BY DAVID F. SALISBURY
You accidentally bump into someone in the lab or hallway and learn something that changes the course of your own research.
It's an experience many faculty and students share, says James Spudich, professor of biochemistry and developmental biology.
"But is there a way to facilitate the accidental coming together of individuals from different disciplines?" he wants to know. "Is there a way to increase the rate of interactions at the global scale?"
Spudich and an eclectic group of faculty members from the schools of Engineering, Humanities and Sciences, and Medicine not only think it is possible, but feel that the course of the much-heralded revolution in the biological sciences makes it imperative. They are backing an ambitious new interdisciplinary initiative, called Bio-X, that is specifically designed to strengthen the links between faculty and students in medical research, engineering, chemistry, physics and biology.
Not to be mistaken for the unknown or alien "X" of TV's popular "X Files," the new undertaking is conceived as an eclectic mix of clinical researchers and basic scientists sharing insights -- but with no predetermined agenda. Last month, Spudich, the Douglass M. and Nola Leishman Professor of Cardiovascular Disease, was designated the head of a four-person Bio-X executive committee that will oversee its development.
Organizationally, Bio-X is an attempt to supplement the departmental research structure with an intellectual hothouse designed to nurture cross-pollination of the disciplines.
"If it all sounds a little vague, that is because we are trying to bring together people who wouldn't otherwise talk to each other, and encourage them to collaborate on projects that wouldn't otherwise be done," says Charles Kruger, dean of research. "So it is impossible to predict what everybody will be doing three years from now."
But Kruger adds that Bio-X "may be as important to Stanford as the decisions made by Terman and his contemporaries 50 years ago."
That view is echoed by Richard N. Zare, the Marguerite Blake Wilbur Professor in Natural Science, who says that "Bio-X represents a most significant change in the way Stanford University, or for that matter any university in the country, goes about doing research."
For the past year, more than a dozen faculty members from medical, science and engineering departments have been meeting weekly in a rare grass-roots effort to establish a new paradigm for research and teaching on campus. The key to the success of Bio-X, the program they conceived, likely will depend on winning the support of their respective departments.
"Our strength and our weakness is the departmental structure," says Nobel laureate Steve Chu, professor of physics and applied physics and one of the initiative's most enthusiastic supporters. "The department is the guardian of its field. It trains students and promotes intellectual excellence. But the departmental structure means that we must carve up all intellectual pursuits into quasi-well-defined segments."
As a result, Chu says, "we have to appeal to [department chairs'] gambling spirit and convince them that the potential upside far outweighs the downside."
Chu, the Theodore and Frances Geballe Professor in the School of Humanities and Sciences, should know. After all, the prize-winning physicist can point to the benefits he already has derived from a long-standing collaboration with Spudich. The biochemist showed Chu ways to attach tiny micron spheres to strands of DNA, which allowed Chu to use optical tweezers to become the first person to study the physical properties of individual polymer strands. In return, Chu's students taught Spudich's students how to build and operate atomic tweezers, which they then used to study protein motors that move things about within cells.
The discovery of the structure of DNA, the master molecule of heredity, is another good example of the fruits of interdisciplinary fertilization. Biologist James Watson was encouraged to enter the DNA-discovery race by physicist Erwin Schrödinger's comment that the future of biology lay in the molecular understanding of the gene. Watson went to Cambridge to work with Francis Crick, a physicist, to determine the structure of DNA. Working together, they deduced the structure from the data of X-ray crystallographers by using rules governing chemical bonds that had been developed by chemist Linus Pauling, who had tapped the principles of quantum mechanics.
Channing Robertson, the Ruth G. and William K. Bowes Professor of Chemical Engineering, a member of the four-person Bio-X executive committee, likes to tell about another example. When he was hired in 1970, Robertson says, he was charged with establishing a program in bioengineering. So he went over to the Medical School and began walking the halls and pounding on doors.
This led him to kidney specialist Roy Maffly, now professor emeritus of nephrology. Maffly, in turn, directed Robertson to an assistant professor at University of California-San Francisco, Barry Brenner, who now is one of the top kidney experts in the world. Brenner had developed a technique for measuring pressure and flow rates in the capillaries that flow into the part of the kidney where the blood is filtered, but he didn't know how to interpret his data.
Robertson and his graduate student took the data and developed a mathematical model of the filtration process that explained these readings. Brenner and Robertson wrote three now-classic papers based on their collaboration. Today, this analysis forms part of the basic textbook description of kidney function.
About the time Brenner was hired away by Harvard, another kidney expert, Rex Jamison, joined the Stanford faculty as a professor of nephrology. He studied a different part of the kidney, the medulla, where urine is concentrated. He was familiar with Robertson's previous collaboration with Brenner, and asked him if he would be interested in working together. Robertson and his students were able to apply many of the techniques he had developed with Brenner to the new study and they also custom-built a video-microscope capable of seeing red blood cells and measuring their speed as they move through the capillaries in the kidney. This provided doctors with a better way to monitor how well the kidney's filtering system and urine concentration machinery was working.
Collaborations like those and the revolution currently taking place in the biological sciences are the catalyst for the "exciting adventure" that is the promise of Bio-X, Spudich says.
"It is our belief that the time has come in the history of medical research, engineering, chemistry, physics and biology that an interdisciplinary approach is needed."
Although Stanford rose from regional to national prominence in the 1950s by building and maintaining "steeples of excellence" -- clusters of world-class researchers working in various disciplines -- Bio-X proponents argue that a new approach is needed today to address the challenges posed by recent progress in the biological sciences. The solution, they say, just might be Bio-X.
"Bio-X is an initiative to continue Stanford University's strong traditions to promote interdisciplinary interactions, " the new Bio-X web page reads (http://cmgm.stanford.edu/biochem/biox/). "Bio-X will foster the coming together of leading-edge research in basic, applied and clinical sciences to enable tomorrow's discoveries and technological advances across the full spectrum from molecules to organisms."
Considerable collaboration has taken place among various disciplines in the past, but it has been largely conducted on an individual basis. Soon the human genome project will be finished, opening a floodgate of new information. At the same time, microelectronic technology is providing new tools for analyzing biological parameters, ranging from the molecular level to that of the whole organism.
"We will be in information overload very quickly if we don't strengthen the links between bioinformatics and computer science," Spudich says.
That is not to say that Spudich and his compatriots see Bio-X as a one-way street with all the benefits flowing to the clinical and biological sciences. They believe the program will be mutually beneficial.
"I see the interaction between computer science and the life sciences [biology, medicine] as a kind of 'next frontier,' beyond the current explosion of the discipline due to the Internet, the web and related areas," says Jean-Claude Latombe, chair of computer science and a member of the Bio-X planning committee.
Right now, he says, the biosciences are raising challenging computational problems -- such as protein folding and DNA sequencing -- that are of interest to researchers in computer science. In the longer term, Latombe adds, the biosciences may inspire new computational schemes and architectures.
In such an atmosphere, departmental divisions increasingly are a problem because the "action" in biological sciences and in the other disciplines is gravitating to various interdisciplinary boundaries.
"Increasingly, people in the different disciplines are asking the same questions," Chu says.
If that indeed is the trend, then the Bio-X backers want to find a way to "grease" the interactions. They argue that if it is done correctly, the initiative could ensure Stanford's pre-eminence into the next century.
The idea isn't unique to Stanford, nor did Stanford have it first. In fact, the project was born more than a year ago when Spudich and Chu were heavily recruited by different universities that wanted to do something similar. The two scientists compared notes and decided they could launch an initiative at Stanford.
As they talked to fellow researchers about the idea, Spudich and Chu found considerable support. They went to their respective deans, who presented the idea to Kruger and then to Provost Condoleezza Rice and President Gerhard Casper, who supported the initial planning efforts.
As it happens, the University of California-Berkeley, Princeton University, the University of Chicago, UC-San Diego's Scripps Institution, Harvard University and the University of Washington all have similar programs under way, and the California Institute of Technology is on the verge of announcing yet another.
Although planning at some of these universities is more advanced, Bio-X backers say Stanford has some advantages that will make it hard to beat.
The university not only has top research programs in all the key areas, but it also has a key geographic advantage over two of its toughest competitors -- Berkeley and Harvard. At Stanford, university researchers and those at the Medical Center are separated only by the four lanes of Campus Drive, whereas Berkeley is separated from its medical complex (UC-San Francisco) by the San Francisco Bay, and Harvard Yard is divided from its medical center by the Charles River.
In addition, Stanford has a system of eight interdisciplinary centers, ranging from the Institute for International Studies to the Laboratory for Advanced Materials, that involve inter-school collaborations that apparently work quite well.
The heart of Bio-X will be a new building of about 220,000 gross square feet that will house about 50 faculty, along with classrooms, an auditorium and a cafeteria. Researchers envision that it would sit between the Medical School and the Gates Computer Science and Mudd Chemistry buildings.
Researchers want the architectural setting to invite foot traffic from surrounding buildings, and they think it should have a first-class cafeteria for pleasant lunch discussions and a large auditorium where lectures on interdisciplinary topics will draw a good crowd.
Most important, clinical researchers and basic biologists, physicists, chemists and engineers would be randomly located throughout the space to facilitate serendipitous encounters.
Although funding, plans and permits must be obtained before ground can be broken on the building, the first manifestation of the Bio-X program will appear next fall with the course "Frontiers in Interdisciplinary Biosciences." It will be taught every quarter and has been assigned the course number 459 in a number of departments from all three schools: Engineering, Medicine, and Humanities and Sciences.
The course will consist of three seminars per quarter, and lecturers will be internationally renowned researchers whose work is distinguished by interaction between the life sciences and other disciplines. What sets the new course apart is the fact that students will meet prior to each seminar for a one- to two-hour tutorial that will be designed to "level the playing field" among students from different disciplines.
"This turns the seminars into real teaching tools, and will show the students that Bio-X is a serious enterprise," says Robertson.
"The success of Bio-X must come from the faculty and it has to stay with the faculty," adds William Mobley, the John E. Cahill Family Professor and chair of neurology, and a member of the Bio-X executive committee.
"In biology, to make something go faster, you have to raise the concentration of one of the reagents. In Bio-X, we are raising the concentration of all the reagents, so the program is biologically defensible!" SR