Gene Editing Rights & Wrongs

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Last November the story broke that a Chinese scientist, Dr. He Jiankui, had genetically modified human embryos and then, going against international ethics standards prohibiting germline modification, implanted the embryos in their biological mothers.1 Twin girls were born last fall, and another pregnancy was underway. In late November, He Jiankui fielded questions on his research at the Second International Summit on Human Genome Editing in Hong Kong, the same summit that three years earlier had laid out the standards for genome editing that he violated.2

In anticipation of the response that news of his experiment would evoke, and at the behest of his public relations manager, Dr. He made YouTube videos claiming that "genetic surgery," as he calls it, has the potential to help millions of people. He also contacted the Associated Press for an "ahead of press" interview that was embargoed (i.e., not allowed to be made public) until after the research reports were published. 

When Dr. He's work came to light, albeit earlier than he had anticipated, the Chinese Academy of Sciences, the Genetics Society of China, and the Chinese Society for Stem Cell Research condemned his work, as did over a hundred Chinese biomedical researchers.3 An investigation conducted by a task force in Guangdong Province revealed that Dr. He had forged consent papers and had worked on the project without oversight. The task force also determined that He had violated prohibitions against germline editing for reproductive purposes and that he seemed to be motivated by a desire for fame and financial gain. He was fired from the Southern University of Science and Technology, from which he had been on sabbatical, and further consequences are still pending.4

Bad Science: Plunging In Without Restraint

The problems with Dr. He's experiment did not stop there. For one thing, it turned out that the experiment itself was not medically indicated. He had used CRISPR-Cas9, a gene editing technique, to edit the CCR5 gene in embryos created using in vitro fertilization (IVF). CCR5 is not a gene that codes for a disease; it is found in everyone. Moreover, those few people with a mutant version of the gene (CCR5-δ32) are less likely than those with the normal version to become infected with HIV, although they are more likely to contract West Nile Virus. This was a case of changing a normal gene to possibly prevent the child from contracting HIV in the event that she came into contact with HIV as an adult.5

Second, among all of Dr. He's volunteer couples, who were the biological parents of the embryos he created, the man had HIV but the woman did not. There is almost no chance of a child acquiring HIV from the father, however, particularly when ­conceived through IVF. Furthermore, there are standard procedures in place for ensuring that HIV is not passed on to the child from either parent.

Third, the investigations showed that He may not have properly informed the couples of the nature of his experiment, since he described it to them as a procedure to produce a genetic vaccine for HIV. He also paid the couples about $40,000 in return for signing a non-disclosure agreement, another violation of ethical standards.6

In sum, Dr. He modified embryos using a technology whose safety and efficacy are still being studied and whose use the international community has proscribed until more studies are done. This was not a medically necessary procedure, as HIV can be prevented in other ways. And contrary to Dr. He's YouTube message, his work would be considered enhancement, not therapy, since he was modifying healthy embryos.7 His research did not comply with the basic standards for research done on human subjects, let alone the more rigorous standards that apply to minors and to enhancement technologies.

Good Science: Taking Time & Observing Restraints

Contrast He Jiankui's experiment with another experiment that was in the news last February.

Scientists at the University of North Carolina at Chapel Hill announced the successful re-insertion of genetically modified cells in patients with Hunter's and Hurler's syndrome. The patients' cells were edited with zinc finger nuclease, a gene-editing technology that pre-dates CRISPR. The cells were then re-inserted into the adult subjects at various doses. The procedure produced no side effects and was deemed safe, and it showed some preliminary signs of efficacy in patients who were given higher doses of the genetically modified cells. Because the procedure was deemed safe, teenage patients were allowed to enroll in the next phase of the trial.

In both the conduct of this experiment and the reporting on it, we observe healthy restraint on the part of the scientists and journalists. It produced some promising results, but as the scientists quoted in the press pointed out, they will need to conduct more tests to find out what the edited cells are actually doing in the body. Although the goal is to be able to use this medical technology on younger patients, before Hurler's syndrome induces bodily damage, the researchers began their trial with adult subjects, who could properly understand the risks.8

This is what good science looks like: it takes a slow, restrained approach that respects the patients involved. And the experiment was designed to minimize the guesswork involved in determining whether or how the procedure worked.

Contrast this to the no-holds-barred kind of research conducted by Dr. He. There is evidence that the gene-editing technique he used only worked in one of the twin girls, while the other has a "mosaic" cellular profile, meaning some of her cells show the CCR5 mutation while others do not. No one knows what effect He's experiment will have on the future health of these girls or on the child from the other pregnancy, so for the rest of their lives they will have to be monitored by the Guangdong Province government for signs of any adverse effects.

Even more disturbingly, while there is research showing that the CCR5 mutation inhibits HIV from infecting cells, there is no way to tell for sure if this particular experiment worked without exposing the girls to HIV. Exposure tests are typically done when testing new vaccines, but they require well laid out informed-consent procedures and safety measures, as well as strong oversight.

The Culture That Facilitated He

Dr. He's experiments, while secretive, did not occur in a vacuum. Both Rice University, where He received his Ph.D. in 2010, and Stanford, where he did postdoctoral work, are investigating the extent to which their faculty may have been involved in He's research. But beyond looking into the institutions, individuals, and countries involved, there is a need to examine the culture surrounding cutting-edge biotechnologies. In fact, Chinese bioethicists Xiaomei Zhai, Ruipeng Lei, Wei Zhu, and Renzong Qiu contend in a report for The Hastings Center that blame should first be placed on the "prevailing international science culture that puts a premium on sensational research and being first." Bio-historian J. Benjamin Hurlbut, who had met with Dr. He several times prior to last November's summit, echoes their sentiment, saying that He was acting in line with a scientific culture "that puts a premium on provocative research, celebrity, national scientific competitiveness, and firsts."9

In his YouTube videos, Dr. He notes how the media hyped the panic over the first baby born through IVF, yet since then, IVF has been used "to help more than 8 million children come into the world."10 He cites Dr. Robert Edwards, who won a Nobel Prize for developing IVF, as one of his heroes.11 It is true that millions of children have been born through IVF since Louisa Brown was so born in 1978, but even now, forty years later, scientists are still asking if these children are just as healthy as their naturally born counterparts. For example, studies done in 2013 and in 2018 yielded conflicting evidence as to whether children born through IVF have a slightly higher risk for certain cancers, and whether adolescents born through reproductive technologies evince increased vascular aging.12 The reality is that all of these children are part of an experiment whose long-term effects are still being studied.

The four Chinese bioethicists also criticize the specific systems in China that allow for lax oversight and permit conflicts of interest on the part of hospitals and researchers to be overlooked. They said that the "promotion of physicians should depend not on the publication of scientific papers, but only [on] the quality of their medical practices and professionalism." While we may turn up our noses at China for not exhibiting the same degree of restraint and transparency as may be found in the U.S. and the U.K., we must keep in mind that we exert our own "publish or perish" pressures that contribute to a laissez-faire culture of biotech and biomedical research.

Limits Foster Creativity

Much scientific endeavor is about overcoming biological constraints. But there are other types of constraints that are not necessarily problems to solve or hurdles to overcome. These include legal, moral, and environmental constraints.

Contrary to the popular narrative, science doesn't flourish when scientists are given free rein to conduct unfettered scientific research, as was commonly claimed in the 2000s with respect to stem-cell research. In reality, creativity and innovation flourish within limits. In fact, the history of stem-cell research is a good illustration of this. Shinya Yamanaka, who shares a Nobel Prize for discovering the factors for pluripotency in adult stem cells, was motivated to find an alternative to embryonic stem cells because he did not want to destroy embryos.

We should laud the work of scientists who practice creativity within the limits of legal, moral, and environmental norms. There are many research groups working on cures for genetic diseases without engaging in research on embryos. It is creativity within limits that breeds good science and promotes human flourishing.

Notes
1. Quartz (Nov. 27, 2018): https://qz.com/1474814/the-cripsr-baby-news-was-carefully-orchestrated-pr-until-it-all-went-wrong.
2. International Summit on Human Gene Editing (Dec. 3, 2015): www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=12032015a.
3. Nature (Nov. 28, 2018): nature.com/articles/d41586-018-07573-w.
4. Chemical and Engineering News (Jan. 22, 2019): https://cen.acs.org/biological-chemistry/biotechnology/Scientist-behind-birth-gene-edited/97/i4.
5. Science (Nov. 28, 2018): sciencemag.org/news/2018/11/ethics-aside-does-crispr-baby-experiment-make-scientific-sense.
6. The Hastings Center (Feb. 7, 2019): thehastingscenter.org/chinese-bioethicists-respond-case-jiankui.
7. Ibid.
8. The Associated Press (Feb. 7, 2019): apnews.com/d728f86d70d94ce68dd4fedffe58d03f.
9. STAT (Nov. 27, 2018): statnews.com/2018/11/27/crispr-babies-creator-soaked-up-bioethics.
10. youtube.com/watch?v=th0vnOmFltc.
11. Unlike Dr. He, Dr. Edwards had published prior safety studies and worked under ethical oversight.
12. Nancy A. Melville, "No Increase in cancer among children conceived in IVF," Medscape (Feb. 11, 2019); "Adolescents conceived by ART show increased vascular aging" (Sept. 13, 2018).

has an M.S. in chemistry from the University of Texas at Dallas, and an M.A. in bioethics from Trinity International University. She resides in Dallas and currently works as a freelance science writer and educator.

This article originally appeared in Salvo, Issue #49, Summer 2019 Copyright © 2019 Salvo | www.salvomag.com https://salvomag.com/article/salvo49/good-chop-bad-chop