Professor George Church, PhD, of Harvard Medical School has published an opinion article in the New England Journal of Medicine today which argues that gene editing within the human germline should not be rejected out of hand. The paper, titled ‘Compelling Reasons for Repairing Human Germlines,’ discusses the main considerations that have delayed human gene editing in the past and why he believes they are insufficient to halt research in this area.

George Church, Professor of Genetics, Harvard Medical School

George Church, Professor of Genetics, Harvard Medical School 

The article begins by considering a natural combination of sperm with a dominant, disease-linked mutation with an unaffected oocyte. In that situation, the best outcome that can be statistically expected is for 50% of the offspring to be healthy and unaffected by the mutation, with the remainder demonstrating the diseased phenotype. Past research (notably Ma, Mitalipov, et al.) has shown that using a gene editing tool such as CRISPR can increase the percentage of healthy offspring above this natural limit to as high as 72%. While Dr. Church acknowledges the need for further data to confirm that the outcome was the result of precise gene editing and not of other factors, the initial data indicates that CRISPR could be used to improve embryo survival rates and health in humans.

Dr. Church goes on to discuss how that 72% could be increased until 100% of embryos were free of the disease-linked gene. One of the improvements he considers is the use of gene editing in the stem cells responsible for producing sperm or oocytes, prior to fertilisation ever taking place.

“Though it’s tempting to dismiss such technology as being limited to a small market or being far off technically, it would be more helpful to prepare thoughtfully for its potential early arrival and broad application, given the pace of development of next-generation sequencing for non-invasive prenatal testing and prenatal genetic screening in conjunction with in vitro fertilization,” Dr. Church wrote. “Of 130 million babies born each year worldwide, roughly 7 million have serious inherited genetic disorders. Even though some of these cases could be averted through non-invasive prenatal testing or prenatal genetic screening, both procedures result in the discarding of embryos, which many people find unacceptable.”

He backs up this position on this by referring to an announcement made by the Vatican, the centre of the Catholic Church, in 2004 when they stated that it would be acceptable for someone to undergo this treatment in order to naturally conceive healthy offspring.

The article then turns to the more political side of the argument, referring to a proposed hold on germline editing research in 2015 from the Congressional Subcommittee on Research and Technology and a more recent report from the National Academies of Sciences, Engineering, and Medicine (NASEM) that called for further research before clinical use. Dr. Church acknowledges the wisdom of the NASEM recommendation, likening it to the role of the US Food and Drug Administration (FDA), but also argues that Congressional intervention in matters like this can harm scientific progress.

The example he gives for this is the Consolidated Appropriations Act of 2016, which states: “None of the funds made available by this Act may be used to notify a sponsor or otherwise acknowledge receipt of a submission for an exemption for investigational use of a drug or biological product… in research in which a human embryo is intentionally created or modified to include a heritable genetic modification.” This, Dr. Church argues, undermines the core role of the FDA and in so doing negatively impacts the ability of the United States to remain at the forefront of scientific technological progression. The concern is that if the NASEM recommendation came to fruition, such legislation would restrict both research and patient choice for American citizens.

“But a deeper question is, do we want to lose the moral high ground on what would be a way of reducing abortions and losses of embryos?” he wrote. “Do we want legal inertia based on lack of awareness of moral options to force Americans to go abroad to have healthy babies by means of sperm editing?”

Finally, Dr. Church considers the position that gene editing in the germline is a ‘slippery slope’ to less ethical outcomes, such as enhancing humans beyond our natural limitations. Against this, he refers to currently-used practices, such as pathogenic extinction through vaccinations, which have changed the disease landscape of the world across many generations. The youngest of these generations were not involved in the initial research or decisions and yet are now able to reap the benefits of them, such as the almost total eradication of polio.

Not making these advancements and implementing them may be just as damaging as using them, he argues. “Doing nothing merely for fear of unknown risks is itself risky.”

Finally, he concludes, “I believe we should be regulating therapies on the basis of measured outcomes, rather than a priori guesses, just as we should evaluate employees on the basis of their actual performance, rather than poor predictors such as appearance. As we reduce the cost and improve the quality of DNA editing, it is critical to enable diverse conversations and broad education on this topic. It will be important for us to guard against commercial manipulation of perceived medical needs, but not at the cost of preventing the development and use of a whole category of promising preventive medicine.”