It is 5 P.M. in Santa Clara, California. Elodie Rebesque, a senior at Los Altos High School, is rushing out of class. She has a medical appointment of sorts. A few blocks away, she pushes open the door of BioCurious, a community lab whose mission is to create a space for amateurs, inventors, entrepreneurs and anyone else who wants to learn and experiment with biology in a friendly, educational environment. Eric Espinosa, Elodie’s mentor, quickly assesses the results of her last experiment to identify next steps.
Growing up, Elodie witnessed her brother suffering from sudden crises called pneumothoraxes, triggered by a disease in which a lung collapses and separates from the chest wall. In severe cases, doctors resort to creating scar tissue on the wall as a grip to stitch back the lungs, an invasive treatment. But for Elodie, it was too painful and too slow. So she came up with her own, less invasive design—a “biological Velcro” that would leverage the inner mechanisms of proteins to bind her brother’s outer lungs to his pleural cavity.
This is not science fiction. Biotechnologies have progressed to a point where it is now possible for high school students to be taught how to use gene-editing techniques, which aim to modify the genetic code underlying cells and proteins. Advances could be unprecedented with the next generation learning how to turn their own ideas and know-how into new bio-constructs. Just like algorithms in software engineering, our cells have become intelligent-design material.
For weeks, Elodie dissected the literature to find the proteins that are responsible for helping cells bind together. After narrowing down her search to a few candidates, she genetically modified them to enhance the binding effect. She made sure her proof of concept was reproducible, obtaining three optimally engineered proteins that bind very tightly to lung cells. Soon she will start bio-printing the engineered proteins on a “molecular patch,” a thin matrix of collagen to be placed between the chest and the lungs. In collaboration with a university research team, she will then explore opportunities for clinical testing.
This is just one example of an upstart revolution where citizens are deciding not to wait around for a cure or even a diagnosis. From analyzing their own genetics and mastering genome editing on simple bacterial and viral cells to prototyping surgical devices, these “bio-citizens” are using newly available biotechnologies and resources to better understand and improve their health. Last September, with hundreds of them from the U.S., Mexico, India and China, we met at the renowned MIT Media Lab to discuss governance models for a “biotech without borders” movement.
We as a society are at a turning point. We could build adaptive regulatory support that ensures safe and responsible citizen participation in health research, or we could drive these emerging communities of innovators underground or out of existence. The way forward is to create a dialogue through which regulators can help bio-citizens embed tailored governance mechanisms into their endeavors.
Until recently, pioneers of democratized health innovation had remained at the margins of our biomedical research and regulatory establishment. Yet in the last two months alone, two individuals widely shared videos in which they injected themselves with unregulated gene therapies. Josiah Zayner is one of the self-experimenters and the CEO of the Odin, a start-up that has a long-term mission of making genetic engineering available to consumers. For about $200, the Odin sells the gene-editing kits required to design gene therapies at home.
Like Zayner, I share the goal of empowering citizens with different abilities and resources to understand and shrewdly act upon the complex information contained in their genes. Yet I fear that without a robust structure for conducting risk assessment, self-experimentation using untested gene therapies will transfer the burden of weighing complex risk-benefit trade-offs to individuals at their own cost and peril.
Is self-experimentation with gene editing techniques something we should herald as a new form of “permissionless” innovation? Or will self-proclaimed biohackers, by testing the regulatory framework, harm the emerging ecosystem of citizens who contribute to biomedical innovation? Could they induce federal regulators to shut down all types of self-experimentation or severely restrain different forms of citizen-driven biomedical research?
While a scientist is required to get approval to conduct research on humans, the U.S. government had not yet explicitly warned against self-experimentation by a practitioner outside of a traditional research institution. Then, on November 21, the U.S. Food and Drug Administration issued a first-of-its kind statement on the practice: “FDA is aware that gene therapy products intended for self-administration and ‘do it yourself’ kits to produce gene therapies for self-administration are being made available to the public. The sale of these products is against the law. FDA is concerned about the safety risks involved.”
Self-experimentation with unregulated gene therapies raises troubling safety and ethical questions, from the potential for infections and immunological reactions to lack of understanding of the risks involved and unrealistic expectations from patients. Yet banning the sale of gene-editing kits is only a weak, temporary solution. What we need is to foster an ethos of responsible innovation outside of traditional research institutions.
We must recognize the urgent need to build legitimacy, but also tailored regulatory support for new forms of democratized health research. The path forward is not to promote radical, unregulated science, but to develop engagement channels that force citizens, patients, ethicists and regulators to rethink and design an adaptive oversight system—one that fosters empowerment and responsibility rather than just adherence to the status quo. The only way to avoid a blanket ban on all self-experiments is to engage stakeholders, and it is worth it.
Elodie is not alone in her quest to improve medical treatments for a disease that runs in the family. A professor of computer engineering, Matt Might, worked with many physicians for multiple years to find even a preliminary diagnosis for his son, who has a rare genetic disease. Just as he analyses the algorithms of a computer program, Matt hunted the genetic mechanisms responsible for Bertrand’s disease with the hope of finding targets for experimental therapies. His subsequent work in building a community of families whose children possessed similar symptoms ultimately aided researchers and physicians in the discovery of a more concrete diagnosis for the rare neurological disorder.
What these stories often have in common is a taste for entrepreneurship. Sean Ahrens, a young Californian with Crohn’s disease, harnessed funding from a few start-up accelerators to build Crohnology, an open platform where patients share and rate their experiences with medications, dietary changes and supplements, leveraging data that had previously gone to waste. Sean went as far as ingesting pig worms, meticulously documenting the daily effect on his Crohn’s, and publishing his findings in a renowned medical journal.
Three intersecting factors—access to technologies, mentorship and funding—are fueling democratized health innovation. First, you can now buy online the tools of an amateur biologist, from secondhand PCR machines and DNA synthesizers to chemical compounds such as peptides and reagents. Better still, the mushrooming of community bio-labs ensures exposure and mentorship into the technologies required for bioengineering and personal genomics analysis. To cap it off, motivated patients have started crowdfunding selected clinical research strategies as a kind of “venture philanthropy” that can generate from several thousand to several million dollars.
Yet empowerment often collides with hard truths. While intending to break new ground in underserved health domains, new forms of participatory health research suffer from a lack of legitimacy. Regulators tend to question the quality and scientific validity of experiments that occur outside of certified clinical trials—maybe, in some cases, rightly so.
Another hard truth is that the potential for citizens to take a proactive role in their own diagnosis and treatments, outside of medical practices, probes many unresolved ethical issues: 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.
The company Wego Health, for instance, connects patients with research and pharmaceutical brands that will ultimately pay the patients for helping to recruit clinical trial participants. In this big-pharma version of the gig economy, the potential looms for these patients to enter conflicts of interest while getting paid for their influence.
Notwithstanding the concerns, we should not simply discount medical research conducted outside of traditional institutions as ipso facto less safe, less reproducible or unethical. Patients often have in-depth experiential knowledge of their conditions along with a vested interest to make sure that a treatment or device will be effective, safe and beneficial. Facing regulatory uncertainty, however, they might not overcome the “chill factor”—the fear of confronting regulators by sharing their prototypes or experimental protocols with others.
The press has recently covered cases of bio-hackers who self-experimented with unregulated gene therapies. But the stories I encountered in community bio-labs, such as BioCurious and Denver Biolabs, are different. As Eric Espinosa, Elodie’s mentor, told me: “The FDA is always at the back of my mind; we want our proof of concept to be safe and reproducible, and we will work towards that.”
The next step is to foster legitimacy for citizen-driven biomedical innovation by supporting citizens and patients to document and share their data, evidence and ethical concerns in ongoing conversations with regulators and society at large.
Because they respect biological safety levels and function as a peer-review culture, community bio-labs constitute an ideal ecosystem for mentorship in the most current bioengineering techniques and their related risk-benefit trade-offs. By the same token, these labs are the perfect place to start a continuing dialogue about how to adapt our regulatory standards to an increasingly democratized form of biomedical innovation.
We need empowerment, but also greater collective intelligence. If risks are properly managed without dampening the energy of this new movement, we might all gain in the process.