Details of a big picture — Alastair Wood

Details of a big picture — Alastair Wood (almost) named to top FDA post

You’re sitting at a corner table in a swanky Washington D.C. bistro and Alastair J. J. Wood, assistant vice chancellor for Research, is about to spin a tale of his near-brush with one of the most influential positions in U.S. public service.

But he begins with a warm-up story about his plane ride in earlier that day, how some guy stood up on the flight, but nobody’s supposed to stand up on a flight into D.C. Flight attendants rush the guy, the pilot yells over the intercom that they’re diverting, lots of chaos, lots of confusion, and you can imagine all the passengers looking for the Pentagon or another terrorist target. The guy was just going to the toilet; he didn’t know. A few minutes later, Wood says, a flight attendant gives a wink, tells them they’re not diverting, just a precaution, but don’t tell the poor sap who started it.

Wood, his iambic Scottish accent limbered, its pitch and timbre, but never its volume, rising and falling with the excitement, then begins his own story about how he was almost chosen to be commissioner of the Federal Food and Drug Administration, and it’s not much different than the one about the guy on the plane — a lot of excitement and high drama, but ultimately a close call. In the end, though, there wasn’t a wink, but a sincere political nod.

Over the winter, as the post-Sept. 11 United States huddled against the threat of biological warfare, as postal workers died from anthrax and Congress members were being evacuated from their office buildings so the air ducts can be cleansed, Wood visited the White House several times, often at night, always dropped off by a cab around back, just outside the gate. The country hasn’t had an FDA commissioner since January 2001; no one overseeing one-quarter of all the consumer goods in the country, from IV drugs to razor blades to salad bars at Wendy’s to Revlon lipstick — an agency that “monitors the manufacture, import, transport, storage and sale of $1 trillion worth of goods annually,” at a time when the threat to food and drug safety has never been more imminent. The administration wants to know if Wood, a relatively quiet, low-key physician scientist, is the man for the job, as many suspect him to be.

All this White House hullabaloo is just the most recent, and most highly publicized account of Wood’s national influence. In the last 10 years Wood has reached the public eye through a trickle-down effect. As editor of the New England Journal of Medicine’s drug therapy series, one of the journal’s most highly read, Wood monitors medications — their development, approval and use — for significant trends affecting patient care, and comments about them in editorials. Sometimes, they make it to the national press, like when he wrote about the lethal dangers of the diabetes drug Rezulin in 2000 before its recall, or his detailing the need for an independent drug safety board.

He’s had a hand backstage in other high-profile issues. When a participant in a Johns Hopkins asthma study died in 2001, Wood was on the official external review committee that made recommended changes. In March he testified to Congress that the federal government should do a better job of approving safer drugs — and, underscoring it with an anti-bureaucratic message, told them that doing so was possible without making them more costly or extending the approval time.

“He’s one of these guys who is on top of all the changes in therapeutics. He’s closely connected to what goes on, and he seems to know everybody,” says NEJM editor-in-chief Dr. Jeff Drazen.

A recent editorial about racial differences in drug metabolism (a topic Wood has studied for more than a decade and which, he maintains, is important to develop drugs for different types of people most effectively) was one of the journal’s most popular, Drazen says. “It generated a lot of attention.” And, Drazen says, when attention about an issue becomes controversial or confrontational, Wood “breaks it down into what we’re trying to do, and that’s to disseminate scientific information to the people who need it, and I think he’s done a very good job of staying focused on that.”

Painting pictures

In conversations, which often become educational sessions, Wood has the uncanny ability to maintain focus on an issue while zooming in and out, from details to a big picture, even to a futuristic one. He sets a topic in context, for clarity and understanding, then challenges whether the context should change, or prompts a shift in focus from the here-and-now to the what’s-next.

The morning after Wood recounts his FDA experience he is at a meeting of PhRMA, the Pharmaceutical Research and Manufacturers of America, the sole academician on a panel with three industry representatives and a senior FDA officer in a room of about 300 industry researchers — a drop of oil in a pot of water except, without changing composition, Wood mixes. In an open discussion about drug safety, industry representatives eagerly discuss drug labeling, which, Wood has maintained for years, doesn’t work. “It’s like the sticker on the back of the sun visor in an SUV,” he tells them. “It doesn’t make the vehicle any safer.”

If an adverse drug interaction is recognized post-market, the FDA can impose labeling and interaction messages to be listed in a 5-pound PDR (Physicians’ Desk Reference) or in packaging brochures and can feel legally secure, while industry doesn’t have to rework its drug. But, Wood says, the drug is still the same. Besides, he says, “where’s the PDR when you’re writing a prescription?”

“When we are talking about managing risk from medicines, we need to recognize the difference between ‘safety’ and ‘public relations,’” he tells the group. And, he cautions, “there’s a huge change coming,” information is becoming proprietary and access to information is going to be limited. “I’m concerned that nobody’s engaged in that conversation.”

The topic of absolute risk — whether a drug that has severe side effects for one group of patients while providing relief to a larger group should be pulled, for instance — arises, and again Wood stirs the brewing issue with an intellectual spoon.

“I think we need to think beyond the issue of absolute risk,” he says, removing the topic from its appointed box for examination from a different angle. Patients who benefit shouldn’t be denied a drug because it adversely affects another group, especially if that group is easily identifiable and steps can be taken to protect them, he says. And then the bigger picture: “We’ve raised people’s expectations to believe that drug prescription and administration is risk-free. We’ve created an impression that life is risk-free, and it’s not.”

The room is quiet for a moment while the point soaks in. Afterward, several industry researchers, the ones doing the work, not the suits, thank him for the candor.

During a break, panelist Dr. Sandy Kweder, acting director of the Office of Drug Evaluation II at the FDA, says, “Alastair brings a credible perspective of the academic medical community. Industry is focused on developing and selling drugs. That’s not necessarily bad, but it’s tunnel vision. Alastair brings people back to a public health perspective that is often missing.” He does it, she says, non-threateningly. “Instead of giving a specific opinion, he reflects on what he’s heard and holds it up like a mirror for everyone to look at. Everyone can’t do that, but he’s very good at it. He creates the opportunity for people to reflect, as opposed to putting them on defense.”

Wood, says Dr. Grant Wilkinson, professor of Pharmacology who was an assistant professor in 1976 when Wood first arrived at Vanderbilt from Dundee, Scotland, “has always had a very critical thinking mind that can foresee problems and get them resolved before moving on. He likes to visualize the paper written before the study’s done, even before it’s begun. He’s going to get a clear-cut answer, yea or nay, so he can write the paper. He takes a very well-organized approach to science rather than fumbling around, gathering data, then asking ‘what am I going to do with all this?’”

Dr. Michael Stein, associate professor of Medicine in Rheumatology, came to Vanderbilt from the University of Zimbabwe in 1990 to work with Wood on ethnic differences in drug metabolism. He recognized the same traits in Wood’s published papers. “The studies were very carefully designed and were obviously put together in a way that would answer the question — there was no stinting on the amount of work going into answering the question.”

Message of the movement

Alastair James Johnson Wood was born at the very front-end of the baby boom. His father spent nearly seven years in World War II and came home in January 1946; Alastair was born that October. When he was 6 he arrived at school to find it on fire. The family lived in Edinburgh, Scotland, the nation’s capital and a big city of about half a million people. While other students contacted their teachers or phoned their parents and waited to be picked up, young Alastair simply turned around and took it upon himself to find his way home, walking across town.

The story still impresses his wife, Dr. Margaret Wood, who met her husband over a cadaver in anatomy class when they were 18, four weeks into medical school (in the United Kingdom, students were put on an educational track early, either academic or technical; at 18 you were either a scholar or pumping petrol, and professional school starts where “high school” ends). “That’s the kind of boy he was,” Margaret says. “He didn’t call his parents; he didn’t worry them. He just walked home. He’d never walked home in his life before. For a 6-year-old boy, that’s pretty remarkable.”

Alastair, his wife says, was always mature for his age, and always the star in school. She credits the other Mrs. Wood, Alastair’s mother, a math and physics teacher who graduated university in the 1930s, when women seldom went to college, and if they did they didn’t study science. She gave Alastair freedom to explore, to go his own way and develop his own ideas, Margaret says.

She couldn’t have had better timing or more cooperation from world events. In 1963 the Beatles had their first No. 1 hit in the U.K., “From Me to You;” Wood was 16, and society was sliding into mini-skirts, the pill, and the sexual revolution. Two years later The Rolling Stones hit No. 1 with “I Can’t Get No Satisfaction,” and the world said they couldn’t either. Wood joined the collective youthful challenge of the conventional wisdom. “We were a generation that thought we would change the world, and we did,” he says. “A generation of arrogance. We didn’t trust anyone over 30. We believed we could fix all the prejudices and irrationality of the past. We were an incredibly optimistic generation — maybe because there were so many of us!”

Wood mentions he and Margaret went to a Stones concert at Giants Stadium in New Jersey. But when asked what his favorite song is, he says he’s not a musicologist. “The music was about the movement, the time — both the period in our lives and the historical time,” he says, and he’s serious.

This from a guy who now color coordinates his shirts and ties rather smartly. There’s a rumor about a graduation photo of him shot in the 1970s with long hair. “Any hair would be good now,” he says. Many of the follicles gave out a long time ago.

After training in Dundee, Alastair was awarded an international fellowship and looked around to decide where to go. “Even then, Vanderbilt was the premiere place for clinical pharmacology,” he says.

Wood continued work in clinical pharmacology he started overseas, trying to understand why drugs react differently in elderly people. He quickly made an impression with a series of pharmacological milestones in understanding drug metabolism. In one of his early published papers, Wood, working with Wilkinson, changed the way drugs are developed by testing a “then-novel” method to gauge the bioavailability of beta blockers, says Dr. John Oates Jr., Thomas F. Frist Sr. Professor of Medicine and professor of Pharmacology. (Oates and others supported Wood for election into the Association of American Physicians, into which he was recently accepted.)

Other pharmacogenetic (genetic reasons for difference in drug response) characteristics Wood has identified include: an enzyme that, when missing, prevents the breakdown and efficacy of codeine; an enzyme deficiency that leads to a systemic beta blocker effect when the beta blocker timolol, typically used to treat glaucoma, is applied to the eyes; and ethnic differences in drug response, and the demonstration of the genetic differences that explain the ethnic differences.

Wood takes things apart and puts them back together to make a much larger thing than he had when he started, not only answering questions but explaining their relevance.

“Much of Alastair’s work has been in teasing out the mechanisms (of drugs), rather than describing data,” Wilkinson says. “Alastair is interested in the hypothesis, but in generalizing that observation from that drug to perhaps classes of drugs. He used propanalol, a classic beta blocker, as a tool to represent many actions and many aspects of beta blockers as they came along. He’s interested in specifics, but in applying them to broader applications.”

Changes at Vanderbilt

In the 1990s the research atmosphere in the United States went through a wringing fiscal cycle that dried up, then partially restored, federal funding. National Institutes of Health dollars shrank while managed care squeezed reimbursement rates and shriveled the amount of money institutions could earmark for clinical research. At the same time, the federal government was cracking down on institutional review boards (IRBs) — the internal consciences that monitor research protocols, making sure regulations are met and subjects are safe.

Vanderbilt, like many academic medical centers, felt the squeeze. Clinical research took the harder hit, says Lee E. Limbird, Ph.D., associate vice chancellor for Research. “We lost a decade of clinical investigators, people who went to medical school, had problems they wanted to solve and couldn’t get funding,” Limbird says. Vanderbilt didn’t want to lose the ground other institutions had. “We wanted to build clinical research and meet the stated goal — bench to bedside research,” she says.

Wood became the architect. In 2000 he was promoted to assistant vice chancellor for Research. In 24 years at Vanderbilt he had built a block of research in pharmacology that set him above most people in the country, had treated thousands of patients and had successfully put the two together, earning him respect across many turfs.

“I had always found Alastair to be an openly, constructively critical person,” Limbird says. “He knew where the problems were, he was not underhanded in addressing them and he would pose one of a number of solutions, so he wasn’t married to a single solution to solving a problem. He also had incredible credibility as a clinical researcher.”

One area badly in need of a retrofit was the IRB. Wood, in what he calls his best move as an administrator, convinced Dr. Gordon Bernard, professor of Medicine and director of Allergy, Pulmonary and Critical Care Medicine, to be the medical director.

“Our IRB three years ago looked like all IRBs around the country,” Bernard says. “It was understaffed and it took forever for a proposal to get through the review. It would be four to six months before researchers would hear back.”

Since then, the staff grew from four to 20, and a closer, more critical review happens more rapidly. Wood’s leadership initially involved him in day-to-day activities, sleeves rolled up, hands on, Bernard says. Once things got rolling, he backed away and let everyone do their jobs. “He’s an extraordinarily reasonable and thoughtful person,” Bernard says.

Dr. Italo Biaggioni, professor of Medicine and medical director of the Clinical Trials Center, says Wood “troubleshoots and solves problems. He gets groups together and gets people working.”

That’s not an easy task, especially considering the changes Wood has overseen — like the ones he often suggests from public platforms for drug development, testing and monitoring — have changed a decades-old system, Limbird, Bernard and Biaggioni say. But they’ve made the process work more efficiently and more effectively.

Wood says of all this, “I see my job as being to facilitate the life of clinical researchers so that they can be more productive, and trying to keep the bureaucracy from getting in their way.”

That Wood has grown from a 60s-generation challenger of the establishment to a senior faculty and administrator loyal to one institution his entire professional career isn’t as much a shift as it might seem. He’s simply applied the challenges and questions to improve the situation internally.

“Dr. Wood effectively presents Vanderbilt’s scientific programs to the world,” says Dr. Steven G. Gabbe, dean of the School of Medicine. “At national meetings, with prominent researchers, politicians, or industry representatives, he’s likely to present a unique point of view, describe it in practical terms, with a real application so that it means something to everyone, and then add that we’ve been doing that very thing at Vanderbilt for some time now with great success!”

That’s exactly what he did at the PhRMA meeting. After warning the industry about handling drug information, he segued into a spiel on Vanderbilt’s own physician computer order entry system, WizOrder, drawing queries about the technology.

Personal message

Wood wouldn’t have the clinical research experience without the clinical experience. He sees mainly hypertensive patients, people whose care he’s closely managed for 20-plus years. On a recent Wednesday morning, Wood is the typical physician, pacing anxiously in a clinic hallway while waiting to defend his patients against disease, their own overindulgent lifestyles and a clinical setting that sometimes has them waiting longer than necessary – again, wanting to make things work simpler, better.

Sam Meek has been a patient for about eight years. When Wood enters the exam room, Meek grumbles, rather gruffly, “do you doctors keep patients waiting to make them think you’re important?”

Wood flushes, truly embarrassed. He offers an earnest apology and gets down to business. Then he talks barbecue with Meek, who brings it up as a possible reason his weight hasn’t dropped.

Meek has followed Wood’s name in the papers the past few months. He comments about the FDA position. “Politics,” he says accusatorily. But, he admits, “From a selfish point of view I’m glad he didn’t get it.”

Alastair and Margaret, an anesthesiologist, were married in January 1972. They came to Vanderbilt together for a two-year stint. “You arrive at a place and have this incredibly sharp learning curve, you’re learning exponentially, and it’s hard to leave,” he says.

The couple has two sons, Alastair and Iain. Alastair the elder, obviously weary of the baggage of two middle names and the odd monogram he’s been plagued with, saved both his sons similar discomfort and left out middle names for them completely.

Margaret was professor of Anesthesiology at Vanderbilt, but left in 1996 to become chair of the department of Anesthesiology at Columbia University in New York City. Alastair the younger went east to Andover School that year while Iain remained in Nashville with his dad, then followed to Andover the next year. Both boys attended Columbia; Iain will be a senior and Alastair graduated two years ago and will be a second-year law student at George Washington in the fall.

Being a commuter family isn’t easy, Margaret says. She maintains an apartment in New York, which the boys and their friends frequent, while Alastair jets back and forth almost every weekend. The family, she says, recognizes that they can do three things in life — family, work and hobbies, but they can only do two things at once and do them well. So, Margaret and Alastair have devoted their lives to their work and their family, folding shared interests into family time, and the boys have been just as supportive of their parents’ efforts.

That explains Alastair’s lack of hobbies. Senior administrative duties, clinical work, editing a major — perhaps the major series for the major medical journal — and overseeing his own research projects and studies creates piles of paperwork stacked around his Robinson Research Building office like shipping containers at a seaport. He’s a high-tech, PDA-wielding manager, systematically making lists and ticking off tasks as they come, often over 15-hour days, and kept on-track by administrative assistant Janice Fruci, who has enjoyed the recent excitement her boss has generated as much as anyone.

Wood purports not to be too closely associated with anything stereotypically Scottish — he drinks wine, doesn’t play golf and seems disgusted at the mention of haggis. He is proud of being frugal, and makes the best use of the characteristic. “You have to explain to your kids that they don’t have certain things growing up because their father is Scottish,” he says, wrapping the truth in a joke.

That story about his walking home — he told his mother, who was frantic when he arrived that day, that he didn’t see the need to spend the bus fare, there was no rush for him to get home.

Wood takes a good bit of ribbing about being a Scot, and his Scottish accent. “We joke about it every chance we get,” says NEJM editor Drazen. And Wilkinson testifies that Wood makes no bones about his frugality.

And there’s wit. Edinburgh was home to many great Scots, including Sir Arthur Conan Doyle, Alexander Graham Bell, Sir Walter Scott, John Knox, Robert Louis Stevenson and, the man who made the brogue sexy, Sean Connery. One thing they shared besides the motherland was the ability to tell stories (what did you think Bell’s motive was?). Alastair fits that mold. “He’s a great raconteur,” Wilkinson says. “I like to sit back after a glass or two and let him talk.”

Wood peppers his speeches with colorful metaphors (he illustrates that science has to keep striving to improve things by pointing out that we don’t know how good something can be unless we try it with a reference, again, to music: “I thought my Beatles LPs sounded pretty good on a record player, but that was before I had heard a CD.”) and engages in good-humored sparring deftly, leading with jabs, releasing punches at the most opportune comedic moments.

But Wood also encourages open criticism. “He’d much rather (his lab personnel) tell him his idea stinks —which happens all the time — than have us bow down in front of him,” Stein says, half-jokingly. “He likes to bounce ideas off people and see what’s going to stick.” His patient, Sam Meek, says, “I’ve been yanking his chain for years.”

On Feb. 20, after months of speculation in the media, from the New York Times to Time magazine, about Wood’s becoming the commissioner of the FDA, the newswire service Bloomberg reported that Alastair Wood was “out of the running.” Like the guy on the plane, his trip ended before he landed.

Reports pointed fingers at the drug industry, saying Wood would be seen as too conservative; ironic, because Wood’s more efficient, more effective style would probably have made more room in the market for drugs, just as Vanderbilt’s own IRB is allowing for more clinical research. Others said he would be too liberal on certain issues. The bottom line, they say: he was true to science, not politics.

During the interview process Wood realized that being political could dangerously alter someone’s sense of reality and integrity. “You have to be careful,” he says. “At a certain level you could say the world was flat, and people would agree with you. You have to be able to look yourself in the mirror and be true to your core values.”

So, what does he think about the whole experience? “At first, it was a gas,” he says, but declines further comment for the record about the specifics of the experience or why he wasn’t chosen.

His story, though, is exciting. It’s obvious he enjoyed some of it, was physically tired by some of it, perhaps a little disappointed. But Wood is a practical man. He’s examined all the angles and harbors no hard feelings. He’s happy at Vanderbilt, directing research, seeing patients and administratively strategizing. His wife says he’s always an exciting person to be with, that even when doing something as mundane as grocery shopping he poses a unique, interesting point of view.