randombio.com | science commentary
Friday, April 08, 2016

Jurassic Park for Humans

Manipulating the human genome is the ultimate grab for power. It would be the biggest gamble mankind has ever taken.

J ust because we are civilized does not mean evolution is not happening. Our transition from hunter-gatherers to farmers produced big changes in our genome. Industrialization and urbanization are producing even bigger changes. Our transformation to a highly technological society will produce still more.

We think of evolution as being slow, but it's not. Small differences in survival rates can quickly eliminate a trait or make it universal. The rate at which this happens is easy to calculate: if a trait provides 20% fewer offspring, the number of descendants bearing that trait is cut in half in four generations and cut by 99% in twenty. Within 100 generations it is eliminated entirely. That's a blink of an eye for nature.

This does not mean that we could turn into frogs. If we could talk to someone from a thousand years ago, in many ways we'd recognize them as the same as us, just as cars of today outwardly resemble those of fifty years ago. But if we looked under the hood, so to speak, we might be shocked at how different we are.

In violent times, warlike behavior improves our chances of survival. In peaceful times, cooperative behavior improves it. Some people fantasize about eliminating our warlike, cruel traits—reprogramming human nature to fit into our current social niche. But if a trait is there, it's because it helped us to survive. Removing it might not do too much harm now, but sooner or later a crisis will occur and the loss of that programming could be devastating.

Darwin taught that organisms evolve to maximize their genetic fitness. But many people misunderstood what that means. Fitness is not the same as physical fitness or strength. It is a parameter in a giant equation with three billion variables, which evolution automatically uses to maximize our chances for survival.

DNA double helix
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Nature has no moral sense, no knowledge of good and evil. It does not care whether we survive or die out. Nature is mindless and inanimate. There could be some environment where fitness means being frail, stupid and physically weak. In the cold equation of nature, all that counts are numbers.

Evolution is part of nature, and its principles apply not just to DNA but to culture as well. We value courage, strength, and intelligence not because we are virtuous, but because the societies of those who did not value them did not survive. The beauty of nature is that it can act as though it has a sense of right and wrong and a purpose even though it does not.

The incredible complexity of these little molecules, the result of billions of years of nature solving the equation of life, is such that even the most materialist scientist regards them as magical, almost biblical in their majesty.

But our equation is never static. If we changed one base in our DNA, the change would spread out among the other three billion bases, like ripples in a pond, as that one mutation changed how we interact with the world, until a new, stable solution was found. We are light years from understanding how this works.

That is why it would be madness to use DNA technology to change the makeup of humans. To imprint the character traits we value today into our genome would record for all time the silliness of our social values: we might condemn future generations to act like little snowflakes who cling to their teddy bears and hide in their safe spaces like some of today's college students. Or we could create a world where everyone looks and sounds like Rambo and we all walk around wearing bandoliers and carrying M60 machine guns.

But we also recognize that some traits are essential for our survival. Thus, despite the dangers, we will be compelled to try. We can learn from the mistakes[1][2] nature itself has made in our struggle with malaria.

Malaria is a strong force for evolution in human populations: even today, 77 years after DDT was invented, over a million people a year still die from it. Malaria and humans co-evolve[3], and this accounts for several genetic conditions: pyruvate kinase deficiency, alpha- and beta-thalassemia, blood group O, hemoglobin E mutations, hereditary spherocytosis[4], G6PD deficiency, sickle cell anemia, and southeast Asian ovalocytosis (SAO)[5]. These are all genetic changes that protect against malaria. Some are fatal, some are not.

Mathematicians know that equations can get stuck in local minima, where the solution is far from optimal but every change requires a change for the worse. The only way out of a local minimum is to take several steps ‘uphill.’

Our susceptibility to malaria is one example. The mutations that protect us against malaria are nature's ways of escaping the local minimum. But finding a solution is enormously difficult, even for nature. Alpha(+)-thalassemia is caused by a mutation in pyruvate kinase. In individuals in which it co-occurs with the sickle cell trait the two mutations cancel out each other's protective benefit. This is called negative epistasis[6].

It's uncertain whether all the 180 different mutations that cause pyruvate kinase deficiency are maintained by the selective pressure of malaria. Even establishing whether they are protective is hard. The effect of introducing new mutations into our genome would be impossible to predict.

I'm not talking about somatic gene therapy, which will be a valuable and safe way of treating many diseases. There is a good argument for eliminating genetic disorders. But using the same technology to imprint our values or our ideas of attractiveness on our descendants is a big gamble.

It's like making a random cut in your body. You might get away with no consequences, or you might just nick an artery and die.

If we're lucky our changes will just do something trivial. We might make it impossible to pilot our flying cars or to walk and chew gum at the same time. Or we might condemn our descendants to hear an endless litany of snotty comments about the foolishness of the 21st century, like those poor bastards on Star Trek. Or we could split into two or more species.

Or we might condemn our mutant descendants to spend the next thousand years searching through old graveyards, fossil records, and ancient databases, frantically searching for clues about how to undo the catastrophe we have unleashed against ourselves.

In a worst case scenario we go extinct, and maybe 65 million years from now some other species comes along, wonders why we died out and what we were like, and clones us like the dinosaurs in Jurassic Park. The stakes are astronomical. But if I know humans we'll throw the dice anyway. It seems to be in our genes.


1. Table of genetic disorders www.kumc.edu/AMA-MSS/Study/table_of_genetic_disorders.htm

2. Genetic diseases www.geneticdiseasefoundation.org/genetic-diseases/

3. Pierre M. Durand, Theresa L. Coetzer (2008). Hereditary red cell disorders and malaria resistance. Haematologica 93: 961–963. Link

4. Da Costa L, Galimand J, Fenneteau O, Mohandas N. (2013). Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders. Blood Rev. 27(4):167–178. Pubmed

5. Liu SC, Palek J, Yi SJ, Nichols PE, Derick LH, Chiou SS, Amato D, Corbett JD, Cho MR, Golan DE. (1995). Molecular basis of altered red blood cell membrane properties in Southeast Asian ovalocytosis: role of the mutant band 3 protein in band 3 oligomerization and retention by the membrane skeleton. Blood 86(1):349–358. Pubmed

6. Penman BS, Habib S, Kanchan K, Gupta S. (2011). Negative epistasis between alpha(+) thalassaemia and sickle cell trait can explain interpopulation variation in South Asia. Evolution. 65(12):3625–3632. Pubmed

last updated apr 09 2016 4:45 am

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