Designer organisms to serve man

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Syed Fattahul Alim
After destruction of the natural environment over the last three centuries, man has come to realise what he has done. He made bold claims that the forces of nature were under his control. But his claims have no solid foundation, for he has not yet been able to synthesise the fuel (fossil fuel) he needs to power his technology, although using mother nature's secret reserves of energy he has meanwhile unlocked many of her secrets.
The secrets include those lying at the heart of matter as well as those beyond the boundaries of the known universe. Phenomenal advancements in nuclear technology, electronics, especially in the area of information technology and space science were the hallmarks of the scientific excellence of the last century. Outside the exact sciences, only medicine produced some wonders by inventing miracle drugs that could treat diseases unthinkable anytime in the past. However, major breakthroughs had already been made in biological sciences, especially in microbiology. The secret of inheritance encrypted in the genes were decoded during the second half of the last century.
What scientific miracles are in store for us in the present century? The pace of developments in the biological sciences point to the trend of scientific progress in this century. Probably revolution in biological sciences is going to change not only man's lifestyle, but his outlook about life itself in a big way.
In the following, Bob Drummond of Bloomberg narrates the frontiers of that upcoming revolution in science.
Designer organisms, and the potential to profit from them, are sparking excitement -- and debate -- among scientists and venture capital investors. Researchers in an emerging field called synthetic biology envision microbes customized with artificial genes to enable them to turn sunlight into fuel, clean up industrial waste or monitor patients for the first signs of disease.
Already, scientists are producing strings of man-made DNA, short for deoxyribonucleic acid, which directs the functions of all living cells. Then they splice the manufactured DNA into the genes of existing organisms, reprogramming bacteria to act like microscopic factories churning out biofuels.
Experiments are taking synthetic biology a step further by working to build new organisms from the ground up with wholly artificial genes.
"It's the coolest stuff of my career,'' Venter says in his office at the J. Craig Venter Institute in Rockville, Maryland. ``We can go from 15 years of reading the genetic code to now maybe harnessing that information for the betterment of mankind.''
Venter, 61, who rocked the scientific world in 2000 by mapping the collection of human genes in record time, is no stranger to big ideas -- or to controversy.
In 2002, he was ousted as president of Celera Genomics, which he helped start to decode the human genome, after the board decided to concentrate on drug development instead of selling genetic data. Later that year, Venter revealed on CBS's 60 Minutes II that his own genes made up most of Celera's database.
Venter's plan to use synthetic genes to create man-made life offers the most headline-grabbing potential to date. That's opening up Venter to suggestions of grandstanding.
``You can win in business in multiple ways: You can either make a product, or you can make something that sizzles -- that seems like a product,'' Harvard Medical School genetics professor George Church says. Church is a co-founder of LS9 Inc. in San Carlos, California, which plans to use modified E. coli bacteria to convert plant matter into a gasolinelike fuel.
Re-engineered microorganisms may inherit all sorts of jobs. For now, top gene researchers are particularly excited about the potential for energy-producing microbes that may become single- celled refineries for ethanol, biodiesel or other petroleum substitutes without using food crops such as corn.
Scientists are forming bioenergy companies with money from some of the same venture investors who once backed computer and Internet start-ups.
``It's a huge, huge market, and at $100 oil, with the climate crisis and our geopolitical situation, it's the right market to go after,'' says Samir Kaul, a partner at Khosla Ventures in Menlo Park, California. Khosla Ventures, run by Sun Microsystems Inc. co-founder Vinod Khosla, is backing Church's LS9 and other synthetic biology companies.
Venter has founded a company called Synthetic Genomics Inc. to design microbes that make fuel from plant matter, carbon dioxide and sunshine, or convert underground coal into a more easily extracted gas.
The energy market is so much larger than biopharmaceuticals that there's room for a plethora of blockbuster products, he says.
``With fuel, we're hoping there could be a hundred to a thousand different unique solutions,'' Venter says, wearing blue jeans and a sport shirt in an office crowded with awards, mementos and sailing memorabilia. ``Each one could be a $100 billion industry on its own.''
Synthetic biology's potential stems from life's vast array of single-celled organisms. Many of them already perform valuable tasks, such as fermenting grain into alcohol.
``The reason biology is cool to me is that I look at all the things it can physically make,'' says Drew Endy, a biological engineering professor at Massachusetts Institute of Technology in Cambridge. ``The list goes on and on and on and on.''
Synthetic biology builds on the more than three decades of genetic engineering behind trailblazing biotechnology companies such as Amgen Inc. and Genentech Inc.
The human gene-mapping project made Venter one of the world's best-known scientists. USA Today placed him fourth in its September ranking of the 25 most influential people from the past 25 years, behind Bill Gates, Ronald Reagan and Oprah Winfrey and just ahead of Osama bin Laden.
Venter says today's body of genetic knowledge is growing so fast that biology likely will dominate 21st-century science and technology, just as discoveries in physics revolutionized the past 100 years.
``It's exciting to think that life is very different than we might have imagined -- that it's not so complex at some levels, that we can design it and build it,'' Venter says. ``These are things from science fiction.''
Synthetic biology's ability to stretch the imagination may not be all blessing. The Sept. 11, 2001, attacks and the anonymous anthrax mailings the same year introduced American society to a heightened threat of terrorism. Today, teenagers with science fair projects can browse Internet databases for the DNA sequences needed to make a novel microbe.
``Engineered biological agents could be worse than any disease known to man,'' the U.S. Central Intelligence Agency said in a 2003 report.
"The whole sci-fi end of this is the part that, from a public-perception point of view, is going to be the big threat to synthetic biology,'' says Kathy Hudson, director of the Washington-based Genetics and Public Policy Center.
In debates about scientific or ethical limits on synthetic biology, Hudson says, it's important to avoid extreme viewpoints from enthusiasts promising the impossible or doomsayers predicting the apocalypse.
"On the benefits side, you can't put on pompoms too early and oversell things. On the risk side, keep it as real as you can.''
Still, some early entrants are expecting big things from the embryonic industry as researchers rush to start companies and venture capitalists hustle to fund them.
"It's equivalent to building the first transistor,'' says Juan Enriquez, chief executive officer of Biotechonomy LLC, a Boston investor in Venter's Synthetic Genomics. ``It changes fundamentally the rules of the game across a whole series of industries.''
Harvard's Church, MIT's Endy and UC Berkeley's Keasling started Codon Devices Inc. in Cambridge to sell made-to-order synthetic DNA and related services. Investors, led by Cambridge's Flagship Ventures, have contributed $33 million in two rounds of venture funding.
Venter started Synthetic Genomics in 2005 with gene researcher and long-time collaborator Hamilton Smith, who won the Nobel Prize in medicine in 1978.
In October 2005, the company sold $30 million of preferred stock to 12 investors in the U.S., according to a Securities and Exchange Commission filing.
It's raised more money abroad. In June, BP Plc, Europe's second-biggest oil company, bought an unspecified stake as part of a research venture to study microbes living in coal and oil fields. Venter says he's investigating ways to engineer microbes to make hydrocarbons more environmentally friendly.
Discoveries of new genes, from microorganisms that survive in hostile environments, are giving synthetic biologists potentially powerful genetic tools for designer microbes.
"We have organisms that can grow under extreme pressure, extreme temperatures, extremes of pH, extremes of radiation,'' he says. "We can't do any of those things. But if we can harness the power of those that can, it gives us a very different potential for the future.''
Some environmentalists, fearing potential damage from microbes never seen in nature, are questioning Venter's plans. ETC Group, a Canadian public-interest organization pressing for government regulation of synthetic biology, has mocked Venter's proposed man-made microbe with the nickname ``Synthia.''
Venter and his research partners want to make their customized microbe with the smallest number of genes required to keep it alive. Like an automobile chassis, the stripped-down organism could act as a frame, supporting strands of synthetic DNA designed to produce chemicals or digest pollutants, Venter says.
"We have to understand the minimal cell to understand and build correctly the next phases,'' says Venter, who has applied for patents on a bacteria with a minimum complement of genes.