Can we genetically improve humans using George Church’s famous list?

“Why should only the big guys have access to the genes of the big guys? And why should only the smart guys have access to the smart genes?…our goal is to give as many people as possible the ability to choose their genes for themselves (and their descendants) rather than just accepting hereditary genetic inequality. Because genetics shouldn’t be a lottery.”

This is the pitch from Bootstrap Bio, a start-up which openly aims to one day offer future parents the possibility of genetically improving their children. I would argue that the children of anyone who could afford such a service will have already won the lottery of life, but the more immediate question is: could we really genetically enhance our children if we wanted to?

To get an idea of ​​what might be possible, I started with the list of “protective and enhancer” genetic variants maintained by biologist George Church of Harvard University. When I asked Church what the list was for, he said he started it as a response to questions raised at conferences, ranging from whether all rare genetic variants were harmful, to what kinds of genetic enhancements might be possible. The list is popular with transhumanists who want to use genetic engineering to create superhumans.

So, let’s take a look at what’s on there.

Do you really want extra fingers?

The list is rather mixed. It now contains more than 100 elements, but only about half are specific mutations or genetic variants that have been identified in humans and linked to specific effects (the rest are from animal studies or medical trials). Church selected mutations that could have an unusually large “positive effect,” from protecting against certain diseases to reducing male aggression.

To me, some of the traits on the list are anything but desirable. For example, it says unspecified changes in a gene could improve a person’s “manipulative ability” by giving them six fingers on each hand. Would it really be? Would you want six fingers even if you did? Imagine you are trying to buy gloves!

Also listed are two genetic deletions leading to insensitivity to pain. But this is not an improvement: we know that children who do not feel pain end up with horrible injuries.

Most of the other traits on the list fall into the “nice to have, but not worth the genetic engineering” category for me. Take “low odor production” – that hardly seems necessary in the age of deodorants. Sure, I wish I could hold my breath longer or do better at high altitude, but I’m not sure any of my descendants would care.

Only a few variations on the list were associated with broadly attractive characteristics such as living longer or having higher intelligence – that is, the kinds of things that wealthy would-be parents might pay for. But we’re still very far from the point where we could be sure that engineering these variants into children would actually make them smarter or live longer. We simply don’t know enough.

Designed to sleep less – but at what cost?

For starters, it may be that some of these associations are spurious, that some genetic variants don’t have the effects we think they do. Or, they could have the desired effect only in association with certain other genetic variants.

What’s more, there are often compromises to be made. According to Church’s list, a variant associated with higher intelligence, for example, may increase the risk of going blind later in life, while resistance to norovirus could increase the risk of Crohn’s disease. I think I’d rather be a little more stupid and endure occasional bouts of norovirus. You might feel differently — and your future children might end up thanking or cursing any choices like this you make on their behalf.

No downsides are noted for most of the variations on the list, but that doesn’t mean there aren’t any. Take for example the variations associated with sleeping less. Given the vital importance of sleep for brain health, it seems very likely to me that there are tradeoffs to be made.

What I think many people don’t realize is that not only is our understanding of genetic variants like these in its infancy, but that in many cases we can never be sure that a specific change will be beneficial. Indeed, to determine the positive and negative effects of a genetic variant, biologists must examine tens of thousands of people who have it, or even more.

How can we really make the lottery of life fairer

This means that to maximize the chances that an individual could actually benefit from genetic engineering, dozens or even hundreds of changes would have to be made at once. This is especially true for the traits mentioned by Bootstrap Bio, as size and intelligence are determined by hundreds of variants that each have a minimal effect. The problem is that we don’t yet have the capacity to safely make a few changes to human embryos, let alone hundreds at a time, as I explained in my previous column on preventing hereditary diseases.

I’m not saying all this because I’m opposed to the genetic enhancement of our children. On the contrary, I’m in favor of it – it’s better than letting children’s fates be determined by random rolls of the genetic dice. But I am very far from convinced that we should attempt hereditary genome editing any time soon. And to get to the point where we could seriously consider it, we don’t need start-ups like Bootstrap Bio. What we need is a massive expansion of studies like the UK Biobank, which follows large numbers of people over several decades, to get a much clearer picture of the pros and cons of genetic variants like those on Church’s list.

As for the idea that companies selling genetic enhancements make the world a fairer place, dismiss the other. A fifth of children born in the world today end up smaller than they should be and with impaired cognitive abilities because they are not nourished properly. Even more do not receive a good education. Anyone seriously concerned about lottery-robbing an infant’s life chances might want to focus on ensuring that these millions of children can reach their existing genetic potential, rather than trying to boost the genes of a few.