The big picture

To understand the story of biology, and the crucial turning point the field has reached, consider the rose.

A 19th-century botanist would have sketched the wine-hued bloom, noted the pattern of thorns winding its stem, and studied the lines on its jagged leaves. A generation later, scientists would use the new tools of chemistry to extract the compounds that lend the rose its distinctive perfume.

In recent years, a scientist interested in roses might look at the sequence of its genetic code.

For more than a century, the way forward

has largely been to study smaller and smaller pieces of the whole.

Now, quite suddenly, biology is being consumed by a fast-moving intellectual revolution that could profoundly change the course of science -- and medicine -- in the new century. Called "systems biology," it is an audacious attempt to transcend molecular biology and understand organisms as complex interacting systems that are more than the sum of their parts -- that the best way to understand ants, for instance, is to study colonies rather than just the individual insects.

In only a few years, the idea has gone from fringe concept to rallying cry as Harvard, MIT and universities around the world scramble to establish large new systems biology efforts.

"This has happened so fast it is astonishing," said Evelyn Fox Keller, a professor of history and philosophy of science at MIT. In a sense, the movement represents a return to some of biology's broader, more basic, questions: How does a heart beat, or a flower bloom? But it is also a recognition that as good as science has become at mapping parts -- including, most spectacularly, the human genome project -- the real genius of life springs from how these pieces interact.

"To do systems biology, you have to capture the dynamic flow of information," said Dr. Leroy Hood, an intellectual leader of the movement and president of the Institute for Systems Biology in Seattle. "You have to put all these different types of information together."

Powered by flexible, automated laboratory equipment and new computers and mathematical techniques, scientists are now able to gather and interpret more data than anyone could have imagined even a decade ago. Biologists have thus gained the ability to catalog every component involved in some bewilderingly complex process, such as the development of a sea urchin, and then use computers to untangle how the pieces interact to make it happen. Adding to the enthusiasm for systems biology is the belief that it will reconnect biology with medicine. Much of what happens in biology labs today is so narrowly focused that it has only the faintest promise of helping doctors treat patients. Very little is known about how any one of these processes fits into the whole, which is why so many promising ideas for drugs eventually fail.

"The advances we've seen in biology over the last 20 years just stagger my mind," said Marc Kirschner, who was just named head of Harvard Medical School's department of systems biology, the school's first new department in 20 years. But "I look at physicians, in a way, as the monks who preserved physiology during the dark ages of molecular biology."

Systems biology faces enormous challenges. Engineers have not been able to design the robotic laboratory tools to gather the detailed information they will need. The computational methods used to make sense of huge batches of information are still relatively unsophisticated in relation to the demands that will be put on them. And nobody can know whether biology has indeed advanced enough -- or whether it is pure hubris -- to attempt what amounts to a full frontal assault on some of the field's deepest problems.

At least as daunting are the cultural and institutional obstacles. Systems biology will require researchers from many fields, including mathematics and engineering and computer science, but today's universities are divided into disciplines that jealously guard their turf.

But the draw of systems biology is strong enough that it could force the old disciplines to change their ways. In January last year, MIT started a Computational and Systems Biology Initiative, a grass-roots effort that involves about 80 faculty from a range of areas. Last year, cross-Cambridge rivals Harvard and MIT announced that they were launching the Broad (pronounced to rhyme with road) Institute, with a $100 million gift and plans to raise $200 million more, to transfer genomic science into medicine.

In the fall, the National Institutes of Health announced a new "roadmap" for its support of scientific research, sending a powerful message that it will be supporting systems biology, and the kinds of interdisciplinary research needed to sustain it.

"The roadmap is made for systems biology," said Peter Sorger, the director of MIT's initiative. And just last month, MIT held a conference on systems biology, drawing the heads of new initiatives around the country.

While Hood and the new Broad Institute are heavily involved in exploring the genetic machinery of cells, there are other popular approaches, too. For example, a team led by Marc Kirschner recently created a detailed mathematical model for an important cellular messaging route called the "Wnt pathway." Disruptions in the route can lead a frog embryo to develop two heads, and are known to be behind colon cancer, one of the nation's top killers.

Life did not come about through a single brainstorm but through many millions of years of small, incremental changes. This means that even a seemingly simple question -- what signals a rose to flower? -- has a profoundly complex answer that involves many systems in the plant that also have myriad other uses.

That is why the only way to know if a new drug will work is to actually test it in people. Interfering with one system may send out a ripple of changes through a system we just don't understand; it could bring on deadly side effects, or changes that counteract the intended effect, rendering the drug useless.

This same logic has humbled attempts to understand the human genome. The dream of biology now is to discover how an organism's genetic code is turned into what the first biologists were fascinated with -- the petal, the claw, the hand, the brain. They want to know how the information encoded in the genome links to the bigger things.

"The failure to connect these two," Kirschner said, "is going to be biology's failure until we succeed."

Gareth Cook can be reached at cook@globe.com.