Imagine that mad scientists defied nature and violated the barriers between species. They injected human DNA into non-human creatures, altering their genomes into chimeras–unnatural fusions of man and beast. The goal of the scientists was to enslave these creatures, to exploit their cellular machinery for human gain. The creatures began to produce human proteins, so many of them that they become sick, in some cases even dying. The scientists harvest the proteins, and then, breaching the sacred barrier between species yet again, people injected the unnatural molecules into their own bodies.
This may sound like a futuristic nightmare, the kind that we will only experience if we neglect our moral compass and let science go berserk. But it is actually happening right now. Today millions of people with diabetes will inject themselves with insulin that was produced by E. coli.
The fact that no one is disturbed by this state of affairs says a lot. It’s like the curious incident of the dog in the night-time Sherlock Holmes notes in the story “Silver Blaze.” When a Scotland Yard detective replies, “The dog did nothing in the night-time,” Holmes replies, “that was the curious incident.” But thirty years ago the dog was barking loudly.
In the early 1970s, a handful of scientists realized that they might be able to insert genes from other species into E. coli. They chose E. coli because, as I explain in my book Microcosm, it was the organism they knew best. With that knowledge came the power to manipulate it. Scientists figured out how to use some enzymes made by E. coli to snip segments of DNA out of the cells of animals. Then they loaded the segments onto tiny rings of DNA called plasmids, and injected the plasmids into E. coli. In 1973 Herbert Boyer, a biologist at the University of California, San Francisco, announced that he and his colleagues had endowed E. coli with DNA from an African clawed frog.
Boyer and others wondered if engineered E. coli might not just be able to carry alien DNA. Maybe it could read those new genes and make proteins from them. The bacteria could become biochemical factories.
A race began. Boyer and colleagues in California vied with a team of Harvard scientists headed by Walter Gilbert to be the first to engineer E. coli carrying the human insulin gene. At the time, diabetics could only get their insulin from the pancreases of pigs. E. coli might be able to create it in vast amounts from little more than sugar. By 1980 the race was won: Boyer’s team had created an insulin-spewing E. coli. Their start-up company, Genentech, passed on the bugs to the pharmaceutical giant Eli Lilly, which breeding it in gigantic fermentation tanks.
In those few frenzied years of scientific research, the world shuddered at the thought of E. coli carrying alien genes. It could trigger unspeakable disasters, they thought. Insulin-producing E. coli might escape from their tanks, take up residence in people’s guts, and cause epidemics of diabetic comas. They might spread cancer viruses, or some other unnatural plague. Erwin Chargaff, an eminent Columbia University biologist, called genetic engineering “an irreversible attack on the biosphere.”
“The world is given to us on loan,” he warned. “We come and we go; and after a time we leave earth and air and water to others who come after us. My generation, or perhaps the one preceding mine, has been the first to engage, under the leadership of the exact sciences,in a destructive colonial warfare against nature. The future will curse us for it.”
At the same time, people warned that we were doing the unnatural, something that humans were not meant to do. “We can now transform that evolutionary tree into a network,” declared Robert Sinsheimer, a biologist at the University of California, Santa Cruz. “We can merge genes of most diverse origin–from plant or insect, from fungus or man as we wish.”
It was not a power that Sinsheimer thought we could handle. “We are becoming creators–makers of new forms of life–creations that we cannot undo, that will live on long after us, that will evolve according to their own destiny. What are the responsibilities of creators–for our creations and for all the living world into which we bring our inventions?”
Engineering E. coli came to be known as the Frankenstein project. The protests sometimes took on almost religious tones. Tampering with DNA, the MIT biologist Jonathan King declared, was “sacrilegious.” Two political activists, Ted Howard and Jeremy Rifkin, condemned genetic engineering in a book called Who Should Play God?
It is striking to look back at this controversy from 2008. We suffered no epidemic of diabetic comas, no cancer viruses spread by E. coli from host to host. None of the dire warnings about engineered E. coli, in fact, came to pass. It appears that the safeguards put in place were good enough, and that engineered E. coli could not compete with its wild cousins. Scientists continued to engineer E. coli, and today it can make all manner of substances, from blood-thinners to jet fuel.
Despite all these bacteria suffering the indignity of being violated with human genes, no one seems to care. No one thinks the dignity of E. coli has been compromised. I have not heard of anyone refusing blood-thinners or insulin because it was produced from human genes put inside another species. In Europe, where protests over genetically modified plants and animals rage today, few seem to be bothered by the fact that a lot of cheese is produced with a cow’s enzyme, chymosin, made by E. coli rather than cows. In fact, this cheese is labeled organic, because it’s produced with “real” chymosin, rather than “artificial” chemicals.
I think that the story of engineered E. coli is an important one to bear in mind these days. Today we are faced with intense debates about whether it’s right to create chimeras–a mouse that carries human neurons, for example. Headlines assault us with the danger that scientists will be playing God by creating life from scratch. We are revisiting old ground.
There’s no question that scientists must think carefully about the potential risks of engineered organisms. And we must beware that we don’t try to use genetic engineering to fix problems it can’t fix. Diabetes can be controlled with insulin from E. coli, but it can’t be cured with biotechnology. In fact, diabetes has exploded since Lilly started producing the stuff from bacteria.
But it’s also important to bear in mind how easy it is to be terrified by a science-fiction caricature of what’s really going on in synthetic biology labs. We have a profound distrust of what seems unnatural, such as crossing species boundaries. Yet a casual glance at E. coli’s genome demonstrates that nature has been inserting foreign genes into it by the hundreds for millions of years. Our own genome is not immune from these violations. We carry the remains of thousands of viruses in our DNA, and most people on Earth may even carry genes inherited from another species of human–Neanderthals. We may be disgusted by the thought of violating species boundaries because of deeply ingrained instincts. But that disgust is an unreliable guide to the realities of biology, whether that biology is in E. coli or in ourselves.
[Picture: "The Young Family," by Patrician Piccini (2002-3). Wikipedia]