Hacking Your Own Genes: A Recipe for Disaster
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.]
Awash in a fluid finely calibrated to keep it alive, a human eye rests inside a transparent cubic device. This ECaBox, or Eyes in a Care Box, is a one-of-a-kind system built by scientists at Barcelona’s Centre for Genomic Regulation (CRG). Their goal is to preserve human eyes for transplantation and related research.
In recent years, scientists have learned to transplant delicate organs such as the liver, lungs or pancreas, but eyes are another story. Even when preserved at the average transplant temperature of 4 Centigrade, they last for 48 hours max. That's one explanation for why transplanting the whole eye isn’t possible—only the cornea, the dome-shaped, outer layer of the eye, can withstand the procedure. The retina, the layer at the back of the eyeball that turns light into electrical signals, which the brain converts into images, is extremely difficult to transplant because it's packed with nerve tissue and blood vessels.
These challenges also make it tough to research transplantation. “This greatly limits their use for experiments, particularly when it comes to the effectiveness of new drugs and treatments,” said Maria Pia Cosma, a biologist at Barcelona’s Centre for Genomic Regulation (CRG), whose team is working on the ECaBox.
Eye transplants are desperately needed, but they're nowhere in sight. About 12.7 million people worldwide need a corneal transplant, which means that only one in 70 people who require them, get them. The gaps are international. Eye banks in the United Kingdom are around 20 percent below the level needed to supply hospitals, while Indian eye banks, which need at least 250,000 corneas per year, collect only around 45 to 50 thousand donor corneas (and of those 60 to 70 percent are successfully transplanted).
As for retinas, it's impossible currently to put one into the eye of another person. Artificial devices can be implanted to restore the sight of patients suffering from severe retinal diseases, but the number of people around the world with such “bionic eyes” is less than 600, while in America alone 11 million people have some type of retinal disease leading to severe vision loss. Add to this an increasingly aging population, commonly facing various vision impairments, and you have a recipe for heavy burdens on individuals, the economy and society. In the U.S. alone, the total annual economic impact of vision problems was $51.4 billion in 2017.
Even if you try growing tissues in the petri dish route into organoids mimicking the function of the human eye, you will not get the physiological complexity of the structure and metabolism of the real thing, according to Cosma. She is a member of a scientific consortium that includes researchers from major institutions from Spain, the U.K., Portugal, Italy and Israel. The consortium has received about $3.8 million from the European Union to pursue innovative eye research. Her team’s goal is to give hope to at least 2.2 billion people across the world afflicted with a vision impairment and 33 million who go through life with avoidable blindness.
Their method? Resuscitating cadaveric eyes for at least a month.
If we succeed, it will be the first intact human model of the eye capable of exploring and analyzing regenerative processes ex vivo. -- Maria Pia Cosma.
“We proposed to resuscitate eyes, that is to restore the global physiology and function of human explanted tissues,” Cosma said, referring to living tissues extracted from the eye and placed in a medium for culture. Their ECaBox is an ex vivo biological system, in which eyes taken from dead donors are placed in an artificial environment, designed to preserve the eye’s temperature and pH levels, deter blood clots, and remove the metabolic waste and toxins that would otherwise spell their demise.
Scientists work on resuscitating eyes in the lab of Maria Pia Cosma.
Courtesy of Maria Pia Cosma.
“One of the great challenges is the passage of the blood in the capillary branches of the eye, what we call long-term perfusion,” Cosma said. Capillaries are an intricate network of very thin blood vessels that transport blood, nutrients and oxygen to cells in the body’s organs and systems. To maintain the garland-shaped structure of this network, sufficient amounts of oxygen and nutrients must be provided through the eye circulation and microcirculation. “Our ambition is to combine perfusion of the vessels with artificial blood," along with using a synthetic form of vitreous, or the gel-like fluid that lets in light and supports the the eye's round shape, Cosma said.
The scientists use this novel setup with the eye submersed in its medium to keep the organ viable, so they can test retinal function. “If we succeed, we will ensure full functionality of a human organ ex vivo. It will be the first intact human model of the eye capable of exploring and analyzing regenerative processes ex vivo,” Cosma added.
A rapidly developing field of regenerative medicine aims to stimulate the body's natural healing processes and restore or replace damaged tissues and organs. But for people with retinal diseases, regenerative medicine progress has been painfully slow. “Experiments on rodents show progress, but the risks for humans are unacceptable,” Cosma said.
The ECaBox could boost progress with regenerative medicine for people with retinal diseases, which has been painfully slow because human experiments involving their eyes are too risky. “We will test emerging treatments while reducing animal research, and greatly accelerate the discovery and preclinical research phase of new possible treatments for vision loss at significantly reduced costs,” Cosma explained. Much less time and money would be wasted during the drug discovery process. Their work may even make it possible to transplant the entire eyeball for those who need it.
“It is a very exciting project,” said Sanjay Sharma, a professor of ophthalmology and epidemiology at Queen's University, in Kingston, Canada. “The ability to explore and monitor regenerative interventions will increasingly be of importance as we develop therapies that can regenerate ocular tissues, including the retina.”
Seemingly, there's no sacred religious text or a holy book prohibiting the practice of eye donation.
But is the world ready for eye transplants? “People are a bit weird or very emotional about donating their eyes as compared to other organs,” Cosma said. And much can be said about the problem of eye donor shortage. Concerns include disfigurement and healthcare professionals’ fear that the conversation about eye donation will upset the departed person’s relatives because of cultural or religious considerations. As just one example, Sharma noted the paucity of eye donations in his home country, Canada.
Yet, experts like Sharma stress the importance of these donations for both the recipients and their family members. “It allows them some psychological benefit in a very difficult time,” he said. So why are global eye banks suffering? Is it because the eyes are the windows to the soul?
Seemingly, there's no sacred religious text or a holy book prohibiting the practice of eye donation. In fact, most major religions of the world permit and support organ transplantation and donation, and by extension eye donation, because they unequivocally see it as an “act of neighborly love and charity.” In Hinduism, the concept of eye donation aligns with the Hindu principle of daan or selfless giving, where individuals donate their organs or body after death to benefit others and contribute to society. In Islam, eye donation is a form of sadaqah jariyah, a perpetual charity, as it can continue to benefit others even after the donor's death.
Meanwhile, Buddhist masters teach that donating an organ gives another person the chance to live longer and practice dharma, the universal law and order, more meaningfully; they also dismiss misunderstandings of the type “if you donate an eye, you’ll be born without an eye in the next birth.” And Christian teachings emphasize the values of love, compassion, and selflessness, all compatible with organ donation, eye donation notwithstanding; besides, those that will have a house in heaven, will get a whole new body without imperfections and limitations.
The explanation for people’s resistance may lie in what Deepak Sarma, a professor of Indian religions and philosophy at Case Western Reserve University in Cleveland, calls “street interpretation” of religious or spiritual dogmas. Consider the mechanism of karma, which is about the causal relation between previous and current actions. “Maybe some Hindus believe there is karma in the eyes and, if the eye gets transplanted into another person, they will have to have that karmic card from now on,” Sarma said. “Even if there is peculiar karma due to an untimely death–which might be interpreted by some as bad karma–then you have the karma of the recipient, which is tremendously good karma, because they have access to these body parts, a tremendous gift,” Sarma said. The overall accumulation is that of good karma: “It’s a beautiful kind of balance,” Sarma said.
For the Jews, Christians, and Muslims who believe in the physical resurrection of the body that will be made new in an afterlife, the already existing body is sacred since it will be the basis of a new refashioned body in an afterlife.---Omar Sultan Haque.
With that said, Sarma believes it is a fallacy to personify or anthropomorphize the eye, which doesn’t have a soul, and stresses that the karma attaches itself to the soul and not the body parts. But for scholars like Omar Sultan Haque—a psychiatrist and social scientist at Harvard Medical School, investigating questions across global health, anthropology, social psychology, and bioethics—the hierarchy of sacredness of body parts is entrenched in human psychology. You cannot equate the pinky toe with the face, he explained.
“The eyes are the window to the soul,” Haque said. “People have a hierarchy of body parts that are considered more sacred or essential to the self or soul, such as the eyes, face, and brain.” In his view, the techno-utopian transhumanist communities (especially those in Silicon Valley) have reduced the totality of a person to a mere material object, a “wet robot” that knows no sacredness or hierarchy of human body parts. “But for the Jews, Christians, and Muslims who believe in the physical resurrection of the body that will be made new in an afterlife, the [already existing] body is sacred since it will be the basis of a new refashioned body in an afterlife,” Haque said. “You cannot treat the body like any old material artifact, or old chair or ragged cloth, just because materialistic, secular ideologies want so,” he continued.
For Cosma and her peers, however, the very definition of what is alive or not is a bit semantic. “As soon as we die, the electrophysiological activity in the eye stops,” she said. “The goal of the project is to restore this activity as soon as possible before the highly complex tissue of the eye starts degrading.” Cosma’s group doesn’t yet know when they will be able to keep the eyes alive and well in the ECaBox, but the consensus is that the sooner the better. Hopefully, the taboos and fears around the eye donations will dissipate around the same time.
As Our AI Systems Get Better, So Must We
As the power and capability of our AI systems increase by the day, the essential question we now face is what constitutes peak human. If we stay where we are while the AI systems we are unleashing continually get better, they will meet and then exceed our capabilities in an ever-growing number of domains. But while some technology visionaries like Elon Musk call for us to slow down the development of AI systems to buy time, this approach alone will simply not work in our hyper-competitive world, particularly when the potential benefits of AI are so great and our frameworks for global governance are so weak. In order to build the future we want, we must also become ever better humans.
The list of activities we once saw as uniquely human where AIs have now surpassed us is long and growing. First, AI systems could beat our best chess players, then our best Go players, then our best champions of multi-player poker. They can see patterns far better than we can, generate medical and other hypotheses most human specialists miss, predict and map out new cellular structures, and even generate beautiful, and, yes, creative, art.
A recent paper by Microsoft researchers analyzing the significant leap in capabilities in OpenAI’s latest AI bot, ChatGPT-4, asserted that the algorithm can “solve novel and difficult tasks that span mathematics, coding, vision, medicine, law, psychology and more, without needing any special prompting.” Calling this functionality “strikingly close to human-level performance,” the authors conclude it “could reasonably be viewed as an early (yet still incomplete) version of an artificial general intelligence (AGI) system.”
The concept of AGI has been around for decades. In its common use, the term suggests a time when individual machines can do many different things at a human level, not just one thing like playing Go or analyzing radiological images. Debating when AGI might arrive, a favorite pastime of computer scientists for years, now has become outdated.
We already have AI algorithms and chatbots that can do lots of different things. Based on the generalist definition, in other words, AGI is essentially already here.
Unfettered by the evolved capacity and storage constraints of our brains, AI algorithms can access nearly all of the digitized cultural inheritance of humanity since the dawn of recorded history and have increasing access to growing pools of digitized biological data from across the spectrum of life.
Once we recognize that both AI systems and humans have unique superpowers, the essential question becomes what each of us can do better than the other and what humans and AIs can best do in active collaboration. The future of our species will depend upon our ability to safely, dynamically, and continually figure that out.
With these ever-larger datasets, rapidly increasing computing and memory power, and new and better algorithms, our AI systems will keep getting better faster than most of us can today imagine. These capabilities have the potential to help us radically improve our healthcare, agriculture, and manufacturing, make our economies more productive and our development more sustainable, and do many important things better.
Soon, they will learn how to write their own code. Like human children, in other words, AI systems will grow up. But even that doesn’t mean our human goose is cooked.
Just like dolphins and dogs, these alternate forms of intelligence will be uniquely theirs, not a lesser or greater version of ours. There are lots of things AI systems can't do and will never be able to do because our AI algorithms, for better and for worse, will never be human. Our embodied human intelligence is its own thing.
Our human intelligence is uniquely ours based on the capacities we have developed in our 3.8-billion-year journey from single cell organisms to us. Our brains and bodies represent continuous adaptations on earlier models, which is why our skeletal systems look like those of lizards and our brains like most other mammals with some extra cerebral cortex mixed in. Human intelligence isn’t just some type of disembodied function but the inextricable manifestation of our evolved physical reality. It includes our sensory analytical skills and all of our animal instincts, intuitions, drives, and perceptions. Disembodied machine intelligence is something different than what we have evolved and possess.
Because of this, some linguists including Noam Chomsky have recently argued that AI systems will never be intelligent as long as they are just manipulating symbols and mathematical tokens without any inherent understanding. Nothing could be further from the truth. Anyone interacting with even first-generation AI chatbots quickly realizes that while these systems are far from perfect or omniscient and can sometimes be stupendously oblivious, they are surprisingly smart and versatile and will get more so… forever. We have little idea even how our own minds work, so judging AI systems based on their output is relatively close to how we evaluate ourselves.
Anyone not awed by the potential of these AI systems is missing the point. AI’s newfound capacities demand that we work urgently to establish norms, standards, and regulations at all levels from local to global to manage the very real risks. Pausing our development of AI systems now doesn’t make sense, however, even if it were possible, because we have no sufficient ways of uniformly enacting such a pause, no plan for how we would use the time, and no common framework for addressing global collective challenges like this.
But if all we feel is a passive awe for these new capabilities, we will also be missing the point.
Human evolution, biology, and cultural history are not just some kind of accidental legacy, disability, or parlor trick, but our inherent superpower. Our ancestors outcompeted rivals for billions of years to make us so well suited to the world we inhabit and helped build. Our social organization at scale has made it possible for us to forge civilizations of immense complexity, engineer biology and novel intelligence, and extend our reach to the stars. Our messy, embodied, intuitive, social human intelligence is roughly mimicable by AI systems but, by definition, never fully replicable by them.
Once we recognize that both AI systems and humans have unique superpowers, the essential question becomes what each of us can do better than the other and what humans and AIs can best do in active collaboration. We still don't know. The future of our species will depend upon our ability to safely, dynamically, and continually figure that out.
As we do, we'll learn that many of our ideas and actions are made up of parts, some of which will prove essentially human and some of which can be better achieved by AI systems. Those in every walk of work and life who most successfully identify the optimal contributions of humans, AIs, and the two together, and who build systems and workflows empowering humans to do human things, machines to do machine things, and humans and machines to work together in ways maximizing the respective strengths of each, will be the champions of the 21st century across all fields.
The dawn of the age of machine intelligence is upon us. It’s a quantum leap equivalent to the domestication of plants and animals, industrialization, electrification, and computing. Each of these revolutions forced us to rethink what it means to be human, how we live, and how we organize ourselves. The AI revolution will happen more suddenly than these earlier transformations but will follow the same general trajectory. Now is the time to aggressively prepare for what is fast heading our way, including by active public engagement, governance, and regulation.
AI systems will not replace us, but, like these earlier technology-driven revolutions, they will force us to become different humans as we co-evolve with our technology. We will never reach peak human in our ongoing evolutionary journey, but we’ve got to manage this transition wisely to build the type of future we’d like to inhabit.
Alongside our ascending AIs, we humans still have a lot of climbing to do.