January 16, 2018

The Coming Age of Genetics is Now Coming-of-Age



In previous posts, I’ve shared some thoughts on the future of genetic modification technologies and the various regulatory and scientific roadblocks they face. Since then, however, it has become clear that these technologies aren’t on the far-flung horizon; they’re at our front door.

On Friday, an article in the journal Science (full version paywalled) described how gene therapy techniques have already begun improving the lives of those with cancer and heritable genetic diseases, and what needs to happen next:

Partnerships with biotechnology and pharmaceutical companies with expertise in manufacturing and scale-up will be required for these therapies to have a broad impact on human disease. Many challenges remain, including understanding and preventing genotoxicity from integrating vectors or off-target genome editing, improving gene transfer or editing efficiency to levels necessary for treatment of many target diseases, preventing immune responses that limit in vivo administration of vectors or genome editing complexes, and overcoming manufacturing and regulatory hurdles.

Among other things, those regulatory hurdles include: an uncertain approval-pipeline process; a congressionally-imposed (via appropriations language) ban on regulatory approval for genetically modified germline cells; overly broad and prescriptive privacy mandates for genome research; and the regulatory intersection of advanced AI analysis, the Internet of Things, big data, and numerous other emerging technologies that will impact genetic research, development, and deployment.

Of course, not all barriers are regulatory. One of the most pressing concerns, and one that is unfortunately not unique to gene therapy and genetic modification technologies, is overcoming the ever-present calls for “having a conversation.” This phenomenon, which is unfortunately all-too-pervasive in the field of technology policy, can best be described thusly: A new technological advancement or scientific discovery will inevitably be met, first and foremost, by a call to have a conversation about its implications. I once jokingly referred to this phenomenon as “Hagemann’s Law,” but whatever you call it, the result is the same: thoughtful, practical, and potentially actionable solutions to identifiable problems are no longer given priority treatment. Instead, abstract and non-actionable objectives aimed at achieving “broad societal consensus” or “consideration of the ethical implications” of technologies replace evidentiary analysis and targeted policy recommendations.

All that remains in the wake of such calls is the never-ending conversation.

Unfortunately, the Science authors default to this recommendation in the context of germline editing:

Importantly, a societal consensus must be reached on the ethics of germline genome editing in light of rapid scientific advances that have made this a real, rather than hypothetical, issue.

A better approach would have been to embrace the recommendations from the National Academy of Science’s (NAS) 2017 report on genome editing, which declared, “Clinical trials using heritable genome editing should be permitted only within a robust and effective regulatory framework.” As the report went on to note, however, “As of late 2015, the United States was unable to consider whether to begin heritable genome-editing trials, regardless of whether the criteria laid out above could be met.” This is because a clause prohibiting the development of regulatory approvals for germline edited cells has been repeatedly included in the annual Consolidated Appropriations Act. As the NAS report points out:

The current effect of this provision is to make it impossible for U.S. authorities to review proposals for clinical trials of heritable genome editing, and therefore to drive development of this technology to other jurisdictions, some regulated and others not.

While the murky ethical questions of this technology necessitate consideration, we shouldn’t be tying the hands of regulators in developing standards for the safe and effective approval of therapies that could help ease the pain of Americans.

Returning to the Science article, although the call for “societal consensus” tends to ring hollow, the authors fortunately recognize the very real and pressing need to reform how we pay for equitably delivering the benefits of this rapidly maturing technology:

Finally, payers and gene therapy clinicians and companies will need to work together to design and test new payment models to facilitate delivery of expensive but potentially curative therapies to patients in need. The ability of gene therapies to provide durable benefits to human health, exemplified by the scientific advances and clinical successes over the past several years, justifies continued optimism and increasing efforts toward making these therapies part of our standard treatment armamentarium for human disease.

That last point about “continued optimism” deserves constant reiteration. There are plenty of outstanding policy concerns that need to be addressed, but we shouldn’t view technologies with the potential to improve the health and well-being of all humanity purely through the lens of worst-case outcomes. Rather, we should embrace the promise these momentous benefits have to make the world a better place.