Issue Date: March 27, 2006
Small-Town Kid Makes It Big
Biographical sketches of eminent scientists sometimes include tales that point to the subject's precociousness or fascination with nature as a kid. Some leading chemists tell stories of how they experimented as youngsters with fire, electricity, or gravity-perhaps recklessly-to satisfy their boundless curiosity.
But not Paul S. Anderson. This year's recipient of the Priestley Medal, the American Chemical Society's highest honor, certainly was inquisitive and a good student in his youth, but his mind wasn't on science back then.
"I loved sports," Anderson says. He started skiing at age six and picked up tennis not long after that when his father, "a pretty good tennis player," in Anderson's words, taught him to play the game. The family was "into the game" so much that they built their own tennis court, which drew neighborhood kids to the Anderson home to play.
As it happens, father and son weren't the only sports enthusiasts in Anderson's youth. "I grew up in a town that really loved its sports," Anderson recalls. Lucky for him, then, that he was a solid athlete because, as he puts it, "Going through school as the superintendent's kid could have been a pretty tough experience for me." But it turned out okay.
Anderson was born in Concord, Vt., in February 1938 and moved across the state to Swanton at age two when his father took a position as the town's school superintendent. Located in the northwest corner of the state and just a few miles from Quebec, Swanton was a small town of some 3,000 people "where everybody knew everybody else."
That kind of intimacy suited Anderson just fine, especially when it came to basketball. Players on opposing teams didn't just know each other socially, Anderson explains with a chuckle. "They knew each other's moves on the court, and that led to very competitive games."
In Anderson's day, Swanton had two high schools-the public school he attended and a Catholic school. "It was a lot of fun growing up in a town with two high schools because we used to have these great cross-town rivalries," he says with a look on his face that shows he remembers those days well.
It's no surprise he still remembers the cross-town competitions. Anderson wasn't just a participant in the games-he led them. In 1955, during his senior year of high school, Anderson was captain of the school's baseball and basketball teams. That's the year Swanton High won the state baseball championship. "That was quite a big deal in our town," he recalls, "because our high school had never won a state championship before."
Some of the credit for the winning season goes to the strict faculty of the Catholic school. Laughing through his explanation of that surprising claim, Anderson confesses that his school would never have done as well as it did "if it weren't for all the kids the nuns threw out of the Catholic school for misbehaving." That group included a couple of really strong ball players who ended up at the public school on Anderson's team. "The joke was that every night we would say our prayers for the nuns-thanking them-because we would have never won the state championship without their help."
When he wasn't skiing or playing basketball or baseball, Anderson found time for schoolwork. He made good grades all the way through school and graduated high school as class valedictorian. As it happens, he didn't take a formal chemistry class until his senior year in high school. His informal training in chemistry, however, started at a much younger age at home.
"When I was in 6th grade, my father used to do chemistry experiments with me at the kitchen sink," Anderson says. He recalls that the experiments were the classic exercises shown in introductory textbooks, such as separating water into hydrogen and oxygen. "It was a lot of fun and really interesting," he comments. Anderson adds that he especially enjoyed handling the apparatus for collecting the gases and was fascinated by demonstrations of the gases' chemical properties.
Looking back on those days, Anderson recognizes that his interest in chemistry was stimulated in part by his father's interest in the subject. "If he could have done it all over again, I think he would have decided to become a chemist," Anderson says of his father. The senior Anderson grew up on a farm in New York's Catskills, where he indulged his curiosity in science in a makeshift chemistry laboratory that he set up in an abandoned farm building. Ultimately, the father chose a career in education, not science. But he remained curious about nature and passed along some of that curiosity to his preteen son through fun demonstrations at the kitchen sink.
Later on, the father guided the son toward chemistry more directly. As Anderson tells the story, even though his first love was sports, he really enjoyed his high school classes in chemistry and mathematics and figured he would teach those subjects after graduating from college. Becoming a teacher seemed like a good idea and a natural choice for Anderson. Not only was his father an educator but the young athlete's mother and two sisters, Betty and Mary Jean, also were teachers. Besides, Anderson was confident he would receive a university scholarship if he majored in education. So he applied and was accepted to the College of Education at the University of Vermont.
"But when I talked about college with my father, he said, 'If you're really interested in chemistry, why not major in chemistry and then take the few extra courses needed for teacher certification?' " Anderson says his father understood that a solid education in the sciences-not the field of education-was the best way to become qualified to teach the subject. "The thought hadn't occurred to me, but it was excellent advice," Anderson acknowledges. So he reapplied to the university as a science student and headed off to study chemistry.
The new surroundings suited Anderson perfectly. "It was terrific being with science majors and in an academic environment," he says. At first, Anderson continued to entertain the idea of teaching chemistry after graduating college. "But after a little while, I realized I was much more interested in science than I was in teaching."
Long after graduating from the University of Vermont, Anderson remembers two of his chemistry professors as "outstanding." Donald Gregg and Clinton D. Cook both taught advanced organic chemistry courses that Anderson took in his junior and senior years. He also took Cook's physical chemistry course and worked in both of the professors' laboratories assisting graduate students and "learning lab techniques that went beyond typical undergraduate textbook experiments." The extra lab experience was very helpful, Anderson says.
But of all Anderson's chemistry instructors, the one who was most influential to him, the one he refers to as "my mentor," was Robert E. Lyle. "I never heard the term medicinal chemistry before graduate school," Anderson says. But shortly after beginning his Ph.D. education at the University of New Hampshire, Anderson took courses with Lyle that addressed the biological and physiological properties of steroids, heterocyclic compounds, and related materials. He also attended special evening seminars led by Lyle that were devoted to medicinal chemistry. "He was a very enthusiastic lecturer," Anderson recalls, "and I picked up on that enthusiasm."
Reflecting on his graduate school days, Anderson says that as a result of Lyle's lectures, he recognized that drug discovery was done by organic chemists. "Based on the things he taught us, it seemed to me that a career in medicinal chemistry would be very interesting. It all sounded so exciting to me."
So Anderson joined Lyle's research group and found a perfect match, not only with Lyle's research program, but also with his teaching style. "He was an excellent mentor," Anderson says. The New Hampshire professor gave his students "breathing room" and allowed them to work independently unless they were having problems. Yet even in that case, according to Anderson, Lyle would get involved only by asking the right kinds of questions to get a student focused on the problem and headed in a direction that would enable the student to solve the problem independently. Anderson adds, "I think he worked that way because he understood that learning from personal experience was a powerful way to learn."
Anderson's admiration and respect for Lyle was reciprocated. "I was lucky to have enticed Paul to join my research group," Lyle says. "He was an ideal person to have working with us-a real sharp kid, very pleasant, and he always got along well with students and other faculty members."
Now 80 years old, Lyle continues to attend scientific meetings and keeps in close contact with a number of his former students, several of whom, like Anderson, reached senior positions in the pharmaceutical world and whom, as Lyle puts it, "I consider close personal friends." The two medicinal chemists are looking forward to spending time catching up at the ACS national meeting in Atlanta, where Lyle plans to attend the awards ceremony and listen to his former student deliver this year's Priestley Medal Address (see page 17).
With a warm laugh and a hint of nostalgia, Lyle switches easily between stories of Anderson working in the lab and skiing on snowy slopes, pointing out that Anderson pursued both activities with equal enthusiasm. Lyle admits, "Naturally, I was pleased for Paul when he graduated, but I have to confess I was disappointed to see him go."
In 1963, not long before leaving New Hampshire for a postdoctoral research appointment at Cornell University, Anderson married Jane Oakes. Perhaps not surprising for two people whose lives have long been intertwined with chemistry, the young couple met at New Hampshire, where Jane was an undergraduate student majoring in chemistry and working in the chemistry library while Anderson was working toward a Ph.D. Anderson confesses he spent more time in the chemistry library than required by his research needs after discovering that Jane worked there.
Over the next 40 years, Anderson flourished in the pharmaceutical industry. In 1964, he took a position as a senior research chemist at Merck Sharp & Dohme Research Laboratories and climbed steadily through the ranks. He was named senior director of medicinal chemistry in 1979 and not long thereafter was promoted to executive director for medicinal chemistry. In 1988, Anderson was appointed vice president for chemistry at Merck's West Point, Pa., research facility.
Thirty years after starting at Merck, Anderson moved to DuPont Pharmaceuticals in Wilmington, Del., where he served as senior vice president for chemical and physical sciences. Some seven years later, in 2001, he moved on again, this time to Bristol-Myers Squibb's Wilmington research facility, where he was appointed vice president for drug discovery and site head. Anderson retired in 2002.
In addition to industry-related responsibilities, Anderson participated in various other professional activities. He served on the boards of directors of several chemical companies and the boards of the Chemical Heritage Foundation and the National Research Council. He also served the American Chemical Society in numerous capacities, for example as a member of ACS committees on publications and on chemistry and public affairs. Most notably, Anderson served as ACS president in 1997.
During nearly four decades of service in the pharmaceutical industry, Anderson and the scientists he worked with uncovered the medicinal benefits of a variety of pharmaceutical agents and designed novel methods for preparing them. The list includes medications for fighting HIV and AIDS, for treating eye diseases and coronary heart disease, and other drugs.
One example of the many drugs that Anderson and his colleagues at Merck developed is Trusopt, which is used to lower the excessive intraocular pressure suffered by glaucoma patients. The medication is unique in that it was the first member of a family of compounds that function as carbonic anhydrase inhibitors to be prepared as an eyedrop formulation. Anderson explains that delivering the medication directly to the eye, rather than taking it orally, as was done prior to the Merck research, avoids many of the side effects associated with these types of drugs.
Aggrastat is another example of a medication that was developed by Anderson and his colleagues at Merck. The substance, also known as tirofiban hydrochloride monohydrate, is used for treating coronary diseases, including unstable angina, and for preventing artery blockage. The principal function of the drug is preventing coagulation factors in the blood from binding to platelet surface receptors.
During his years in the pharmaceutical industry, Anderson had the opportunity to work with many outstanding and gifted researchers. One of them was Ralph F. Hirschmann, whom Anderson describes as "one of Merck's most distinguished and creative scientists." Anderson says it was a privilege to have had Hirschmann as a boss for many years. "He led by example and set a high standard for scholarship and performance that had a positive influence on the whole organization."
It comes as no surprise that Hirschmann speaks highly of Anderson. "Paul's work stands out for the creative way in which he reflects on the stereochemical significance of structure-activity relationships," Hirschmann says. Certainly that skill is required of all successful medicinal chemists, he emphasizes, "but Paul's grasp of those relationships is remarkable."
As an example of the outstanding work led by Anderson, Hirschmann points to MK-801, a compound that Anderson and his colleagues discovered as part of a research program that focused on designing and synthesizing ligands with high affinity and specificity for therapeutically important neurotransmitter receptors. MK-801 is described as a noncompetitive antagonist for the N-methyl-d-aspartate subset of glutamate receptors.
Hirschmann explains that the compound is important because of its potency, selectivity, and blood-brain transport properties, which led to the substance being used extensively in clinical investigations to study the amino acid hypothesis for ischemic brain damage. (The hypothesis is based on a toxic flow of calcium into brain cells.) Not long after the compound was made available for research purposes, MK-801 became one of the most studied central-nervous-system-active compounds; it has been cited in more than 1,000 research papers. "That is what creative medicinal chemistry is all about," Hirschmann states.
In Hirschmann's view, Anderson also possesses excellent people skills. "Taken together, Paul's scientific creativity and his leadership qualities make for a mighty combination." Hirschmann adds that he was more than happy to recommend that Anderson take over his position as head of medicinal chemistry at Merck upon Hirschmann's retirement.
It isn't only Anderson's superiors who think the world of him. "You couldn't ask for a better colleague," Joel R. Huff says about Anderson. Huff worked with Anderson at Merck for some 20 years before taking over the lead position in medicinal chemistry when Anderson moved on.
"Paul was a terrific scientist, very curious and enthusiastic about his work," Huff comments. He adds that like other Merck scientists, Anderson was motivated by "the possibility of discovering new drugs that would make a difference in medicine and in people's lives."
Huff echoes the opinions of other scientists with whom Anderson worked over the years. "Paul has exceptional leadership skills," Huff says. "He understands what motivates people and was always able to draw the best out of his coworkers." Anderson also was "very down to earth, unassuming, and very approachable as a boss," according to Huff. He adds that Anderson was fun-loving, playful, and prone to "plastering" people with a wet Nerf ball during company canoe trips down the Delaware River.
With the benefit of nearly four decades' worth of conducting and directing research in medicinal chemistry, Anderson says that teamwork is one of the keys to succeeding in the field. "Drug discovery is a team sport that requires input from chemists, biologists, pharmacologists, and others," he says.
Just as the teams full of players with unique talents with whom he played as a youngster succeeded by working together cohesively, so too, Anderson says, "scientists working in drug discovery succeed by building interdisciplinary teams that bring a diverse array of knowledge and skills to the discovery mission." No doubt the tip is a valuable one, considering that it comes from the former high school captain and industrial research director who led his teams through winning seasons time and time again.
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