Genetically Engineering Humans Isn’t So Scary (Don’t Fear the CRISPR, Part 2)

Yesterday I outlined why genetically engineered children are not imminent. The Chinese CRISPR gene editing of embryos experiment was lethal to around 20% of embryos, inserted off-target errors into roughly 10% of embryos (with some debate there), and only produced the desired genetic change in around 5% of embryos, and even then only in a subset of cells in those embryos.

Over time, the technology will become more efficient and the combined error and lethality rates will drop, though likely never to zero.

Human genome editing should be regulated. But it should be regulated primarily to assure safety and informed consent, rather than being banned as it is most developed countries (see figure 3). It’s implausible that human genome editing will lead to a Gattaca scenario, as I’ll show below. And bans only make the societal outcomes worse.

1. Enhancing Human Traits is Hard (And Gattaca is Science Fiction)

The primary fear of human germline engineering, beyond safety, appears to be a Gattaca-like scenario, where the rich are able to enhance the intelligence, looks, and other traits of their children, and the poor aren’t.

But boosting desirable traits such as intelligence and height to any significant degree is implausible, even with a very low error rate.

The largest ever survey of genes associated with IQ found 69 separate genes, which together accounted for less than 8% of the variance in IQ scores, implying that at least hundreds of genes, if not thousands, involved in IQ. (See paper, here.) As Nature reported, even the three genes with the largest individual impact added up to less than two points of IQ:

The three variants the researchers identified were each responsible for an average of 0.3 points on an IQ test. … That means that a person with two copies of each variant would score 1.8 points higher on an intelligence test than a person with none of them.

Height is similarly controlled by hundreds of gene. 697 genes together account for just one fifth of the heritability of adult height. (Paper at Nature Genetics here).

For major personality traits, identified genes account for less than 2% of variation, and it’s likely that hundreds or thousands of genes are involved.

Manipulating IQ, height, or personality is thus likely to involve making a very large number of genetic changes. Even then, genetic changes are likely to produce a moderate rather than overwhelming impact.

Conversely, for those unlucky enough to be conceived with the wrong genes, a single genetic change could prevent Cystic Fibrosis, or dramatically reduce the odds of Alzheimer’s disease, breast cancer or ovarian cancer, or cut the risk of heart disease by 30-40%.

Reducing disease is orders of magnitude easier and safer than augmenting abilities.

2. Parents are risk averse

We already trust parents to make hundreds of impactful decisions on behalf of their children: Schooling, diet and nutrition, neighborhood, screen time, media exposure, and religious upbringing are just a few.  Each of these has a larger impact on the average child – positive or negative – than one is likely to see from a realistic gene editing scenario any time in the next few decades.

And in general, parents are risk averse when their children are involved. Using gene editing to reduce the risk of disease is quite different than taking on new risks in an effort to boost a trait like height or IQ. That’s even more true when it takes dozens or hundreds of genetic tweaks to make even a relatively small change in those traits – and when every genetic tweak adds to the risk of an error.

(Parents could go for a more radical approach: Inserting extra copies of human genes, or transgenic variants not found in humans at all. It seems likely that parents will be even more averse to venturing into such uncharted waters with their children.)

If a trait like IQ could be safely increased to a marked degree, that would constitute a benefit to both the child and society. And while it would pose issues for inequality, the best solution might be to try to rectify inequality of access, rather than ban the technique. (Consider that IVF is subsidized in places as different as Singapore and Sweden.) But significant enhancements don’t appear to be likely any time on the horizon.

Razib Khan points out one other thing we trust parents to do, which has a larger impact on the genes of a child than any plausible technology of the next few decades:

 “the best bet for having a smart child is picking a spouse with a deviated phenotype. Look for smart people to marry.”

3. Bans make safety and inequality worse

A ban on human germline gene editing would cut off medical applications that could reduce the risk of disease in an effort to control the far less likely and far less impactful enhancement and parental control scenarios.

A ban is also unlikely to be global. Attitudes towards genetic engineering vary substantially by country. In the US, surveys find 4% to 14% of the population supports genetic engineering for enhancement purposes. Only around 40% support its use to prevent disease. Yet, As David Macer pointed out, as early as 1994:

in India and Thailand, more than 50% of the 900+ respondents in each country supported enhancement of physical characters, intelligence, or making people more ethical.

While most of Europe has banned genetic engineering, and the US looks likely to follow suit, it’s likely to go forward in at least some parts of Asia. (That is, indeed, one of the premises of Nexus and its sequels.)

If the US and Europe do ban the technology, while other countries don’t, then genetic engineering will be accessible to a smaller set of people: Those who can afford to travel overseas and pay for it out-of-pocket. Access will become more unequal. And, in all likelihood, genetic engineering in Thailand, India, or China is likely to be less well regulated for safety than it would be in the US or Europe, increasing the risk of mishap.

The fear of genetic engineering is based on unrealistic views of the genome, the technology, and how parents would use it. If we let that fear drive us towards a ban on genetic engineering – rather than legalization and regulation – we’ll reduce safety and create more inequality of access.

I’ll give the penultimate word to Jennifer Doudna, the inventor of the technique (this is taken from a truly interesting set of responses to Nature Biotechnology’s questions, which they posed to a large number of leaders in the field):

Doudna, Carroll, Martin & Botchan: We don’t think an international ban would be effective by itself; it is likely some people would ignore it. Regulation is essential to ensure that dangerous, trivial or cosmetic uses are not pursued.

Legalize and regulate genetic engineering. That’s the way to boost safety and equality, and to guide the science and ethics.


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