Interview with Robert Ruffolo
Known by the Society He Keeps
By his own admission, Robert R. Ruffolo, Head of Research and Development at Wyeth-Ayerst, is a bit of a nerd. Opting to spend seven nights per week with his textbooks at the expense of all else, he earned his pharmacy degree summa cum laude, and his PhD in pharmacology in just over three years. He speaks with unabashed enthusiasm for the pharmaceutical industry, for biomedicine, and particularly for the future of pharmacology. Even if you don't know Ruffolo, you've probably seen him—if not at a science symposium, then surely as the lead “actor” in televised promotions that ran throughout 1999 on behalf of the Pharmaceutical Research and Manufacturers of America (PhRMA; scenes reproduced here, with permission). “Actor” belongs in quotation marks, because if there is such a thing as type casting, then Ruffolo is certainly an example in the PhRMA ads: passionate about good drugs and the people who need them; proud of his profession and his contributions; dedicated to science as well as to his colleagues; and grateful for the opportunities he has had to contribute. The commercial's requisite happy ending, where three generations of a coronary-prone farm family ride off into the sunset, reflects Ruffolo's own success story in helping to bring carvedilol to market. In all of this, however, Ruffolo's sincerity transcends the hokey as well as the nerdy. His devotion to science includes a mission to help others, and he would argue that in this and most ways, he is not so different from his academic colleagues.
MI: You've won lots of awards that generally go to academics, and you've also had a publishing record and an editorial presence that is very indicative of a high-profile academic—and yet your whole career has been in industry. So how do you describe yourself?
RR: You know, it's interesting. When people ask me what I do, I tell them I'm a scientist, rather than a pharmaceutical executive, although I'm very proud of that, too. When I travel to the UK and they ask for an occupation, I write, “Scientist.” I’ve worked my entire career in the pharmaceutical industry, and the companies that I was attracted to allowed me to be a scientist, and then to develop executive skills and assume greater leadership responsibilities in the industry, without forcing me to stop being a scientist. And that I liked. So, I had the best of both worlds.
MI: You went to pharmacy school. Were you planning in college to become a pharmacist?
RR: No. Pharmacy is a great discipline, and I loved every part of pharmacy school. But I especially liked pharmacology and I thought, if I went to pharmacy school, the worse that could happen would be that I could fail as a scientist and still be a pharmacist. And what a great career that would be!
MI: Did you really have that thought—“What if I failed?”
RR: I did! But I really wanted to be a scientist. So pharmacy was a way to get into science, something I was familiar with—I came from a family of pharmacists—and something I liked.
MI: So, with an eye set on pharmacy school, and with the hope of becoming a scientist, what made you head from your hometown in New York to Ohio State as an undergraduate?
RR: I was a swimmer…
MI: So you weren't just a science nerd!
RR: No, well I was a nerd, and that hasn't changed. I was probably the last one to give up a slide rule. But I was a very good swimmer in high school, and my swimming coach had gone to Ohio State. So I went to Ohio State and did swim, but not for all that long. I decided I could never make a career out of swimming—it was really hard work. And so I decided no more swimming. Every night at 6:00 I started studying and I never finished studying until after midnight. And I never dated, I never did anything except studying. Seven nights a week. I did very well in school, and then it's sort of reinforcing.
MI: What was driving you so much at that point?
RR: I had an underlying fear that I was going to be a failure. I just wanted to be able to support myself. I didn't have aspirations to be rich…I mean everybody who goes into science wants to be recognized and get certain accolades, but I wanted to make sure that I could support myself and do science. So I studied hard. And it turned out to be a really smart thing to have a pharmacy background. There's probably no better background for going into any sort of biomedical science than a pharmacy background…I think it's even better than medicine. You get all the physical sciences, as well as biology, that relate to pharmaceuticals. I have always argued that people with pharmacy backgrounds who go into pharmacology probably have more breadth.
MI: Do you still see it that way? Is pharmacy still a good place for pharmacologists to start?
RR: I would still encourage people to go into medicine or pharmacy. I mean you can become a pharmacologist with any background, but I still think pharmacy is special, because of the intersection of disciplines, with all the chemical and biological sciences.
MI: When you arrived at college as an undergraduate, did any other discipline attract you at all?
RR: No. I was totally focused. It was going to be pharmacy to get to pharmacology to do research. Already as an undergraduate I was working in the laboratories. When I entered the pharmacy program and met my adviser, Popat N. Patil, I learned that this was a very important pharmacologist—a true hard-core pharmacologist by the 1960s and 70s standards. And he put me to work in a laboratory in my second year of college and I worked in a laboratory all the way as an undergraduate. So I had an uncommon degree of laboratory experience when I got into grad school.
MI: And so you stayed for grad work at Ohio State because of Patil?
RR: He's the main reason I stayed. I had already a lot of exposure to the laboratory, and I thought I would start graduate school with a leg up. And as an undergrad I had taken lots of extra courses—as I did in grad school.
MI: And yet you still finished your grad program in three years?
BR: A little over three years. I was working seven days a week. I never took any days off. I used to work holidays. I used to work Christmas day.
MI: Did you just like it that much?
RR: Oh, I loved it. I loved doing experiments. I loved analyzing the data. I liked everything about the laboratory. And there was nothing else I would rather be doing. I found it relaxing. People at work here say—I'm here at 5:30 in the morning—“Take some time off.” But if I weren't here, I’d probably be wishing I were here doing something. Besides my work and my family, there isn't anything else that interests me. I don't like going out to dinner…I don't like socializing that much. Outside work, I just like to be with my family.
MI: And your work—do you find this to be a social life?
RR: I do. I never did have many friends outside of work or the laboratory and I don't now, either. I have a very close friend, and his wife is my wife's best friend, and he happened to work for me for years at SmithKline. And I don't need a lot of friends. I have my family and the job and the people here at work.
MI: You oversee a staff of over 4500. Can you talk about being in the pharmaceutical industry as a kind of culture?
RR: Sure. In grad school I had never planned to go work in the pharmaceutical industry. I thought I would work at a University, doing research, and teach. That's all I wanted to do. But when I was at the NIH doing my postdoc, I got a call from a guy named Jerry Fleisch at Lilly, inviting me to interview for a job. I owe Jerry a great deal, because a couple of days before my interview, I called and I said, “I don't really want to work for the pharmaceutical industry, I’d like to cancel.” And he said, “Come on out. Give a lecture, get a free meal.” So, I went, and I saw all these first-class facilities, and I saw high-class scientists. My first role model, Ray Fuller, was at Lilly at the time. And I met him during the interview and I immediately thought, “That's what I want to do. I want to be like Ray Fuller. I want to do good research. And I can do it here!” So I went to Lilly, and I spent seven years there, and I had a wonderful time.
Now, to answer your question, I didn't know anything about the pharmaceutical industry then. I walked into Lilly, they gave me a lab and a couple of technicians and they gave me enormous freedom. And I immediately started to identify not only with Ray but then I met my second role model, Ron Tuttle. He's the guy who discovered dobutamine. And I started doing some work with dobutamine, and I started working and trying to discover drugs. And I went from only wanting to do basic research—no interest in products—to all of a sudden wanting to do what Ron and Ray did. I wanted to make drugs and make people better! It was a big change of direction for me. I wanted to help make a drug plus do basic research and I found it was all consistent! People often asked me, “How much time does the company give you to do your own research versus company-related research to make drugs?” And there's no answer to that. It's the same thing! So I never felt that I had to walk a line. And then I learned a little bit about management. I didn't have really very many management responsibilities at Lilly. I only supervised three or four people when I left, but I had some management role models at Lilly, too. I had good bosses, like Pat Murphy, who was an excellent manager—he was good with people, and I learned a lot from him. And then after seven years, SmithKline called, and they said, “We have this job, Director of Cardiovascular, and we think you can do the job. You've got the scientific background. It's a stretch, managerially, because now you're going to manage twenty to thirty people.” And I went to SmithKline.
MI: Any fear of failure there, having to become a manager?
RR: Yes. Because now it was a little different. I was leaving a secure job that I loved, and still to this day I only have fond memories of Lilly. Going into SmithKline, I could still be a scientist—in fact, that's what they wanted, they wanted me to be a scientist and a manager. I didn't have to be one or the other. And so I still had a laboratory, I still got to work and make drugs.
MI: You say you've never been a social creature, but it sounds like you are very much a social creature. It's just that you found social outlets in science.
RR: That's a good point. Science has been really good to me. I got to see the world through science. Through that period, in the early to mid eighties through the end of my time at Lilly and the early part of SmithKline, I was all over the world, partly because of my work on adrenoceptors, and my friends were leaders in the field. And we would always be together at these different symposia and we became true friends. And then CoregR, took me all over the world. The lectures on that drug…trying to get people interested in it. You know, there are always a lot of doubters on any new drug, because most drug candidates are likely to fail. And this is one of the rare cases where it worked. And there's no better feeling in the world than to be associated with a product that improves people's lives. And still, the thing I'm most proud of in my whole career is Coreg (carvedilol).
MI: When did Coreg start becoming a project for you at SmithKline?
RR: In the mid 80s. Very early. It became a product in 1996 or 1997. So that's how long it takes to get a product to the market. And that drug probably has, of any drug used in heart failure, the most profound effects on the disease. Decreasing mortality and making people better. And so I feel really fortunate and privileged to be associated with that product.
MI: Looking at the odds of bringing a successful drug to market, how much luck is involved?
RR: Lots.
MI: Does that make it more or less of a privilege for you, to be involved in a drug success story?
RR: If it were all brilliance and genius, it would be better! But there is a lot of luck. A lot of great ideas, a lot of wonderful scientists, a lot of good molecules can fail in this industry for reasons that you can't predict. There may be people who have done better science, better research, had a better idea, but to be totally honest with you, with Coreg, there was a great deal of luck.
MI: And besides luck, what else do you think put you on the path to a successful drug?
RR: I was doing a lot of research on adrenoceptors, talking about our research, and I was also at many symposia that my academic friends in adrenoceptors never knew about, dealing with Coreg—more medical types of symposia.
MI: So do you feel that becoming an industrial pharmacologist somehow deepened your science?
RR: You bet it did! And that's one of the advantages I’ve had over my friends in academia. I was exposed to all aspects of biomedical science, not just my own area of interest. You can't survive in the industry by being in a relatively narrow area, as is often the case in academia—you know, where one grant leads to another that leads to another. In industrial science, you're exposed to everything.
MI: Why are you exposed to everything?
RR: Because that's what it takes to succeed in the industry. It's purely collaborative, whereas in academia a talented scientist—of course they collaborate—but it's more of an individual achievement than making a drug. The academic picks a niche. Here, you sort of migrate to where the opportunity is. And there's a much greater emphasis on collaboration.
MI: And so you have to collaborate to know where the opportunities exist—you can't just make your own niche?
RR: Exactly. So I sort of competed in two different fora. Coreg interacted with adrenoceptors which was the pure basic science side, and then I had the more practical part in that Coreg became a drug—and in that respect there was a whole different set of people that I was interacting with. So there were two different areas going on at the same time, and I feel enormously privileged to have had the opportunity to do be involved with both.
MI: While you're making the comparison between academic and industrial pharmacology, other industrial scientists have said, especially early on, that academics kind of looked sideways if you said you were going into industry. How was that for you?
RR: Yes, that's absolutely true. There was, and there still is, by the way, some degree of stigma associated with going into industry. I think it's better than it used to be but it still exists. At one point it was believed that you went into industry because you couldn't get a job at University. I don't think it was ever really like that, but the stigma was attached. And I’ve had people come in to interview for jobs in my laboratory, and some of them talked down to me and assumed, “He's in industry, how good could he be?” These people are not born with those biases, they get them from their advisers in graduate school. And you know, I had it too. So I understood it. And that's one of the reasons that I felt I had to work harder… I had more to prove…that I could compete with people in academia—and I did—but that I also worked in industry and I was very proud of it. I love the pharmaceutical industry.
MI: Can you talk about the challenge of becoming a manager? Because you're not just a scientist…you're not just discovering drugs.
RR: It's something that evolved over time. If you had asked me twenty years ago while I was still at Lilly, would I be here in my present job, I would have said, “No! No, I want to do science—I love it.” But you know what happens, as you do more and more science, the really good companies decide they want you managing science and so you get more administrative responsibilities. And so early on in my career, at Lilly, I just did science. Now, of course, I probably couldn't find a laboratory. But for most of the time in between, which has been the bulk of my career, I’ve been able to do both. And I would argue now that although I don't now direct a postdoc or a laboratory, my contact with science is still strong—now, it's about judging science, maintaining the standards of science, setting the objectives of science.
MI: Manage and judge science…and yet you had to start managing without managing experience…
RR: You have to start some place! If you're a good scientist, you know good science from bad; you can set standards. And the best companies peer review everything, just like academia does. We don't write NIH grants, but we also don't have license to do anything we want. We have to compete for the limited resources within the company. You have to propose and defend projects, identify the resources you need, and explain why the world is going to end if your project is not funded. Just like an NIH grant.
MI: I'm amazed that you have 4500 people under you, and yet you started out this interview saying that you were never a social person. It rather seems that you're demanded to be social at a level that few people face.
RR: Sure. A lot of it is personality and being able to get along with people, and manage every kind of person you can imagine. EVERY kind of person you could imagine. And manage large committees. And I think I can do that. When I say social, I just meant like going out to dinner. I like being around scientists. I like dealing with the way that scientists think, even when they're crazy. You get every personality in science. You get the zealots and you get the people who couldn't care less. And you have to manage all of them and motivate people to go further than they thought they could go—especially in industry, more so than in academia.
MI: You mentioned that you started out as a hard-core pharmacologist. Is there still a place for classically trained, hard-core pharmacologists in the pharmaceutical industry now?
RR: Less so. Of course we will always need people who can do the more traditional things that we associate with pharmacology, but the world is changing, and the pharmaceutical industry has changed, too. We approach science the same way as my friends do in academia. You identify the molecular target; drugs are discovered on a molecular basis. Yes, we still do testing in animals, but it's much later now. And we do less of it. So the same sort of transformation that occurred in pharmacology over the last twenty or thirty years at universities occurred here. But we will always have a bit more of a need for the classical aspects, as well. I would argue that pharmacologists, whether they want to work at a university or the pharmaceutical industry, should follow the same path. I worry about people who go to graduate school to work in the pharmaceutical industry. I worry that they may believe the stereotype, that it's easy, that you make a lot of money, and it's not cut-throat. My message is, “No. It's not easier to work here.”
MI: You described your own excitement at being a pharmacy major—at studying at the intersection of so many different disciplines. What is the graduate student missing from that experience by deciding to concentrate on molecular biology? What if I say, “I'm a cloner…industry is going to need my skills.” Is that a proper approach to take?
RR: That's a bit narrow. I get asked that question a lot: “Should I become a molecular biologist?” Why not become a molecular pharmacologist? Yes, we need people who can clone genes. But you know what: That's still a technology. So you go to graduate school and you come out with a technology. It's not the same as having broad training in pharmacology. What I liked about pharmacology was that it involved all of the subjects I liked. It involved physiology, biochemistry, chemistry. Now you include with all those, molecular biology, genomics—all of those are parts of pharmacology. And I’d rather have people with a broad background in those areas than somebody that comes with a technology, someone who can just clone a gene.
MI: Is innovation going to remain dependent on broadly trained people?
RR: Yes, I think so. There's a reason: You can clone a gene from any species. But you need to know what you're going to do with it, and why I, as somebody who's going to decide whether to fund this or not, should be interested. What commits me to doing that? What's the medical use going to be? And that's why I like something more than someone who knows a technology. I’d like them to use their brains to apply that technology and tell me what kind of drug they're going to make. How they're going to help people, and how they're going to help us to support ourselves. Because at the end of the day we're still a business we have to earn our money. I want somebody doing cutting-edge science, but applying it to pharmacology, or physiology, and biochemistry.
MI: Now I want to talk about social pressures that are converging on the pharmaceutical industry. I know that you served as an expert witness in Fen-Phen cases. Talk about representing the pharmaceutical industry, especially in those instances where the industry is vilified.
RR: The image of the industry is something that I'm very concerned about. I like what this industry does. We're here to make people better, and yes, we make a profit, and a big one. And there's a reason for that. Drugs are expensive to produce, and you know this is an industry that has enormous risk in it. It's riskier than any other industry. We spend as an industry seventeen percent of our sales on R&D. That's a lot of money. No other industry comes even close to the pharmaceutical industry. Industry at large is just about three percent. And the reason we have to spend so much is that we're risky. We in the pharmaceutical industry exist because of our shareholders. And if we were going to return on your investment at the same rate as a less risky industry, who would you invest in? If we were to give you, as an investor, seven percent return on your dollar to invest in us, and a company that makes alarm clocks is going to give you seven percent, and we're really risky—they're not—who are you going to invest your money in? You're going to invest in the alarm clock company because there's less risk and you're going to get the same return. The reason we have to be profitable is that we have to reward people who take the chance to invest in us. If they didn't have that chance to profit from their investment, they wouldn't take the risk. Yes we're profitable, but we give much of our profits back to the shareholders who took a chance. But it doesn't always look good because we're making money. And our drugs are expensive and they're expensive because we're risky. It costs us a lot to develop a drug. And we fail often.
MI: In some ways, that's an unsavory message, however true. Do you think the industry has held back from delivering the facts of pharmaceuticals?
RR: Well, I think we probably haven't done a good job during the last few decades explaining to the world what we do and how we're unique because of this risk that we face compared to other businesses—why drugs are expensive. For instance, we often consume a lot of the patent life while we're developing a drug. It takes us so many years to discover and develop a drug that a significant amount of the patent life can be used up prior to market launch. Not always, but often. So you've got to make up your development costs, which are higher than most other industries, in a shorter period of time—while you still have patent life left. So we have a unique dynamic that's not like other companies. And it's all centered around the extraordinary risk in the pharmaceutical industry that protracts the time it takes to make our products, inflates the cost of making our products, shortens our oppourtunity for making up that investment, and requires us to be more profitable than other industries. And remember, if we're not successful, patients will not be supplied with effective drugs.
MI: And so you think the lack of communication explains why the industry is often demonized?
RR: Partly, and also, sometimes the process goes wrong. No product is perfectly harmless. We're talking about taking a foreign substance—a drug—and putting it into a human and expecting it to cure or at least treat a disease that usually involves one system and maybe even one protein in one system, and not do anything else. So it's a tough business from that standpoint. We don't want our products to injure anybody. We don't make money by hurting anybody, and we worry about this and agonize all the time. In spite of what you hear about this industry, we care about safety more than anything else. Putting a dangerous drug on the market doesn't help our company or our image.
MI: Is that word not getting out, or are people just not believing you?
RR: Well, when you're profitable, and drugs are expensive, and people have trouble affording them, and then something goes wrong…what does that look like? It looks like greed. Is it greed? Well, I’ve already admitted we have to be more profitable than most other industries. That's a fact. And another reality that is problematic for our image: Everybody knows that when you have a heart attack, you want a thrombolytic. But you also know that some people are going to have some pretty severe strokes as a result of that thrombolytic. But you help far more than you hurt. The risk/benefit—that's what the FDA weighs. So what happens? You almost always know who you hurt—the people who had the stroke. But you don't always know whose lives you saved. And we always worry about the potential hurt. And as sort of an anecdote: When I was told about the results of the clinical trials for Coreg, I was in England. And my boss, George Poste, who was the head of R&D at SmithKline called, and he said, the studies with Coreg were stopped. And my immediate reaction was, “Oh my God! We’ve killed people with heart failure!” That was my reaction. I assumed we hurt people. He said, “No. Let me finish!” The drug was so effective—it reduced mortality by 65%—that it was unethical to maintain the program. And I cried for hours. But my initial reaction was, “We hurt people and it's my fault.”
MI: That's not the face that's put on the industry, is it?
BR: No, and you know what? There are drugs in heart failure that have hurt people, and behind each one of those is somebody who wanted to help and was associated with a drug that turned out to hurt. That's why we do clinical trials. This really is risky business. We're dealing with people here, taking a foreign substance.
MI: Tell your story of Coreg. Why did SmithKline pursue this drug, despite all the risk you've spoken of, and the fear you felt, even well after clinical trials began.
RR: Not only was it a risky disease—heart failure—but this drug was also a beta-blocker, and they were contraindicated in heart failure. So here we're asking the company to take a drug into a risky patient population—50% die in five years. And then to take a drug that's contraindicated. And then to spend hundreds of millions of dollars to do clinical trials?! Of course there's going to be some resistance from the company! But you know when you're younger, you're more idealistic; you push, and push, and push. So I kept showing them more, and more, and more exciting data. They believed this drug was different—but they were still reluctant to take this big risk, but they finally did it. After twelve years, it produced a 65% reduction in mortality, it has kept people out of the hospital, it has lowered health care costs for heart failure. But it was a tough twelve years. And I have to say about SmithKline—despite the hard push—when the drug worked, they gave me credit as a scientist.
MI: So you're now facing drug discovery in the new millennium at Wyeth-Ayerst. Where is pharmacology going? Are we really looking at an age of personalized prescriptions based on one's own genome?
RR: Well, I think theoretically it's possible. I don't think we’ll see it in our life time. This is the debate that goes on. There are people who believe it's just around the corner. I don't think so. But pharmacology is changing. And in my opinion it's getting better.
MI: Apart from genomics?
RR: Well, again, remember pharmacology is not a discipline by itself. It's biochemistry, physiology, molecular biology, and now, genomics. And the people who are turning genomic targets into drug targets are pharmacologists. And I think the smart pharmacologists are the ones that will treat these major advances as important new technologies as opposed to fads and trends. I still describe myself when given the question, “What kind of scientist?” as a pharmacologist! And I want to be hiring those people at the cutting edge who can deal with genomics, reduce a genomic target to a drug target, work with the medicinal chemist to make a drug—that's a pharmacologist! And those people, people who stay at the cutting edge, are the people that I want to hire.
- © American Society for Pharmacology and Experimental Theraputics 2001
