The Earth is moving under the worlds of academia, technology, and biology. Chemists, geneticists, and neuroscientists are leaving their cozy university labs to become executives of heavily endowed biotech start-up companies. Entrepreneurs who once brewed beer are CEOs of drug companies. Technologists and engineers without science degrees are solving the riddles of human genomics and proteomics. Think Niels Bohr and Albert Einstein with stock options. Think Henry Ford and Thomas Edison cooking up drugs. Traditional demarcations between biology and commerce, science and technology, advisers and inventors, business folk and ivory-tower researchers have dissolved.
They nurture visions of a future as enticing as our human imaginations can bear: Yes, they insist, we really will conquer cancer, see paraplegics walk again, grow new skin for burn patients, and live to be 300.
Most of the visionaries on this list remain obscure, but that is likely to be temporary. All have soared to superstar status within the science industry, which went white hot after the announcement two years ago that the human genome had been decoded. Since January 1, 2000, investors have pumped $59 billion into the hands of such people. No one is quite certain how many of their promises will come true or what unknown perils may await us as we tinker with the basic building blocks of life. But for these 20 geniuses, the biotech revolution is under way, and none are looking backward as they transform cash, moxie, and imagination into the drugs and treatments of our dreams.
4. What biologist popularized the term systems biology and twice quit university positions to go into business?
7. Will this Rockefeller University cell biologist eventually leave academia to help men regrow their missing hair?
8. What former Harvard business professor became lead author on the historic paper that mapped the human genome?
12. What former doughnut-shop owner is running a hot biotech company with a market cap in excess of a billion dollars?
17. What Harvard chemistry professor and winner of the National Medal of Science tinkers with self-assembling molecules?
18. What vice president of the Howard Hughes Medical Institute thanks a tiny insect for much of his success?
1. Joshua Lederberg Professor Emeritus of Molecular Genetics and Informatics, Rockefeller University |
Although he is passionate about the possibility of life elsewhere in the universe and considered a trailblazer in artificial intelligence, knowledge-based computer systems, and emerging infectious diseases, Lederberg's overwhelming interest is still focused on the subject that won him a Nobel Prize in 1958— bacteria. Lederberg's Nobel was based on his discovery of recombination in bacteria. His work in identifying the genetic structure and cell functions of bacteria has become central to a biotech industry that he helped found as an adviser to companies such as Affymetrix. "Right now, I'm looking to see how fast bugs grow," he says. "What are the limits to how much a cell can replicate?" That information is crucial to figuring out how to shut down rapid cell growth in cancer cells. He is also a member of the U.S. Defense Science Board, an important forum in the wake of September 11.
2. Peter Schultz Director, Novartis Research Foundation's Genomics Institute |
In 1999 Schultz founded Novartis's Genomics Institute in La Jolla, California. There, 220 researchers peruse everything from nanotechnology to learning and memory. His favorite question: Why did life settle on four DNA bases— represented by the letters A, C, G, and T— and 20 amino acids? To find out, Schultz and his colleagues have invented 80 new amino acids. They also began experimenting with a bioengineered bacterium that contains unnatural amino acids. "You could create powerful new proteins," he says, such as proteins with new side chains that kill tumor cells. Blending business and research, Novartis has spun off three new companies: one that hopes to unravel the structure of previously unmapped proteins, another that is experimenting with mouse cells to test for mutations that might apply to humans, and a third that scours cells for undiscovered pathways, proteins, and immune responses. Schultz was 32 years old when he founded his first company, Affymax, in 1988. He hooked up with entrepreneur Alejandro Zaffaroni. "I was uninterested in companies," remembers Schultz, "but Alex convinced me and changed my life."
3. Craig Venter Chairman, The Institute for Genomic Research (TIGR) |
A decade ago, when Venter was working as a section head and researcher at the National Institutes of Health, he got an idea for speeding up gene discovery. Rebuffed by superiors, he quit the institute and started up the nonprofit TIGR in Rockville, Maryland. In 1998 he founded the for-profit Celera. Within months it became obvious that Venter's rapid-sequencing technology would win the race to decode the human genome. In June 2000 Venter stood in the White House beside his rival, Francis Collins, director of the NIH's genome project, as President Bill Clinton announced a compromise victory, declaring that Celera and the NIH had nearly completed decoding the genome. Since then the commercial promise of the genome has become muddled. The NIH posted a free version of the genome online, and investors realized that accumulating genetic data may be less lucrative than discovering new drugs based on the knowledge. Venter subsequently tried to reshape Celera into a drug-discovery company, then resigned in January. A week before his departure, he said he believed that the next wave of biotechnology will be personalized medicine in which massive computing power will be used to tailor treatments to an individual's own genetic map.
4. Leroy Hood President and Director, Institute for Systems Biology |
When Hood was a young instructor at the California Institute of Technology, the chairman of the biology department asked him to stop teaching technology and stick to biology. He refused, quit Caltech, and eventually popularized the term systems biology to describe the integration of biology, technology, and other disciplines. The synthesis stuck: In the 1970s and 1980s, Hood was a pioneer who created automated sequencers for DNA and proteins, which led to the discovery of key proteins and chemical structures in the body. More impatience with academia led him to ditch another high-profile academic position in 1999 to start up the Institute for Systems Biology. He describes the innovative firm as a "grand experiment" in combining business methods with research and academic freedom. "The challenge for the future is with whole systems and theories of integration," he says, "and with being free to use your imagination."
5. William Haseltine CEO, Human Genome Sciences |
A prominent cancer and AIDS researcher at Harvard's Dana-Farber Cancer Institute and the Harvard Medical School for 17 years, Haseltine made the jump from lab to business suite in 1992, when he founded Human Genome Sciences in Rockville, Maryland, just up the road from rival Craig Venter's headquarters at Celera. Haseltine's company now has a market capitalization of $3 billion and seven drugs in clinical trials, including treatments for growth hormone deficiency, hepatitis C, and venous ulcers. Hundreds more drug targets are in the company's plans. But the 57-year-old Haseltine's passion has turned to "regenerative medicine," a term he claims as his own. "It starts with the very simple notion that our bodies are machines that either become worn or broken, and there's an age-old desire to repair or replace those worn and broken parts. A number of avenues will allow us to do that." He envisions a medical future in which human tissues will routinely be used to replace aging organs.
6. Stuart Schreiber Chair of Chemistry and Chemical Biology, Harvard University |
In 1973 he had already planned to drop out of the University of Virginia to become a carpenter. "On a lark, I went to a chemistry class," he says, "and it seemed beautiful to me. It opened a window on a whole new world." Now a professor of chemistry and chemical biology at Harvard, Schreiber is opening a few windows of his own synthesizing small molecules that can be used to tweak proteins and protein pathways in cells. These are the mechanisms that control everything from immune response to memory. In the 1980s Schreiber created small molecules that stimulate mechanisms in the body's immune response system, leading to the discovery of a signaling network of proteins and receptors crucial not only for immune functions but also for heart development and the acquisition of memory in the hippocampus. He uses computers and specially designed molecules that work as probes to study proteins and other natural molecules, hoping to map the inner genetic workings of the body. Once that infrastructure is understood, he says, scientists will know which particular genetic system does what, and "that's when the exciting part begins."
7. Elaine Fuchs Head of the Laboratory for Mammalian Cell Biology and Development, Rockefeller University |
Fuchs recently discovered how to induce hair growth by working with a protein that instructs embryonic skin cells to become hair follicles. She tweaked the stem cells of mice to make them extra furry. "Skin has been looked at very closely for years by dermatologists— every blemish, every permutation— because it's all exposed, unlike other organs," she says. "This information can be linked with genetics." Fuchs is exploring proteins that provide strength to skin diseases, others that cause blistering skin, and those involved in carcinomas. She is reluctant to go commercial but suspects she may anyway. "You can't stop it," she says. "It's how research is transferred into products for people."
8. Eric Lander Director, Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research |
Back in 1981, when it took geneticists a year or more to identify just a single gene, Lander was a 24-year-old Rhodes scholar with a fresh mathematics doctorate in hand and a summer to kill. His brother, a neurobiologist, suggested that he learn something about mathematical neural biology. So Lander began to study cell biology, then molecular biology, and finally genetics. Meanwhile, he taught finance at the Harvard Business School. "It's a shaggy dog story," he says, but one that eventually led him to believe that biology's future lay not only in accumulating a mass of genetic data quickly but also in concocting mathematical models to analyze it. By 1990 Lander was director of the Whitehead Center for Genome Research, overseeing labs that deciphered a third of the human genome. He chaired the committee that analyzed the rough genomic data and in 2001 was lead author on the historic paper that offered the complete map of the human genome. Now 45, Lander continues to lead the center's efforts to apply the genome to analyze how cells function and to discover the complex genetic pathways of disease. He advises a number of biotech companies and has become the Carl Sagan of biotech, a charismatic explainer on television programs such as NOVA. "Solving the genome was the first step," he says. "Now comes the fun part, when we see how genetics works."
9. Corey Goodman CEO, Renovis |
For 25 years this neurobiologist mapped brain mechanisms such as how neurons behave as they fire off billions of commands that make us move, think, and remember. Using fly brains, Goodman discovered a raft of brain-control genes with equivalents in humans, including several involved with brain development. The research could lead to repairs for injuries to the brain and spinal cord. He is a cofounder of two biotech companies: Exelixis and Renovis. The latter hopes to turn his discoveries into therapies for pain, eating disorders, depression, schizophrenia, and Parkinson's disease. Despite a talent for business, Goodman had always chosen to remain in his lab at the University of California at Berkeley, where he had been director of the Helen Wills Neuroscience Institute since 1999. But Renovis investors recently asked him to become their chief executive. "Initially, I said no. But I think that in the next 10 years, the commercial route will have more of a direct impact on spinal-cord injuries, and maybe on psychiatric disorders, so I decided to take a chance."
10. Sydney Brenner Distinguished Professor, Salk Institute |
In 1962 this South African chemist teamed up with Nobel Prize-winning geneticist Francis Crick at Cambridge University to discover the essence of genetic coding: Every three DNA base pairs (made up of A, C, G, and T combinations) are a code for a single amino acid. Brenner went on to find messenger RNA in cells. Last year, at age 74, he retired as president and director of science at the Molecular Sciences Institute in Berkeley, California. But he continues to pick apart pufferfish in a quest to study gene regulation. "I am taking genes from a pufferfish and inserting them into a mouse to see if they can be read by the mouse," he says. Brenner holds numerous patents, mostly for computational inventions to sequence DNA and other molecules, and remains on the board of Lynx Therapeutics and NeoGene Technologies. He still works with pufferfish, now in a lab at the Salk Institute near San Diego.
11. George Rathmann Chairman, Hyseq |
More than a decade ago, a colleague faked a Time magazine cover with Rathmann's photo and a headline about his triumphs at the pharmaceutical company Amgen. "It was almost laughable because it was so absurd. We were nothing in the equation of biotech companies, much less American industry," Rathmann remembers. Now Amgen is worth more than $64 billion. Two of its biotech drugs— Epogen, for anemia in kidney-dialysis patients, and Neupogen, used to prevent infection in chemotherapy and bone-marrow transplant patients— earned $3.5 billion last year. Rathmann's contribution to the company's rise came not only from discovering new protein pathways but also from helping to pioneer a business culture for a company that successfully fuses research and industry. Before he went to Amgen, Rathmann worked as a scientist and executive at 3M and at Abbott Laboratories. In 1990 he founded a company called ICOS, which now has nine drugs in human trials for conditions such as sepsis and hypertension. Recently, the 74-year-old became the head of the start-up Hyseq, another new drug company. Is the pie big enough for so many firms? "There are $15 billion to $20 billion of biotech sales today," says Rathmann. "Twenty years ago sales were zip. The potential seems unlimited."
12. Mark Levin CEO and Chairman of the Board, Millennium Pharmaceuticals |
In 1979 he owned a doughnut shop in Eden, North Carolina, where he also helped start up and manage a new brewery for Miller Beer. Now éclairs and lagers are less meaningful for Levin. Since 1993 he has been the chief executive officer of Millennium, one of a handful of biotech companies with a market capitalization of more than a billion dollars. Under Levin, Millennium has already launched two drugs, one for heart disease and one for leukemia, and has 10 more in trials to treat conditions such as prostate cancer, asthma, and inflammation. Levin earned a master's degree in biochemical engineering from Washington University in St. Louis. His business-science acumen was developed at Eli Lilly, Genentech, and the Mayfield Fund, where he founded 10 biotech companies. Levin's vision of success for Millennium is to have it lead a revolution in personalized medicine. He foresees a day when "we can go into a doctor's office, and our genome will be available on a chip, and the doctor will be able to treat us for our own genome."
13. Robert Langer Professor of Chemical and Biomedical Engineering, MIT |
Langer has created a blizzard of inventions and discoveries in his lab at MIT, including polymers that deliver macromolecules such as peptides, magnetically controlled implants that release drugs, and 3-D polymer scaffolds on which human tissue can be grown. The 53-year-old has also seen 80 companies develop from his licenses and patents, developed 401 patents, and published 704 articles, not to mention 13 books. His drug-release mechanisms are now the basis of a $20 billion industry and part of his vision for the future. "A time is coming when the medicines we take will be automated, and tissue engineering will be a part of life," Langer says.
14. Tom Cech President, Howard Hughes Medical Institute |
Cech was only 41 when he and Yale's Sidney Altman won the 1989 Nobel Prize in chemistry by proving that RNA could be a biocatalyst. That research led to the discovery of tiny ribozymes that can be used as drugs. Cech also discovered the first protein component of telomeres, as well as the catalytic subunit of the telomere-replicating enzyme, telomerase. He holds 12 patents and helped start Ribozyme Pharmaceuticals. And now, as president of the $12 billion Hughes Medical Institute, he is bucking a trend, trying to lure scientists from the biotech business back into research. Before Cech, the institute focused on funding individual scientists' research at universities. Under his leadership, the institute is building a $500 million 281-acre campus in northern Virginia, where physicists, engineers, computer scientists, and biologists can do pure research in an environment that mimics a biotech company. Cech says, "We want to apply principles from biotech to academic research, to break down the barriers in traditional academia so that chemists, biologists, and engineers can work together, with an infrastructure of assembly lines, shops, and labs."
15. David Goeddel CEO, Tularik |
In 1978 Genentech chief Robert Swanson lured this 26-year-old Stanford University postdoc to the biotech company as its first full-time staff scientist. "I was very green, which shows how much trouble they had hiring more experienced people," Goeddel says. "We wanted to make a new drug, and we did it by the next summer." The idea of the drug was old— insulin— but Goeddel developed a way to manufacture it synthetically. He went on to pioneer gene cloning and gene expression techniques for proteins involved in human growth hormone, interferon-alpha, and others that became the basis of Genentech's early pharmaceuticals. In 1991 he cofounded Tularik, a drug-discovery and development company. It now has three anticancer drugs in clinical trials.
16. David Baker Associate Professor, University of Washington; Assistant Investigator, Howard Hughes Medical Institute |
A great conundrum facing biology is how proteins fold— that is, form themselves into shapes like balls of spaghetti— which allows them to attach themselves to other molecules, including drugs. When they do, they can turn something on or off. Geneticists can identify these shapes only through a costly process called X-ray crystallography. First, proteins must be made into crystals, then X-rayed and modeled on a computer. Baker has short-circuited the process. In 1997 he created a sensation with his Rosetta algorithm, a computer program that predicts how proteins will fold by using just the sequence of amino acids provided by DNA. So far the program is only 40 percent accurate, but it is far easier than anything else available. This year Baker licensed Rosetta to Structural Genomix, a protein-identification and drug-discovery company in San Diego. "We are about two or three years away from making this useful," he says, "though I've learned that predicting the rate of progress is even harder than predicting proteins."
17. George Whitesides Professor of Chemistry, Harvard University |
Small is hot. Nano-enthusiasts talk about building cell-size cancer-killing submarines and creating tiny self-assembling robots that snatch raw ingredients from the environment to self-replicate. Skeptics say that so far it's only talk, and they warn of self-replicating nano-gizmos that could run amok and ravage the planet. Calmly presiding in the middle of the controversy is a 63-year-old National Medal of Science winner and Harvard chemist. One of the first scientists to put the "tech" into "biotech," Whitesides has pushed the boundaries between chemistry and just about every other science. While still in his thirties, he pioneered the bioengineering of molecules present in mammalian cells, laying the foundation for modern biomolecular medicine. Today Whitesides tinkers with neural networks, drugs that interact with multiple proteins, and self-assembling molecules that mimic cell components. "We are about to challenge some basic assumptions about who we are," he says. "What is a machine? What is life?"
18. Gerald Rubin Professor of Genetics and Development, University of California at Berkeley; Vice President, Howard Hughes Medical Institute |
Nature tends to be efficient and therefore repeats basic genetic systems in almost all organisms. Flies are no different, which means flies and humans share an extraordinary number of genes. That simple fact, and lots of work understanding the genetics of the common fruit fly, Drosophila, has made quite a success of this 52-year-old professor at the University of California at Berkeley. Drosophila is a crucial stand-in for experiments and discoveries applicable to human genetics, making the flies an underpinning of biotech research. "Most of the ways that cells talk to each other are fairly ancient," says Rubin. These days he divides his time between studying systemic gene functions and gene regulation in Drosophila and helping Tom Cech at the new Janelia Farm research campus for the Howard Hughes Medical Institute.
19. Charles Cantor Chief Scientific Officer, Sequenom |
This chemist and inventor is up before dawn every morning, running six miles no matter where he is, which could be anywhere as he relentlessly promotes Sequenom, the drug company he cofounded in 1994. On leave as director of the Center for Advanced Biotechnology at Boston University, Cantor, 59, is a pioneer of "pharmacogenomics," the creation of drugs individually designed for one person's genome. Cantor invented techniques that separate large DNA molecules and detect tiny quantities of DNA and protein. He recently coinvented a fast assembly-line process to discover and analyze single nucleotide polymorphisms— pieces of genes responsible for specific genetic proclivities, including such conditions as cardiopulmonary diseases, depression, and anxiety. "I like to solve problems," he says. "I get bored very quickly. I fall asleep. To stay awake, I just invent my own problems and try to solve them."
20. Arthur Levinson Chairman and CEO, Genentech |
If there is an ancestral birthplace of the biotech industry, it's Genentech. Founded in 1976 by legends Robert Swanson and Herbert Boyer, it began as an experiment to see whether Boyer's new recombinant DNA technology could be turned into a business. In 1980 Boyer recruited Levinson, a young microbiologist from the University of California at San Francisco. Unlike many biotech luminaries who cut their teeth at Genentech and left, Levinson stayed, moving up from senior scientist to chief executive officer in 15 years. He took over the company in 1995, when biotech stocks were plummeting as drug after drug fizzled. Levinson ratcheted up the research budget and raised money using innovative alliances with other companies. He now presides over a business with 10 drugs on the market and a $27 billion market cap.
For more about these biotech visionaries and their discoveries, see the following Web sites:
David Baker: University of Washington laboratory, http://depts.washington.edu/bakerpg.
Sydney Brenner: Institute of Molecular and Cell Biology's Fugu Genome Project, www.imcb.nus.edu.sg/fugu/fugu.html.
Charles Cantor: Sequenom, www.sequenom.com.
Tom Cech: University of Colorado, http://petunia.colorado.edu.
Elaine Fuchs: University of Chicago, http://bmb.bsd.uchicago.edu/index3.html?content=faculty.html.
David Goeddel: Tularik, www.tularik.com. Corey Goodman: Renovis, www.renovis.com.
William Haseltine: Human Genome Sciences, www.hgsi.com.
Leroy Hood: Institute for Systems Biology, www.systemsbiology.org.
Eric Lander: Whitehead Institute Center for Genome Research, www.genome.wi.mit.edu.
Robert Langer: MIT, http://web.mit.edu/beh/people/langer.htm.
Joshua Lederberg: Professional profile, http://profiles.nlm.nih.gov/BB.
Mark Levin: Millennium Pharmaceuticals, www.mlnm.com.
Arthur Levinson: Genentech, www.gene.com.
George Rathmann: Hyseq Pharmaceuticals, www.hyseq.com.
Gerald Rubin: Howard Hughes Medical Institute, www.hhmi.org.
Stuart Schreiber: Professional profile, www.chem.harvard.edu/faculty/schreiber.html.
Peter Schultz: Professional profile, http://schultzweb.scripps.edu.
Craig Venter: The Institute for Genomic Research, www.tigr.org.
George Whitesides: Professional profile, www.chem.harvard.edu/faculty/whitesides.html.
