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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


SUEDDEUTSCHE ZEITUNG
August 13 , 2009
FEUILLETON

THE WALKMAN OF GENETIC ENGINEERING: THE MOVE FROM SCIENCE TO A NEW WORLD OF PRODUCTS

[Walkman der Gentechnik; Der Schritt von der Wissenschaft zu einer neuen Warenwelt]

By Andrian Kreye,
Editor, The Feuilleton, Sueddeutsche Zeitung

...Genetic engineering is now at a point where computer science was around the mid-eighties. The early PCs were limited as to purpose and network. In two and a half decades, the computer has led us into a digial world in which every aspect of lives has been affected. According to Moore's Law, the performance of computers doubles every 18 months. Genetic engineering is following a similar growth. On the last weekend in July, Craig Venter and George Church met in Los Angeles to lead a seminar on synthetic genetic engineering for John Brockman's science forum Edge.org.

Genetic engineering under Church has been following the grwoth of computer science growing by a factor of tenfold per year. After all, the cost of sequencing a genome dropped from three billion dollars in 2000 to around $50 000 dollars as Stanford University's Dr. Steven Quake genomics engineer announced this week. 17 commercial companies already offer similar services. In June, a "Consumer Genetics" exhibition was held in Boston for the first time. The Vice President of Knome, Ari Kiirikki, assumes that the cost of sequencing a genome in the next ten years will fall to less than $1,000. In support for this development, the X-Prize Foundation has put up a prize of ten million dollars for the sequencing of 100 full genomes within ten days for the cost of less than $10,000 dollars per genome sequenced.

It is now up to the companies themselves to provide an ethical and legal standing to commercial genetic engineering. The States of New York and California have already made the sale of genetic tests subject to a prescription. This is however only a first step is to adjust a new a new commercialized science which is about to cause enormous changes similar to those brought about be computer science. Medical benefits are likely to be enormous. Who knows about dangers in its genetic make-up, can preventive measures meet. The potential for abuse is however likewise given. Health insurances and employers could discriminate against with the DNS information humans. Above all however our self-understanding will change. Which could change, if synthetic genetic engineering becomes a mass market, is not yet foreseeable. For example, Craig Venter is working on synthetic biofuels. If successful, such a development would re-align technology, economics and politics in a fundamental way. Of one thing we can already be certain. The question of whether genetic engineering will becomes available for all is no longer on the table. It has already happened.


SPIEGEL ONLINE
13.08. 2009
FEUILLETON-PRESSESCHAU

HEUTE IN DEN FEUILLETONS

Süddeutsche Zeitung, 13.08.2009

Von aktuellen Entwicklungen aus der schönen neuen Welt der Genom-Sequenzierung berichtet Andrian Kreye: "Am letzten Juliwochenende trafen sich Craig Venter und George Church in Los Angeles, um für John Brockmans Wissenschaftsforum Edge.org ein Seminar über synthetische Gentechnik zu leiten. Die Gentechnik, so Church, habe die Informatik dabei längst hinter sich gelassen und entwickle sich mit einem Faktor von zehn pro Jahr. Immerhin - der Preis für die Sequenzierung eines Genoms ist von drei Milliarden Dollar im Jahr 2000 auf rund 50.000 Dollar gefallen, wie der Ingenieur der Stanford University Dr. Steven Quake diese Woche bekanntgab. 17 kommerzielle Firmen bieten ihre Dienste schon an."


Nearly impossible to put down: engaging original essays from brilliant young scientists on their work — and its fascinating social, ethical, and philosophical implications. The Barnes & Noble Review Long List

The engrossing essay collection which offers a youthful spin on some of the most pressing scientific issues of today—and tomorrow...Kinda scary? Yes! Super smart and interesting? Definitely. The Observer's Very Short List

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WHAT'S NEXT?
Dispatches on the Future of Science
Edited By Max Brockman

If these authors are the future of science, then the science of the future will be one exciting ride! Find out what the best minds of the new generation are thinking before the Nobel Committee does. A fascinating chronicle of the big, new ideas that are keeping young scientists up at night. Daniel Gilbert, author of Stumbling on Happiness

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John Brockman, Editor and Publisher
Russell Weinberger, Associate Publisher

Alexandra Zukerman, Editorial Assistant
contact: editor@edge.org

Copyright © 2009 By Edge Foundation, Inc
All Rights Reserved.

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