WASHINGTON -- More than a decade ago, the NIH director explained his ethical, moral, and religious views on the subject of in utero gene editing -- a debate framed in Hollywood and the media as one of "designer babies" -- using an abstract diagram in a presentation to colleagues.
Flash forward to 2016, and "a lot of the issues are still the same, except we now have this new tool," said Francis Collins, MD, PhD, director of the National Institutes of Health, referring to the CRISPR-Cas9, an enzyme that can, with remarkable accuracy, slice DNA at targeted points.
A month ago, Collins shared that same diagram to restate his view of gene editing and other "enhancements" with a panel of scientists, doctors, lawyers, and other academics on the Committee on Human Gene Editing, which met at the National Academy of Sciences here, earlier this summer.
The committee is tasked with providing an "in-depth review of the science and policy of human gene editing," and the group's recommendations regarding the use of gene editing in biomedical research and in medicine are expected by the end of the year.
Already gene therapies -- treatments that enable "corrected" genes to implant themselves in cells, often using a virus -- have shown promise in research studies of cystic fibrosis, HIV, and Duchenne muscular dystrophy (DMD).
But along with such enormous promise, there are also tremendous risks.
For example, in April 2015, Chinese scientists at Sun Yat-sen University in Guangzhou were the first to use CRISPR-Cas9 on human embryos, according to Nature. The embryos were defective and could not have produced a live birth, the story noted. However, in December 2015, a group of international scientists called for a moratorium on gene editing that could cause "inheritable changes to the genome," as noted in The New York Times.
Earlier this year, James Clapper, the director of National Intelligence, listed CRISPR as one of several weapons of mass destruction, alongside Russian nukes and North Korean missiles, according to Science magazine.
In his presentation last month, Collins used a somewhat abstract diagram with an X-axis marked "level of concern," ranging from "admirable" to "unacceptable," and a Y-axis labeled "timetable to feasibility," marked "now" to "never," with 10 years and 100 years somewhere in between.
In the space that correlated with admirable enhancements that are currently available, the NIH Director marked activities such as immunization, chlorinated water, and prayer -- Collins is an evangelical Christian.
He used numbers to represent each type of enhancement, resulting in what looked like an unplayed game of connect the dots.
In the area of "questionable" and "unacceptable" from now until roughly 75 years in the future, lay the "zone of concern" where Collins charted mood-altering drugs, sex-selective abortions, and growth hormones given to children to improve athletic abilities.
The final item, "designer babies with precisely predictable phenotypes," was designated under the region "never" and "unacceptable."
"A lot of what people are talking about in terms of enhancement of human embryos imagine[s] that you are then going to be able to dial in the characteristics of this kid to play first violin in the orchestra, and be the star of the football team, and get an A+ in math," Collins said. "Those things are not going to be determined by their genomes."
Setting aside such simplistic views, though, the idea of germline editing for the purpose of enhancement is a "non-starter," he said. "We have to be aware of the hubris that it would take for human beings to be so smart that we thought we had the ability and the ethical principles to do such a thing."
For instance, suppose one eliminates the apolipoprotein E (APOE) gene: This seems like a smart decision because the gene has been linked to Alzheimer's disease. Yet, there is also evidence that APOE is associated with better brain function in young adults, Collins noted.
In addition, the needs for gene editing are not justified, he said. In almost every scenario where that has been considered, pre-implantation genetic diagnosis could be used "without any fancy manipulation and probably with much lower risk."
He listed several other concerns:
- Off-target effects of the technology could cause unanticipated mutations;
- Lack of consent from future generations whose genome will be altered;
- Lack of consensus regarding the meaning of enhancement (i.e., the threat of eugenics);
- Fear of the "commodification" of children;
- Rejection of disability as a suitable outcome; and
- Unequal access due to socioeconomic factors.
And for those who believe in God, Collins said, the technology raises philosophical and theological questions, around "humans taking charge of our own instruction books" -- "I am totally bullish about somatic cell gene editing for clinical benefit, and I think we should be pushing that at maximum speed and energy," he said.
The committee co-chair, R. Alta Charo, JD, professor of law and bioethics at the University of Wisconsin Law School in Madison, asked Collins how his personal views differ from his role as a public servant. Collins replied that excluding his theological comments which are "strictly personal," his position on gene editing aligns with that of the majority of the senior leadership at the NIH.
He also noted that the NIH is prohibited from doing research on human embryos by the Dickey-Wicker amendments (made law in 1995).
However, when pressed about whether he supports a blanket prohibition against germline editing, regardless of outcome -- meaning even in cases of severe illness -- Collins softened his stance: "There is this other ethical principal: benevolence. ... If there is a protocol approach that gets you there, then as in everything, you have to balance that against the potential intervention in a space in which we normally wouldn't go -- but it would have to be really compelling, a high bar," he said.
Another panel member, Matthew Porteus, MD, PhD, associate professor of pediatrics at Stanford University School of Medicine, said that one challenge he has is that as a physician he was taught that the most important person is the patient in front of him. This is the view he brought to the panel's discussion. On the other hand, the impact of new gene editing technology reaches far beyond a single patient, he noted.
"If we could give parents a safe and effective way of making sure that their kids were not going to have diseases, then as an MD, that is absolutely something that we should be able to do."
Porteus also pointed out that, in the panel discussions, initially germline editing had been conflated with embryonic manipulation. However, some types of germline editing do not involve an embryo at all, he said.
By editing a stem cell, a precursor to a sperm, for example, the embryo can be indirectly altered -- bypassing some, but not all, of the ethical hurdles around embryo manipulation, he explained.
Porteus agreed with Collins that pre-implantation genetic diagnosis is often a more reliable option than gene editing, but there are exceptions -- for example, male infertility. Editing the precursor to sperm of an infertile man could allow him to have his own biological child.
Porteus told MedPage Today that his views did not represent those of the full committee and might not reflect what is ultimately published in its report.
But he added, "Where we are in 2016 around this thought process ... may be very different in 2026."