Hacking Your Own Genes: A Recipe for Disaster
Employees of ODIN, a consumer genetic design and engineering company, working out of their Bay Area garage start-up lab in 2016.
Editor's Note: Our Big Moral Question this month is: "Where should we draw a line, if any, between the use of gene editing for the prevention and treatment of disease, and for cosmetic enhancement?" It is illegal in the U.S. to develop human trials for the latter, even though some people think it should be acceptable. The most outspoken supporter recently resorted to self-experimentation using CRISPR in his own makeshift lab. But critics argue that "biohackers" like him are recklessly courting harm. LeapsMag invited a leading intellectual from the Center for Genetics and Society to share her perspective.
"I want to democratize science," says biohacker extraordinaire Josiah Zayner.
This is certainly a worthy-sounding sentiment. And it is central to the ethos of biohacking, a term that's developed a bit of sprawl. Biohacking can mean non-profit community biology labs that promote "citizen science," or clever but not necessarily safe or innocuous garage-based experiments with computers and genetics, or efforts at biological self-optimization via techniques including cybernetic implants, drug supplements, and intermittent fasting.
They appear to have given little thought to whether curiosity should be bound in any way by care for social consequence.
Against that messy background, what should we make of Zayner? The thirty-something ex-NASA scientist, who describes himself as "a global leader in the BioHacker movement," put his interpretation of democracy on display last October during a CRISPR-yourself performance at a San Francisco biotech conference. In that episode, he dramatically jabbed himself with a long needle, injecting his left forearm with a home-made gene-editing concoction that he said would disrupt his myostatin genes and bulk up his muscles.
Zayner sees himself, and is seen by some fellow biohackers, as a rebel hero: an intrepid scientific adventurer willing to risk his own well-being in the tradition of self-experimentation, eager to push the boundaries of established science in the service of forging innovative modes of discovery, ready to stand up to those stodgy bureaucrats at the FDA in the name of biohacker freedom.
To others, including some in the biohacker community, he's a publicity-seeking stunt man, perhaps deluded by touches of toxic masculinity and techno-entrepreneurial ideology, peddling snake-oil with oozing ramifications.
Zayner is hardly coy about his goals being larger than Popeye-like muscles. "I want to live in a world where people are genetically modifying themselves," he told FastCompany. "I think this is, like, literally, a new era of human beings," he mused to CBS in November. "It's gonna create a whole new species of humans."
Nor does he deign to conceal his tactics. The webpage of the company he launched to sell DIY gene-editing kits (which is advised by celebrity geneticist George Church) says that Zayner is "constantly pushing the boundaries of Science outside traditional environments." He is more explicit when performing: "Yes I am a criminal. And my crime is that of curiosity," he said last August to a biohacker audience in Oakland, which according to Gizmodo erupted in applause.
Regrettably, Zayner, along with some other biohackers and their defenders in the mainstream scientific world, appear to have given little thought to whether curiosity should be bound in any way by care for social consequence.
In December, the FDA issued a brief statement warning against using DIY kits for self-administered gene editing.
Though what's most directly at risk in Zayner's self-enhancement hack is his own safety, his bad-boy celebrity status is likely to encourage emulation. A few weeks after his San Francisco performance, 27-year-old Tristan Roberts took to Facebook Live to give himself a DIY gene modification injection to keep his HIV infection in check, because he doesn't like taking the regular medications that prevent AIDS. Whatever it was that he put into his body was provided by a company that Gizmodo describes as a "mysterious biotech firm with transhumanist leanings."
Zayner doesn't outright provide DIY gene hacks to others. But among his company's offerings are a free DIY Human CRISPR Guide and a $20 CRISPR-Cas9 plasmid that targets the human myostatin gene – the one that Zayner said he was targeting to make his muscles grow. Presumably to fend off legal problems, the product page says: "This product is not injectable or meant for direct human use" – a label as toothless as the fine print on cigarette packages that breaks the news that smoking causes cancer.
Some scientists warn that Zayner's style of biohacking carries considerable dangers. Microbiologist Brian Hanley, himself a self-experimenter who now opposes "biohacking humans," focuses on the technical difficulty of purifying what's being injected. "Screwing up can kill you from endotoxin," he says. "If you get in trouble, call me. I will do my best to instruct the physician how to save your life….But I make no guarantees you will survive."
Hanley also commented on the likely effectiveness of Zayner's effort: "Either Josiah Zayner is ignorant or he is deliberately misleading people. What he suggests cannot work as advertised."
Ensuring the safety and effectiveness of medical drugs and devices is the mandate of the US Food and Drug Administration. In December, the agency issued a brief statement warning against using DIY kits for self-administered gene editing, and saying flat out that selling them is against the law.
The stem cell field provides an unfortunate model of what can go wrong.
Zayner is dismissive of the safety risks. He asks in a Buzzfeed article whether DIY CRISPR should be considered more harmful than smoking or chemotherapy, "legal and socially acceptable activities that damage your genes." This is a strange line of argument, given the decades-long battles with the tobacco industry to raise awareness about smoking's significant harms, and since the side effects of chemotherapy are typically not undertaken by choice.
But the implications of what Zayner, Roberts, and some of their fellow biohackers are promoting ripple well beyond direct harms to individuals. Their rhetoric and vision affect the larger project of biomedicine, and the fraught relationships among drug researchers, pharmaceutical companies, clinical trial subjects, patients, and the public. Writing in Scientific American, Eleanor Pauwels of the Wilson Center, who is sympathetic to biohacking, lists the down sides: "blurred boundaries between treatments and self-experimentation, peer pressure to participate in trials, exploitation of vulnerable individuals, lack of oversight concerning quality control and risk of harm, and more."
These prospects are germane to the current state of human gene editing. After decades of dashed hopes, including deaths of research subjects, "gene therapy" may now be close to deserving the promise in its name. But with safety and efficacy still being evaluated, it's especially crucial to be honest about limitations as well as possibilities.
The stem cell field provides an unfortunate model of what can go wrong. Fifteen years ago, scientists, patient advocates, and even politicians routinely indulged in wildly over-optimistic enthusiasm about the imminence of stem cell therapies. That binge of irresponsible promotion helped create the current situation of widespread stem cell fraud: hundreds of clinics in the US alone selling unproven treatments to unsuspecting and sometimes desperate patients. Many have had their wallets lightened; some have gone blind or developed strange tumors that doctors have never before seen. The FDA is scrambling to address this still-worsening situation.
Zayner-style biohacking and promotion may also impact the ongoing controversy about whether new gene editing tools should be used in human reproduction to pre-determine the traits of future children and generations. Much of the widespread opposition to "human germline modification" is grounded in concern that it would lead to a society in which real or purported genetic advantages, marketed by fertility clinics to affluent parents, would exacerbate our already shameful levels of inequality and discrimination.
With powerful new technologies increasingly shaping the world, there's a lot riding on our capacity to democratize science. But as a society we don't yet have much practice at it.
Yet Zayner is all for it. In an interview in The Guardian, he comments, "DNA defines what a species is, and I imagine it wouldn't be too long into the future when the human species almost becomes a new species because of these modifications." He notes in a blog post, "We want to grow as a species and maybe change as a species. Whether that is curing disease or immortality or mutant powers is up to you."
This brings us back to Zayner's claim that he is working to democratize science.
The conviction that gene editing involves social and political challenges, not just technical matters, has been voiced at all points on the spectrum of perspective and uncertainty. But Zayner says there's been enough talk. "I want people to stop arguing about whether it's okay to use CRISPR or not use CRISPR….It's too late: I already made the choice for you. Argument over. Let's get on with it now. Let's use this to help people. Or to give people purple skin." (Emphasis added, in case there's any doubt about Zayner's commitment to democracy.)
With powerful new technologies increasingly shaping the world, there's a lot riding on our capacity to democratize science. But as a society we don't yet have much practice at it. In fact, we're not very sure what it would look like. It would clearly mean, as Arizona State University political scientist David Guston puts it, "considering the societal outcomes of research at least as attentively as the scientific and technological outputs." It would need broad participation and demand hard work.
The involvement of serious citizen scientists in such efforts, biohackers included, could be a very good thing. But Zayner's contributions to date have not been helpful.
[Ed. Note: Check out Zayner's perspective: "Genetic Engineering for All: The Last Great Frontier of Human Freedom." Then follow LeapsMag on social media to share your opinion.]
Breakthrough therapies are breaking patients' banks. Key changes could improve access, experts say.
Single-treatment therapies are revolutionizing medicine. But insurers and patients wonder whether they can afford treatment and, if they can, whether the high costs are worthwhile.
CSL Behring’s new gene therapy for hemophilia, Hemgenix, costs $3.5 million for one treatment, but helps the body create substances that allow blood to clot. It appears to be a cure, eliminating the need for other treatments for many years at least.
Likewise, Novartis’s Kymriah mobilizes the body’s immune system to fight B-cell lymphoma, but at a cost $475,000. For patients who respond, it seems to offer years of life without the cancer progressing.
These single-treatment therapies are at the forefront of a new, bold era of medicine. Unfortunately, they also come with new, bold prices that leave insurers and patients wondering whether they can afford treatment and, if they can, whether the high costs are worthwhile.
“Most pharmaceutical leaders are there to improve and save people’s lives,” says Jeremy Levin, chairman and CEO of Ovid Therapeutics, and immediate past chairman of the Biotechnology Innovation Organization. If the therapeutics they develop are too expensive for payers to authorize, patients aren’t helped.
“The right to receive care and the right of pharmaceuticals developers to profit should never be at odds,” Levin stresses. And yet, sometimes they are.
Leigh Turner, executive director of the bioethics program, University of California, Irvine, notes this same tension between drug developers that are “seeking to maximize profits by charging as much as the market will bear for cell and gene therapy products and other medical interventions, and payers trying to control costs while also attempting to provide access to medical products with promising safety and efficacy profiles.”
Why Payers Balk
Health insurers can become skittish around extremely high prices, yet these therapies often accompany significant overall savings. For perspective, the estimated annual treatment cost for hemophilia exceeds $300,000. With Hemgenix, payers would break even after about 12 years.
But, in 12 years, will the patient still have that insurer? Therein lies the rub. U.S. payers, are used to a “pay-as-you-go” model, in which the lifetime costs of therapies typically are shared by multiple payers over many years, as patients change jobs. Single treatment therapeutics eliminate that cost-sharing ability.
"As long as formularies are based on profits to middlemen…Americans’ healthcare costs will continue to skyrocket,” says Patricia Goldsmith, the CEO of CancerCare.
“There is a phenomenally complex, bureaucratic reimbursement system that has grown, layer upon layer, during several decades,” Levin says. As medicine has innovated, payment systems haven’t kept up.
Therefore, biopharma companies begin working with insurance companies and their pharmacy benefit managers (PBMs), which act on an insurer’s behalf to decide which drugs to cover and by how much, early in the drug approval process. Their goal is to make sophisticated new drugs available while still earning a return on their investment.
New Payment Models
Pay-for-performance is one increasingly popular strategy, Turner says. “These models typically link payments to evidence generation and clinically significant outcomes.”
A biotech company called bluebird bio, for example, offers value-based pricing for Zynteglo, a $2.8 million possible cure for the rare blood disorder known as beta thalassaemia. It generally eliminates patients’ need for blood transfusions. The company is so sure it works that it will refund 80 percent of the cost of the therapy if patients need blood transfusions related to that condition within five years of being treated with Zynteglo.
In his February 2023 State of the Union speech, President Biden proposed three pilot programs to reduce drug costs. One of them, the Cell and Gene Therapy Access Model calls on the federal Centers for Medicare & Medicaid Services to establish outcomes-based agreements with manufacturers for certain cell and gene therapies.
A mortgage-style payment system is another, albeit rare, approach. Amortized payments spread the cost of treatments over decades, and let people change employers without losing their healthcare benefits.
Only about 14 percent of all drugs that enter clinical trials are approved by the FDA. Pharma companies, therefore, have an exigent need to earn a profit.
The new payment models that are being discussed aren’t solutions to high prices, says Bill Kramer, senior advisor for health policy at Purchaser Business Group on Health (PBGH), a nonprofit that seeks to lower health care costs. He points out that innovative pricing models, although well-intended, may distract from the real problem of high prices. They are attempts to “soften the blow. The best thing would be to charge a reasonable price to begin with,” he says.
Instead, he proposes making better use of research on cost and clinical effectiveness. The Institute for Clinical and Economic Review (ICER) conducts such research in the U.S., determining whether the benefits of specific drugs justify their proposed prices. ICER is an independent non-profit research institute. Its reports typically assess the degrees of improvement new therapies offer and suggest prices that would reflect that. “Publicizing that data is very important,” Kramer says. “Their results aren’t used to the extent they could and should be.” Pharmaceutical companies tend to price their therapies higher than ICER’s recommendations.
Drug Development Costs Soar
Drug developers have long pointed to the onerous costs of drug development as a reason for high prices.
A 2020 study found the average cost to bring a drug to market exceeded $1.1 billion, while other studies have estimated overall costs as high as $2.6 billion. The development timeframe is about 10 years. That’s because modern therapeutics target precise mechanisms to create better outcomes, but also have high failure rates. Only about 14 percent of all drugs that enter clinical trials are approved by the FDA. Pharma companies, therefore, have an exigent need to earn a profit.
Skewed Incentives Increase Costs
Pricing isn’t solely at the discretion of pharma companies, though. “What patients end up paying has much more to do with their PBMs than the actual price of the drug,” Patricia Goldsmith, CEO, CancerCare, says. Transparency is vital.
PBMs control patients’ access to therapies at three levels, through price negotiations, pricing tiers and pharmacy management.
When negotiating with drug manufacturers, Goldsmith says, “PBMs exchange a preferred spot on a formulary (the insurer’s or healthcare provider’s list of acceptable drugs) for cash-base rebates.” Unfortunately, 25 percent of the time, those rebates are not passed to insurers, according to the PBGH report.
Then, PBMs use pricing tiers to steer patients and physicians to certain drugs. For example, Kramer says, “Sometimes PBMs put a high-cost brand name drug in a preferred tier and a lower-cost competitor in a less preferred, higher-cost tier.” As the PBGH report elaborates, “(PBMs) are incentivized to include the highest-priced drugs…since both manufacturing rebates, as well as the administrative fees they charge…are calculated as a percentage of the drug’s price.
Finally, by steering patients to certain pharmacies, PBMs coordinate patients’ access to treatments, control patients’ out-of-pocket costs and receive management fees from the pharmacies.
Therefore, Goldsmith says, “As long as formularies are based on profits to middlemen…Americans’ healthcare costs will continue to skyrocket.”
Transparency into drug pricing will help curb costs, as will new payment strategies. What will make the most impact, however, may well be the development of a new reimbursement system designed to handle dramatic, breakthrough drugs. As Kramer says, “We need a better system to identify drugs that offer dramatic improvements in clinical care.”
In today's podcast episode, law professor Gaia Bernstein talks about the challenges of keeping control over our thoughts and actions, even when some powerful forces are pushing in the other direction.
Each afternoon, kids walk through my neighborhood, on their way back home from school, and almost all of them are walking alone, staring down at their phones. It's a troubling site. This daily parade of the zombie children just can’t bode well for the future.
That’s one reason I felt like Gaia Bernstein’s new book was talking directly to me. A law professor at Seton Hall, Gaia makes a strong argument that people are so addicted to tech at this point, we need some big, system level changes to social media platforms and other addictive technologies, instead of just blaming the individual and expecting them to fix these issues.
Gaia’s book is called Unwired: Gaining Control Over Addictive Technologies. It’s fascinating and I had a chance to talk with her about it for today’s podcast. At its heart, our conversation is really about how and whether we can maintain control over our thoughts and actions, even when some powerful forces are pushing in the other direction.
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We discuss the idea that, in certain situations, maybe it's not reasonable to expect that we’ll be able to enjoy personal freedom and autonomy. We also talk about how to be a good parent when it sometimes seems like our kids prefer to be raised by their iPads; so-called educational video games that actually don’t have anything to do with education; the root causes of tech addictions for people of all ages; and what kinds of changes we should be supporting.
Gaia is Seton’s Hall’s Technology, Privacy and Policy Professor of Law, as well as Co-Director of the Institute for Privacy Protection, and Co-Director of the Gibbons Institute of Law Science and Technology. She’s the founding director of the Institute for Privacy Protection. She created and spearheaded the Institute’s nationally recognized Outreach Program, which educated parents and students about technology overuse and privacy.
Professor Bernstein's scholarship has been published in leading law reviews including the law reviews of Vanderbilt, Boston College, Boston University, and U.C. Davis. Her work has been selected to the Stanford-Yale Junior Faculty Forum and received extensive media coverage. Gaia joined Seton Hall's faculty in 2004. Before that, she was a fellow at the Engelberg Center of Innovation Law & Policy and at the Information Law Institute of the New York University School of Law. She holds a J.S.D. from the New York University School of Law, an LL.M. from Harvard Law School, and a J.D. from Boston University.
Gaia’s work on this topic is groundbreaking I hope you’ll listen to the conversation and then consider pre-ordering her new book. It comes out on March 28.
