What a year 2017 has been! From several unexpected election results to the #MeToo movement to record stock prices, this year has brought multiple surprises. While these events were widely reported and discussed, 2017 also produced some exciting activity in the field of medical technology and genetics; admittedly a less mainstream topic of conversation, but one in which I nevertheless take a deep interest.
This year, I watched as the first American scientists edited the genomes of human embryos, as scientists attempted to edit a gene in vivo in an adult for the first time, as the Food and Drug Administration announced several innovative policy proposals to regulate new digital health technologies like smartphone apps, and as paper after paper was published heralding new breakthroughs on gene editing systems.
With each passing milestone, it seems the science races forward ever faster, and since this is still a relatively young field, that trend seems likely to continue into the next year. Several experts have already noted that this radical forward momentum has outstripped our ability to control or consider the implications of these new technologies and predict this will cause problems in the future. As we near the end of 2017 and look forward to 2018, I would like to consider four likely candidates for problems in the year ahead.
1: DIY Gene Editors Vs. The FDA
The discovery and continued improvement of CRISPR gene editing systems have allowed do-it-yourself bio-hobbyists known as “biohackers” to experiment with these technologies alongside institutional researchers. These technologies are democratizing gene editing because of their relative inexpensiveness and ease of use.
Already there have been at least four examples of unsanctioned self-experimentation with gene editing treatments. Recently, Josiah Zayner, a molecular biologist and founder of a company that sells kits that enable home enthusiasts to tinker with gene editing in bacteria, has notably attempted several gene editing experiments on himself, including publicly injecting himself at a biotech conference in early October. Similarly, Tristan Roberts, a computer programmer, injected himself with an experimental therapy on Facebook Live also in October.
Seemingly in response to these displays, the Food and Drug Administration posted a statement on their website entitled “Information About Self-Administration of Gene Therapy” in late November. The short statement notes that “FDA considers any use of CRISPR/Cas9 gene editing in humans to be gene therapy.” The agency then reminds readers that these products are regulated by FDA and that 1) any clinical studies must be preceded by an investigational new drug application, and 2) any marketing of such products must be preceded by a biologics license application. Finally, the statement makes clear that:
“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.”
While the language used in this statement is (most likely intentionally) general and slightly ambiguous, it seems clear that the agency is laying the groundwork for legal action against companies providing unapproved gene therapies for use in humans; for instance, the company that produced the concoction used by Roberts, Ascendance Biomedical.
Zayner’s case is more complicated. He created and used the gene therapy all himself. There was no changing of hands involved, either in the form of a transaction or giveaway, and no company that provided him with the product. It is as yet unclear whether FDA would have any jurisdiction in this case and how far that jurisdiction would extend. Professor Patti Zettler of Georgia State University considered this question in a recent blog post.
As more of this self-experimenting with gene editing techniques occurs, FDA will likely use the foundation laid down in this statement to take action. How aggressively FDA will pursue companies like Ascendance and whether they will take any action against individuals like Zayner remains to be seen.
2: Keeping Up With Iterative Technologies
As my colleague Adam Thierer and I wrote in our essay “‘Build & Freeze’ Regulation Versus Iterative Innovation,” FDA has acknowledged that its old regulatory regime does not work well with AI-infused software products. In order to maintain its control over the explosion of these new digital health products, the agency has announced its plan for adapting, called the “Digital Health Innovation Action Plan.”
The goal of the plan is to “reimagine FDA’s approach” to the digital health space in order to foster “digital health innovation while continuing to protect and promote the public health.” The plan has two major components. First, the agency is establishing a pilot program that it calls “Pre-Cert,” intended to look “first at the software developer or digital health technology developer, not the product.” The agency would essentially pre-approve companies that demonstrate “a culture of quality and organizational excellence based on objective criteria,” and then those companies would face little to no additional FDA review of their digital health products.
The second pillar of the plan, which the agency has been working toward for the last several years, is to develop a risk-based regulatory framework. To accomplish this, the agency is taking advantage of its enforcement discretion and focusing its activity on those products that “present higher risk to patients” and actually “choosing not to enforce compliance for lower risk mobile apps.”
FDA hopes that these adaptations will allow it to protect patients and allow for the quick, iterative development that characterizes software products. The agency deserves some praise for focusing on innovation and trying to adapt to modern medical technology. Thus far, it seems that these steps have proved a boon to innovation. The Pre-Cert program has recruited nine companies that include Apple, Fitbit, and Google’s life-sciences arm Verily, and has been underway for several months.
And yet, the same characteristics that the FDA is cultivating in order to promote efficiency and innovation (namely its flexibility and speed), could, under different leadership in the future, be used to the opposite effect. As Commissioner Gottlieb admitted, “many of FDA’s polices are advanced through guidance documents and other proposals,” instead of through the laborious notice-and-comment rule-making process. Since “soft law” regulatory mechanisms like guidance documents bypass the normal process spelled out in the Administrative Procedure Act, their legal enforceability is ambiguous and they lack the oversight provided in the APA, thus allowing for abuse.
The flexibility being cultivated by the FDA, combined with the large degree of discretion that they are exercising in digital health technology, could end up actually harming innovation in the long run because there is no guarantee of long term stability. Many ambiguities still exist in the Pre-Cert program and the FDA’s new approach generally that will need to be sorted out in 2018 and beyond.
3: Using Gene Drives
While clinical use of gene editing in the human germline is still at least several years away, using gene editing commercially to modify the inheritable traits of insects and animals is already “on the table.” Proponents include farmers and public health officials who believe the technology could be useful for controlling pests that damage crops (like the fruit flies giving California’s cherry growers a colossal headache) or carry life-threatening diseases (like the mosquitos that carry malaria). But there are also many calling for a complete ban of the technology, or at least heavy regulation, saying that gene drives are potentially too powerful and could damage the environment, lead to the extinction of a species, or be used as a bioweapon.
The issue of gene drives took a backseat to discussions of the ethics of editing human embryos and proceeded under the radar for much of the year. However, as the technology is now on the cusp of being deployed, the topic has exploded with experts weighing in on both sides, companies being formed, and several lab studies being conducted (DARPA is currently funding eight separate gene drive studies, each in a different species).
The idea of a gene drive is to install a “selfish gene” that gets inherited by almost all of an organism’s offspring instead of just half, as is usually the case. This “super-Mendelian” effect quickly “drives” a particular gene through an entire population.
Regulators will likely be forced to grapple with this technology in 2018. Several scientists are pushing for the deployment of gene drives in several African countries. The Bill and Melinda Gates Foundation gave a $70 million grant to the Target Malaria project, which aims to eliminate malaria using gene drives in Burkina Faso, Mali, and Uganda. Brazilian researchers have also been developing gene drives to control mosquitoes that transmit the Zika virus. In the United States, the California Cherry Board is funding researchers from the University of California to develop a gene drive to get rid of the flies ruining their cherry crop.
The United Nations investigated the technology last year and issued a statement urging caution when testing, but rejecting requests for a complete ban on gene drive research. The international body also convened an advisory group of experts to make recommendations on gene drives and other synthetic biology-related topics. This group was recently mired in controversy when gene drive opponents accused the scientists of trying to “game the system and manipulate the United Nations Convention on Biological Diversity.”
This controversy will likely continue to evolve next year as both international and domestic regulatory bodies consider their approaches to gene drive technology.
4: Germline Gene Editing
Finally, germline gene editing could once again become an issue if Congress reconsiders its ban on research involving the editing of embryos.
Like gene drives, germline editing has passionate supporters and adversaries all lobbying for government to support their side of the argument. This will only intensify if Congress allows the FDA to consider investigational new drug applications that involve germline editing, thus opening a path for using the technology in the clinic.
Regulators in the U.K. and China have already developed regulatory frameworks to oversee such research and have approved projects that include embryo editing. The United States National Academies of Sciences and Medicine produced a consensus report earlier this year that recommended permitting clinical trials involving germline editing “within a robust and effective regulatory framework.”
These moves could be enough to persuade the United States’ Congress to develop its own framework for germline editing next year or beyond, leading to additional regulations from the FDA and other agencies, as well as lobbying activity from both medical and policy groups interested in influencing such important guidelines.
I believe these four issues will drive at least part of the genetics and synthetic biology conversation in 2018. Each poses significant challenges that regulatory bodies, both private and governmental, must address if the science is to move forward and begin impacting real lives.
While getting these problems right may be difficult, it is absolutely imperative that we attempt to muddle through them. Each of these technologies promises life-saving improvements for many future generations of patients if used responsibly. Yet, recklessness could be devastating. Additionally, regulatory inaction seems unlikely and, perhaps, even impossible. Some of these technologies will move from the lab into the “wild” regardless of official actions.
But whether these challenges will be resolved next year or will stretch into 2019 and beyond is impossible to say. As the old saying goes: Predictions are hard, especially about the future.
I have spent most of the year writing in depth about the topics discussed above. Find my work below.
“That AI You Hate, You Really Love” Co-authored with Adam Thierer
Food and Drug Administration
“FDA Needs a Fresh Approach, and Fast” Co-authored with Adam Thierer
“Insurance costs just the tip of the iceberg. Time to reform the FDA.” Co-authored with Dr. Robert Graboyes
“Opening the Door for Medical Innovation” Co-authored with Dr. Robert Graboyes
“A Full Toolbox Will Speed Regenerative Medicine” Co-authored with Adam Thierer
“‘Build & Freeze’ Regulation Versus Iterative Innovation” Co-authored with Adam Thierer
“Will Genetic Editing Advance Faster Than Our Ability to Regulate It?” Co-authored with Adam Thierer
“Ignoring the Future Won’t Forestall It” Co-authored with Chris Koopman
“Might We Avoid a CRISPR Technopanic Altogether?” Co-authored with Adam Thierer
“A Model Roadmap for Genome Education” Co-authored with Adam Thierer