The onslaught of new genomic biotechnologies, which show promise for correcting some serious health disorders, also challenge scientists to confront important social responsibilities.
George Q. Daley, M.D., Ph.D., dean of Harvard Medical School and an international leader in stem cell science and cancer biology, discussed those responsibilities in Dean Henri R. Ford’s Distinguished Lecture Series, reflecting on many decades of exploration at the interface of science, policy, ethics, and beyond.
“Arguably the most vexing recent challenge in biotechnology is the application of genome editing in the context of in vitro fertilization,” Dr. Daley said, “and the prospect that we can now really take control of human heredity.
“The question is, if we can, should we?”
The origins of this question and the current “fascination with gene and genome editing” go back to the creation of a hybrid DNA molecule by splicing the DNA from two different organisms. The Asilomar Conference was called in 1975 to talk about the safety of this gene splicing technology. “It really was a momentous occasion because it resulted in a series of biosafety practices that are now promulgated across the globe, and it established a precedent for self-regulation by scientists,” said Dr. Daley, who was introduced by Dr. Ford as “a central force in establishing international guidelines for stem cell research.”
“It was clear that this idea of gene splicing might one day be applied to the human genome,” Dr. Daley said. “But because it was seen as so far in the future, the issues of the ethics of gene splicing were put off.
“What I’m going to argue is that we can no longer put off those considerations.”
There have been tremendous advances in the use of recombinant DNA technology for the treatment of human diseases, “arguably most recently in the phenomenal triumph of gene therapy,” said Dr. Daley, whose research paved the way for Gleevec, a “magic bullet” drug for chronic myeloid leukemia.
The advancement of what was initially cumbersome gene technology came “from a completely unanticipated area of science.” Food scientists working on the science of fermentation led to the discovery of the genome editing machinery known as CRISPR. Then other scientists figured out that they could design a guide RNA in an afternoon, have it synthesized, “and within a matter of days you could have an entire system for editing a gene.”
Further research showed that the technology could engineer the whole genetic makeup of a mouse, and soon after it was being used in a monkey. Dr. Daley was involved in reviewing papers that made it “absolutely clear that the technology for editing the human genome and passing it into the germline was now present and facile. And indeed, this raised quite a bit of alarm.”
After a two-day meeting, a group of experts “strongly discouraged any attempts at germline modification for clinical application in humans. There needed to be a respite. … We called for forums to actively bring scientists together with other stakeholders – bioethicists, religious leaders, patients and patient advocates – so that we could discuss the application of this technology.”
The understanding that “we could be on the cusp of a new era in human history” led to an International Summit on Human Gene Editing in 2015 that concluded too little was known about the technology to apply it then. In 2016, in response to an increase in applications of embryo science, a revision of international guidelines led by Dr. Daley “called for a prohibition on the use of genome editing in the context of in vitro fertilization – once again, primarily predicated on the fact that we could not be sure it would be safe.”
But a highly publicized genome editing project for birthing a gene-edited baby was performed and drew serious criticism for lack of transparency, concerns about informed consent, and questions about the fidelity of the gene editing. “Despite the worldwide condemnation for this experiment, others proceeded,” Dr. Daley said. “So I think we’re still at an impasse – knowing where this work is going on, and what its future is.”
Much work has been done to determine in what serious genetic diseases gene editing might be acceptable. “There are rare cases where there are no alternatives – both parents are affected, for example – and the only option is genome editing,” said Dr. Daley, who was director of the Pediatric Stem Cell Transplantation Program at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. “The rarity of these instances is enough to say we should not cross the Rubicon. But I can tell you as a physician of children with rare genetic immune deficiencies and immune disorders, the possibility of using genetic editing is going to get more common for these types of indications.”
A deeper concern is that if the technology becomes successful at correcting genetic disease, there will be a market for enhancement. “That raises the notion of eugenics, which has a deep and long history,” Dr. Daley said. “The notion that through selective breeding we could improve the natural, physical, mental and temperamental qualities of the human family.”
The discussions and arguments are happening again, he said. “If we could make kids smarter, if we could make them learn better or faster, who would disagree with that?
“The question is who gets to choose? And who gets to use? Would you be comfortable, given the tremendous disparities in the delivery of health care around the globe, that we could apply such a technology with equality?”
More international studies are being conducted to determine whether there would be appropriate applications. These come in the context of several other technologies “with applications that really run ahead of our ability to understand,” Dr. Daley said. Artificial embryos, gene drives and altered biospheres, synthetic biology and a host of other emerging biotechnologies “warrant thoughtful, prudent oversight by physicians and scientists,” he said.
Dr. Daley is co-chairing a new committee of the National Academics – the Committee on Emerging Science, Technology and Innovation – “that is going to try to take a systematic approach to think about the proper scientific and regulatory oversight of these technologies.”
“The technology is here,” he said. “The question is, should we use it?”