by Craig Klugman, Ph.D.
In the film Gattaca, a couple desiring to have a child visits their neighborhood geneticist:
Marie Freeman: We didn’t want… Diseases, yes, but– [looks at Antonio]
Antonio Freeman: We were just wondering if it’s good to leave a few things to chance?
This movie is a dystopian vision where children are designed to be the very best of their parents. Those children born without such interventions are second class citizens who lack opportunity for education, professional employment, and even marriage.
This week the world took one more step toward that vision. Researchers at the Oregon Health Sciences Center corrected a genetic mutation (MYBPC3) in a human embryo. The mutation causes hypertrophic cardiomyopathy (HCM), a disease that affects the hearts of 0.05-0.2% of the population (about 1 in 500 people). The severity of the symptoms varies from unnoticed to debilitating. People with the mutation are at higher risk for cardiac death than the general population and are thus discouraged from heavy physical activity and playing sports.
Of course, this is not the first effort at genetically engineering a human embryo. In 2015, Chinese researchers announced they had genetically modified, abnormal embryos created for IVF, which could not have led to a live birth. Their work corrected for β-thalassaemia. A year later, different researchers in China engineered an embryo to create an immune system resistant to HIV. The mutation they introduced, CCR5Δ32 is found in people with natural resistance.
In both the Oregon and Chinese experiments the embryos only grew for a few days and were never intended for implantation. However, the efforts also differed in several important ways. First, the Oregon embryos were normal. Second the embryos were created specifically for this experiment. The OHSU IRB approved the study in a full-board review in 2016 and required continuing oversight through a Data Safety Monitoring Committee. The study recruited patients with the mutation through the university’s heart clinic. The embryos were created using artificial reproductive technologies (specifically intracytoplasmic sperm injection-ICSI). There were control as well as experimental embryos.
In general, bioethics usually has one of three responses to new technologies like that. The first is to declare that such technologies are wrong and should be banned. In his 1970 book The Fabricated Man, theologian-bioethicist Paul Ramsey argued against genetic engineering: “Because those who come after us may not be like us, or because those like us may not come after us, or because after a time there may be none to come after us, mankind must now set to work to insure that those who come after us will be more unlike us. In this there is at work the modern intellect’s penchant for species suicide.” In other words, to change the germ-line genome means that what is considered human DNA changes for all future generations and that is not anything two which an individual can consent. Ramsey also has concern with humans designing their own evolution saying that such things are divine responsibilities.
The second bioethics response is that the genie is out of the bottle but we should follow a voluntary moratorium while the social, ethical and legal studies are examined. The experiment comes only 2 years after UNESCO’s International Bioethics Committee called for a moratorium on such genetic engineering. They emphasized that under the Universal Declaration of Bioethics and Human Rights (2005), that “the human genome is part of the heritage of humanity” and thus should not be altered lightly.
Currently, federal funding is prohibited on genetic engineering research. The FDA is also banned from approving research in which a human embryo is intentionally created or modified and even prohibits conversations on germline and mitochondrial gene manipulation. The result of these bans has not been a prohibition on such research but rather that this work has gone underground into private funding and only voluntary oversight. Another worry is that the U.S. will be behind in these technologies and in the ethical and social conversation when the work is done overseas. In a recent OpEd piece, Arthur Caplan stated three concerns with the new genetic engineering: (1) We need oversight of the work; (2) We need to figure out the patent battles that are determining who owns the technology and the genes; and (3) We need to monitor genetic engineering—research and clinical.
The day after the Oregon announcement, a group of 11 professional organizations released a statement saying that public funding should be available for genetic engineering, but that no engineered embryo should be implanted into a womb. They are supportive of somatic cell (born-body whose cells will not be transmitted to subsequent generations). In addition, they call for engaging the public for its opinions on the technology as well as to get their input on what the ethical issues might be.
The third bioethics response is to say that humans now have the ability to transform themselves and control our own evolution and thus this new technology should be embraced to better ourselves. The Oregon announcement comes six months after the National Academy of Sciences and the National Academy of Medicine released a report supporting germ-line genetic engineering. Germ-line refers to altering cells that can pass on the alteration to future generations. Last year the U.K. licensed the first lab in that country to edit human embryos through its Human Fertilization and Embryology Authority which approved applications for such work. Thus the U.S. bans do not prevent the science from happening, but simply take it away from any transparency.
The reality is that human genetic engineering is here. The choice is whether the U.S. pretends it does not exist—which means that it will take place in private institutions, behind closed doors, in other countries, and without any oversight or regulation—or whether we embrace this. The current thinking is that genetic engineering is limited to correcting disease. The question of human enhancement—choosing eye color, intelligence, athletic ability—is not here, yet. Even for medicinal purposes, the engineering, at this stage, can only work with diseases where the genetic cause is simple (one or two genes) and the mechanism is well known. Certainly, we can agree that having children who avoid (not treat or cute) disease is a good thing for their lives and for the costs to society.
But even that presumption is controversial. For example, some people in the deaf culture would prefer to have children who are also deaf and might choose to engineer children with that quality similar to people choosing embryos because they carry a gene for deafness. Adrienne Asch argued that choosing embryos—or engineering them—to avoid disability “reinforces the belief that disability is inimical to is inimical to a worthwhile life…life with disability can be valuable to individuals, their families and society.” These views beg the question as to what diseases should be altered? One might think avoiding cancer would be good, but that would ignore dozens of stories of people who say that cancer changed their life for the better.
For the time being, I would suggest that (1) clinics pursuing this research establish genetic engineering committees (GECs) that, similar to a transplant committee, would be composed of a group of physicians, ethicists, social workers, a clergy member, and even a person living with the condition (or their family) in question. These committees could review requests for genetic engineering on a case-by-case basis. The technology would not be outlawed, it would simply undergo a significant review. (2) Any children born from this technique would need to be monitored for their health and safety. Similar to the idea of a phase 4 trial, the results in the engineered children would be helpful for understanding if the modification was a useful one or a dangerous one that should not be attempted again. (3) Develop a pre-genetic engineering advance directive. The couple, along with the physician and geneticist, should complete a form detailing decisions in the event of unanticipated outcomes. For example, would abortion be on the table if there was a dangerous mutation, or that correcting one condition caused a second problem. (4) The U.S. Congress and the FDA should withdraw the ban on funding and clinical trials. Instead, all trials should be part of a public database. Together with government funding would make this work more transparent. (5) The U.S. Congress should pass a law that genes belong to the person rather than to the company. Considering the fights over who owns the techniques one might wonder if the U.S. Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics would apply to altered genes? This ruling stated that DNA is a product of nature that cannot be patented (thus voiding 4,300 patented genes). The ruling does not apply to DNA sequences that do not exist in nature such as synthetic DNA.
The television show Zoo is a thriller based on the notion of genetic engineering of human and animal DNA. The results of this science are disastrous—animals that attack humans, worldwide sterility, and chimeric hybrids that destroy much of the world. While pursuing this work, we should at least consider the possibility of creating dangerous mutations. Therefore, it is even more imperative that we conduct this work openly and with oversight.