PRISM Magazine Online - May-June 2000 - Special Conference Issue
Dr. DNA and Dr. MRI - plenary speakers
Human genome sleuth Robert Waterson and MRI inventor Paul Lauterbur help kick off this year's conference with a bio-tinged main plenary.

This year's plenary speakers are both eminent figures in bioengineering, with claims to fame from opposite ends of the basic/applied research spectrum.  Don't miss this chance to hear from Robert H. Waterson, a leader in the effort to decode the human genome, and Paul C. Lauterbur, the inventor of MRI technology.

By Ray Bert

When you talk to Robert Waterston about his work, your first impression may be that this 56-year-old genetics expert is the stereotypical "detached scientist." In a careful, measured way, he'll lay out some of the difficulties he faces in the pursuit of his complex goal--the mapping of the entire human genome. You may even wonder if the man--in seeking the fundamental knowledge encoded in the cells of every human being--has somehow missed the larger implications of his work, if in peering through his microscope he has forgotten to look out his window at the society he may be helping to irrevocably alter. You may wonder--but you'd be dead wrong.

"The DNA sequencing work we do is pretty far removed from the potential applications of the science, but we're well aware that what we're doing can be misused," says Waterston, the James S. McDonnell Professor of Genetics, genetics department head, and director of the Genome Sequencing Center at the Washington University School of Medicine in St. Louis. "This is a powerful thing for the good and the health of society, but people are right to be concerned."

But concern isn't the only, or even the primary, response that Waterston gets to his work. "I do hear from skeptics, but people don't have a hard time seeing the potential benefits of genetic research," he says, adding that some of the earliest benefits will likely come from understanding and treating genetic diseases, by identifying which genes cause which ailments. "Something like cystic fibrosis will probably be the first, then later, things like cancer," he says.

For all of Waterston's commitment to--and excitement about--genetics, it hasn't always been his primary interest. He received an M.D. and a Ph.D. in 1972 from the University of Chicago, after an undergraduate major in engineering at Princeton. He was an intern in pediatric medicine at Children's Hospital in Boston, and served a postdoctoral fellowship in cell biology at a laboratory in Cambridge, England, before arriving at Washington University in 1976 as a professor of anatomy and neurobiology. In 1980, when a planned expansion of his department became tenuous, Waterston finally moved fully into his current field. "I had been doing genetic work on C. elegans, an experimental animal, since 1972," he says. "The genetics department at Washington had gotten started, and I was a natural transfer."

Transferring between departments is something that Waterston sees a lot of now in the students who pass through his lab. Biotechnology's rise, and the many opportunities to branch out, makes the field an easy sell to students. But how does one teach eager, bright young minds about the potential darker side of genetic manipulation, suggested in books like Aldous Huxley's Brave New World and more recently in films such as Gattaca?

"We have begun engaging the law school and ethics programs to see what might be done to develop some kind of formal instruction in bioethics," Waterston says. "Certainly, it [the instruction] will have to deal with eugenics movements of the past, to teach the lesson that society is not always benign. My message is that this is powerful information, and that in a democratic society, it's important for citizens to inform themselves."

Ethical questions also play a part in the looming legal battles over the patenting of genetic information, which could be worth billions of dollars. On this "Should we or shouldn't we?" issue, Waterston comes down in the middle. "I have a layman's view of patent law," he says, "but the position I've evolved is that the basic DNA sequencing information should not be patented, and should be freely available. But there has to be patent protection at some level--when someone figures out the utility of the information, for example, in developing a cure for a form of cancer, then patents are appropriate."

Those issues weren't even on the horizon when Waterston first began trying to determine the genetic makeup of C. elegans--a difficult task, given the experimental methods of the day, he says. "But then we began mapping the DNA, and it proved to be enormously successful." It wasn't exactly sequencing, Waterston notes, but it was the foundation of the process that has now nearly unraveled the mystery of a decidedly more complicated type of DNA--that of humans.

The Genome Sequencing Center is one of five major laboratories working on the Human Genome Projects. A pilot program began in 1996, and the final push has been underway since spring of last year. By this spring or summer, Waterston says about 90 percent of the genome will be decoded. A polished, complete version should be ready in a few years, he estimates.

The prospect of finally having a biological blueprint of what makes us human is what pushes him onward. The legalities and the social ramifications of his work are important, but the thrilling part for Waterston is the mission he is on, the quest for the Holy Grail that is so nearly in his hands. "We're capturing part of our inheritance," he says, "and that is very exciting."

Paul Lauterbur is a Ph.D. chemist, and the inventor of the technology that eventually produced the magnetic resonance imaging (MRI) machines that are an indispensable part of modern medicine. He has won dozens of awards and holds a fistful of honorary degrees. So what was this esteemed scientist doing when the pivotal moment of his career arrived?

"I was having a hamburger in a fast-food joint," he begins matter-of-factly, and with a smile. It was 1971, and Lauterbur was a chemistry professor at SUNY-Stony Brook. Having recently observed an experiment by a colleague, who was using nuclear magnetic resonance on dead tissue samples, Lauterbur suddenly had his french-fry-fueled insight. Wouldn't it be neat, he thought, to use the same process on humans as a diagnostic technique--without cutting "bits" out of the person?

"It was pretty much a 'Eureka!' moment," he says, and over the next few days he expanded on the brainstorm. Those few days ultimately stretched into a new career path. "A symptom of a good idea is that once it starts, it just won't stop," he says, adding with a laugh: "I am still a chemist, but I'm on a very long detour from chemistry."

Lauterbur ran with the idea largely on his own for several years, doing what he could with the equipment in his chemistry lab. He applied for an NIH grant, gave numerous talks, and published the first of many papers on the subject in late 1972. He is quick to point out that the basic technology already existed. "My contribution was to realize that there was a principal whereby you could turn NMR signals into pictures," he says. Others in the field, including groups in England and Switzerland, began picking up on his work--and things accelerated from there. "It was like starting a brush fire," he says. "Developing my initial idea was really a community effort." That effort bore fruit in 1980, when a company called Technicare produced the first MRI machine for hospital use; today they are ubiquitous, and researchers also make extensive use of the technology.

Before he hit his biomedical bend in the road, Lauterbur had followed a more standard path for a chemist. After receiving his bachelor's degree in chemistry in 1951 from Case Institute of Technology, he went to work for the Mellon Institute for twelve years. Along the way, he spent two years in military service at the Army Chemical Center and worked toward his Ph.D. in chemistry, which he received from the University of Pittsburgh in 1962.

Lauterbur arrived at Stony Brook in 1963, and stayed until 1985, when he moved to the University of Illinois at Urbana-Champaign. That switch, in which he became the head of the medical information sciences department in the college of medicine, made Lauterbur's transition away from traditional chemistry complete--though he had long since decided to cast his lot with developing the biomedical applications of his idea.

His expertise in the applications of his discovery made him the logical choice as the founding president of the Society of Magnetic Resonance in Medicine, and as director of UIUC's Biomedical Magnetic Resonance Laboratory. In that laboratory, in particular, he's noticed something about students and the way they approach learning and researching. "Undergraduates are just as smart as grad students, except braver," he says. "The expectations and pressure are lower, so they can try anything--they don't know yet that nothing ever works," he adds facetiously. But he is, of course, living proof that sometimes, ideas do work. And he has clearly enjoyed the ride: "It's fascinating to see a new field grow and develop, and to have something to do with it."

Lauterbur credits his success in developing his fundamental idea into useful applications to a strong grounding in engineering. Case Institute, in the first two years, gave students the basics of every kind of engineering, he says. In fact, that aspect of the school is a large part of why he chose to attend in the first place--his father, an engineer, believed engineering was a more practical choice of career. However his father saw it, Lauterbur feels that his motivations were somewhat different from those of his classmates. "I was more interested in broadly educating myself," he says. "Astoundingly, I even appreciated art and music classes!"

Though his hard work is mostly responsible for his success--in addition to his status as a pioneer, he has won forty-five awards, including the National Medal of Science--Lauterbur knows that he is in some ways lucky that his brainstorm panned out. Asked if he would encourage his students to make a leap like the one he made, he demurs. "It's easy for me to say--I took a chance and it worked out."

But he notes that what was a leap nearly thirty years ago might not be so remarkable today. "There will always be separate disciplines, of course," he says, "but there is a growing and intensifying area of overlap." He adds that UICU is developing a bioengineering department because of an increasing sense that "you can't not get on that bandwagon. The association between biology and engineering is a lively area for the future--to use a much overused phrase, there is a lot of synergy."

Lauterbur knows whereof he speaks. After all, how many people could have connected a hamburger and nuclear magnetic resonance with such spectacular results?