The American National Academies of the Sciences, Engineering, and Medicine released a report on genome editing ten days ago. Here‘s their brief presentation, and the document itself can be downloaded here. Here are some of the crucial points about the document.
1. What are the conclusions of the NAS report on genome editing?
a. Somatic genome editing – modifying the genes of body cells (i.e., non-sex cells)
The NAS (National Academy of Sciences – here short for the three academies) recommends that in the future, genome editing should be used to cure or relieve “disease and disability” after birth. These changes would not be heritable. They would be made either in tissue extracted from the body (ex vivo) or inside the body (in vivo). To begin with, however, the chances of unwanted side-effects must be reduced first, according to the panel. The state of the patients treated should then be monitored after the procedure, since this is a new procedure.
b. Genetic modification of embryos
Genome editing should not be prohibited for treating embryos in the course of in vitro fertilisation, as long as certain safety requirements are met, according to the report. It notes that only such changes would be heritable, as sex cells and body cells aren’t segregated in the early embryo. This increases potential risks. Another source of risk comes from the fact that embryonic development is still not understood in great detail. For this reason, the need for more pre-clinical research is even greater. In spite of risks,the panel values the modification early in development as that way, a genetic cause of disease would be corrected before it can manifest.
The report argues for intense research to bring down side effects, hoping also for further insights stemming from non-heritable genome modifications done after birth (i.e., on somatic cells). Persons having been treated as embryos and even their descendants should be monitored medically. The report acknowledges that genetic modifications in embryos would have an impact on people born with disability without drawing further conclusions from this.
There are further preconditions for embryonic genome editing that may or may not make a real difference in real life:“stringent oversight”, the absence of “reasonable alternatives”, restrictions to cases of “serious disease” only, “credible pre-clinical and/or clinical data on risks and potential health benefits”.
c. Genetic “enhancements”
After making certain philosophical and historical points, the report rejects enhancements on the technical grounds that benefits less profound than relief from an illness do not justify the risks posed by genome editing, at least at the moment or in the slightly more distant future. Whether more fundamental historical and ethical points have any bearing on the question is left open. The report does call for greater public debate about enhancements, however.
2. Who’s writing?
The report is put together by a commission appointed by a high level US institution, the National Academies of Sciences, Engineering, and Medicine. This is a highly prestigious body of experts that is independent of the government, which advises the American public and lawmakers on scientific issues.
The setup of the commission already suggests that the statement is heavy on science and legal issues. However, the subtitle of the report is “Science, ethics, and governance,” so this raises the question how the attention to “ethics” is reflected in the setup of the commission. The commission is headed by two co-chairs, one legal expert with a science background (A. Charo), and one scientist (R. Hynes). The remaining 20 commission members are scientists as well except for three legal experts, one bioethicist (a philosopher), one sociologist, and one public policy expert. The committee does not include experts in philosophical ethics more generally or religious or theological ethics, nor does it include any historian or scholar in disability studies, although the report touches explicitly on both religion and disability. As far as I can tell, there are no indications that the panel includes anyone – or even invited a speaker – with disability.
3. What’s at stake?
US research in genetics and medicine is a powerhouse, but as far as the modification of human genes is concerned, it is far from unfolding its full potential. For the time being, researchers in these areas cannot draw on public funds when modifying the genes of a human embryo, and such procedures cannot be approved for clinical use in principle. Yet the report suggests that we are coming closer to the point where those restrictions will no longer be legitimate.
Meanwhile, for over a year now a London lab has been carrying out research in modifying the genes of human embryos – so American geneticists may feel the need to catch up. Chinese labs have also modified embryos, but their procedures in ethical oversight remain unclear, presumably resting mostly with internal review boards of universities. Here the reasoning is that American researchers might set a good example. Whether or not this is realistic to begin with, the question is if it would have helped to include a significant number of ethicists in the NAS panel.
In more positive terms, the report contributes to the future of American research and medicine by negotiating four important societal goods: health care, freedom of research, protection of citizens from undue harm, and the moral integrity of both the science and the health care sector.
4. Why now?
Of course it is never too soon to do the right thing, if that is what one is doing. But in more pragmatic terms, the US congress instituted a rule that prohibits the modification of human DNA that expires at the end of April 2017. The regulation states that new medical procedures require approval by the American Food and Drug Administration, which itself is a public agency, yet public funds are prohibited not only for pre-clinical research on the modification of human DNA, but also in evaluating clinical procedures modifying human DNA. So even if, potentially, private funds have brought medical procedures to clinical maturity, they cannot be used. In the US, this is not the only regulation barring the modification of human genes, but it is an important one.
5. Why not rely on PGD for therapeutic purposes?
Potentially, an alternative to editing the DNA of embryos is to screen embryos for genetic irregularities (PGD) during in vitro fertilisation (IVF) and not to implant those embryos with particular problems. Both procedures would require IVF. So why embark on a new methodology of which we have relatively little practical experience?
The report adduces four reasons especially, which essentially come down to a numbers question. Since the NAS has access to excellent people and scientific resources, the question is if the report might have broken these cases down to actual numbers, which would have made it easier to balance the gravity of the reasons with the risks involved in the modification of embryonic DNA. The four reasons for the new methodology are:
- Dominant genetic diseases: The report writes that “dominant late-onset genetic diseases, like Huntington’s disease, can occur at high enough frequency in some isolated populations that one parent will be homozygous for the mutation.” (86)
- The number of embryos left after PGD might not be very high: Both parents may have one irregular allele and one regular one. In that case “only one in four of the embryos would be free of a disease-causing mutation. Those unaffected embryos could be identified by PGD [pre-implantation genetic diagnosis], but the number of embryos potentially available for implantation would be significantly reduced.”
Depending on the age of the parents, the number of embryos implanted in the course of a full, regular IVF procedure can range between two and six embryos, with the hope of one developing into a foetus in the womb. These embryos are obtained by extracting egg cells from the woman, which would then be fertilised with her partner’s sperm. Not all egg cells would end up fertilised, however, and crucially, the number of fertilised egg cells is reduced by deselecting those with genetic irregularities. The question is, then, if enough regular egg cells can be obtained in order to end up with one growing foetus in the womb that does not show the genetic irregularity that was screened out.
- More potential parents with severe recessive diseases: “As the survival of people with severe recessive diseases like cystic fibrosis, sickle-cell anemia, thalassemia, and lysosomal storage diseases improves with advances in medical treatments, the possibility cannot be dismissed that there will be an increase in the number of situations in which both prospective parents are homozygous for a mutation.” (87)
- Mutations that compromise fertility: “There can be an additional problem in the case of mutations that compromise fertility, which is the case for women who carry mutations such as Fragile X, BRCA-1 and others that cause the loss of oocytes during development or postnatally.” (87)
6. What could the report have done differently?
Three points especially come to mind for me. To begin with, it would have been helpful to include more ethicists as well as to bring in a few more experts from the humanities. At the moment, there is no such thing as a President’s Council in Bioethics, however. Presumably a body comparable to the National Academies of the Sciences, Engineering, and Medicine could be created to gather experts in the humanities, and ethics especially.
Further, it would have been beneficial to distinguish between disability and disease. People with disability have consistently been marginalised in Western societies, and many find it difficult to differentiate a judgement on their disability from a judgement on their person. Without serious discussion, the report joins Philip Kitcher’s speculation that “It would seem that ‘encouraging attempts to reduce the incidence of a genetic disease is compatible with continuing respect for those born with the disease and for support for their distinctive needs’” (97). It would be helpful to examine how realistic this proves to be in practice, and why not draw on more than just one expert who studied such questions in greater detail? Why not even hear testimony from people with disability and their close relatives?
Finally, in the section on modifying the genome of embryos, the report argues that experience in modifying body cells after birth will be helpful in the process of modifying embryos. This suggests that the modification of embryonic cells should only be embarked on at a later step, if at all. After all, the argument on enhancements is that even after significant progress in research, considerable risks remain. Would it have made sense to highlight work on somatic cells as the new step that, for now, researchers would be recommended to work on, while the next question, sex cells, should not be decided upon quite yet?