Dopers vs superhumans

Today I achieve a long held ambition of mine, which is to find a way of talking about my obsession with doping in sport – in the context of the world’s next tech breakthrough.

This is part three, by the way, in a series of pieces I’ve written to talk about CRISPR – the gene editing technology I wrote about in The Exponentialist (free copy here) and something I believe is going to define the next century.

We’ve already discussed how CRISPR fits into a pattern of other adaptive world-changing technologies, like the steam engine, the silicon computer chip or the internal combustion engine.

And yesterday we talked about how CRISPR is flexible enough to be wielded in any number of ways, from fighting disease to increasing crop yield.

Today I want to take look beyond even that, and explore some of the logical conclusions of being able to reshape and rewire living things in new ways. If you can edit your genes so your immune system is better able to spot and destroy cancer, what other improvements can be made?

Perhaps enhancements is a better word than improvements. Right now CRISPR is mostly being developed with fighting disease in mind. But there’s no logical reason, or physical constraint, stopping the technique being used to enhance our existing abilities.

Fight the instinct to consider that idea sci-fi or a vision of the far future. It may be nearer than you think. It may even already be happening…

Let’s dive in.

Superhuman technology

In the 1990s, a scientist called Lee Sweeney achieved some notoriety by developing what were termed “Schwarzenegger mice”.

Effectively, Sweeney found a way to isolate the gene responsible for muscle growth and repair in mice. It’s called IGF-1, if you’re interested. By isolating the gene Sweeney was able to breed mice that were 30% stronger than regular mice.

Effectively a race of supermice.

Fast forward to the 2008 Olympics and Sweeney was – according to some reports – getting calls from athletes asking if the technique could be adapted for humans.

You can see the appeal, in a weirdly perverted way. A certain percentage of athletes will seek out ways of bending the rules to cheat. That might be gaming the system, using corrupt doctors to allow you to use the rules to take performance enhancing drugs, or it might be taking illegal substances in the belief you won’t be caught.

Given dopers tend to be ahead of the testers, there’s logic to that. A new drug may not even be detectable, giving you a first-mover advantage.

But what if you push that idea even further: what if you hack your body to produce an increase in strength, speed or stamina? Rather than relying on outside intervention (drugs) that can be detected, you could instead change the makeup of your body itself in order to improve.

You could argue that’s what training is – forcing your body to adapt and improve. But you’re not changing your genetic code itself, using new medical techniques to do so. The two approaches are clearly different.

Here’s an example of what I’m talking about. EPO use was endemic in the cycling world in the 1990s and 2000s. EPO is a form of blood doping. It’s a drug that makes your body produce more red blood cells. More red blood cells enable you to carry more oxygen, which leads to an increase in performance. In a sport like cycling, that’s enough to mean an EPO user will almost always beat a non-EPO user over a three-week race.

But what if you could change your body’s genetic code so it automatically created an abnormal amount of red blood cells? Some people naturally have this advantage already, though it’s inherited rather than created. Is the next frontier of doping gene doping – teaching your body to do the work previously done by drugs?

You could debate whether we’ve actually gone beyond the frontier already, and some athletes are already using techniques like this – but that’s an argument for another day (in a pub, probably).

I bring this up because this, in a microcosm, is what gene editing could do to the world. Creating people who are genetically better, faster, stronger, smarter – whatever you like. If there’s a gene for it, it could theoretically be hacked, tweaked or enhanced.

I think that’s both tantalising and scary. But I think it’s a debate humanity is going to have, one way or another, in the coming decades. (I think you can get a head start on 99% of people by reading my book, but of course I’d say that.)

Today, I want to help you understand what all this means, or could mean, by sharing part of an interview my team did with one of the people behind CRISPR’s discovery, Professor George Church. I’ve reproduced it below.

And of course, if you find this kind of insight into world-changing technology valuable, you’ll love The Exponentialistget your free copy here.

Q: You are one of the chief developers of the CRISPR-Cas9 gene editing technology. Can you describe the technology and say how it was developed?

A (Professor George Church): In nature, it works to kill bacterial invading viruses by remembering previous invasions. It does that by keeping a little piece of the DNA from the [invading] virus, and then that makes it super easy for it to reprogram a cutting machine, the CRISPR nuclease. That’s what it does in nature.

Slowly, people adapted it. As a technology, it became editing: changing from killing viruses to editing DNA very precisely – not just making a mess, as you might with killing, with cutting, but replacing DNA. That was announced in January 2013 by two groups, mine and one of my ex-post-docs, Feng Zhang, who was by that time an independent investigator at the Broad Institute.

Soon thereafter, it became evident that, unlike some technologies which are hard, this one was easy. There is no way you could have predicted that. It’s easy to adapt to other organisms once you solve how to adapt it to humans, which is what we did first.

Q: Can you explain the implications and potential uses of this technology, now and in the future?

A: Any method of gene editing has some similarity to previous genetic engineering tools in what it can be applied to. Those applications include agriculture – plants and animals and to some extent microorganisms like fungi. It can be used for curing genetic diseases. It can be used for fighting infections, just like its original use for cutting viruses. It already is in use for fighting leukaemia and HIV-Aids. I’m being broad here, talking about genome editing – not just CRISPR.

It can be used for xenotransplantations – moving organs from pigs to humans – and making those pigs virus-resistant, or making a variety of things virus-resistant.

Finally, it can be used for gene drives, where you can engineer wild populations at low cost and high precision to fight diseases like malaria, dengue, lime disease and so on.

Q: You talk about the application of gene editing technology to cancer and HIV. Any other areas in human therapy where there could be breakthroughs?

A: Gene therapy is a big category that includes classically and typically inserting new genes. Then you can use more precise gene editing to both remove and insert, and that’s where CRISPR comes in.

There are 2,000 gene therapies in clinical trials, and many of those are already curing people. It doesn’t mean they’ve been approved for general use. They’re in the process of doing the gene therapy trials to get a fair number of people cured of, for example, blindness. There are some genetic causes of blindness that are curable by gene therapies. In most cases, you have to do it very early in life, like in young children – or else they’ll be able to cure them to the point where they can see light but they can’t interpret the light or stasis because their brains have developed too far.

There are other infectious agents like hepatitis viruses, blood diseases that cause hemolytic anemia – the list is long. There are thousands of genes that are so well understood that some of them can be addressed by genetic counselling. But once you have a child that has the disease, then you need to have some kind of cure or prevention for the development of downstream technologies.

Q: There are also potential risks and drawbacks. Can you talk about the risks related to CRISPR – for example, the risk of editing errors?

A: Almost every therapy has off-target effects, where it will affect something in addition to its target. Small molecule drugs do, protein drugs do, and CRISPR does.

The difference is that there are computer programs that help you design wherever CRISPR is targeting. If you use those well, then you can find something where there really is no off target. Furthermore, there are ways in which you can change the CRISPR enzyme that makes it much more specific. When you put all these together, you end up with, essentially, off-targets that are undetectable.

Now, that doesn’t mean they’re undetectable in any reasonable laboratory experiment. It doesn’t mean they’ll be undetectable if you started treating a billion people with it, or a billion animals or plants. But our bodies are constantly mutating due to radiation and other chemicals, chemotherapies and so forth. So CRISPR is way, way below the spontaneous rate of mutation.  Also, you can direct it. So it’s a fairly hypothetical risk.

I think the bigger risk than off-target mutation is the systems risk: that it does what it’s supposed to do, but what it’s supposed to do has ramifications. It’s the reason all new drugs are tested by FDA-approved chemical trials. You see whether all your theories and all your simple tests on animals play out in humans accurately in terms of safety and efficacy.

Q: There’s also a risk that parents in the future are going to want designer babies, and pick and choose their future children’s traits. How do you rate that risk?

A: Again, that’s a risk of all new technologies. If you want your child to have computers and cars and education and so on, all of these could backfire, and they provide the parent with an awful lot of decision-making dilemmas and power. This would be no exception. It’s not clear to me that it’s more powerful than these other things, because the genetics takes a long time to arrive. It takes 20 years to arrive – while giving the child a very powerful toy could cause damage right away.

With all these things, you have feedback where you see the impact on society. Usually the things that are hardest to reverse are things that are attractive to society, or some section of society. If we want to prepare ourselves for them, we need to have discussions like the one that we’re having right now. It shouldn’t be limited to a particular technology, but all ways in which parents can influence their children.

For more… just follow this link to get a free copy of The Exponentialist.


Nick O’Connor
Publisher, Southbank Investment Research

Category: Genetics and Biotechnology

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