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The Great Integrator

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What does World Cup soccer have to do with systems biology? Ask Hiroaki Kitano.

by Sara Harris

Hiroaki Kitano believes that systems biology might be just what Japan needs to regain its edge in the life sciences. A 40-year-old computer scientist-turned-microbiologist, robot fanatic, and self-taught language expert, Kitano is on a quest to advance a newer than new biology that marries computer simulations with lab-based efforts to tease out an understanding of the as yet unknown mechanisms of life.

Kitano, who manages to self-promote while maintaining an unassuming kid-next-door persona, claims he coined the term “systems biology” before Lee Hood did. In fact, he considers his Kitano Symbiotic Systems Project — a five-year, $15 million, government-funded effort housed in an apartment building in the heart of Tokyo’s trendy Harajuku district — to be the hub of the nascent discipline.

Following Sony’s 1999 launch of the popular pet robot dog Aibo, a project that he shepherded as executive director, Kitano turned his attention to promoting systems biology to sympathetic bureaucrats and the scientific community, and within his own labs.

Kitano not only claims to have named the field, but to have laid the tracks it will travel: His is a three-pronged approach consisting of the Perfect C. elegans Project, the Virtual Drosophila Project, and the Virtual Cell Laboratory Project, which looks at yeast and human fibroblasts. While the organisms Kitano decided to tackle are foremost data-rich resources, they pose unique modeling problems and together could overlap to create a more widely applicable system.

Ultimately, Kitano aims to build a “class library” of simulation patterns and technology on which other researchers can draw. A Systems Biology Markup Language that his international group of researchers developed is a recent effort to achieve consistency across the field.

Office art and soccer robots Kitano has infused his offices, which were featured recently in an exhibit at the Museum of Modern Art in New York, with creative thinking, planning, and work spaces; tabletops for projecting images; and walls on which workers scribble ideas. Upstairs is a jury-rigged amalgam of 32 computer processors he bought and assembled in a matter of weeks. The cluster hums away at the task of processing simulated images that Kitano and his team of young researchers construct from data culled from biological experiments conducted at California Institute of Technology.

About 30 percent of his lab’s effort is focused on developing humanoid bipedal robots — a project of personal interest to Kitano. Kitano heads the international RoboCup competition for which engineering teams are developing fully autonomous, soccer-playing robots. Annual trial competitions are aimed at fielding a team by 2050 to beat the human World Cup champions.

The developmental biology research Kitano is pursuing would seem to offer a lot of hints for the robotics work going on next door. But Kitano says the opposite is true. Advances in robotics and vision technology research instruct advances in micro- scopy and automatic image analysis. They might also prove instrumental in developing needed precision-measuring techniques and other high-throughput processing technology.

It is the ability of this former English-language debate star to master and integrate the arcana of so many disparate fields that impresses. “I can attest here that he is a genius,” raves collaborator Shin-ichiro Imai, a cellular aging specialist at MIT who remarks upon Kitano’s great capability to absorb any knowledge that is totally new to him.

Artificial Intelligence Roots

What turned this engineer/ computer scientist on to life sciences? Kitano traces his biology beginnings to the summer of 1994, two years after he earned a PhD from Kyoto University and a year after he won the prestigious Computers and Thought Award for powering a spoken-language translation system with massively parallel computing. As an invited speaker at a seminar for scientifically talented youths, Kitano met Imai, who was then at Keio University School of Medicine, and MIT neurobiologist and Nobel laureate Susumu Tonegawa.

When the issue of a computational approach to biology was raised, Kitano recalls that Tonegawa argued that “all the data and experimental results [were] not precise enough to do the computer simulation.”

It was a green light for Kitano: “If he thinks it’s not possible now, probably it’s worth challenging,” he says he reasoned.

Kitano has never been one to let a challenge pass him by. In the corporate world, the undergraduate physics major wasn’t satisfied until he had created a side career as an interpreter to supplement his “boring” day job developing software at NEC. When Kitano returned to school it was to get involved in the “wild” young field of artificial intelligence, working simultaneously as a visiting researcher on a spoken-language translation system at Carnegie Mellon.

Whether his approach is from language, physics, or biology, Kitano’s goal has always been the same: a better understanding of human intelligence. “I thought, if I understand matter and space — which is physics — and intelligence and life, probably I’ll [understand] quite a bit of what’s going on in this world.”

It was in collaboration with Imai that Kitano developed the ideas he later dubbed systems biology. Their goal was to elucidate mechanisms that had given Imai some quirky data not fully explainable by existing theories of cellular aging. Their Virtual Cell Laboratory software system, which simulated developmental processes by modeling 50,000 virtual cells and tracing the products of more than 1,000 genes, helped them identify aging-controlling mechanisms in regions they labeled heterochromatin islands. They used their findings to expand on the then-controversial telomere hypothesis of cellular aging.

Aside from the approval of his fellow scientists, Kitano is striving for the support of his government. Already, he has set up an institute to carry on after the Symbiotic Systems Project’s funding dries up two years from now. He envisions his Systems Biology Institute becoming Japan’s first independent research institution in the vein of Scripps or Cold Spring Harbor.

Simulation technology, Kitano believes, will guide otherwise hit-and-miss experiments with knockout genes and encourage advances in drug design, organ cloning, and disease studies. With continued monetary support, scientists could even build a Systeome Project, he says. Among several “strategic goals for the nation” that he set forth in the Nikkei Weekly last year, Kitano argued for detailed cell and organ models by 2020 and, by 2030, “a comprehensive system-level analysis of the relationships between mutations and drug sensitivity.”

If he wants to be around to see the end results of his RoboCup project, Kitano figures he will need to reach age 90. That may require the fruits of his own research, he jokes, “So I need to finish that project much earlier.”