TEN years from now, you will not have to spend hours in a doctor's office to complete a comprehensive health check-up. Instead, with just a single pin-prick, a nanotechnology device will quickly measure and analyse 1,000 proteins in a droplet of your blood. Based on this “molecular fingerprint”, your doctor will prescribe drug regimens tailored to your personal state of health that will not only be able to reverse many diseases, but will also prevent their manifestation in the first place.

That, at least, is how Leroy Hood, the president and co-founder of the Institute for Systems Biology, a non-profit organisation based in Seattle, lays out the future of medicine. “The Human Genome Project has given us a parts list,” he explains. The next step is to capture the information from all the elements in a biological system: DNA, proteins, cells and organs, and then create new mathematical models that will represent the relationships between them. The ensuing digitisation of biology, he reckons, will revolutionise the entire health-care system and usher in a new era of predictive, preventive and personalised medicine.

Today, it sounds far-fetched. But as many of his colleagues and friends attest, Dr Hood, an avid outdoorsman, has never been shy of climbing a mountain or going out on a limb. Throughout his career, the 66-year-old has made it a habit to champion ideas that were initially unpopular but later proved correct. For one thing, he was one of the early proponents of the project to sequence the human genome, at a time when many of his contemporaries had doubts about its viability. Moreover, the very instrument that turned the endeavour into a success, the automated DNA sequencer, originated in his laboratory.

Yet the machine for which he is best known is only one of many inventions Dr Hood has successfully commercialised. To date, he has co-founded more than ten companies, including Applied Biosystems, which went on to become the biggest life-science instrument company in the world, and Amgen, the largest biotechnology firm in the world. He also holds 14 patents, has won numerous awards, and has co-written four textbooks—with a fifth, about systems biology, now in the works. But, most important, he has become one of medicine's boldest visionaries.

Even at a young age, Leroy Hood showed an independent streak. Growing up with his family in rural Montana, he developed an early affinity for the outdoors and started hiking in the nearby mountains as a young boy. While he excelled in the sciences, he was never a nerd. He learned to play the piano, among other instruments, joined a successful debating club and, during high school, was quarterback in an American football team that was undefeated for more than three years.

He finally set his sights on biology when his high-school chemistry teacher asked him to help teach a class on the subject for younger students. He agreed on the condition that he could base his lectures on articles from Scientific American, a popular science magazine. One article from 1956, about the structure of DNA, made a lasting impression on him. The same chemistry teacher also pushed the young Hood to apply to the California Institute of Technology, where he would spend much of his student and professional life.

Immune response

As a PhD student at Caltech in the mid-1960s, Dr Hood got his first taste of scientific controversy, when he became involved in an argument over how the human immune system produces such a wide diversity of antibodies to fend off disease. Up until then, the explanation for antibody diversity had been based on the theory that one gene provides the recipe for one protein, or polypeptide chain. (An antibody consists of four such chains, in two identical pairs.) But when it became apparent that the human genome contained at most 100,000 genes, while the body could create hundreds of millions and possibly billions of antibodies, that explanation was thrown into question.

Together with his mentor, William Dreyer, Dr Hood proposed a radical new hypothesis. They suggested that antibodies were encoded by a relatively small number of genes that can rearrange themselves to make up new sequences, akin to creating new sentences by breaking up and reshuffling a string of words.

The suggestion that some genes might not have a permanent structure, but could splice and rearrange themselves, seemed outrageous at the time, and it catapulted Dr Hood into the midst of a cutting-edge discussion in immunology. As a result of all the hoopla, and despite being only a graduate student, he was invited to travel and give lectures at prominent universities and national meetings (though he also spent hours in the laboratory sequencing proteins by hand). In the end, it took another ten years until all the tools became available to prove the theory right, which led to a 1987 Lasker prize for Dr Hood, Philip Leder and Susumu Tonegawa (who also received the Nobel prize later that same year).

Frustrated by the limitations of manual laboratory work, Dr Hood concluded that it was essential to invent new tools that could drive biological discovery. So when Caltech hired him in 1970 as an assistant professor, he decided to divide his time between technology and biology. By the end of the decade, his efforts had born fruit—his laboratory created a new protein sequencer that was much more sensitive than previous instruments. And when a friend suggested mass-producing the device, Dr Hood went knocking on doors.

Finding a sponsor was easier said than done. After 19 rejections, Dr Hood was somewhat discouraged. Fortunately, a venture capitalist heard about the prototype and offered him $2m to start a company. Dr Hood was elated, but his difficulties were still not over. Today, eager universities help professors to file patents and commercialise ideas. But back then it was uncommon for academic institutions to be so co-operative. Caltech's president at the time, Marvin Goldberger, was reluctant to make commercial deals, although he finally relented and gave the go-ahead for the creation of Applied Biosystems.

“Critics suggest that systems biology may simply be too complex for mathematics. Dr Hood is unfazed.”

The company's success was based on four machines, all of which originated in Dr Hood's laboratory during the 1980s. (As a result, Caltech still receives patent royalties of approximately $10m a year.) Together, they opened up new fields in biology. The protein sequencer, for example, made possible the analysis of small amounts of protein that had previously been inaccessible. Next, the protein synthesiser assembled long chains of amino acids, making it possible to produce large quantities of proteins. The third machine, the DNA synthesiser, could churn out pieces of genes to aid in DNA mapping and cloning. But the most sophisticated instrument was the automated DNA sequencer. It replaced confusing radioactive labels with laser-activated fluorescent dyes, making sequencing faster and much more precise.

Back in 1985, however, when Dr Hood participated in the first meeting to discuss the possibility of sequencing the human genome, biology was still very much a manual science. People worked with Petri dishes and cultures of goo, explains Michael Hunkapiller, a former research fellow in Dr Hood's lab who went on to become president of Applied Biosystems, and is now a venture capitalist. “The molecules that affected biology were viewed at that time as too complex to analyse easily,” he says.

As a result, many biologists were wary of the project. They worried that the technology was not up to the job, that it would take too much time and cost a fortune, thus drawing away valuable resources from other research. Others were repelled by the idea of “big science”, fearing that the sociology of the field might change to one that would be dominated by expensive, large-scale enterprises.

Biology without borders

In the end, the project—which finished in 2003, ahead of schedule and under budget—fundamentally changed how biology is practised. According to David Baltimore, the current president of Caltech, it highlighted the need to involve scientists from fields outside biology, leading many universities to adopt cross-disciplinary approaches to the subject. This approach is, of course, vintage Leroy Hood, observes Roger Perlmutter, executive vice-president of research and development at Amgen, and who also heads the board of the Institute for Systems Biology. “Since he joined Caltech as a faculty member, he has been trying to marry engineering and the physical sciences with biology in order to produce tools that could revolutionise biomedical research,” he says.

Over the years, as the ambition of Dr Hood's plans grew, so did his staff. When he first arrived at Caltech in 1970 he had fewer than ten people associated with his lab. By 1990, there were more than 100. Dr Hood then became interested in creating an entirely new department, explicitly dedicated to cross-disciplinary efforts and comprised of biologists, chemists and engineers. But such a grand vision for the relatively small school did not sit well with the rest of the faculty. In the end, the majority of biologists reacted negatively to the idea.

In 1992, Dr Hood was invited to chair the new cross-disciplinary Department of Molecular Biotechnology at the University of Washington in Seattle. With $12m in start-up funds from Bill Gates, he accepted. “But the seeds of tragedy were sown for the next thing,” says Dr Hood, even though he achieved a lot over the following years. Among other activities, his department operated two of the 16 centres for sequencing the human genome, and one of its members helped create the field of proteomics, the cataloguing of the proteins for which the genome provides the recipes. But in the end he was unable to convince the dean of the medical school to allocate more space for his once-again growing department.

Experiences like this convinced Dr Hood that it is virtually impossible to develop revolutionary new ideas within existing structures. So in 2000, at the age of 61, he decided to leave academia behind. Together with two former colleagues, he formed the Institute for Systems Biology—without a penny of endowment.

Already, the institute has more than 170 staff members and an annual operating budget of $28m, mostly from government contracts and grants. Moreover, Dr Hood has been able to attract an amazing calibre of collaborators, including Michael Phelps, the inventor of positron-emission tomography, who chairs UCLA's Department of Molecular and Medical Pharmacology, and James Heath, a physical chemist at Caltech who belonged to Richard Smalley's group that discovered “buckyballs” (soccer-ball shaped carbon molecules). Together they have founded the NanoSystems Biology Alliance, with the aim of developing a nanosensor device capable of making five measurements from a blood sample by the end of this year, and 1,000 or more within ten years. “These nanotechnology tools will be mass-produced and used by every scientific investigator, even in small labs,” predicts Dr Hood.

Despite his track record, his new ideas have proved as controversial as ever. Critics point out that systems biology may simply be too complex for mathematics; others say the timetable for creating the proposed nanotech instruments is too ambitious. But Dr Hood, who has heard similar arguments before, is unfazed by the scepticism. “It doesn't bother me in the slightest,” he says. “In the end what counts is what you do.”