JULY 3, 2019
TWO BOOKS THIS YEAR with “hacking” in their title — Hacking the Code of Life and Hacking Darwin — prompt the thought that this might be the defining trait of Homo sapiens. From our earliest days, we saw trees and thought, “Hack them down and we can make shelters”; wool on a sheep, hide on a cow? — “They’ll do for clothing.” With time, our hacking has become more subtle. Long before we ever saw the image of an atom, we were making molecules never intended by nature, like those pesky plastics now contaminating the planet. We have bent the electromagnetic spectrum to carry our voices, text, and pictures to any pinpoint on the globe. Those who yearn for humans to return to something like a natural state should recognize that being human means “not natural” — we are a rogue species that has always flouted every natural norm.
I wrote those words before I had seen Nessa Carey’s book, and was pleased to note that she uses the same trope in the introduction: “A human is a person who hacks stuff about.” Her mock name for the species is Persona hackus. But there’s hacking and hacking: these books are about the deepest cuts of all — into the heart of life itself. Genetic engineering has been with us since 1982 — when insulin, instead of being extracted from the pancreases of cows, sheep, and pigs, was made in bioreactor vats from the human insulin gene inserted into a bacterium or yeast. Such techniques are developing all the time, the latest being the precision gene-editing tool CRISPR-Cas9, discovered in 2012 and already transforming pure biology and therapeutics. More accurate than any previous technique, CRISPR is also cheap and easy to use. This ability to manipulate genes has gone hand in hand with the revolution in genome sequencing — a single genome now costs around $700 (and in recent promotions has been sold for as little as $199) against the three billion dollars spent (over 13 years) to produce the first reference Human Genome.
“After such knowledge, what forgiveness?” T. S. Eliot’s hand-wringing is relevant here. Jamie Metzl is a futurist focusing in his book on the genetic enhancement of human beings. He gives it a fiendish twist: in 2012, John Gurdon and Shinya Yamanaka won the Nobel Prize for showing how adult cells could be reprogrammed to become germ cells and hence potentially able to create a new adult. This technique has now produced live mice from adult skin cells. Metzl shows that, coupled with gene editing and standard IVF procedures, this same technique could in theory lead to a designer baby beyond our wildest nightmares. Experiments can already be done on directed, sped-up evolution in a test tube using bacteria or viruses. It has been used, for instance, to develop the best-selling drug Adalimumab to target autoimmune disorders.
This accelerated evolution is easy to achieve over a great many generations in bacteria and viruses because they reproduce every 30 minutes or so. Metzl shows how the average human generation span of 28 years is a drawback if genetic improvement is the aim. Using IVF to produce the best offspring obtainable from two parents (according to available genomic information), if coupled with the Gurdon-Yamanaka process, could theoretically enable another selection cycle derived from the newly constructed embryo without allowing it ever to become a human being … and then another cycle, and so on for as long as you like (or can afford) until some notional perfection is achieved. This form of reproductive cycle without adults has already been achieved in mice. For technical reasons, this generational cycle wouldn’t quite match that of the bacteria, but Metzl estimates that 56 generations could be packed into the 28 years of a single natural generation: a leap equivalent to the time that has elapsed since Kublai Khan (who died in 1294). This technique, he suggests, might be able to create geniuses with an IQ of 1000. Ethics aside, to me this is a meaningless concept.
The idea of breeding geniuses has always been a goal of fascism. Is there a nice, modern way to do it? No — I don’t think there is. The world produces enough geniuses as it is, and quite a few of them are evil. Having raised alarmingly far-fetched ideas, Metzl himself acknowledges that “in a world where differences of opinion and belief are so vast and levels of development so disparate, [this technique] has the potential, at least if we’re not careful, to be cataclysmic.”
Nessa Carey, author of the second book with hacking in its title, is by contrast not a futurist. Her background is in the biotech and pharmaceutical industry. She discusses the here and now and the near future, extrapolating from the techniques currently under practical development. She is an excellent, brisk guide to what is likely to happen as opposed to the fantastically remote. Perhaps the most telling passages in her book are not about the techniques but the extreme human obduracy and contrariness that has been obstructing them.
Genetic modification has managed to get people in a twist that you could hardly make up. As she recounts, the ability to alter genomes arrived in 1973, when Herbert Boyer and Stanley Cohen used bacterial restriction enzymes as molecular scissors to cut DNA in particular locations. Synthetic insulin arrived a scant nine years later. In the realm of foodstuffs, new breeds of plants have long been produced by irradiation. This causes random scattergun mutations, some of which, if beneficial, lead to new varieties. Many such are on the market.
Now, by using CRISPR-Cas9 editing, we can introduce the single change we want without those scattergun effects. In some quarters — Europe especially, which is quite a large domain — environmental lobbies deem this to be just another version of the Genetic Modification (GM) they deplore, fear, and, in the case of foodstuffs, have managed to ban.
So we have a scenario in which genetically identical products are not treated identically because one has been produced by irradiation (that’s okay?) and the other by precise gene editing (that’s unacceptable!). What is especially provoking is that radiation was always the prime Frankenstein fear factor. Gene editing apparently renders it cozy and harmless!
In the case of animals, the situation is even more bizarre. There are grotesque breeds of cattle such as Belgian Blue that have enormous double-banked muscles. The cause is a mutation that truncates the gene for the anti-growth protein somatostatin. With this brake off, the muscles pile on. The Belgian Blue was created first by natural crossbreeding, but now the identical mutation can be introduced by CRISPR: the genomes are identical. To circumvent the embarrassment caused by the identity of these products, anti-GM lobbies have asked for an alien genetic tag to be introduced into CRISPR-edited foodstuffs to label them as GM. This is akin to that notorious placard plonked, according to legend, in the middle of a field with the sole notice: “Do not throw stones at this sign.”
Reading about this, one wonders if it would not be better to stop the research now and institute a crash program in common sense and scientific logic: attendance compulsory. Between Metzl’s fantasies of IQ 1000 and the twisted logic of the anti-GM lobby, one has to fear that we aren’t yet ready for science that cuts so deep.
But the work won’t stop, of course. Gene editing is now producing therapies for horrific genetic diseases, especially those such as cystic fibrosis that are caused by a single mutation. The most ingenious application so far has been the Friendly Mosquito (2002), engineered to combat malaria by means of a suicide gene that is timed to allow it to breed (and pass on its lethal genetic cargo) before the gene cuts in.
CRISPR is already solving many of the great puzzles of biology; it isn’t all about hard choices and terrible ethical dilemmas. Carey recounts one of the most delightful research conundrums: that of the creation of butterfly wing patterns. CRISPR has shown how nature “paints” by sketching an outline with one gene and then filling it with color by another: a sort of paint-by-numbers approach that I suggested in my 2009 book Dazzled and Deceived, before CRISPR was around to confirm it.
Carey finishes with an all-too-human story about the financial battles being waged over CRISPR technology. Two rival groups, each with a patent to protect, are fighting it out in the courts, racking up huge legal bills, because when the therapies, modified crops, and ecological interventions arrive in volume, the payoff will be enormous.
In 1944, the year penicillin was introduced, the world also learned that DNA was the chemical agent of inheritance; how it worked was still nine years away. Now, 66 years after Watson and Crick, we are taking control of the recipe for life. This all happened within a single lifetime. It is an awesome achievement, but that someone well informed in the science is drawn to speculation about creating a person with an IQ of 1000 suggests that we are no better prepared to use this knowledge wisely than we were for any of the other great discoveries that preceded it.