



FRANKFURTER ALLGEMEINE ZEITUNG

15. August 2009

FEUILLETON GENETIC ENGINEERING



THE CURRENT CATALOG OF LIFE

[ Der Aktuelle Katalog Der Schöpfung Ist Da ]

By Ed Regis [ED. NOTE: Among the attendees of the recent Edge Master Class 2009 — A Short Course on Synthetic Genomics, was science writer Ed Regis (What Is Life?) who was commissioned by Frank Schirrmacher, Co-Publisher and Feuilleton Editor of Frankfurter Allgemeine Zeitung to write a report covering the event. A German translation of Regis's article was published on August 15th by FAZ along with an accompanying article. The original English language version is published below with permission.]

GENETIC ENGINEERING



THE CURRENT CATALOG OF LIFE

By Ed Regis In their futuristic workshops, the masters of the Synthetic Genomics, Craig Venter and George Church, play out their visions of bacteria reprogrammed to turn coal into methane gas and other microbes programmed to create jet fuel 14. August 2009 — John Brockman is a New York City literary agent with a twist: not only does he represent many of the world's top scientists and science writers, he's also founder and head of the Edge Foundation (www.edge.org), devoted to disseminating news of the latest advances in cutting-edge science and technology. Over the weekend of 24-26 July, in Los Angeles, Brockman's foundation sponsored a "master class" in which two of these same scientists — George Church, a molecular geneticist at Harvard Medical School, and Craig Venter, who helped sequence the human genome — gave a set of lectures on the subject of synthetic genomics. The event, which was by invitation only, was attended by about twenty members of America's technological elite, including Larry Page, co-founder of Google; Nathan Myhrvold, formerly chief technology officer at Microsoft; and Elon Musk, founder of PayPal and head of SpaceX, a private rocket manufacturing and space exploration firm which is housed in a massive hangar-like structure near Los Angeles International Airport. The first day's session, in fact, was held on the premises of SpaceX, where the Tesla electric car is also built. Synthetic genomics, the subject of the conference, is the process of replacing all or part of an organism's natural DNA with synthetic DNA designed by humans. It is essentially genetic engineering on a mass scale. As the participants were to learn over the next two days, synthetic genomics will make possible a variety of miracles, such as bacteria reprogrammed to turn coal into methane gas and other microbes programmed to churn out jet fuel. Still other genomic engineering techniques will allow scientists to resurrect a range of extinct creatures including the woolly mammoth and, just maybe, even Neanderthal man. The specter of "biohackers" creating new infectious agents made its obligatory appearance, but synthetic genomic researchers are, almost of necessity, optimists. George Church, one of whose special topics was "Engineering Humans 2.0," told the group that "DNA is excellent programmable matter." Just as automated sequencing machines can read the natural order of a DNA molecule, automated DNA synthesizing machines can create stretches of deliberately engineered DNA that can then be placed inside a cell so as to modify its normal behavior. Many bacterial cells, for example, are naturally attracted to cancerous tumors. And so by means of correctly altering their genomes it is possible to make a species of cancer-killing bacteria, organisms that attack the tumor by invading its cancerous cells, and then, while still inside them, synthesizing and then releasing cancer-killing toxins.



Church and his Harvard lab team have already programmed bacteria to perform each of these functions separately, but they have not yet connected them all together into a complete and organized system. Still, "we're getting to the point where we can program these cells almost as if they were computers," he said. But tumor-killing microbes were only a small portion of the myriad wonders described by Church. Another was the prospect of "humanized" or — even "personalized" — mice. These are mammals whose genomes are injected with bits of human DNA for the purpose of getting the animals to produce disease-fighting antibodies that would not be rejected by humans. A personalized mouse, whose genome was modified with some of your very own genetic material, would produce antibodies that would not be rejected by your own body. Beyond that is the possibility of creating synthetic organisms that would be resistant to a whole class of natural viruses. There are two ways of doing this, one of which involves creating DNA that is a mirror-image of natural DNA. Like many biological and chemical substances, DNA has a chirality or handedness, the property of existing in either left-handed or right-handed structural forms. In their natural state, most biological molecules including DNA and viruses are left-handed. But by artificially constructing right-handed DNA, it would be possible to make synthetic living organisms whose DNA is a mirror-image of the original. They would be resistant to conventional enzymes, parasites, and predators because their DNA would not be recognized by the mirror-image version. Such synthetic organisms would constitute a whole new "mirror-world" of living things. Church is also founder and head of the Personal Genome Project, or PGP. The project's purpose, he said, is to sequence the genomes of 100,000 volunteers with the goal of opening up a new era of personalized medicine. Instead of today's standardized, one-size-fits-all collection of pills and therapies, the medicine of the future will be genomically tailored to each individual patient, and its treatments will fit him or her as well as a made-to-order suit of clothes. Church also speculated that knowledge of the idiosyncratic features that lurk deep within each of our genomes — genetic differences that give rise to every person's respective set of individuating traits — will bring us an unprecedented level of self-understanding, and, therefore, will allow us to chart a more intelligent and informed course through life. Toward the end of the first day Elon Musk, for whom the word charismatic could have well been coined, described a genomic transformation of another type. While a video of his Falcon 1 rocket being launched from the Kwajalein Atoll in the South Pacific played in the background, Musk spoke about sending the human species to the planets. That might have seemed an unrealistic goal were it not for the fact that on 13 July, just twelve days prior to the Edge event, SpaceX had successfully launched another Falcon 1 rocket that had placed Malaysia's RazakSAT into Earth orbit. Earlier, competing against both Boeing and Lockheed, SpaceX had won NASA's Commercial Orbital Transportation Services competition to resupply cargo to the International Space Station. Then, like an emperor leading his subjects, Musk gave the conference attendees a tour of his spacecraft manufacturing facility. We saw the rocket engine assembly area, several launch vehicle components under construction, the mission operations area, and an example of the company's Dragon spacecraft, a pressurized capsule for the transport of cargo or passengers to the ISS. "This is all geared to extending life beyond earth to a multiplanet civilization," Musk said of the spacecraft. Suddenly, his particular version of the future was no longer so unbelievable. The leadoff speaker on the second and last day of the conference was J. Craig Venter, the human genome pioneer who more recently cofounded Synthetic Genomics Inc., an organization devoted to commercializing genomic engineering technologies. One of the challenges of synthetic genomics was to pare down organisms to the minimal set of genes needed to support life. Venter called this "reductionist biology," and said that a fundamental question was whether it would be possible to reconstruct life by putting together a collection of its smallest components. Brewer's yeast, Venter discovered, could assemble fragments of DNA into functional chromosomes. He described a set of experiments in which he and colleagues created 25 small synthetic pieces of DNA, injected them into a yeast cell, which then proceeded to assemble the pieces into a chromosome. The trick was to design the DNA segments in such a way that the organism puts them together in the correct order. It was easy to manipulate genes in yeast, Venter found. He could insert genes, remove genes, and create a new species with new characteristics. In August 2007, he actually changed one species into another. He took a chromosome from one cell and put it into different one. "Changing the software [the DNA] completely eliminated the old organism and created a new one," Venter said. Separately, Venter and his group had also created a synthetic DNA copy of the phiX virus, a small microbe that was not infectious to humans. When they put the synthetic DNA into an E. coli bacterium, the cell made the necessary proteins and assembled them into the actual virus, which in turn killed the cell that made it. All of this happened automatically in the cell, Venter said: "The software builds its own hardware." These and other genomic creations, transformations, and destructions gave rise to questions about safety, the canonical nightmare being genomically engineered bacteria escaping from the lab and wreaking havoc upon human, animal, and plant. But a possible defense against this, Venter said, was to provide the organism with "suicide genes," meaning that you create within them a chemical dependency so that they cannot survive outside the lab. Equipped with such a dependency, synthetic organisms would pose no threat to natural organisms or to the biosphere. Outside the lab they would simply die. That would be good news if it were true, because with funding provided by ExxonMobil, Venter and his team are now building a three to five square-mile algae farm in which reprogrammed algae will produce biofuels. "Making algae make oil is not hard," Venter said. "It's the scalability that's the problem." Algae farms of the size required for organisms to become efficient and realistic sources of energy are expensive. Still, algae has the advantage that it uses CO2 as a carbon source — it actually consumes and metabolizes a greenhouse gas — and uses sunlight as an energy source. So what we have here, potentially, are living solar cells that eat carbon dioxide as they produce new hydrocarbons for fuel. George Church had the final say in a lecture entitled "Engineering Humans 2.0." Human beings, he noted, are limited by a variety of things: by their ability to concentrate and remember, by the shortness of their lifespans, and so on. Genomic engineering could be used to correct all these deficiencies and more. The common laboratory mouse, he noted, had an average lifespan of 2.5 years. The naked mole rate, by contrast, lives ten times longer, to the ripe old age of 25. It would be possible to find the genes that contributed to the longevity of the naked mole rat, and by importing those genes into the lab mouse, you could slowly increase its longevity. An analogous process could also be tried on human beings, increasing their lifespans and adding to their memory capacity, but the question was whether it was wise to do this. There were always trade-offs, Church said. You may engineer humans to have bigger and stronger bones, but only at the price if making them heavier and more ungainly. Malaria resistance is coupled with increased susceptibility to sickle cell anemia. And so on down the list. In a conference characterized by an excess of excess, Church provided a welcome cautionary note. But then he proceeded to pull out all the stops an argued that by targeted genetic manipulation of the elephant genome it might be possible to resurrect the woolly mammoth. And by doing the same to the chimpanzee genome, scientists could possibly resurrect Neanderthal man. "Why would anyone want to resurrect Neanderthal man?" a conference participant asked. "To create a sibling species that would give us a fresh outlook on ourselves," Church answered. Humans were a monoculture, he said, and monocultures were biologically at risk. His answer did not satisfy all of those present. "We already have enough Neanderthals in Washington," Craig Venter quipped, thereby effectively bringing the Edge Master Class 2009 to a close.



Ed Regis is the author of several science books, most recently, What Is Life? Investigating the Nature of Life in the Age of Synthetic Biology [Permalink]