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They’ve Got the Whole Genome in Their Hands


When Watson and Crick described the structure of DNA, none of the 16 people on the following pages had been born. Nine years later, when Watson, Crick, and Wilkins won the Nobel Prize, these 16 still weren’t born. When Lee Hood invented the automated sequencer, none of them had taken high-school biology yet. When the Human Genome Organization was established, many of them were home playing computer games. Same goes for the year Amgen was founded and the year Kary Mullis invented PCR.

And yet it will be the men and women profiled here (and their many brilliant peers whom we regretfully fail to feature) who will make history with the genome. Their mentors, seniors, and peers selected them, by an entirely unscientific survey, as some of the most promising professionals of the new biology.

Ranging in age from 27 to 33, these up-and-comers have the talent, drive, and prescience to make great strides in science, technology, and business.

You’ll notice that most possess PhDs. Most also have strong computer science skills. Perhaps as importantly, each of them also has polished people skills and powers of persuasion (two of them quite convincingly nominated themselves for the section). But what most benefits these folks, intent on making their marks in the biotech sector, is the work that’s been cut out for them by their predecessors. Generation G has the whole genome.



Christopher Ahlberg, CEO

Spotfire, Cambridge, Mass.

Swede Success

“It doesn’t mean anything,” admits Christopher Ahlberg when asked to explain the term Spotfire. “It’s just a cool name that’s not boring. Never boring.”

Not that being boring is something Ahlberg, 32, will ever have to worry about. Swedish by birth, Ahlberg launched Spotfire — a bioinformatics company that purveys a platform for database exploration — in 1996 while he was wrapping up his PhD at Chalmers University of Technology in Göteborg. “It was pretty intense,” he says with a grin.

In fact, the technology used at Spotfire is based on his graduate studies in human-computer interactions. “A lot of cognitive psychology,” he explains, sipping his Earl Grey tea. Spotfire is now used by dozens of pharmaceutical companies and academic labs for mining and analyzing data in a visual way.

Aside from Spotfire, Ahlberg has never had “a real job” — unless you count his compulsory military service in a Swedish ranger unit. That’s where he says he learned many important survival skills, including how to kill a chicken by swinging it around by the legs.

As for his gig as corporate CEO, Ahlberg figures his job is “to make people think Spotfire is the most amazing company on earth.”

If anyone can do it, he can. With his close-cropped hair, lean build, and intense gaze, he somehow manages to appear relaxed yet ready to spring into action. On his tiny Visio, Ahlberg maneuvers through a microarray data set with fluid grace, isolating interesting gene expression patterns, clustering their profiles, and pulling up functional descriptions from a linked Proteome database.

He also spends a great deal of time navigating in the real world. Almost half of Spotfire’s 148-person staff is still in Sweden, so Ahlberg shuttles back and forth from the Cambridge, Mass., headquarters at least once a month. The travel gives him plenty of time to read. His current fave: Harry Potter. “My wife and I each bought a copy of number four so we could read it in parallel,” he says.

When he’s not flying, Ahlberg enjoys cooking, kickboxing, and listening to gangsta rap. The boxing is great exercise, he says. “After sitting in a chair all day, it’s very refreshing.” And Ahlberg adores competition. On his filing cabinet sits a pair of wooden moose — trophies for winning the company soccer tournament.

“Chris likes to win,” agrees Ed Tobin, Spotfire’s VP of professional services. When it comes to soccer, though, “Chris doesn’t always play fair,” he adds. “He did elbow one of my guys in the face.” Of course, it could have been worse, considering what Ahlberg can do to a chicken.

Off the soccer field, though, Tobin says Ahlberg is a real team player. “He gives people confidence and makes everyone feel like an important part of the company.”

And Ahlberg himself is quite modest about his success. “I’ve been really lucky,” he notes.

Where does he see himself in 10 years? “I’m not really one for planning,” he demurs. “I hope it’ll be something cutting edge, something that’ll make a difference. Maybe I’ll start another company,” he muses. Doing what? “I prefer not to say.”

—Karen Hopkin


Ewan Birney, Team Leader

European Bioinformatics Institute, Cambridge, UK

Britain’s Bioinformatics Boy Wonder

Ewan Birney’s first job was as a 16-year-old student guide at Eton. “I gave a good tour,” he recalls. “Americans liked it big and brash. British school kids liked stories about ghosts eating kids. You pitch to your audience.”

Birney, 28, is still pitching, but his audience is much bigger. It includes everybody who uses Ensembl, which he runs for the European Bioinformatics Institute; Gene-Wise, the program he wrote as a biochemistry undergraduate at Oxford; and Bioperl, a collection of open source tools, which he runs and co-founded. He also finds the time to supervise PhD students, advocate for the open source community, and plug into various projects that friends and colleagues run by him.

“He’s got his fingers in a lot of different projects,” says Sean Eddy, associate professor of genetics at Washington University Medical School and a friend of Birney’s. “He gets people fired up about a project. He’s just everywhere.”

Getting to where he is now can be traced to 1991 when he was between Eton and Oxford. He was a research assistant at Cold Spring Harbor Laboratory studying protein families. Birney recalls, “We had a computational problem and the computer people weren’t turned on to it. I had a lot of time and I said ‘sod it’ and gave it a try. So I wrote a piece of code that takes a mathematical description and compares it to ESTs.”

He hasn’t looked back. While studying biochemistry at Oxford, he attended bioinformatics conferences and wrote software that tackled the challenge of mapping DNA to a protein sequence. This eventually led to Gene- Wise. “I was 20 at the time, so people took persuading that I had something to offer. I learned you just have to do it and the best way to do that was to give it away.”

That lesson has informed much of what Birney has done since, including the open sourcing of GeneWise. “Everyone can do whatever they like with it, but if you combine with your own code you have to distribute all the code. But not a great deal of people want to modify the source code, it’s very complicated. Most often companies take the whole thing and use it and that puts a big smile on my face.”

After completing his bachelor’s degree, Birney went on to earn his doctorate at Cambridge under the tutelage of bioinformaticist Richard Durbin. Along the way, he also worked as an equity researcher at an investment bank and as a seminal contributor to Linux. It was the latter, which put him on the “friends and family” list to buy VA Linux Systems stock at institutional prices, combined with know-how garnered at the former, that enabled him to buy his current mode of transportation: a British-racing-green BMW Z3 Roadster in which he fashionably makes the reverse commute from London to EBI’s Cambridge campus.

At EBI he leads a six-person-and-growing team with a five-year, £8 million budget. “I have become a team leader. When I started it was terrifying. It’s still terrifying. You’re responsible to the team. At the end of the day I have no excuse for not making the team the best in the world.”

He has also assumed a leadership position among a new crop of bioinformaticists. “The open-source community meets once a year and now I feel like an old man. All these really young kids are jumping around all excited and I’m giving sage advice. Twenty-eight is old enough to start giving advice,” he says, sounding like he is also trying to convince himself. “It’s exciting to see a new generation being taught proper bioinformatics.

“I really believe bioinformatics is crucial to biology. I want to make it all work, the computers and the people,” he says. “I want to bring it all together.”

—Ken Howard

Steven Brenner, Assistant Professor

UC Berkeley Department of Plant & Microbial Biology, Berkeley, Calif.

Perl in the Sand

Steven Brenner, 29, says he is doing exactly what he always wanted to do. Although he didn’t think up computational genomics as an undergrad sitting in the hallowed halls of Harvard University or during his collegiate summers as a Microsoft intern, he did wonder how he could combine his passions for molecular biology and computer science, which at the time seemed unrelated.

Lucky for him, by the time he finished his PhD at the University of Cambridge, biology and computer science had met, married, and were spawning a new era of biological research. Bioinformatics had been born, and Brenner’s work was ripe to deliver it though the World Wide Web.

Perhaps best known for what he calls “a snippet of code called”(cgi-lib stands for the common gateway interface library), Brenner provided behind-the-scenes functionality that made it easy to write programs to provide data on the Web.

The cgi-lib code is available for free, and for several years it was the standard way to handle Web-form input in Perl. His book, Introduction to CGI/Perl, made the top 0.1 percent on while it was in print. And according to mentor Michael Levitt, Brenner’s postdoctoral advisor at Stanford, the name “Steven Brenner” has more than 26,000 hits on the Google search engine.

In the company of Alexey Murzin, Loredana Lo Conte, Tim Hubbard, and Cyrus Chothia, Brenner co-authored the SCOP: Structural Classification of Proteins database. SCOP, which has been used for a wide variety of applications, provides a comprehensive classification of all of the proteins of known structure, organizing them according to their structural and evolutionary relationships.

He began working on SCOP while he was serving a one-month stint as a patient at a UK hospital with repeatedly misdiagnosed appendicitis. He sneaked out every night to the MRC Laboratory of Molecular Biology across the parking lot until the early morning hours.

These days, Brenner can be found at UC Berkeley, working as an assistant professor in the Department of Plant and Microbial Biology. He also has affiliated appointments with UC Berkeley’s Department of Molecular and Cellular Biology and Department of Bioengineering, and has a faculty scientist post at Lawrence Berkeley National Laboratory.

So, what drives this over-achiever? He says that it’s curiosity. But it’s hard to believe it’s not his genes — Brenner’s family is full of scientists. His father trained as a physicist with Norman Ramsey, and his mother is a successful psychotherapist. His paternal grandfather was an electrochemist who discovered the phenomenon of electroless plating — a technique used, for example, in the manufacture of hard drives. Both Brenner’s brother and sister are in medicine, and university faculty in his family include two uncles, a paternal grandmother, and his late maternal grandfather.

Growing up in a stimulating environment certainly helped Brenner develop his analytical personality, as well as his speculative nature. Often found traveling across the world, Brenner actively investigates the great outdoors. Whether he is backpacking on the John Muir Trail in Yosemite, or exploring Yogyakarta (a desired destination), Brenner’s love of inquiry keeps him motivated to continue learning more. His current location is California’s Bay area, where he plans on remaining for at least the next five years, continuing his research, teaching at UC Berkeley, and taking in the view of the Bay from his back door.

—Hannah Peterson


Rowan Chapman, Director of Business Development

Rosetta Inpharmatics, Kirkland, Wash.

Dealing Her Own Hand

Rowan Chapman sees herself someday as CEO of a cutting-edge technology company in the biotech sector. And though she won’t speculate on a date, Rosetta Inpharmatics’ business development director has plenty of time to realize her goal. The scientist-turned-genomics-dealmaker is only 30.

Since joining Rosetta in November 1999, Chapman has negotiated seven deals — “a mixture of big pharma and strategic deals,” she says — many of which have not yet been announced. “I’m really proud of them,” she adds with characteristic enthusiasm.

“She’s extremely intelligent and she’s very good at getting teams together and driven to a cause,” says Mary Drummond, Rosetta’s senior director of marketing.

Despite her knack, the genome business hasn’t been Chapman’s life quest. She played violin for 20 years, though her days in orchestras and quartets didn’t appeal as a career. And when she began schooling at the University of Cambridge, where she earned a bachelor’s in biochemistry and a PhD in cellular and molecular biology, genomics wasn’t in the picture. “I was going to be an ivory-tower professor,” she recalls, laughing.

Chapman was working on her doctorate when the completion of the first genome sequence sparked her interest “about all and anything to do with genomics.” As a postdoc, she was able to experiment with Affymetrix arrays before they were commercially available. Then, following fellowships at Cambridge and UC San Francisco, Chapman landed at Incyte.

“My first job,” she says, “was to build up an expression database for microbes of infectious disease.”

Nevertheless, Chapman soon wanted out of the lab. “I love science. I love reading about it, I love talking about it, but I don’t like actually doing it,” she says. It may also have stemmed from another trait: “I get really keen on things, and then I move on and get really keen on something else,” says the tall, slender woman who never admitted her age when she was in her twenties.

She tested the waters on the business side as Incyte’s marketing manager, and then Chapman moved north to work for Rosetta. “I wanted to come to a company that was young, that was small, where I could make an impact,” she says.

According to Drummond, Chapman’s experience in science and business makes her invaluable. And while some may fear youth as code for inexperienced, Rosetta had no such qualms. “If she weren’t a natural at it,” Drummond remarks, “she probably wouldn’t be where she is today.”

Though she no longer practices science, Chapman relies on her years of experience in the lab. “I can communicate with [science] guys and understand what they’re doing and at the same time have them feel reasonably trusting of me when I explain it to somebody else. And they probably wouldn’t trust someone without a PhD.”

Her move to Seattle was more than just a new job adventure. Chapman and her husband Guy Cavet bought their first house — a 75-year-old fixer-upper. “I spend my time with saws and drills. I’m cutting holes in walls and putting in windows and making frames with two-by-fours,” Chapman says.

Had she not gone into science, Chapman imagines she would have been a park ranger. But leaving the genomics industry now isn’t an option: “I’ve got too much invested in it,” she says.

Still, she says wistfully on a Thursday afternoon in December, “I could kill to go to Yosemite for the weekend right now.” As in other angles of her life, she likes to scale the cliffs.

—Meredith Salisbury


Michele Clamp, Team Leader

Sanger Centre, Cambridge, UK

Driven by Distraction

Michele Clamp loves a new challenge, sometimes to the point of distraction. For instance, the excitement of being a new student at Oxford University came close to derailing her education and future prospects. “I was almost thrown out after my first year for not doing much work. It was my first time living away from home,” she says.

Fortunately for Clamp, Sanger Centre’s 33-year-old team leader for Ensembl (which is managed jointly with Ewan Birney’s team at EBI), the novelty of exclusive partying wore off and she found physics fresh enough to stay interested through a PhD in high-temperature superconductors at Manchester University.

But by the time she graduated, she had discovered something even more interesting. “I realized I liked the computing side much better. I had an experiment I was supposed to monitor all night. I wasn’t going to do it so I automated it on a PC. I realized I enjoyed programming.”

In addition to steering Clamp toward bioinformatics, the epiphany got her out of the physics lab, and possibly saved her life: “I used to electrocute myself quite a lot,” she admits.

Her new interest led her to a job at a Manchester biochemistry lab designing algorithms for molecular dynamics. “Walking into a biochem lab was a complete revelation from working in a physics lab for four years. There were both sexes for starters, and people under 50. And it seemed like there were a lot of problems to be tackled that you didn’t need a particle accelerator for.”

Clamp also began working with genetic algorithms for protein folding — a comfort zone. “Physicists can relate to protein folding,” she explains. “It’s a language they know. It’s about atoms, potentials and crystals, the atomic level of things.”

After three years in the biochem lab, Clamp spent a “happy year setting up an analysis pipeline for genomic sequences” at the Wellcome Trust Centre for Human Genetics.

Next, she coded and developed visualization tools and Web servers, including the protein secondary structure predictor Jpred, on the Cambridge campus of the European Bioinformatics Institute.

Then something else beckoned. “I was at EBI and saw this data being generated at the Sanger Centre,” Clamp says. “The sheer amount of data coming out of the Sanger Centre needed attention. The lure of the Human Genome Project became too much and I moved into the human analysis group [at Sanger].”

The ambitious task of sifting through genomic data may hold her, at least for a while. “She’s never taken on anything that’s not exceptionally difficult,” says her fiancé, James Cuff, who is systems administrator for the Ensembl project. She excels at “doing nontrivial things and getting them going. People respect the amount of energy she puts in and focuses [on] the challenge of a difficult problem,” he adds.

While she acknowledges that she’ll likely be drawn in another direction before long — “There may be something else that attracts me, some new thing” — her position at Ensembl seems tailor-made for Clamp. “I want to be the first to come out with something, to do it before anybody else does it. It’s always given me pleasure to be the first person to see a gene structure,” she says. “I’m very proud to be working on Ensembl annotating large genomes — the mapping, sequencing, and fingerprinting. It’s a great honor. We’re part of history.”

—Ken Howard



Cyrus Harmon, VP of Computational Genomics

Gregg Helt, Principal Scientist

Affymetrix, Berkeley, Calif.

Metamorphic Men

One was president of the University of California ski team; the other a high-school hacker with a Commodore 64. One was expecting his first baby in January; the other wears his blond hair in dreds and enjoys going dancing with his hipster friends. One just bought his wife a Porsche 911; the other just bought his first bed.

Meet Cyrus Harmon and Gregg Helt, cofounders of Neomorphic — a four-year-old bioinformatics company that was bought by Affymetrix last Halloween for more than $70 million in stock. When the two first met in a genetics lab course at UC Berkeley, little did they imagine they’d wind up starting a company together. “I definitely noticed Cyrus in that class,” recalls Helt, who was the course TA. “He was always back at the computers while his partner worked at the bench.”

The recollection nicely sums up Harmon’s career trajectory. A Berkeley boy born and bred, Harmon, 30, completed his undergraduate degree in molecular biology and computer science at Berkeley, and then spent a few years in Gerry Rubin’s lab developing functional databases for the Drosophila genome project. “There was a real need for such analytical tools in the genomics community,” Harmon says, “but I was a lot more excited about doing the sort of science and engineering we were doing in a fast-paced commercial setting rather than an academic setting.”

Impatient by nature, Harmon is driven by a desire to tackle unsolved problems — and by a love of challenge. “I like to do things people tell me I won’t be able to do,” he explains. In the case of Neomorphic, Harmon says, “People in the back of their minds were thinking, ‘They’re never gonna make it.’”

But make it they did. From a company that once held its meetings around Harmon’s dining-room table (“a good place for brainstorming”), Affy-Berkeley — as Neomorphic is now known — has some 50 employees and is preparing to expand even further. Since the merger, the team is planning to beef up the programs researchers can use to view and analyze the gene expression data obtained from the microarray chips that are Affy’s claim to fame.

Which is where Helt comes in. “Gregg really captured the interest of the bioinformatics world with his visualization programs,” says Harmon. “He comes across as quiet, but people are intrigued by him and his ideas.”

Helt, 33, grew up on a farm outside Marion, Ind., where the major crops were corn, soybeans, and Christmas trees. “I planted a lot of Christmas trees,” says Helt with a shy smile. He left home to get an undergraduate degree in philosophy and biochemistry from Rice University in Houston and then made his way to UC Berkeley, where he joined Corey Goodman’s lab to work on fly neurobiology.

“It was pretty cool stuff in the abstract,” says Helt, “but day to day it’s pretty tiring.” So Helt started playing around with UNIX and eventually moved down the hall to Rubin’s lab to work on gene prediction in Drosophila. When he completed his PhD, his thesis included sections on graphical user interfaces for looking at data, programs for fly gene prediction, “and a one-page appendix on the three years of benchwork I did,” he chuckles.

As for outside interests, Helt says, “I have a lot of things I’d like to do.” Starting a business, he’s learned, can be all-consuming. Helt hasn’t even had time to upgrade his housing situation: Despite his six-figure income, he still has three roommates (although he does have the master suite, “with my own bathroom,” he’s quick to add). Helt thinks that his “hermit tendencies” may draw him to an isolated house among the redwoods, although the setup might force him to face his deepest phobia: “stepping on a banana slug in the dark when headed out to the hot tub.”

Where do Harmon and Helt see themselves in five years? That’s too far-off to predict, they agree. “What’s going to be out there?” wonders Harmon. “What will be the interesting questions?”

Helt hopes he’ll be doing something that will affect people’s lives. He talks about a former coworker — a friend with cystic fibrosis who died after receiving a double lung transplant. In a portrait that hangs over Harmon’s desk, the organs float eerily across the canvas. “It really drove home to me that there’s more to this than just thrill of discovery,” says Helt. “Hopefully our work will make a difference for the way we treat disease in the future. It wasn’t soon enough to help him, but I believe we’ll be changing the way medicine is done and the way we think of disease.”

—Karen Hopkin



Ian Holmes, Howard Hughes Medical Institute Associate

Berkeley Drosophila Genome Project, Berkeley, Calif.

Holmes Sweet Holmes

At 12, while others his age were playing video games, Ian Holmes was busy creating his own. “All my heroes were game-coders back then,” says Holmes.

For two years he spent his spare time, still dressed in his Cambridge, UK, lower school uniform, at his BBC Microcomputer (non-Brits: think Commodore 64) developing an action-adventure game called Pipeline.

At age 15 he sold Pipeline to Superior Software for £3,000 and several years later sold his second game, Galactic Dan.

Now 27, Holmes is a Howard Hughes Medical Institute associate at the Berkeley Drosophila Genome Project. His computer has been upgraded, but his work developing algorithms that use small RNA structural motifs to predict gene expression often tests the limits of its compute power.

Holmes recently made waves at ISMB presenting an algorithm that integrates DNA sequence and expression analysis. And he has revealed what’s under his kimono (k-means integrated models for oligonucleotide arrays) program that executes the algorithm for all to see on the Internet.

“One of the biggest problems that Ian has,” says Bill Bruno, for whom Holmes worked as a Fulbright fellow at Los Alamos National Laboratory for much of 1999, “is that he is technically so good that a lot of people don’t understand what he’s talking about.”

Holmes’ evolution from pubescent game programmer to promising young bioinformaticist was a happy accident.

Intent on tackling big complex random systems, Holmes says he was “into chaos theory, probably like most other people my age.” He studied theoretical physics at the University of Cambridge, but his dreams were dashed when Cavendish put him on a waiting list for admission to its PhD program in stochastic physics.

Surfing the Net while waiting for word from Cavendish, he came across the Sanger Centre. Cracking the code of life seemed a grand enough ambition to lure him. He joined Richard Durbin’s group there and earned a PhD in bioinformatics. “I was lucky to catch the first wave.”

Holmes, whose recent readings include Please Kill Me: The Uncensored Oral History of Punk, doesn’t regret passing up the stodgy Cavendish for the sequencing startup. “It was a really good environment,” he says of Sanger, which was housed in an old factory when he joined in 1995. He worked in an adjacent trailer cabin looking for transposons in what there was of the worm genome. Things got especially interesting when the holidays came around. “The informatics group would always dress in drag,” says Holmes. “That was the standard Christmas tradition.”

It hasn’t been all fun and games, however. Holmes nearly got beaten up by an anti-evolutionist barfly at Sultan’s, a seedy after-hours bar frequented by Sanger-ites. He recalls telling the fellow, “For someone so obviously related to a monkey, that can only be called denial.”

With characteristic British wit Holmes explains, “I was staring at alignments of primate sequences just that morning and the evidence was pretty strong. And I guess I had a few drinks.”

Now at the Berkeley fruit fly project, Holmes spends his spare time at his girlfriend Eliza’s eco-commune trying to convince her friends that not all genetics is evil, as well as selectively swatting away faculty position offers.

He’d like a position with the resources to implement his accumulating ideas. “It takes an afternoon in the coffee shop to come up with the idea, but then it takes a long slug to actually realize it,” he says.

—Aaron J. Sender



Christian Marcazzo, Director of Product Marketing

Lion Bioscience, Heidelberg, Germany

Lion’s Cub

By rights, 28-year-old bachelor and Berkeley grad Christian Marcazzo should be about halfway through his PhD, or bouncing from one job to the next, trying to figure out what he wants to do for a living.

Instead, Marcazzo, director of product marketing for Lion Bioscience, has already experienced the best and the worst of the bioinformatics business, having worked for one company that saw an early demise, and another that achieved a super-successful IPO. Along the way, he’s built a name for himself by launching Lion’s SRS 6 platform and enlisting almost 40 customers, including Celera, DeCode, Merck, Novartis, and Pfizer.

He graduated from UC Berkeley with a bachelor’s degree in molecular and cell biology. “I was looking for some way to be in biology but not be doing all the not-so-glamorous things you do in the lab,” he says. He stumbled across Molecular Applications Group in 1995, where mentor Charlene Son taught him about bioinformatics and marketing.

But MAG was in a downward spiral; Marcazzo moved to the UK in September of 1998 to join Lion and prepare the commercial release of SRS. “During the first days,” he recalls, “we were building the desks ourselves.”

He responded well to the start-up atmosphere and was promoted two years later to his current position at Lion’s German headquarters. For the native New Yorker who grew up in five different states, the relocations have been enjoyable. “Heidelberg is a great town and a great place to live,” he says, not only for its own qualities but because it’s a convenient jumping-off point to explore Europe.

It’s also a great place to work. “My responsibility is to be the interface between our sales and marketing team and our development team,” he says. “We really sit at the edge of product development in terms of driving and prioritizing our products.”

Another perk of his new position is fewer conferences — he’s down to four or five a year, compared to as many as 14 previously.

It’s hardly all work, though, says the man known to stay out with company friends till four in the morning. Drew Arnold, a Lion colleague, recalls a sales and marketing team exercise when they all raced for hours around a track in go-carts. Marcazzo was so competitive that he didn’t stop racing even after they left the track — and finally picked up a speeding ticket in Heidelberg. “There are numerous wanted posters of Chris around Heidelberg,” Arnold jokes.

But Arnold says Marcazzo is nothing if not a professional, and that he knows the industry better than anyone his age. “Every day the industry is growing so fast and changing so much,” Marcazzo says. “It’s exciting to think when you get up in the morning about all the new things that are going to happen during the day.”

This novelty is a thrill. Marcazzo confesses, “There’s something about the adrenaline of a start-up company that is kind of addicting.” Though he sees himself staying with Lion in the years to come, he’s tempted by the idea of building a spinoff of the company.

His own spin-off plans include eventually getting married and, within a year or two, finding a villa in Spain or Italy. (He has dual citizenship through his father’s father’s father in the latter.) Aside from scouting out the perfect place, he uses his precious spare time for skiing and mountain biking. For less exerting times, he reads postmodern fiction (Salman Rushdie is a favorite) or listens to music (hip-hop, jazz, and Cuban).

Along the way of his rapid rise, Marcazzo also used the time to grow more confident about his footing in the industry and to shed his self-conscious aversion to telling people his age, though he has by no means lost all of his self-consciousness.

“I’m sure I’ve said quite a few things I’m going to regret when this comes out in print,” he groans.


—Meredith Salisbury



Kevin McKernan, Team Leader for Automation

MIT’s Whitehead Institute, Cambridge, Mass.


After earning a bachelor’s degree from Emory University, Kevin McKernan followed the standard advice for pre-med students: Try something different before medical school. “I did that and got so busy, I didn’t have time for medical school,” McKernan says.

First he took a pharmaceutical marketing job that didn’t really click. In 1996, he got a position in a technology development group at MIT’s Whitehead Institute and was running the group within a year.

Soon, all thoughts of medical school fell by the wayside. “I realized I could have a more dramatic influence on medicine by focusing on research and development,” he explains. “I’d rather be in the lab, devising technology that can change the face of medicine, than in a hospital waiting for new tools to become available.”

Now, at age 27, McKernan has already made considerable progress toward that goal. “Kevin’s one of the biggest reasons we’re where we are today — the center with the biggest throughput in the Human Genome Project,” claims Jamie Walsh, a biologist in his Whitehead group.

As the Institute’s team leader of automation and development, McKernan has overseen the introduction of several generations of robotic technology. Last summer Agencourt Bioscience was formed to commercialize his patents for automating DNA isolation and purification processes. He serves as the company’s co-chief scientific officer.

With the sequencing phase of the Human Genome Project completed, McKernan says, “A thousand different races are about to begin. My goal is to make sure the Whitehead is well-positioned to venture into any of these emerging fields.”

He also intends to play an active role in translating insights from the genome into drugs and other medical benefits.

“Our research group is probably a few months ahead of the Genome Project as a whole, and Kevin is always a few months ahead of us,” Walsh says. “The key to development is trying new things, but you have to know what’s worth trying. Kevin has a great intuitive sense as to what will work.”

As a manager, McKernan is the type who likes to “get in the trenches” and “kick the tires” of every single robotic instrument in his lab. That’s part of the reason he’s proficient in nine computer languages — “because just about every robot that comes in here speaks a different language.”

His Whitehead job consists of “long days of wrestling with the equipment so that I can get it to do my job for me.” Juggling that effort with his Agencourt responsibilities has forced him to change his metabolism so he can survive on five hours of sleep per night.

That same metabolism may account for his trim, athletic frame, since his schedule affords little time for his favorite sports: scuba diving, rock climbing, and skiing. He reads about science in his spare moments, although his wife, an archaeologist, wishes he’d branch out a bit more. On the rare nights that he cooks, he admits to being “a dangerous person to have around the spice cabinet.”

McKernan exudes confidence and ambition without a trace of arrogance. “What motivates me,” he says, “is being in the right place at the right time, knowing I’m in a field that is about to mushroom.”

—Steve Nadis



Moira Regelson, Project Leader for Bioinformatics Systems

Paracel, Pasadena, Calif.

Paracel’s Paradox

Forget her role as a bus-riding Martian in a student play at Barnard College. Put aside her martial art ability to reach the head of a 6-foot-2-inch person with a flying kick. By her own admission, “the weirdest thing about me is that I’m female in this field.”

Which means that Moira Regelson, 33, is both not so strange and also pretty unique — one of several contradictions maintained by a New Yorker living in a 1906 Craftsman house in California.

She’s a mathematician who ended her formal biology education in junior high, yet now solves complex genomics problems for a living.

Her ability to straddle different sciences has served Regelson well in her job at Paracel where, as she describes it, she “brings things into compliance with the rest of the world.” This includes making company products compatible with industry standards for software such as HMMER, GCG Profile Search, and GeneWise.

Michael Sievers, Paracel’s manager of applications science and Regelson’s former supervisor, says Regelson’s contributions have been significant. “To be able to understand exactly what’s going on with the algorithms and then translate them so an engineer or a computer scientist can understand them is crucial,” he says. “She does the upfront mathematical analyses, but also the detailed implementation.”

Her job is a fusion of the pure math she studied as an undergraduate, where she grew tired of “theorems about theorems,” and the work she did on her way to a PhD in applied mathematics from the California Institute of Technology.

Asked about mentors, Regelson names Georgeda Buchbinder, a family friend who died while Regelson was in college. “She had a PhD in anthropology, an MD, a black belt in karate, a couple of masters’. She did so much with her life, she was an inspiration.”

The influence is clear. “During grad school I tried a lot of things,” Regelson says. “I read a lot of papers and got ideas. I tried to go from ideas to functional code, making that leap from some vague idea and putting it in tangible reading code.”

At Cal Tech, she became involved in the research her advisor Jerry Solomon was doing in protein structure prediction. This rekindled an early interest in DNA, which she thought was “cool” but had not pursued after her initial exposure to biology. “The last formal biology class I took was in eighth grade where we dissected things. It seemed way too empirical, just cataloguing.”

As a trainee with the Human Genome Project while at Cal Tech, Regelson began applying hidden Markov modeling to protein structure prediction. This would eventually lead her, via a casual walk through a job fair, out of the “battling egos and politics” of academia and into the high-tech industry.

“Paracel had a booth with Markov models,” she says. “I left my résumé. Fifteen minutes later I got a telephone call from them.”

She hasn’t looked back. After developing software for about two years, she was made a project leader. Though she now directs a team in designing, implementing, and validating new algorithms for Paracel’s GeneMatcher hardware, she still enjoys what initially attracted her to the field. “I find it entertaining to make sense out of some complicated sets of facts or make a complicated algorithm run.”

While that interest may be shared by many of her mostly male colleagues, Regelson points out that she claims “no global domination plan like some other people.” Then again, few other people can deliver a brutal kick to the head of anyone who might get in their way.

—Ken Howard



Doug Rusch, Scientist

Celera Genomics, Rockville, Md.

Blowin’ and Goin’

Doug Rusch isn’t known as a bruiser. Actually, people say he’s an all-around nice guy, funny albeit a bit goofy. So when he and a coworker showed up at work black and blue with stitches, people wondered. Was it a fight? A car accident?

Nothing of the sort. As winter took hold over Maryland, Rusch and five of his colleagues sat in a dark, smoky, underground pub, six people crammed in a four-person booth. As they relaxed with their first beers, Rusch leaned to say something to his neighbor at the same moment that she turned to do the same. Skulls and eyeglasses collided, generating bruises, blood, and hysterical laughter.

Fortunately for Rusch and Celera —where he’s an up-and-coming scientist — he’s no klutz when it comes to science.

Rusch, who is 31, just shy of six feet tall, and sports a goatee that he forgets is there, has a PhD in genetics from Indiana University and a penchant for writing computer programs “to relax” at home. So it’s only natural that he serves as a go-between for lab biologists and computer scientists at Celera, where he works to find genes and use computers to uncover what they do.

His background in computer programming and biology allows him to do this gracefully. “Computer scientists have a good understanding of how to write algorithms to do certain things,” he says, “but they don’t always understand the biology and how it might affect the behavior of their algorithms.”

Rusch makes sure that Celera’s biology and its algorithms mesh by helping write code that takes the science into account, while helping biologists and computer scientists convey information to each other in terms they can all understand.

“It’s tough sometimes,” he says, “because they speak very different languages.” Though he says he’s no linguist, Rusch speaks a few languages that make him a valuable asset in his field: he’s fluent in biology and computer, and speaks “a little bit of English.”

“He’s just blowin’ and goin’,” says his colleague Mark Yandell, the coordinator of genome annotation software at Celera. “He’s all over the place, and he’s savvy about creating programs that deal with biology in a meaningful way. He has a great biology background and a phenomenal knowledge of software ¯ that’s a killer combination in informatics.”

Celera was just getting off the ground as Rusch went onto the job market; the two seemed a perfect fit, and he’s content staying there for the foreseeable future. On a path that began as a child fascinated with dinosaurs and outer space, Rusch has moved from a teenager flipping burgers in a hot, greasy restaurant at SeaWorld to a scientist who reads Harry Potter books and makes his own computer games.

He isn’t sure what will come next. Perhaps he’ll get married and travel around the country, maybe he’ll move into academia, or stay in the private sector indefinitely. “I leave the future up as a surprise,” he says with a chuckle, “because I like to be surprised by little things, like bumping heads in a bar.”

—Rebecca Skloot



Maciek Sasinowski & Heather Sasinowska

CEO and VP Incogen, Clemson, SC

Dynamic Duo

Maciek Sasinowski seems always to have been wise beyond his years. At 14 he was hired by a computer shop in Hamburg to translate for Polish customers. He figured out as an undergrad at Youngstown State in Ohio that the socially isolated life of an academic physicist was not for him. He knew long before she did that he would marry a college acquaintance. And he was subtle enough to let her believe it was mere coincidence when he ended up two states away at the same graduate school as she.

Today, the 28-year-old CEO and his 31-year-old wife, Heather Sasinowska (she followed Polish tradition by taking the feminine variation of his name), run their own bioinformatics company with the management flair of Stephen Covey.

At genomics conferences, Incogen (Institute for Computational Genomics) staff stand out like an interloping family reunion. They’re the group you’ve seen looking spiffy on the exhibit floor in business dress on opening day, or clad in Hawaiian prints after hours in Miami.

Sasinowski says he does his best to make the 12-hour workdays and intense start-up workload enjoyable for his team. The close-knit group, which includes another married couple and Heather’s father, Lou DiSimone, eats lunch together twice a week to mull over current events or listen to invited speakers.

Brian Kamery, Incogen’s 32-year-old principal scientist, says that at the root of the company’s team spirit is the Sasinowskis’ genuine enthusiasm and kindness. But he also hails the pair, who look more like homecoming queen and football captain than science spouses, as “two of the most intelligent people I’ve ever known.”

Sasinowska, who has a fondness for fashion design and quilting but confesses to having been labeled a “brain” in high school, holds one master’s degree from William and Mary and another, as well as a PhD in Bayesian statistics, from Duke University. She abandoned a tenure-track position teaching statistics at Clemson last May to become VP for her husband’s early-stage firm — a post that she says is more rewarding than what she gave up.

Her counterpart earned a PhD in computational physics from William and Mary and worked briefly for a friend’s computer-game company while Sasinowska finished her PhD. They were hired together by Clemson, where he established the Bioinformatics Center at the school’s Genome Institute before launching Incogen.

The two, who say they haven’t found time in five years for a honeymoon, published their first joint bioinformatics paper in 1998 on a program they developed to construct physical maps from hybridization and fingerprint data. At Incogen, they continue to codevelop bioinformatics analysis and visualization tools.

Kamery observes that Sasinowski and Sasinowska slide effortlessly between their professional and personal relationship and attend to Incogen like a first child. The duo says sharing a career is a pleasure, but that separate hobbies keep them sane: In December, while he spent leisure time zipping around a track in his Porsche, she raced to quilt a bedspread by Christmas.

Their formula seems to be working. Incogen’s staff grew from five to 15 this year, and its software and turnkey bioinformatics services have captured fans in the genomics market. The company has partnerships with Time Logic, Sun Microsystems, Baylor College of Medicine, and University of Minnesota. Customers include Aventis/RhoBio, BASF, Edge Biosystems, Michigan State University, Sigma-Aldrich, Syngenta, and University of Delaware. Though he won’t put a dollar value on the firm, Sasinowski says Incogen’s annual revenues “aren’t that far behind some of the bioinformatics companies who just had $100 million IPOs.”

Incogen’s 2001 goals call for further growth and several “high-profile” deals as well as a financing round. Sasinowski envisions several possible future scenarios — IPO, merger, or acquisition — but says that ultimately he defines success as “being in the position to work when you don’t have to.” Wise beyond his years.

-Adrienne Burke



Christophe Schilling, Chief Technology Officer

Genomatica, San Diego, Calif.

A Full Schilling

Christophe Schilling, 27, wasted no time making his way into the real world after receiving his PhD in bioengineering from UC San Diego last year. He jumped immediately into a job as chief technology officer of Genomatica, a company he founded to develop software tools for drug target identification.

It was during his final year of graduate school that Schilling and his professor Bernhard Palsson incorporated Genomatica, put together a business plan, raised start-up capital from angel investors from Palsson’s homeland, Iceland, and landed an SBIR grant from the National Science Foundation.

By spring 2000, as soon as Schilling had his diploma, he began hiring staff and building modeling approaches for studying cellular systems.

Genomatica takes gene sequences from single cell organisms — bacteria, yeast, human cell lines — to develop genomic analyses that piece together cellular networks. It combines the data with results from gene expression and protein interaction studies to provide a picture of the molecular interactions inside a cell. The company’s bet is that models of these interactions will furnish the structure for a range of applications including drug discovery and bioprocessing.

“Christophe’s research applies high-performance computing to better predict and understand cellular function,” says Daniel Joy, business development manager for the chemical and biological sciences group at Compaq Computer, who recently dined with Schilling. “He understands the need to apply advanced computing systems and develop innovative algorithms.” Joy predicts that Genomatica’s efforts will help the pharmaceutical industry become “more predictive” in drug discovery.

Schilling explains, “I’ve always been application-oriented, and the company represents the ability to take technology that I assisted in developing in the very early stages and now apply it to what it was ultimately intended for, rather than moving on to another academic research project and not following through.”

Schilling also has entrepreneurship in his blood: both his father and brother run their own companies. As Schilling puts it, the companies he grew up around — ski clothing manufacturing and automotive parts — were not at all like biotech companies, “where millions of dollars are raised based on future promise.”

He says his brother and father ask him: “‘So, who are your customers? What’s your product?’ They keep me well grounded in the realities of business.”

Schilling was first in his family to get an advanced degree. As an undergraduate at Duke, he majored in biomedical engineering. “I was going down a double path of biology and electrical engineering. But my real interest was always in genetics so I got a minor in that, which propelled me in grad school to work with Bernhard and the types of problems we do now, applying engineering principles to study biology.”

Just as he does for the soccer team he coaches, Schilling says he views “everything that goes on around me as one part of a system of interacting components.”

—Karen Young Kreeger


Adam Siepel, Acting Director of Information Technology

National Center for Genome Resources, Santa Fe, NM

Making Sense of Babel

“It’s very simple,” says Stephen Joseph, president and CEO at the National Center for Genome Resources in Santa Fe, when articulating Adam Siepel’s abilities. “He has a kind of focus about him that’s not obsessional, an intensity of dedication to what he’s doing to make it work.”

Simple is a relative term. Siepel, 28, is NCGR’s acting director of information technology. His other title is program leader for integration, which belies a job that is no small task. The Center has several programs, most of which are oriented around such biological data types as gene expression, pathways, and structural genomics. “The integration program is an exception to that rule,” explains Siepel.

He sees two dimensions to integrating the cacophony of database languages and content. The goal is to provide software that spans biological data types and species databases to create connections among the disparate data types. “If you look at resources available now in bioinformatics, many are providing information along one of those dimensions but not the other,” notes Siepel.

The fundamental problems standing in the way of merged databases range from dissimilarities in syntax and semantics to differences in operating systems and platforms.

But Siepel is no stranger to constructing what he needs from the ground up. When he was about 10, his family’s farm home in upstate New York burned to the ground. He and his father, a physician and skilled carpenter, felled their own red pines, cut planks, and rebuilt the timber-frame structure from scratch.

That experience ignited Siepel’s lifelong interest in creating and building. Siepel says he’s driven to understand how things work, and attracted to the aesthetics of establishing order out of messy, complex things like databases.

After graduating with a BS in agricultural and biological engineering from Cornell University in 1994, Siepel worked at the Los Alamos National Laboratory before landing at NCGR in 1996. He dove full-time into an MS program at University of New Mexico in August 1999. In his future, he sees a PhD in computer science, and eventually a position at a research facility.

Aside from his father, Siepel credits Los Alamos computational biologists Gerry Myers, Bette Korber, and Aaron Halpern with inspiring him to move into genomics.

At NCGR, he says chief scientific officer Bill Beavis showed him how to blend being a scientist and manager, while Andrew Farmer taught him how to bring experiences from other parts of his life to bear on technical problems.

And it’s likely Siepel’s wife of three years — a humanities major at a nearby university — who influences his leisure-time activities: Siepel went on a Russian historical novel kick last spring, curling up with War and Peace and Anna Karenina. But integrating biology and machinery is never far from his thoughts. Darwin Among the Machines by George Dyson, sits on his bedside stand now.

—Karen Young Kreeger

The Scan

Drug Response Variants May Be Distinct in Somatic, Germline Samples

Based on variants from across 21 drug response genes, researchers in The Pharmacogenomics Journal suspect that tumor-only DNA sequences may miss drug response clues found in the germline.

Breast Cancer Risk Gene Candidates Found by Multi-Ancestry Low-Frequency Variant Analysis

Researchers narrowed in on new and known risk gene candidates with variant profiles for almost 83,500 individuals with breast cancer and 59,199 unaffected controls in Genome Medicine.

Health-Related Quality of Life Gets Boost After Microbiome-Based Treatment for Recurrent C. Diff

A secondary analysis of Phase 3 clinical trial data in JAMA Network Open suggests an investigational oral microbiome-based drug may lead to enhanced quality of life measures.

Study Follows Consequences of Early Confirmatory Trials for Accelerated Approval Indications

Time to traditional approval or withdrawal was shorter when confirmatory trials started prior to accelerated approval, though overall regulatory outcomes remained similar, a JAMA study finds.