By Ken Howard
We are pleased to report that the inaugural Genome Technoloy All-Stars vote was decided without any dangling chads or Supreme Court intervention. Instead, we harnessed the technology of the Internet to provide you a clean ballot to elect the individuals you consider most outstanding in the genomics field.
Here we list the first place and runners-up for each of nine categories, and on the following pages we profile the winners. We asked your top choices — Craig Venter, Eric Lander, Elliott Sigal, Michael Hunkapiller, Gene Myers, Pat Brown, John Yates, and Tony Frudakis — to tell us about their path to the top and to make some predictions about where they and the industry are headed next.
In addition to the winners and runners-up, four people emerged as stars in the election process.
Pat Brown, Stephen Fodor, Lee Hood, and Maciek Sasinowski each received multiple votes in at least three categories. Peers see these individ-uals as Renaissance men — master multitaskers in a field dominated by researchers with an interdisciplinary bent.
For those of you who aspire to All-Star status, hereÂ’s a tip gathered from this yearÂ’s winners that you will not see in any business school text, read in a science book, or learn at a corporate improvement seminar: get a pet. All the top All-Stars have lived with animals outside the lab. Dogs dominate, but parakeets, rabbits, cats, and even rats apparently put you in the running.
Thanks to all our readers who voted. Happy reading!
2001 GT All-Stars
Academic/Public Sector Genomics Technology
1. Eric Lander, Whitehead Institute Center for Genome Research
2. John Sulston, The Sanger Centre
3. Robert Waterston, Genome Sequencing Center, Washington University
4. Lee Hood, Institute for Systems Biology
5. Francis Collins, The National Human Genome Research Institute
Biotech Industry Genomics Technology
1. Craig Venter, Celera
2. Jonathan Rothberg, CuraGen
3. John Harrington, Athersys*
Randy Scott, Incyte Genomics*
5. Michele Bakis, Genome Therapeutics *
Stephen Friend, Rosetta Inpharmatics*
Mark Levin, Millennium Pharmaceuticals*
Most Important CEO or Senior Executive
1. Craig Venter, Celera
2. Jonathan Rothberg, CuraGen
3. Michael Hunkapiller, Applied Biosytems*
Tony White, Applera*
5. Mark Levin, Millennium Pharmaceuticals
Big Pharma/Big Agriscience Genomics Technology
1. Elliott Sigal, Bristol-Myers Squibb
2. Steven Briggs, Torrey Mesa Research Institute
3. Robb Fraley, Monsanto*
Allen Roses, GlaxoSmithKline*
David Searls, GlaxoSmithKline*
Genomics Tools Development
1. Michael Hunkapiller, Applied Biosystems
2. Stephen Fodor, Affymetrix
3. Maciek Sasinowski, Institute for Computational Genomics
4. Andrew Conway, Silicon Genetics*
Lee Hood, Institute for Systems Biology*
Bioinformatics/Computing
1. Gene Myers, Celera
2. Philip Green, University of Washington
3. Ewan Birney, European Bioinformatics Institute*
Jamie Cuticchia, The Hospital for Sick Children*
5. Mark Boguski, Rosetta Inpharmatics
SNPs/Genotyping
1. Tony Frudakis, DNAPrint Genomics
2. Charles Cantor, Sequenom
3. Michele Bakis, Genome Therapeutics*
Pui-Yan Kwok, Washington University School of Medicine*
5. Mark Chee, Illumina*
Bjorn Ekstrom, Pyrosequencing*
Gene Expression
1. Pat Brown, Stanford University
2. Mark Boguski, Rosetta Inpharmatics*
David Botstein, Stanford University*
Stephen Fodor, Affymetrix*
David Lockhart, Salk Institute for Biological Studies*
Proteomics
1. John Yates, III, The Scripps Research Institute
2. Ruedi Aebersold, Institute for Systems Biology
3. Zed Varrone, CuraGen
4. Jon Klein, University of Louisville Proteomics Lab*
Steve Martin, Applied Biosytems*
*Tie
Biotech Industry Genomics Technology & Most Important CEO or Senior Executive
Craig Venter
President and Chief Scientific Officer
Celera Genomics
PhD: physiology and pharmacology, University of California, San Diego
Age: 54
Mr. ToadÂ’s Wild Ride
Craig Venter dominated the categories he won, receiving overwhelming majorities in Biotech Industry Genomics Technology and Most Important CEO or Senior Executive. Venter is the only person to grab top spot in two categories.
Voters have, not surprisingly, many things to say about Venter. They call him a “gadfly” and “lightning rod” and note his “sheer conviction” and “bravado.” One voter calls him the “driving force behind the revolution in biology and medicine, whose impact will last a very long time.” Another credits Venter with “making genomics the game of the millennium.”
As a major player in the genomics industry and an aggressive and outspoken scientist and businessman, Venter acknowledges the drama that he has at times been instrumental in stirring up. “The average person understands conflict, they understand ego, they understand jealousy and envy, and that’s what the scientific community’s played out in spades for the world to see,” he says about the private/public sequence rivalry. “I try to find the good in everything even though I haven’t enjoyed the controversy. It’s what’s brought genomics to the public attention.”
For all of that attention, including the 2001 “Sequencing of the Human Genome” Science paper itself, Venter says he is most proud of earlier published work: EST development in 1991, and the sequencing of Haemophilus influenzae in 1995 and Drosophila melanogaster in 2000.
“Public-wise, the thing that’s had the most impact is the success that we’ve had with humans,” says Venter, “but scientifically, the few experts in the field who really understand the assembly and the process understood that the game was over when we published Drosophila.”
Over the last 17 years, Venter moved from NIH to TIGR and then Celera, going where science and opportunity have taken him. “None of the moves I’ve made have been calculated,” he says. “A lot of people in this field are very Machiavellian. I’m not one of them. Each discovery has just opened my eyes and I saw a new direction it would take. It’s been Mr. Toad’s wild ride.”
Venter doesn’t see that ride ending anytime soon. “This is the beginning of the genomic era … of holistic biology,” he explains. “Just go stare at the Science centerfold map and try to think of how to put all of the information together. We’re in one of these rare moments in time where things change exponentially. I assume most people like to be in a position where they can make things happen and make things change.”
For the time and for himself, he says: “I can’t imagine a better position to be in.”
Academic/Public Sector, Genomics Technology
Eric Lander
Director,Whitehead Institute Center for Genome Research
PhD: mathematics, Oxford University
Age: 44
The Straw that Stirs the Drink
Eric Lander ran away with the number one spot in the most heavily voted category, Academic/Public Sector Genomics Technology, earning nearly twice as many votes as the runner-up. So it’s probably not just hyperbole when voters describe him as “a giant in genomics” and “the straw that stirs the drink.”
The drink that Lander so dominates includes the genetic and physical mapping of the human and mouse genomes, the study of genetic variation, and the links to disease genes. But for Lander, and to many of his colleagues, he is also integral to laying the foundation for research efforts — a “talk-show host of genomics,” says one voter — who prods debate and offers direction for an international genomics agenda.
In addition to his research and managerial duties as head of the Whitehead Institute Center for Genome Research, Lander also maintains a professorship at MIT where he has taught an introductory biology course since 1990.
“[I want to] light the fire and help excite the spectacular collection of young scientists here and elsewhere to see the tremendous potential of genomics to affect science and medicine,” he says. “It’s much more important than any one project. Any one person can only do so much.”
Lander likes to keep his own fires stoked via his willingness “to constantly overthrow past paradigms every couple of years. The field keeps you young,” he proclaims.
Medical genetics is one of the areas Lander has next set his sights on, using haplotype structures to trace genes. He sees tool development, including drug-targeting tools, on the verge of an explosion. And he believes responsibility falls on all scientists to achieve the promise of genomics: “The academic world has tremendous responsibility to research fundamentals, and industry to apply them. The opportunities today are unprecedented,” he adds. “I can’t imagine a more exciting time to be doing science.”
Big Pharma/Big Agriscience Genomics Technology
Elliott Sigal
Senior Vice President, Drug Discovery and Exploratory Development, Bristol-Myers Squibb
PhD: engineering, Purdue University; MD: University of Chicago
Age: 49
Integrator at the Intersection
Elliott Sigal decisively landed the number one position for Big Pharma/Big Agriscience Genomics Technology, capturing more than 50 percent of the vote. In his top spot at the intersection between big pharma and biotech-level genomics, he has created “a biotech company within a pharmaceutical company,” as one voter puts it, and has positioned his division as a “powerful integration of the two to accelerate leveraging of the Human Genome Project,” explains another.
It could be said that Sigal was groomed for his present position merging drug development and clinical applications with genomics and bioinformatics.
Before being called to Bristol-Myers Squibb in 1997 to put together an applied genomics effort, Sigal had been CEO of Mercator Genetics (which later merged with Progenitor), a VP at Roche Bioscience, and executive director of cell biology at Sytex Discovery Research. Prior to that he had served in a number of academic posts at the University of California, San Francisco, as a physician, and had also been a founder of a management consulting firm specializing in computer simulation and software.
Many commend Sigal’s ability to leverage the efforts of his 100-plus staff with strategic alliances, most notably with the Whitehead Institute and the SNP Consortium. Sigal views his team’s genomics, proteomics, structural biology, and combinatorial chemistry efforts as “integrated technologies.”
For Sigal, the endgame is better and faster drug discovery and a more personalized approach to medicine. “At the beginning with better targets, in the middle with safer drugs, and at the clinic to match the right drug with the right patient and to make the drugs safer and more effective,” he says.
In the next three years, Sigal sees markers for DNA or RNA information being used in clinical trials, and a significant increase in novel drug targets. He raises a caution flag, however: “DNA is high throughput, but biology is not. The new bottleneck is associating function with gene-based ideas.”
Genomics Tools Development
Michael Hunkapiller
President, Applied Biosystems
PhD:chemicalbiology, California Institute of Technology
Age: 52
The Market Maker
Michael Hunkapiller captured the top spot in Genomics Tools Development by garnering more than twice as many votes as the runner- up. Industry peers credit him with “mass producing and marketing” DNA sequencers and “driving the Human Genome Project” via his company’s 3700 sequencers. Voters consider Hunkapiller the Henry Ford of genomics.
Having worked in Lee Hood’s Cal Tech laboratory during the development of the first automated sequencer, Hunkapiller is an inventor as well as a mass producer of the DNA sequencer. He made the transition from academia to industry in 1981 when he was recruited to head research and development at the newly formed Applied Biosystems. He considers his crowning achievement to date to be “the development of the DNA sequencer [that] made it possible for Celera and the Human Genome Project to envision, and then sequence, the entire human genome.” Says Hunkapiller, “Without this contribution, researchers might have been years behind in achieving this goal.”
Hunkapiller credits his success to his ability to “anticipate the needs of academic and commercial researchers.” Where does he foresee those needs emerging next? “Because of the complexity of proteins, there won’t be one solution in the field of proteomics, and researchers will require a multitude of instruments to answer specific questions,” he predicts. “Over the next few years, I believe we will see some novel technologies evolving that will assist researchers in unraveling the mysteries of life.”
Hunkapiller is, of course, betting that Applied Biosystems will be the dominant player in developing and marketing those technologies. And that he will be the one leading the charge. “I can’t imagine a more fulfilling job or way to spend my time,” he says.
Bioinformatics/Computing
Gene Myers
Vice President for Informatics Research, Celera Genomics
PhD: computer science, University of Colorado
Age: 47
Gene Machine
A voter neatly sums up the reason Gene Myers landed the number- one spot in Bioinformatics/Computing: “1.BLAST, 2.Brought Whole Genome Shotgun Assembly to market.”
Myers’ work in designing algorithms and building a software team at Celera culminated in the publication of the genome sequence of Drosophila melanogastor in 2000 and then the human genome in 2001, both in Science. “Nobody challenged the idea that you could produce the data,” says Myers. The challenge was “that you could reconstruct the underlying genome with any fidelity.”
Having risen to that challenge and built up an R&D department of 30 in the process, Myers has moved his team on to the next hurdles; building comparative gene finders, tools for whole genome comparisons, and algorithms for proteomics, spectra comparison, and SNP and disease association. “The wave of the future is aimed at helping interpret the text,” explains Myers. “We have all the letters but we’re still a long way from having all the landmarks nailed down.”
Getting to the next level, Myers believes, will require understanding underlying principles of what are currently just isolated observations. “A lot of molecular biology now is vignettes,” he says. “There are all these case studies of things going on in a cell. But what are the patterns and how did all of this come about and how did these things evolve?”
Today Myers says he’s enjoying a respite from two years of frequent 24-hour workdays. Despite a still-hectic schedule that includes a recent round-the-world speaking jaunt, he’s making time for scuba diving in the Caribbean, “hanging out” in Italy, and getting back in shape by jogging near his DC digs.
But he’s also excited about throwing himself into his next big intellectual pursuit. “I figure I’ve got 20 good years left,” he predicts. “I would like to make another contribution. My plans are to learn a lot about how cells work at the molecular level and [from this] try to build convincing and complete models.”
He adds, “I just love seeing patterns and designing things and understanding what’s going on. You don’t need to pay me to do that stuff. But don’t tell Craig that!”
Proteomics
John Yates, III
Associate Professor of Cell Biology, The Scripps Research Institute
PhD: chemistry, University of Virginia
Age: 43
Paradigm Pusher
“New paradigm” is the comment voters most often ascribe to John Yates for his work developing mass spectrometry and software techniques for the analysis of proteins. “Revolutionary” and “cutting edge” also pop up.
To have something new implies surpassing the old. For Yates, this occurred in the mid-nineties when he introduced protein sequence analysis by tandem mass spectrometry. “Typical protein biochemistry used to be one protein, one analysis,” he explains. “The shift that came about with software and tandem mass spectrometry [allowed] you to take samples with approximately 30 proteins and figure out what the mix is.”
The database-search approach that Yates designed has become “the gold standard,” according to his peers. And he continues to refine it to characterize proteins directly as mixtures using novel multi-dimensional liquid chromatography methods, among other approaches.
Yates is also looking for the next big thing in proteomics. “The shift could come any time,” he says. “The technology for proteomics is still rudimentary. There’s a push to make it more sensitive and higher throughput. I think the complexity of the proteome and type of questions you want to ask are so much harder than the genome that the technology will continue to develop.”
As befitting someone who had Lee Hood as his post-doctoral adviser while at the University of Washington, Yates is looking to push the next paradigm by tackling proteins grouped together. “I’m pushing in the next five to 10 years to take all the proteins in a cell and map out all the sequences and modifications in as few experiments as possible, maybe two, three, or four,” he says. “That’s a fairly big undertaking, but I think it’s something that’s achievable.”
Gene Expression
Pat Brown
Professor, Stanford University School of Medicine
Associate Professor, Howard Hughes Medical Institute
MD and PhD: biochemistry, University of Chicago
Age: 46
Renaissance Man
Pat Brown was voted number one in Gene Expression with a decisive majority, gathering four times as many votes as any of the runners-up. The number of his votes, however, were in inverse proportion to the wordiness of voters comments, which tended instead toward the succinct but telling: “microarrays” and “DNA chips.”
Brown himself is not inclined to talk about the importance of the DNA microarray technology and databases he has advanced — nor of his pioneering work to map gene expression in the yeast genome and to use microarrays to catalogue gene expression data for thousands of samples of human cells and tissue under diverse conditions. He prefers instead to talk about how his lab approaches expression gathering and analysis.
“It’s like learning a language,” says Brown. “We have to see what the genome is saying under a very wide range and diverse state of conditions over time. The conceptual model is of the genome in a cell continuing to write a detailed script, where every aspect of the expression program plays a part.”
As the tools are developed to record this expression data, Brown sees a growing importance for systematic, public databases. “With gene expression data, every single data point is potentially important, including cellular composition of the sample, metabolic and physiologic state, the history of the organism it was taken from, etc.,” he points out. “We have no systematic way of recording that data, and intellectually, it’s a nontrivial challenge. It’s completely unlike DNA sequencing.”
Brown, though, is optimistic about the databases emerging by incremental improvement. And he is happy to be, in his view, perfectly positioned in time and place to continue having a significant impact.
“It’s hard to imagine a greater opportunity than what’s given to a basic research scientist,” says Brown. “We’re trying to work on things that can make people’s lives better and someone is providing funding for the sole purpose of exercising your imagination. The closest equivalent we have [to being a scientist] right now is to being an artist in the Renaissance and having the Medicis as your patron.”
SNPs/Genotyping
Tony Frudakis
CEO, DNAPrint Genomics
PhD: molecular and cell biology, University of California, Berkeley
Age: 33
Media-Savvy Maverick
Tony Frudakis, who captured most influential in SNPs/Genotyping, might also be said to take top honors in the most successful Get Out the Vote campaign, having beaten some venerable players in the category to capture top spot. His ability to garner attention for himself and his one-year-old company is perhaps best summed up by one voter’s comment: “Patents pending.”
Frudakis is leading his development team in the design of high-throughput informatics platforms to quantify genetic variation in populations and linking them to physical traits such as drug response. He sees these tools, in various stages of development and application for patent protection, as the next generation of genomics-based personalized medicine.
“The fruit will be plucked from the tree over the next two or three years, and it will be a very consumer-driven field,” Frudakis says. “It’s not the size of your computer or speed of your genotyping. It’s developing algorithms for the analytical bottleneck, and that’s what we’re doing. The real test of our contributions will be the strength of our associations between haplotypes and phenotypes.”
Before moving with his wife and two small children to Florida to start his company — originally a contract genomics service firm called GAFF Biologic — Frudakis developed RNA fingerprinting techniques and high-throughput gene discovery programs at Seattle-based Corixa. Another of his functions was luring research and development partners, which served him well in raising venture capital for DNAPrint Genomics.
The Sunshine State, where Frudakis and his family lived on a 37-foot sloop on an inland waterway as he scrambled to raise funds, would strike most people as an unconventional location for a genomics startup. Frudakis, who has since moved with his brood into a house, agrees.
“The secret is to figure out how to do things completely different,” he says. “I’m in Florida, not Silicon Valley. We get tons of samples of blood in this area. We wouldn’t get it in Silicon Valley. I don’t have to deal with employees who like to bounce around from company to company. You have to be a maverick.”
Hotbeds of Talent
These organizations have the most individuals who received votes
Public Sector
1. Washington University
2. Whitehead Institute*
Columbia University*
4. National Institutes of Health *
Stanford University*
The Institute for Genomic Research*
University of Washington*
Private Sector
1. Incyte Genomics
2. CuraGen
3. Celera Genomics*
DoubleTwist*
5. GlaxoSmithKline*
Applied Biosystems*
Lion Bioscience*
Rosetta Inpharmatics*
* Tie
Outtakes
Unique reasons given for a nomination
Craig Hall, DNAPrint Genomics, because he “exhibits candor” and “drives least conspicuous car”
Tim Harris, Structural Genomix, because “anyone who drives a Porsche with a ‘Big Dog’ license plate deserves to be nominated”
Max Wallace, Cogent Neuroscience, as he is a “serial entrepreneur”
Ewan Birney, EBI, because he is “young, brash, and arrogant” (and very possibly wrote that about himself)
Alexey Murzin, Centre for Protein Engineering, University of Cambridge, because the voter’s choice “is not some code crunching gearhead who couldn’t tell a beta-trefoil domain’s protein fold (and possible biochemical correlates) from their unwashed coffee cup”
Jonathan Rothberg, CuraGen, because “he is my boss”
Tim Wilhelm, Incyte Genomics, as he “can genotype 60 words per minute”
Big Wheels
Match the automobiles to their fast-track owners
A. Red Hummer
B. Blue Nissan Quest Minivan
C. Racing Green BMW 330 Convertible
D. Granite Gray Honda Odyssey Minivan
E. Maroon Ford 250 Pickup/White Chevy 3500 Van/Millennium Porsche (one of 911 manufactured that changes color with the strength of the sun)
F. Silver Audi A6 2.7 Turbo
G. 12 year-old (very weathered) Gold Ford Taurus (back-up for Cannondale bicycle)
H. Lexus SC 400
Pat Brown, Tony Frudakis, Michael Hunkapiller, Eric Lander, Gene Myers, Elliott Sigal, Craig Venter, John Yates
All-Star Reading List
The books that influence the movers and shakers
Consilience: The Unity of Knowledge by E. O. Wilson (Random House, 1999) — Craig Venter
Guns, Germs and Steel: The Fates of Human Societies by Jared Diamond (W. W. Norton, 1999) — Eric Lander
In Quest of Tomorrow’s Medicines by Jurgen Drews (Springer-Verlag, 1999) — Elliott Sigal
The Double Helix: A Personal Account of the Discovery of the Structure of DNA by James Watson (Penguin, 1976) — Michael Hunkapiller
The Seven Habits of Highly Effective People by Stephen R. Covey (Simon & Shuster, 1989) — Gene Myers
The Coming Plague: Newly Emerging Diseases in a World Out of Balance by Laurie Garrett (Viking Penquin, 1995) — John Yates
The Code Book: Evolution of Secrecy from Ancient Egypt to Quantum Cryptology by Simon Singh (Vintage Anchor, 2000) — Pat Brown
Genetics and Analysis of Quantitative Traits by Michael Lynch and Bruce Walsh (Sinauer, 1998) — Tony Frudakis