Feb 20 2017
Human Gene Editing
The recent rapid development of CRISPR technology, which has made gene editing fast, affordable, and accurate, has rekindled the ethical debate about human gene editing. Last week a special panel put together by the National Academy of Sciences gave a “yellow light” to human germline gene editing – saying that such editing might be ethical once the risks were properly assessed.
Germline editing means that the changes would be part of the gametes, the sperm or egg, and would therefore be passed down to offspring. If gene editing were done to a fertilized then this would affect all cells, including the germ cells.
By contrast somatic cell editing would affect only adult cells and not be passed down to the next generation. Such editing would only affect the individual.
The ethical controversy over germline editing is that such changes essentially can become a permanent part of the human population.
What Changes are Acceptable?
The NAS report essentially lays out two criteria for human germline editing. The first is that research shows that such editing is safe in humans without any unintended consequences. They want to make sure that dangerous changes to the human genome will not enter the human population. This is, of course, a perfectly reasonable criterion.
The second is that such editing would be used only as a last resort for couples who cannot otherwise have a child without a serious genetic disease. This would essentially mean that one parent has a double dose of a dominant gene for a serious disease, or both parents have the disease gene.
In many cases it is possible to avoid genetic diseases with in vitro fertilization where the embryos carrying the disease gene are discarded. Gene editing would be reserved for rare cases in which this option is not available.
If these recommendations are followed, it would be many years (5-10 at least) before such an option is available to people.
The Future
Essentially the NAS panel wants to limit human germline editing to the most severe cases where there is no other option, after sufficient safety research is done. This is a reasonable place to start, but I predict it will not end there, and it shouldn’t end there.
If the technology turns out to be safe and effective for human gene editing, and at this time there is no reason to suspect that it won’t, then I think it will slowly gain acceptance.
The technique is already being looked to for animal gene editing. At a recent AAAS meeting, UC Davis animal scientist Alison Van Eenennaam argued that this is an important tool to complement what we are already doing to optimize farm animals.
For example, over the last hundred years we have used artificial insemination, embryo transfer, crossbreeding and, genomic selection to improve milk yield from dairy cows. As a result:
…dairy cows in the United States dropped from a high of 25.6 million in 1944 to about 9 million today, even as the country experienced a 1.6 fold increase in total milk production.
That means less greenhouse gas production from dairy farming. Now farmers want to add gene editing to the list of options. This may be necessary if we want to sustain improvements, as we are getting to the limits of existing techniques.
Gene editing is also a potentially more precise technique – we can make the changes we want without bringing along changes we don’t want.
Genetic modification of crops and animals is already controversial, but the loudest critics are largely basing their criticism on demonstrably false or misleading arguments. I certainly hope that the technology becomes less controversial with better science communication on the topic, and as the benefits of the technology become more apparent, while the feared disasters fail to manifest. Further, as we put more and more strain on the environment, genetic modification could become the environmentalist’s best friend.
In vitro fertilization may be the historical template most appropriate to this situation. Initial protests were based on unfamiliarity and fear of frankenbabies. Now no one thinks twice about in vitro fertilization.
We will likely gain significant scientific experience with CRISPR on animals. The technology is still new, but before long it will become familiar. It is a big leap to go to humans, but the NAS has just opened the door.
By editing the germline, we could significantly reduce the incidence of horrible genetic diseases like Huntingtons or Tay Sachs. (You can never eliminate such diseases because there is a baseline spontaneous mutation rate.) This is such an undeniably good thing criticism of the technology used to achieve it will likely be marginalized.
What will happen once we have been using CRISPR-like technology to edit the human genome for 50 years, even if we have only been using it to address these limited conditions? At what point will it be deemed safe, and the fears of unintended damage to the human genome are alleviated?
Also keep in mind that human gene editing of somatic cells, without germline editing, is more acceptable because the changes only affect one person. We could potentially cure adults of horrible genetic illness by editing enough of their cells.
Gene editing is likely to become an accepted part of advanced modern medicine. We will probably get to the point where everyone will know someone who has benefited from the technology.
At that point it is easy to think that the threshold for using the technology will begin to lower. The list of genetic diseases for which the technology is a choice will expand. Then it will become a first choice, rather than a last choice.
What about genes that present a clear and significant predisposition to a horrible disease? There are genetic alleles which increase the risk of Alzheimer’s disease 10 fold (if you have two copies). One could make a sound ethical argument that if we have the ability to dramatically reduce burdensome diseases by editing the human genome, we have a moral obligation to do so.
Consider our rising health care costs. Gene editing may become the most cost effective health care intervention since vaccines.
We will likely progress from eliminating genetic diseases to reducing genetic predisposition to diseases. The next line to cross is genetic enhancement. Right now that is a bright line, and there is a moratorium on genetic changes that are intended to enhance humans. But, in reality, there is a fine line between disease prevention and health enhancement. What about children who are destined to be in the 5th percentile for height? Is extreme shortness a disease? Would editing their genes to give them average height be treating a disorder or enhancing them?
My point is that the line is blurry. This does not necessarily lead to a slippery slope, but it could significant ease anxiety about the technology and uncomfortableness with altering human genes.
It is not a stretch to predict that eventually we will see gene editing as just another medical intervention, useful for therapeutic, enhancement, and even cosmetic purposes. The difference with germline editing is that it does affect the human population, not just the individual, so I can see indefinite limits on that technology. Perhaps there will always need to be laws that restrict germline editing to changes that enhance the overall health and well being of the human population, and does not risk or fundamentally alter humanity. Perhaps such editing will be permissible only if the subject is also sterilized, which may be increasingly acceptable if we continue to have an expanding population.
I am getting deep into speculation here, but it is interesting to think about how this technology will play out. The potential is almost unlimited. What if different nations see it as a way to compete with others. One country may decide they want to create the smartest scientists, for example. That will put pressure on other countries to ease their restrictions. We may seek international regulation on this issue, but a lot will depend on the future status of international organizations and law.
It will be fascinating to see how this plays out in the next 20 years or so. One thing is certain – gene editing is a powerful tool and we will make increasing use of this technology.