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Whether Genetically Engineered Babies are Fact or Fiction Doesn’t Really Matter

Richard Gronostajski by Richard Gronostajski
11/30/18
in Opinion
He Jiankui

Chinese university professor He Jiankui posted a video on YouTube saying that the twin girls, born a few weeks ago, had their DNA altered to prevent them from contracting HIV. Photo: screenshot from the HE Lab video, Youtube

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There are some facts and a lot of speculation around the recent announcement of genetically engineered babies being born in China. The title of this article is to stress the point that whether this announcement is true or false, it is definitely time to be discussing the ethics and safety of genetic engineering of humans.

In many people’s minds, there are two major issues about the genetic engineering of humans: is it safe and is it ever ethically appropriate?

Benefit vs Risk

The safety issue should revolve around risk/benefit analysis. Is there a benefit great enough to overcome the inherent risk in the genetic engineering of human embryos? Unfortunately, at the present time, it is very difficult to quantify both the risks and the potential benefits. For example, changing a gene of interest in one population may have unforeseen consequences in another population, even if that change is already present.

Rack with test tubes
Chinese scientist He Jiankui claims to have created the world’s first genetically edited babies. Photo: AFP

In the field of mouse genetics, it is well known, though a rarely discussed phenomenon, that the same mutation in one inbred strain of mice might have a very different effect in another strain of mice. While two human populations are not as inbred as two mouse strains, they do differ in a number of genes. That is why we can trace ancestry by genetic analysis. Thus, even if the genetic engineering is perfect (which we know it isn’t), there could still be unforeseen interactions with the rest of the genome that would be dangerous.

Undetected secondary mutations, referred to as “off-target” events are also a source of concern. While it is theoretically possible to do whole genome sequencing on single edited cells of an embryo to test for off-target events, at the present time this isn’t practical.

Any testing other than whole-genome sequencing could allow off-target mutations to be present in the embryo and be propagated to the next generation. Are these off-target mutations any worse than the normal mutational load that every embryo already has from the sperm and egg that generated it? My personal feeling is that they aren’t significantly more dangerous than regular old random mutations, but that is a feeling without a lot of evidence. We need more evidence in my opinion before creating humans with potentially engineered genetic flaws.

AP Exclusive: Chinese researcher claims he helped make world's first genetically edited babies _ twin girls whose DNA he said he altered to try to help them resist possible future AIDS infections. There is no independent confirmation of his claim.https://t.co/cCL2QnLIjD

— The Associated Press (@AP) November 26, 2018

You may notice that I’ve left the benefits part out of this so far. That is also because quantifying benefits can be tricky. Theoretically, the benefit to the (possibly) newly born twins is that they might be more resistant to HIV and some other viral infections.

There is also some evidence that deletions in the CCR5 gene, the gene that was reportedly edited, may confer some resistance to multiple sclerosis (MS). But these benefits are not proven, and this study cannot demonstrate one way or another whether they actually occur. Even if they do occur, is this work, or any genetic engineering of humans, ethically appropriate?

Ethics in Eye of Beholder

Whether a particular act is considered ethical depends on quantifiable issues like risk/benefit analyses, and qualitative issues such as religious beliefs or worldviews.

In most well to do countries, rules have been put in place to try to protect innocent individuals from those who have power over them. For human clinical trials, informed consent must be given by patients to participate, and the potential risks and benefits must be spelled out in considerable detail.

A major question, however, is whether any unfair inducements are offered to the patients to get them to participate? In the case of this clinical trial, free IVF treatments were promised to the patients to convince them to participate. It is unclear whether such a powerful inducement would have been allowed by clinical trial oversight committees in most western countries. But the circumstances of these couples differ significantly from those of most well-off westerners, and we must be careful judging others by our standards.

So I suppose there are really again two questions to address: was gene editing ethically appropriate in this particular case (assuming it has actually happened) and is it ever justifiable and ethically appropriate?

To the former, I believe, after some thought, that it was not. There were too many inducements given to the participants and the potential benefits in my analysis don’t warrant the potential risk of the gene editing.

To the question whether it is ever justifiable and ethically appropriate, I have to be more open. While I cannot see why one would need to do gene editing on embryos, there may be in the future the need to do so. To justify this latter feeling I have to stress that gene editing is simply not needed to “cure” most genetic diseases.

If IVF is done with families, and mutated embryos are simply not implanted but non-mutated embryos are, then the disease gene doesn’t go the next generation. This would work with both recessive and dominant genes and no editing is required, just screening. Only if both parents were homozygous for a recessive gene this would not work, but that would be very rare. So I foresee very few instances in which gene editing would be ethically justifiable.

But just to throw out one thought, what if there were a way to eliminate most human cancer by genetic engineering?

There is the fairly famous gene TP53, that is mutated in most human cancers.  Theoretically, if we added another perfectly working copy of TP53 into the human genome it might make us resistant to most cancers. This experiment has already been done in mice successfully.

So if we could demonstrate that we could make it work in humans, would that be enough of a potential benefit to outweigh the potential risks?

I leave it to the readers to ponder. And it is for this reason that the title of this opinion piece has the phrase “it doesn’t really matter.” Because even if this particular case is a hoax, the time has come for all of us to be thinking about whether we, as mankind, want to participate in this brave new world of human genetic engineering.

Disclaimer: The views and opinions expressed here are those of the author and do not necessarily reflect the editorial position of The Globe Post.
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Richard Gronostajski

Richard Gronostajski

Professor of Biochemistry at the University at Buffalo (UB), Founder and Head of the Developmental Genomics Group at the New York State Center of Excellence in Bioinformatics and Life Sciences, and Director of both the Western New York Stem Cell Culture and Analysis Center and the Genetics, Genomics and Bioinformatics Graduate Program at UB

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