haydar; Altshuler, David; Cappellini, M. Domenica; Chen, Yi-Shan; Domm, Jennifer; Eustace, Brenda K.; Foell, Juergen; de la Fuente, Josu; Grupp, Stephan; Handgretinger, Rupert; Ho, Tony W. (21 January 2021). "CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia". New England Journal of Medicine. 384 (3): 252–260. doi:10.1056/NEJMoa2031054. ISSN 0028-4793. PMID 33283989.
^ "Synthego | Full Stack Genome Engineering". www.synthego.com. Retrieved 21 February 2021.
^ "1st Patients To Get CRISPR Gene-Editing Treatment Continue To Thrive". NPR.org. Retrieved 21 February2021.

Categories:

3/18

https://www.nature.com/articles/d41586-018-02477-1

CRISPR–Cas gene editing, once considered arcane, is fast entering mainstream use in research. Most people with an interest in science have probably heard about the technique, which uses a combination of a synthetic guide RNA molecule and an enzyme (typically Cas9) from the bacterial immune system to edit DNA with unprecedented ease and precision. It is a flexible tool with a variety of applications. Most of the media interest in the CRISPR–Cas system has focused on its potential for treating diseases with a genetic basis. Yet CRISPR–Cas also has a big part to play in drug discovery, which could prove to be as important as its therapeutic use — if not more so.

In a comprehensive 2017 review, scientists from the University of California, Berkeley, including co-discoverer of CRISPR–Cas Jennifer Doudna, emphatically concluded that this type of gene editing is “ready to have an immediate impact in real-world drug discovery and development”1.

Part of Nature Outlook: The future of medicine

Christof Fellmann, a biotechnologist and co-author of the review, explains that the ability of CRISPR–Cas to help identify target molecules will have a crucial impact on drug discovery. By using the system to deliberately activate or inhibit genes, researchers can determine the genes and proteins that cause or prevent disease, therefore identifying targets for potential drugs. CRISPR–Cas is also making it easier to create cellular and whole-animal model systems that precisely mimic diseases. This is enabling scientists to more accurately verify the safety and efficacy of drugs, which ensures that such models are better predictors of what will happen in clinical trials. As these uses are pursued, researchers are also refining and extending the capabilities of CRISPR–Cas to make it an even more powerful gene-editing tool.

“It makes everything easier,” says Jon Moore, chief scientific officer at biotechnology company Horizon Discovery in Waterbeach, near Cambridge, United Kingdom. In March 2016, at an event at the Science Museum in London, Moore declared, “The targets we’re finding with CRISPR–Cas9 are going to guide the drugs coming out in the 2020s.” He stands by that assessment two years on. “If it’s not right, then I’ll be in trouble,” he laughs.

A knock-out tool

The mechanism that underlies CRISPR–Cas gene editing is relatively simple. A short strand of RNA, tailored to target a specific sequence of DNA, is linked to an enzyme that is capable of cutting double-stranded DNA. Cas9, the enzyme to which Moore refers, is the most widely used, but other enzymes are being explored. After the RNA and enzyme are delivered to the cell nucleus, the RNA binds to its complementary DNA sequence, acting as a guide for the enzyme that then chops the DNA. After that crucial cut is made, DNA-repair enzymes in the cell fix the break in a way that either disables or modifies the targeted gene — its activity can be turned up or down, mutations can be introduced, or sections can be inverted.

The simplicity of using guide RNAs to target any location in the genome is making gene editing accessible to many more researchers. “CRISPR–Cas has taken gene editing out of the hands of those specialists who are expert in complicated molecular biology,” says Moore.

Researchers engaged in drug discovery are eagerly exploiting CRISPR–Cas to switch off — or ‘knock out’ — specific genes to see what they do. Methods of introducing such knock-out mutations have been in use since about 2000, but these earlier approaches, which rely on engineered enzymes to cut DNA, often only partially knock out genes, commonly produce unwanted effects on unintended targets, and lead to inconsistent results between similar studies. CRISPR–Cas avoids these deficiencies and, since rising to prominence in 2012, has made it straightforward to knock out genes of choice. “The difference is in the quality of information you can get,” says Moore. CRISPR–Cas is better at knocking out the targeted gene more fully, as well as avoiding unwanted effects, which has made large-scale gene-function experiments much more reliable, he explains.

Knock-out screening to identify genes involved in drug resistance is fast becoming one of the most widely used applications of CRISPR–Cas gene editing in drug discovery. Researchers expose large numbers of cells to a pool of CRISPR–Cas systems carrying guide RNAs that target various genes. This allows them to generate and select individual cells that each have a specific gene knocked out. The cells are then exposed to chemicals or drugs of interest. Genes that confer resistance to drugs can be identified through cells that become sensitive to such compounds after the CRISPR–Cas treatment.These genes, or the proteins they encode, can then be targeted with other drugs to get around the problem of resistance.

Identifying genes that promote disease uncovers some obvious targets for drug development. The simplest candidate drugs bind to and interfere with the proteins encoded by these genes, rather than affect the genes directly. But more-subtle targets for drugs can be revealed by a better understanding of the importance of multiple genes and proteins, their interactions and their mutual regulatory effects. Many diseases, for example, arise when things go wrong in a regulatory pathway that involves a complex network of intracellular interactions. Using CRISPR–Cas to identify, with ease and accuracy, combinations of genes involved in these networks should offer a more sophisticated approach to treatment.

Researchers are also using CRISPR–Cas and the DNA-repair processes of the cell to incorporate — or ‘knock in’ — selected sections of DNA. This can introduce mutations that transform the protein encoded by the targeted gene, leading to beneficial effects that a drug could then be designed to induce more simply. Some variants of CRISPR–Cas systems can make changes that either inhibit or promote the activity of a gene without changing its actual function. Turning gene activity up or down is a subtler way of investigating the importance of genes and proteins that could be activated or inhibited by drugs to treat disease.

“CRISPR–Cas is enabling nearly unlimited genetic manipulation,” says Fellmann, and it is bringing researchers much success. “We have already found exciting new targets using CRISPR–Cas technology,” says Moore. He will not reveal what the target molecules are, but does say that his company’s research involves mutations in “undruggable” tumour-suppressor and cancer-causing genes that other researchers have been unable to target.

Model making

Cell and animal models of human disease are crucial elements of drug development. The initial stages of testing candidate drugs for efficacy and toxicity can rarely be done in people, for ethical reasons. However, many of the disease models that are available to researchers are far from perfect. The main problem has been the complexity — and therefore the time and expense — of building superior models for the huge variety of human diseases that exist. “In industry, speed and cost are as important as feasibility,” says Fellmann. If it would take too long and cost too much to make a great model, a less perfect one might be preferred. Yet the developers of drugs would like to avoid such a compromise.

Both Moore and Fellmann agree that the simpler and more reliable gene editing made possible by CRISPR–Cas has enabled researchers to create models of disease more quickly and cheaply. “We can now, pretty much, change any gene in whatever way we want to mimic a disease,” says Fellmann. He also emphasizes that the “surgical precision” of CRISPR–Cas gene editing means that little or no trace remains of the editing process. With older genetic-engineering techniques, extra changes to the DNA sequence can be left in or around the altered genes, similar to a surgeon leaving instruments inside a patient after an operation. The precision of CRISPR–Cas greatly reduces the chances of the gene-editing tool having an undesired effect.

Ways to improve

Fellmann and his colleagues are now trying to find and develop innovative versions of the existing CRISPR–Cas tools that might bring further flexibility and precision. Part of this effort is exploring other bacterial gene-editing systems, and alternatives to Cas enzymes have already been found2 (see *Nature* :{536,:(style="font-weight:bolder;box-sizing:inherit"):}: 136–137; 2016). An enzyme known as Cpf1, for example, can cut DNA at sites to which CRISPR–Cas is unable to bind. Other such enzymes, including Cas13, can cut RNA — the intermediary between DNA and protein — rather than DNA. This opens up flexibility in the options for modifying the activity of genes, beyond their basic editing.

A more adventurous approach is to engineer the genes from bacteria that encode the enzymes used in existing CRISPR–Cas systems, to add extra abilities.For example, a team of researchers at the University of California, Berkeley, has added a binding site for the hormone oestrogen to the enzyme Cas93. This demonstrates the possibility of subtly controlling the activity of the gene-editing system through an external signal such as the level of a hormone or its analogue. As an example of its utility in drug development, Fellmann says that the technique could be used to control the timing of gene editing to more closely mimic the timing of the effects of drug molecules in disease models. These engineering efforts are at an early stage, but should eventually lead to a range of innovative functions.

Drug development is a long process: it can take more than a decade for researchers to move from the discovery of a target molecule to the production of a clinically approved drug. So it could be some time before the first drugs to be developed using CRISPR–Cas gene editing hit the market. “But,” says Fellmann, “people are already using it now, and in the long term it will definitely have a significant impact.”

His is one of countless research groups throughout academia and the pharmaceutical and biotechnology industries that now use CRISPR–Cas tools in the search for drugs. Predicting when gene editing will bear fruit is difficult; the drug-development pathway is long and clinical trials are laced with uncertainty, no matter the tool. But with so much ongoing activity, Moore’s prediction that CRISPR–Cas will transform drug discovery seems unlikely to get him into trouble.

“There’s been a massive investment in CRISPR–Cas by pharma,” he says. “I am not alone.”Jonathan Wrigley, associate director of the Innovative Medicines and Early Development Biotech Unit at AstraZeneca in Cambridge, offers a similarly confident outlook from big pharma. “We are applying CRISPR–Cas technology across our drug-discovery pipeline,” says Wrigley.

He says that teams at AstraZeneca have generated more than 100 disease models with the aid of CRISPR–Cas in the past three years, and are constantly finding ways to improve the technology.“It has proved transformative in the generation of cellular models to support drug-discovery projects,” Wrigley adds. Engineered cell-based models with precise genetic modifications were previously rare in drug discovery, owing to the challenging and time-consuming techniques that were required to generate them. “The CRISPR–Cas technology has enhanced both the feasibility and speed of this process, thereby enabling such models to become integral tools in the early stages of our drug-discovery projects, in a manner not seen before,” Wrigley says.

Nature 555, S10-S11 (2018)

doi: https://doi.org/10.1038/d41586-018-02477-1

OMG

https://www.washingtonpost.com/news/speaking-of-science/wp/2016/05/13/secret-harvard-meeting-on-synthetic-human-genomes-incites-ethics-debate/

no lnx

A secret Harvard meeting has raised concerns about scientists going too far with synthetic life; surely this image of a robot Frankenstein perfectly matches the text below.

Joel Achenbach

Reporter

May 13, 2016 at 12:50 p.m. PDT

About 150 scientists assembled at Harvard on Tuesday for an off-the-record, no-media-allowed discussion of how to create, from scratch, an intact genome, including the genetic code of a human being. The idea is to go beyond "reading" genetic material to actively "writing" it, George Church, a Harvard Medical School researcher who helped organized the event, told The Post in an interview Friday morning.

A Harvard professor says he can cure aging, but is that a good idea?]

Scientists can synthesize DNA chemically, and these techniques could ultimately lead to complete genomes that could be implanted in cells for research purposes. No one should panic just yet about mad scientists running amok: The researchers are not talking about making synthetic human beings. But the gathering drew a rebuke from two academics who heard about the event and didn't think it should have been held behind closed doors.

Drew Endy

If you need secrecy to discuss your proposed research (synthesizing a human genome) you are doing something wrong.

View image on Twitter

Drew Endy, associate professor of bioengineering at Stanford University, and Laurie Zoloth, a professor of medical ethics and humanities at Northwestern University, published an essay this week raising questions about whether the gathering at Harvard had gone too far. After citing the beneficial possibilities of such research, they raised the thornier ethical questions:

In a world where human reproduction has already become a competitive marketplace, with eggs, sperm and embryos carrying a price, it is easy to make up far stranger uses of human genome synthesis capacities. Would it be OK, for example, to sequence and then synthesize Einstein’s genome? If so how many Einstein genomes should be made and installed in cells, and who would get to make them? Taking a step back, just because something becomes possible, how should we approach determining if it is ethical to pursue?

Meanwhile, Marcy Darnovsky, executive director of the Berkeley, Calif.-based Center for Genetics and Society, a politically progressive organization that has had a skeptical view of biotechnology, issued a statement Friday criticizing the Harvard gathering: "If these reports are accurate, the meeting looks like a move to privatize the current conversation about heritable genetic modification."

Church told The Post that the meeting was originally supposed to be open.

The organizers had planned to stream video of the event, and invite numerous journalists, he said. But they had also hoped to pair the event with an article, written by many scientists, that had submitted to a major scientific journal.

The article still hasn't been published and the organizers decided to keep the event private, Church said. He said the organizers wanted to avoid being accused of "science by press release" without a peer-reviewed article backing them up.

He said the video of the event will be released when the peer-reviewed article is published, likely in the very near future. "It wasn't secret. There was nothing secret or private about it," Church said. But he added: "Probably with 20-20 hindsight we shouldn't have tried to couple it with a peer-reviewed paper.”

Something tells us this isn't the last time we're going to be talking about synthetic humanoids.

Scientists debate the ethics of an unnerving gene-editing technique

Pondering 'what it means to be human' on the frontier of gene editing

Joel Achenbach covers science and politics for the National desk. He has been a staff writer for The Post since 1990.

https://onezero.medium.com/crispr-cheat-sheet-the-most-important-gene-editing-stories-of-2019-e93733ff12a0

University of California CRISPR researchers form drug discovery alliance with pharma giant

BY JON COHENJUN. 13, 2019

Top CRISPR researchers at two University of California (UC) campuses have teamed up with pharmaceutical giant GlaxoSmithKline (GSK) to form a new laboratory in San Francisco that will exploit the genome editor to screen for new drugs.

Drawing on a GSK commitment of $67 million over 5 years, UC Berkeley’s Jennifer Doudna, a co-inventor of the powerful CRISPR tool, and UC San Francisco’s Jonathan Weissman will select the academic talent to work in the new Laboratory for Genomics Research (LGR). “This is really, for us as academics, kind of a dream come true,” Doudna says.

Although Doudna has already co-founded two CRISPR-related companies and co-runs the Innovative Genomics Institute with Weissman, she says the LGR “takes the not very interesting parts of the screening efforts out of the picture.” A friend who visited her lab a few years ago described it as “artisanal,” she recalls and wondered why they weren’t using more automation. “It was a nice way of saying that it seems really fusty,” Doudna says. She hopes the LGR will allow them to use “genome editing and CRISPR, in particular, as a tool to understand the causes of disease in a way that had really never been possible in the past.”

Weissman, a physicist who morphed into a protein-folding specialist, specializes in using CRISPR to construct large-scale probes of gene functions. “We don’t have the capability, the knowledge, or the resources to develop drugs,” he says. “I’m trying to understand what are the problems that [GSK is] facing and what are the tools that would really solve the problem. As a tool builder, my biggest fear is we build a bridge to nowhere.”

In all, London-based GSK will fund 24 full-time UC researchers—only some of whom will come from Doudna’s and Weissman’s labs. GSK will contribute as many as 14 of its own employees. UC will own the intellectual property (IP) of any new tools invented in the lab, while GSK hopes to patent new drug targets. UC will receive a “financial benefit if a drug that requires licensed IP comes to market,” a GSK spokesperson says, noting that the exact terms are “confidential.”

Hal Barron, GSK’s chief scientific officer, says 90% of genes still have opaque functions. He hopes that by using CRISPR to knock out or turn on genes in cells and animal models, the LGR will be able to double the number of genes with known functions. “Think about the impact of that as being able to develop twice as many drugs,” Barron says.

Other academics who have had similar partnerships said they are useful, but can be tricky. “Overall, the model is great and the [CRISPR] space is ripe for innovation that’s not fundamental biology or chemistry but an engineering problem,” says UC San Francisco’s Jeffrey Bluestone, an immunologist who for the past 9 years has taken part in a collaboration between the school and Pfizer. The challenge, he says, is that there can be a “disconnect” when there’s a discovery about a potential drug that targets a disease not in the company’s portfolio.

The Harvard Stem Cell Institute took part in a collaboration with GSK between 2008 and 2013 to develop new drug targets for regenerative medicine. “It was a really great interaction,” says Harvard stem cell biologist David Scadden, who notes it ended because GSK got out of the regenerative medicine business.“Having academics who are bilingual in terms of understanding how companies have to think as they develop products is a good thing,” he says.

The lab, located at UC San Francisco’s Mission Bay campus, is already up and running.

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University of California CRISPR researchers form drug discovery alliance with pharma giant