The Gray Areas of Gene Editing
In the early 1980s, I remember listening to the song “2525” by the American rock-pop duo Zager and Evans. To say the lyrics left me with the heebie-jeebies would be an understatement. I’d never heard a song with such a foreboding message about the world. The verse that stuck with me the most was about the year 6565, a distant time when people would choose their sons and daughters from the bottoms of long glass tubes. It sounded like something from an episode of the TV series, The Twilight Zone, but later I found out something eerily similar had already been done — in 1977. The first successful test tube baby was about my age, even more astounding. Mind blown!
I’m talking, of course, about invitro fertilization, which is now a common practice, essentially to remove a woman’s eggs, fertilize them with sperm outside her body, then implant viable embryos into her uterus to continue their gestation. However, this scientific marvel created quite an ethical debate that continues today, especially in religious populations.
This practice horrifies those whose beliefs dictate that life starts at conception. Not only because of the artificial implantation of lab-fertilized embryos into a woman’s body but because of the backup embryos that are frozen, sold, or terminated. Others see invitro as a beautiful scientific advancement that lets infertile couples realize the dream of having a family. Some fertility clinics offer, as an add-on, parents’ choice of their baby’s gender and eye color, an exciting yet formulated advancement. In the United States, choosing your baby’s gender or eye color is available only for couples with infertility issues, but could these choices tempt fertile couples to push for an elective invitro, thus soliciting policy change?
The second time I remember being spooked by the entertainment industry was in 1997. I saw the movie Gattaca, and that same eeriness I’d felt as a child when I heard “2525” swept over me. The movie’s premise is that people born naturally, without genetic enhancements, are shut out of specific careers, athletic opportunities, and society. Total science fiction, but I wondered if that kind of gene manipulation would one day be possible. Turns out, it is. CRSPR-Cas9 made headlines in 2012 as a gene-editing tool, a protein that can cut DNA, remove flawed sections of the genetic code, and insert desirable genes instead. CRSPR-Cas9 has massive potential for eliminating genetic diseases, viruses, and even some cancers. There’s usually nothing unethical about curing disease, but curing illness is only the beginning of how gene-editing technology could be used in the future.
Because of CRSPR-Cas9, it is now possible to alter DNA in the human germline, that is, the genetic instructions packaged up inside every sperm, egg, and resulting embryo. This means scientists can create designer babies:
Babies with immune resistance to genetic diseases.
Babies with advanced memory abilities.
Babies with enhanced physical traits.
Babies who look just the way their parents want them to.
The Ethical Debate
With germline editing, not only will the child’s DNA be altered, but their offspring will inherit the alteration, and so on, thus changing the future of human DNA. This also means that the decision to pursue germline alteration is more profound and abiding than altering DNA in somatic (non-reproductive) cells.
Not that the human germline is stagnant from one generation to the next. Our DNA constantly changes since numerous mutations occur through the natural evolutionary process. It’s how some genes become amplified or deleted over time and how certain cancers arise. However, when these changes are directed and accelerated by scientists, it opens the door to more sinister applications such as eugenics and preferential treatment for those who can afford it. Should scientists be allowed to control human evolution? The European Medical Research Council didn’t think so in 1991 when they declared germline gene therapy violated “the implied right to inherit a genetic pattern that has not been artificially changed.” And while the CRSPR-Cas9 technology is far from perfect, the potential exists to make precise and permanent alterations.
It’s no wonder the scientific community is wrestling with the ethical and moral boundaries of CRSPR-Cas9, and in March 2019, declared a five-year moratorium on pursuing germline editing. Dr. J. Craig Venter, biochemist-geneticist and a primary force behind the human genome project, told Forbes magazine, “I think editing human embryos with CRSPR should be a long way off.” But by then, human germline editing had already been performed — illegally, but nevertheless done by Chinese Biophysicist Jiankui He.
He’s lab recruited volunteers, eight couples seeking fertility treatments. The couples he chose for his study had something in common: the husbands were HIV positive, their infections were under control with antiviral drugs. He edited their sperm cells to be HIV-resistant, then proceeded with regular IVF treatment. In 2018, one of the couples successfully gave birth to twin girls. As for He, he was arrested for violating the ban on germline editing. Since He’s lab altered the father’s germline cells, the twins and their future offspring should be HIV-immune. However, the twins’ health is currently unknown — at least to the public.
He’s experiment violates the conditions of the ban on germline editing, but it is also problematic because of unknown side effects. The human genome is complex, and making cuts to DNA, pasting new information, or eliminating sections can be dangerous. For example, turning off one gene can unintendedly turn on another. This happened in a 2002 gene therapy study in Paris, where two young boys underwent gene therapy for X-SCID, a devastating, heritable immunodeficiency disorder. The boys later developed Leukemia, a harsh side effect even though gene therapy differs from gene editing in that the unhealthy gene is not altered or removed. Instead, a healthy version of the gene is inserted into the genome to offset the mutated, disease-related gene’s effects. Even so, the scientists involved in the X-SCID study unknowingly activated a gene that promoted cell growth, which unfortunately caused cancer.
Informing the Public
The countries agreeing to the five-year moratorium on germline research were entrusted with discussing the future of this technology within broader society. It’s a conversation that, I believe, is worth having because it’s possible germline editing will one day be mainstream. But who should determine when and if scientists are allowed to continue this work? Scientists? Politicians? Moms? Or should the development of germline editing technology be on voting ballots in democratic nations?
Surveys have been conducted in several countries to gauge the general population’s feelings about the morality of germline editing, often with some version of the all-important question, “Do you understand this technology?” It’s a difficult question for people who have never heard of CRSPR-Cas9. The journal of human genetics at Nature.com reports that surveys conducted in Japan show that most of the general population is agreeable to developing germline genome editing for eliminating disease but is wary of risks.
In the United States, during two surveys conducted in 2014 and 2016, the Pew Research Center found that religiosity plays a significant role in how people view gene editing. People with high religiosity tended to have more negative feelings toward developing gene-editing technology. The survey also highlighted a gender gap in views about gene editing, with women less accepting of it than men. People with higher scientific knowledge and greater familiarity with gene editing tend to be more accepting of it. A later survey asked Americans how they felt about testing gene editing on human embryos — to learn about risks — a necessary action to progress the science, and 65% were opposed, believing that it crossed a moral line.
Regulating the Research
Despite the publicity given to the 2019 moratorium, bans on germline editing are not new. UNESCO, The United Nations Educational, Scientific and Cultural Organisation, reports a study published in 2014 by Hokkaido University, Japan, showed that 29 of the 39 countries reviewed already had a ban on human germline editing. The ban was legally binding in 25 countries. The other four had guidelines, yet the remaining ten had rules that were described as ambiguous. Regarding the moratorium, in which some but not all countries are involved, two questions come to mind: How are the regulations enforced, and what’s to stop other countries from developing germline editing technology?
Historically, ethical agreements have been established with international collaboration, some as a response to unethical research on human subjects or harmful drugs that made it to market. The Nuremberg Code, an agreement to make human experimentation without consent illegal, was established in 1948 after German scientists conducted horrific experiments on unwilling human subjects during WWII. In 1962, the United States added the Kefauver Amendments to the Food, Drug, and Cosmetics act after the drug Thalidomide, prescribed to pregnant women in the 1950s, caused deformities and congenital disabilities in 12,000 babies worldwide. Then in 1964, the World Medical Association established the Declaration of Helsinki, an ethical guide for doctors who conduct behavioral and biomedical research with human participants. One principle of the declaration states, “Physicians must consider the ethical, legal, and regulatory norms and standards for research involving human subjects in their own countries as well as applicable international norms and standards.” The guidelines from the Declaration of Helsinki are still used today. However, a 2006 paper written by doctor/philosopher Soren Holm and bioethicist Bryn Williams-Jones, concluded that “exploratory studies support the position that there is no unified global field of bioethics.”
The international moratorium on germline editing comes to an end in four years. Scientists working with CRSPR-Cas9 are taking that time to determine how to proceed responsibly and ethically, possibly on a case-by-case basis. This will inevitably vary by country. Will the rewards outweigh the risks of their work? Will there be a public consensus? How will culture and religion define the parameters for each country moving forward?
Will opting out of germline gene editing be the unethical thing to do in the future? When considering the disease resistance and elimination of genetic disorders, it’s not hard to imagine judgment on those who refuse to partake. Why would anyone not want the absolute healthiest, strongest, smartest baby they can conceive? Just look at how far somatic gene therapy has come. Gene therapy for X-SCID has all but been perfected since the Paris Leukemia incident. In 2019, the National Institute of Health said infants diagnosed with X-SCID can now safely correct their immune systems with gene therapy treatment — a remarkable advancement. Gene therapy has also successfully treated hemophilia and blindness from retinitis pigmentosa.
For anyone struggling with Alzheimer’s, X-SCID, or Sickle Cell Anemia, CRSPR-Cas9 gene editing offers real hope. Of course, this therapy does not affect the offspring of the patients in any way. Germline editing, on the other hand, can potentially eliminate these conditions from the population altogether. Can you imagine a future in which no child suffers from Cystic Fibrosis? Imagine a future where the fear of Alzheimer’s doesn’t even exist. Think of what a more intelligent, healthier human race could accomplish. Sound bright? Will the benefits outweigh the risks? Time will tell, but for now, I’m off to read Aldous Huxley’s Brave New World.