I gave up trying to reason with him, and went to Paul’s personal physician. Paul, I said, was not in his right mind. I lied: depression had muddled his thinking, I said; and: I had power of attorney over his medical matters, just as he had over mine. Paul’s doctor was perhaps as eager to believe this as I was, since he knew he could save his patient’s life and that Paul could live a comfortable future if only he would accept treatment. I called the lawyer’s office to send over the papers, and went back to Paul to tell him what I had done. He then angrily agreed to surgery and was whisked off nearly instantaneously.
Throughout his illness Paul was grateful to find refuge in the Department of Chemistry, where Greg Gerrolami, then department head, and the rest of the faculty welcomed him. It’s strange how some environments fit and some don’t. After years of struggling for understanding at the Beckman Institute and the Medical School, Paul found acceptance and support simply waiting for him at Chemistry. He was now over seventy and looking for a research project he could do without NMR or MRI equipment. One thing for sure was that it had to have the absolute highest scientific significance. What better then, after over half a century of days and of scientific experience, to return to his childhood interest in the origins of life? Some people may have retired at this point, but Paul, pushed out of the field he invented, had another interest ready to pursue.
Honors Rose Up for Him
Ironically, Paul’s esteem beyond our university walls was all the while growing, and the university’s development and publicity offices eagerly trumpeted every flash of media hyperbole. Altogether, Paul won fifty-six awards from various organizations, two of them after his death. While most of these were for his work at Stony Brook, mostly they were awarded while we were at the University of Illinois. Among these was the Kettering Prize from the General Electric Cancer Research Foundation. In addition to the usual gold medal and plaque, during the ceremonies a rather big deal was made of handing Paul a check for the $100,000 cash prize. As Paul returned to his seat he, with an exaggerated flourish visible through the whole auditorium, handed the check to me. The audience loved it. The GE Foundation later sent the cashed check back to us in a fine frame.
May 29, 1987, was an interesting day. That morning Paul received word telling him he had won the National Medal of Science, to be presented by President Reagan in a White House ceremony. He telephoned me and we exulted over this wonderful occasion. That afternoon he phoned me again. “Are you sitting down?” he asked. This time it was the Fiuggi International Prize,9 an honor begun that year by an Italian foundation to honor people who have devoted their lives to the betterment of humanity in the fields of medicine, science, culture, or art. It came with a generous monetary award. We built our house with it.
Figure 9.6
The Lauterbur family after Paul received the National Medal of Science in 1985. Bottom row, left to right: Paul’s sister Margaret McDonough; Paul’s mother, Gertrude Vetter; and Joan Dawson. Top row: Mike DiGeronimo, Sharyn’s husband; Sharyn Lauterbur DiGeronimo, Paul’s daughter; Paul; and Dan Lauterbur, Paul’s son.
Physiological MRI
Paul was surprised at how quickly MRI became a fixture in clinical medicine. By 1983, ten years after his first paper was published, there were twelve MRI machines in use around the world. By 2000 there were 25,000 worldwide. The decade from 1983 to 1993 saw continual expansion of anatomical studies, but also a great development of the sensitivity of MRI to physiological and pathological events. The MR behavior of the atomic nucleus is determined by the surrounding magnetic field it experiences, and thus by a large number of different parameters, including blood flow, chemistry, chemical exchange, diffusion, and other physiological and pathophysiological phenomena. An image that contains information about these parameters provides information on how tissues and organs function, both normally and in disease. Most of Paul’s work during his thirty-year imaging career consisted of efforts to make MRI more sensitive to physiology and pathology. Specific MRI techniques have been developed and continue to be developed that highlight changes in physiological phenomena and emphasize different physiological states, or aid in the differential diagnosis of disease.
Paul first studied flow using MRI in 1973,10 a surprisingly early date. He had in mind MR angiography, which generates pictures of arteries to evaluate them for potential ruptures or abnormal narrowing. MR angiography was finally introduced in the late 1980s, and a number of different specific methods are now used.
Functional imaging is based on Seiji Ogawa’s discovery with his colleagues in 1988 that small veins in the active brain give extra contrast to the image.11 The phenomenon was named the BOLD effect, for blood oxygenation level–dependent signal changes. Deoxyhemoglobin in blood is ferromagnetic and therefore distorts the magnetic environment of the surrounding water molecules. In general, the brain uses more oxygen when it is active, and the local blood flow increases to supply even more oxygen than is required. This oversupply leaves its carrier, hemoglobin, more oxygenated, and the magnetic distortion by deoxyhemoglobin decreases. This is the basis of the BOLD effect and of most functional MRI, a noninvasive way to assess brain function. It has been shown that the BOLD effect correlates directly with electrical communication among nerve cells, the synaptic activity. Functional imaging was a major breakthrough. It captured a broader audience of medical scientists than anything MRI had previously offered.
Diffusion imaging records the rate and direction of water (or sometimes of metabolites) diffusion within body organs. The technique is useful in observation of strokes, in which the water of edema diffuses particularly freely. A variant, “diffusion tensor imaging” or “diffusion tractology,” provides spectacular images of tracts of muscle or nerve fiber bundles because water diffusion is much faster along the length of the fibers than across them. These images are clinically useful in showing interruption of normal fiber anatomy by tumors or trauma. Paul’s first studies of diffusion imaging were done in 1972. Diffusion tensor imaging really got started in 1995.
Paul first described spectroscopic imaging in 1972. The technique combines the effect of molecular structure on the magnetic field experienced by an atomic nucleus, the chemical shift, with the effects of the magnetic field gradients used in MRI. Chemical shifts show different chemical entities in a spectrum and are thus the basis of NMR in chemistry. Chemical shifts are combined with MRI to make physical maps of molecules that are important to cellular function.
This spectroscopic MRI or chemical shift MRI has enormous potential because it allows direct observation of the chemical basis of disease. Spectroscopic MRI is difficult because of formidable sensitivity problems, and has not yet lived up to its promise. Metabolically important chemicals are best observed using insensitive atomic nuclei that are present in concentrations only about a thousandth that of body water. The sensitivity may be improved by the use of a priori techniques (such as the use of a high-resolution proton image to constrain the computation of the spectroscopic image); these approaches appear promising.
Figure 9.7
Paul’s seventieth birthday cake—before being eaten. The cake was made with peaches and bananas and scanned at fast spin echo (TE 16/98). From C. Maxton and Jens Frahm, “MRI of P. C. Lauterbur’s Birthday Cake: Bananas, Peaches, and Susceptibilities,” in Proceedings of the International Society for Magnetic Resonance in Medicine Eighth Scientific Meeting (2000), 1528. Reproduced by permission.
Summary
These were years of success and failure, of good science and bad politics. It was like a roller-coaster ride, or perhaps like The Perils of Pauline, a show my grandmother had listened to on the radio in which the heroine ends every episode in very bad straits, then solves the problem in the next episode but encounters new difficulties at the end of it. The low blows within the university, the high recognition without. I was never able to reconcile all of this. Paul had set in motion new areas of research in MRI, some of which have come to fruition, but been forced out of this, the
field he founded. Stress made him ill, but illness didn’t stop him. He went on to his next phase of research.
10
The End and the Beginning
There was always something serendipitous, even wild, about Paul Lauterbur’s approach to science.
—Economist
When I was a graduate student in the 1970s at the University of Pennsylvania, I knew a legendary figure who had made significant contributions to the study of mitochondria that he and many others thought was Nobel-worthy. Stories had it that every year when the Nobel Prize in Physiology or Medicine was announced, and not for him, he would come in late and be irritable for several days. It was as though he had missed the Oscar for really smart people once again. In my student purity, I disapproved of this putative behavior, believing that science is its own reward and that desire for recognition is in bad taste. I still believe this, but a little more humbly.
When stories that Paul might win a Nobel Prize were circulated, I tried my best to ignore them. As the years went by, this became harder and harder, and Nobel week became something of a nightmare. I couldn’t help anticipating the honor that I felt my husband richly deserved, and even worse, I couldn’t help thinking of how very nice all that money (hundreds of thousands of dollars) could be. So much for high-minded! I was always relieved when Nobel week was over and I could rid myself of the anticipation and anxiety for another year. As time went on this anticipation abated, as it began to seem that if Paul were going to be awarded the prize, it would already have happened. I remained grateful for all the previous honors that had come to him.
So, by 2003, I didn’t notice when the first week in October rolled around—until I was jolted awake by the phone ringing at 3:30 a.m. Classic—the Nobel Committee calls the recipients in order to inform them before the press conference (11 a.m. Swedish time) announcing the award. A very pleasant voice announced that he was Hans Jörnvall, secretary of the Committee for the Nobel Prize in Physiology or Medicine, and could he speak to Paul. I tried to wake Paul up, shouting in his ear and shaking him hard. The response was extreme irritation, turning away, and pointing out to me that he wanted to sleep, which he duly returned to. Hans informed me that Paul had just been awarded the 2003 prize and was co-laureate with Peter Mansfield of Britain. I continued to shake Paul and began kicking. What a dolt my husband is, I thought; he wins a Nobel Prize and won’t even wake up to learn of it! I finally thought that I could safely turn the phone over to him, but as Hans put it later, “I wasn’t sure that Paul understood what I was saying, but his wife did.” Hans kindly informed me that I had about half an hour before the “craziness starts,” when the press would begin calling. Paul and I were both truly waking up now. He went to wash his face and prepare. (The papers were full of his “only comment” of that early morning, “There goes my day!” He really did say this, a bit disingenuous, but true testament to how he believed one should react to honor.) We were both astonished, dumbfound, amazed, overwhelmed, overpowered, engulfed.
What should I do in this promised half hour? Oh yes, call the kids. And Paul’s sister. And my mom! And yes, the calls did start right on schedule, not one at a time but all at once in a deluge. The European news media were first (they were awake), and a little later the North Americans. The calls from South America and Asia came later. While Paul was talking on one line, I was fielding the other. NPR’s Morning Edition wanted an interview. So did the New York Times, the Washington Post, USA Today, and the Chicago Tribune. Some of the reporters seemed angry that they had such a hard time getting through. I took names and telephone numbers as best I could, promising that Paul would call back, but there were too many to accommodate. CNN called twice and I kept telling them they would have to wait. I couldn’t believe I was telling CNN we just didn’t have time for them! I made mistakes transferring calls to Paul, I cut people off while I tried to answer the other line, and I got names wrong, and I really, really needed a cup of coffee.
Then, at 7 a.m., tripping over the construction site of our front entrance landscape project came our neighbors Vera Mainz and Greg Girolami. Greg was head of the Department of Chemistry at the time, and Vera was head of the department’s NMR center. Both were colleagues and friends of many years. The paving and stairs down the hill to our home had been ripped out, replaced by piles of gravel, sand, and mud. Intrepid, Vera and Greg climbed and slipped until they managed to reach our front door. “We thought you might need some help.” Did we ever! They took over, took calls, and prepared coffee and breakfast. Vera chose Paul’s tie, and even put together a Crockpot dinner to be ready when we returned home that evening. They scheduled the press conference and the university president’s reception later that morning, and drove us so we would not have to deal with the parking. Greg made himself Paul’s chauffeur for the day.
All kinds of people said wonderful things about Paul, things he hadn’t heard around campus in years. Paul was calm and pleasant, trying to help the others do their jobs of reporting and administrating. The University News Bureau began trying to coordinate the calls from the press and setting up interviews. Neither Paul nor I had a secretary at this time, so this was extremely helpful. Mary Jane Ham received many calls at the Biological Magnetic Resonance Laboratory where she had remained after we were kicked out. Debbie McCall, now administrative assistant to the dean of the Medical School, set aside her normal duties to help. She didn’t ask her boss; she told him. The pool secretaries for the Biological Chemistry Group, of which Paul was now a part, tried to do what they could. But it was mayhem, and only the Press Office was able to keep any kind of order.
Things went on like this until two days later, when our own Tony Leggett was announced to be a recipient of the Nobel Prize in Physics for his work on superfluidity. Not one Nobel Prize on our campus this week, but two! Even the governor, Rod Blagojevich (yes, that one), noticed, he who was busy cutting as much funding to higher education as he could get away with. “There is always fat that can be cut from somewhere,” he said at the same time we were eliminating undergraduate laboratory courses for lack of funding. He visited and made the famous remark that “This year, the University of Illinois had more Nobel Laureates than victories in the Big Ten.”
It’s funny about those two guys, Paul and Tony. Greg Girolami noted, with a hint of incredulity in his voice, “On the day when he heard the Nobel Prize was awarded to him, Paul said, ‘I have a scheduled meeting with my students at 4:00 today and, no matter what happens, I want to keep that appointment.’” He did keep the appointment, despite requests from NBC, CBS, CNN, and all the others. Interestingly, most of these young people did not know that Paul was the inventor of MRI or that he could even be considered for a Nobel Prize. Tony Leggett amazed people in a similar way. He taught his regular class the next day. I have to contrast this with written screeds about the superscientists who do no teaching at public universities. And when both new laureates were asked what advice they had for students, their answers were similar, and completely different from the usual advice to keep your head down, focus, and work very, very hard. They said to do things that are interesting and fun, keep alert for new opportunities, and think for yourself.
Our house was filled with flowers from well-wishers. I have never seen it more beautiful. People called, emailed, wrote their congratulations. We couldn’t keep up. We felt truly loved.
I spent pretty much all my time for the next six weeks dealing with all of the various obligations, from coordinating with the Nobel Foundation, the press, and other interested parties to finding and inviting Paul’s guests. Perhaps the most interesting assignment was to find Don Hollis. Don had been a professor at Johns Hopkins University and was an early entrant into the field of in vivo NMR spectroscopy and imaging. He had dropped out of the scientific and academic rat race after a sudden heart attack. His life seemed somewhat more important to him than his scientific career. Paul felt that Don should be on the guest list in part because he had published a book, Abusing Cancer Science,1 wh
ich set straight some of the issues vis-à-vis Raymond Damadian. For years, we had been referring people to Don’s book when questions about Damadian’s role in MRI research needed answering. I knew that Don had run a motel in Chahalis, Washington, and could think of nothing better than to call the police there. They were at first suspicious but ultimately led me to him.
Stockholm
It is traditional that laureates stay at the Grand Hotel in Stockholm, known for the graciousness of the staff. Early December is the busiest time of the year for them, and they were a little overwhelmed, but they clearly deserved their top-flight reputation. The hotel overlooks the waterfront, the old city, and the Imperial Palace beyond, so that simply being there feels uplifting. All of Stockholm seemed to be celebrating the Nobel festivities, and I was told that this is the high point of the social year in all of Sweden. It didn’t hurt that Nobel week is also the week of St. Lucia Day. St. Lucia, saint of light, appears in the blackest of Nordic winter, when the sun rises around ten in the morning and sets at three in the afternoon. Everyone had candles to St. Lucia in their windows, and the city was alight in festivity. My heart glowed.
Paul explained some of his philosophy in the first paragraph of a traditional lecture (“MRI Is Not Only Radiology”) given in Lund during Nobel week:
It has been noted that the Nobel Prize for the development of MRI was awarded to a chemist and a physicist. That is not accidental. The field developed from a discipline that was at first the province of physicists, two of whom share a Nobel Prize for it, and then became most prominent in its applications to chemistry, so that chemists received the next two Nobel Prizes, for novel techniques and applications. Although the needs of medical diagnosis stimulated the development of MRI, it was firmly grounded in the knowledge and instruments of physicists and chemists, as well as in those of mathematicians and engineers, all far from the knowledge and concerns of physicians, who became its greatest beneficiaries. How this came about is a complicated story.
Paul Lauterbur and the Invention of MRI Page 20