- Email: [email protected]
An interview with Raymond L. Woosley
TIPS-1141; No. of Pages 3
Scientific Life: TrendsTalk
An interview with Raymond L. Woosley [email protected]
Raymond L. Woosley, MD, PhD is the founding President of the Arizona Center for Education and Research on Therapeutics (AZCERT), a nonprofit organization dedicated to the safe use of medications. He is Emeritus Professor of Medicine and Pharmacology at the University of Arizona and Visiting Scholar at the College of Medicine in Phoenix. Dr Woosley received his medical degree from the University of Miami, his doctorate in pharmacology from the University of Louisville, and his bachelor’s degree from Western Kentucky University. After an internship and residency in internal medicine at Vanderbilt University, he completed a fellowship in clinical pharmacology before joining the faculty and rising to the rank of Professor of Medicine and Pharmacology. In 1988, Dr Woosley was appointed Chairman of the Department of Pharmacology at Georgetown University Medical Center in Washington, DC. In 2001, Dr Woosley joined the faculty at the University of Arizona as Vice President of the Arizona Health Sciences Center and the Dean of the College of Medicine. In 2005, he founded the Critical Path Institute (C-Path), an independent, nonprofit organization created jointly by the US FDA and the University of Arizona to help implement the FDA’s Critical Path Initiative. Dr Woosley’s research has been published in more than 280 peer-reviewed publications and in 11 patents. For his contributions to medicine, Dr Woosley has received numerous awards from academic institutions, government agencies, and professional organizations. 1. How did you first become interested in pharmacology? It was simply by accident that I chose a career in pharmacology. I was a chemistry/biology double major planning for a career in chemistry when my advisor told me of a new National Institutes of Health (NIH) training program in pharmacologic sciences at the University of Louisville. After grabbing a dictionary to look up the definition of pharmacology (this is before Google or Wikipedia), I realized that this discipline was the blend of chemistry, biology, physiology, and medicine that I sought. My mentor in pharmacology at the University of Louisville, Kee Chiang Huang, MD, PhD, was one of the medical school’s most gifted teachers and one of the few physicians in the basic sciences. He always emphasized the clinical context for my research and in doing so had a major influence on how I approached biological questions. He 0165-6147/ ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tips.2014.05.002
stressed scientific rigor in our research but also taught me to ask ‘is the answer to this question likely to be relevant to human health?’ I have no doubt that his early influence led me to later apply to the University of Miami’s school of medicine and eventually train in internal medicine and clinical pharmacology at Vanderbilt. I was attracted to Vanderbilt because of its excellent program in clinical pharmacology that, still today, bridges the departments of medicine and pharmacology, a model created in the 1970s by Alan Bass, MD and Grant Liddle, MD, chairs of pharmacology and medicine, respectively. After training and spending 13 exciting years as a member of the faculty at Vanderbilt, I left to become Chairman of Pharmacology at Georgetown University. I found it difficult to leave Vanderbilt but I was excited about the opportunity to recreate the ‘Vanderbilt model’ by working closely with my new colleague and subsequent good friend John Eisenberg, MD, who was Chairman of Medicine at Georgetown. At the time, we didn’t refer to our efforts as ‘translational’, but, in retrospect, that was our goal. We sought to have a clinical pharmacologist in every division of the Department of Medicine to stimulate collaborations between the clinical and basic scientists in the Medical School. We had a lot of success but our work was cut short by John’s untimely death due to brain cancer. I’ve never felt that pharmacology was just another of the basic biomedical sciences. Over the years, I have become convinced that biomedical scientists generally fall into only one of four categories. Some study structure (anatomists), function (physiologists), or dysfunction (pathologists), and some want to perturb biology (pharmacologists). So I’m proud to be a pharmacologist and able to perturb the system, hopefully for the better. Unfortunately drugs are not always medicines. Nor are they always as safe as their inventors would have liked. Too often, I and my colleagues in clinical pharmacology find ourselves studying toxicology. 2. You are currently the President and Chairman of the Board of AZCERT. What can you tell us about AZCERT’s mission and your role within it? I am very proud that I had the opportunity to serve as director of one of the nation’s Centers for Education and Research on Therapeutics (CERTs). They are home to a lot of pharmacologists working under many other labels as agents for change. The idea for CERTs began in the early 1990s when it became clear to many of us in medicine that there was an unmet need for independent research and educational programs that focused on the safe use of medicines. I published a series of papers calling for an Trends in Pharmacological Sciences xx (2014) 1–3
1
TIPS-1141; No. of Pages 3
Scientific Life: TrendsTalk independent network of CERTs. I had recently moved to Georgetown, and living in DC you quickly become aware of the opportunity to work with members of Congress (yes, lobby). My former Vanderbilt colleague and surgeon Bill Frist, MD had just been elected to the Senate and he became our congressional champion for CERTs. In 1997, the Food and Drug Modernization Act (FDAMA) was being enacted and Senator Frist included legislation authorizing the Agency for Healthcare Research on Quality (AHRQ), working with the FDA, to establish a network of centers that conduct research and educational programs to foster the safe use of medicines and other therapeutics. In 1999, Georgetown University applied for and was awarded one of four center grants and AHRQ launched the network of CERTs. At its peak, the CERTs network had 14 centers and a coordinating center, each located at one of the nation’s leading universities. The importance of federal funding for the CERTs was to enable them to remain independent of market forces (not just independent of pharmaceutical companies, but all commercial influence such as health insurers). Independence was an essential characteristic of these centers, one that has been difficult to sustain due to limited federal funding. In 2001, the Georgetown CERT moved with me to the University of Arizona and became AZCERT. In 2005, it moved with me again to the C-Path. After 12 great years, the AHRQ funding for AZCERT and seven other centers was not renewed and today there are only six federally funded CERTs. However, all 14 continue to perform essential research and educational programs on the safe use of medicine. Since 2012, AZCERT has been a free-standing 501(c)3 nonprofit organization supported by volunteer efforts, research grants, and charitable contributions. AZCERT has become the internationally trusted source for information on drug interactions and a particular form of drug toxicity; that is, drug-induced QT prolongation and the potentially lethal arrhythmia torsades de pointes (TdP). AZCERT analyzes evidence and maintains lists of drugs that are categorized according to their risk of causing TdP. These lists are regularly accessed by thousands of researchers and healthcare providers. Originally termed the QTdrugs.org website, it is now branded as CredibleMeds.org to emphasize the goal of providing credible, independent assessment of evidence that can improve the safe use of medicines. The site has three portals, especially designed for the public, healthcare providers, and research scientists. In the last 9 months, the site has had over 150 000 unique users from 174 countries, and 8200 are registered users who have requested that they be notified as the drug lists are revised. The lists have been used in at least 14 research publications and cited as valuable resources on drug safety in three clinical practice guidelines. 3. Given that all drugs will have side effects, how do you think we should approach the concept of drug safety from a societal standpoint? (That is, how should we decide if a particular drug is ‘safe’ or ‘unsafe’? Who should decide?) The essential caveat to this question is ‘for what purpose’. No medicine is completely safe under all conditions of 2
Trends in Pharmacological Sciences xxx xxxx, Vol. xxx, No. x
use. As prescription of a medicine – old, new, or investigational – is being considered for a patient, it is essential to ask ‘why is it being prescribed?’ and ‘how will it most likely be taken?’ Our current drug-regulatory system requires that drug sponsors submit data demonstrating that a new drug is effective and relatively safe when used as directed. Unfortunately, drugs are often not used as directed and the FDA lacks the authority and the means to ensure that they are. Until recently, our society lacked the technology to monitor effectively how medicines are being used and to assess their relative impact on patients (both for safety or effectiveness). In the USA, we still rely on a voluntary reporting system of adverse events and rarely do we have adequate data to assess the comparative effectiveness or safety of medicines. To select the optimal therapy for a specific patient (i.e., personalized medicine), healthcare providers need a reliable assessment of the potential benefits and relative risks of therapeutic alternatives. Today we have the technology but we still lack the data or, more precisely, we lack the investment to obtain the data. In 2007, Congress mandated the FDA to create (without sufficient funding) the ‘Sentinel’ system. Sentinel was expected to monitor drug safety by active surveillance of the health records of at least 100 million Americans by 2012. It is still in the pilot phase and has only limited funding. I have come to believe that drug safety and prevention of adverse drug reactions (ADRs) are not the sole purview of the FDA. Because medications are the fifth leading cause of death in the USA, drug safety science should be a major focus for NIH-funded biomedical research. NIH research could examine and enable better understanding of the mechanisms of drug toxicity and the biological and clinical risk factors for individual patients who develop ADRs. Furthermore, prevention of drug-induced illness (ADRs) should be a leading public health goal and, for that reason, I believe the responsibility for surveillance and quantification of ADRs should include the Centers for Disease Control and Prevention (CDC), just as does surveillance for other illnesses. Ideally, the FDA could work with the NIH and CDC to set priorities for research and surveillance and still retain the responsibility to make the regulatory decisions regarding whether a drug should carry special warnings or if it should be marketed. New technologies are also creating the opportunity for us to rethink our nation‘s regulatory approach to drug development and approval. As our nation finally develops the technology to have integrated electronic health records, we will have an opportunity to develop a ‘learning healthcare system’. We should no longer be forced to rely on outdated and inefficient methods such as randomized controlled trials to learn about the benefits or risks of medical interventions. Having timely and accurate outcome data available would enable the FDA to approve drugs earlier for carefully evaluated and defined populations. Later, as the sponsor obtains post-market data from the learning healthcare system, the agency could consider allowing the expansion (or constriction) of a drug‘s indications for use. I have termed this concept ‘rolling approval’ and others have called it ‘adaptive licensing’, but it will require a rapid learning environment to monitor how drugs are used and
TIPS-1141; No. of Pages 3
Scientific Life: TrendsTalk how they perform. Adaptive licensing is now being piloted in Europe, where more advanced and uniform healthcare data systems are available. 4. You’ve served in so many different aspects of pharmacology, publishing hundreds of papers and receiving numerous awards. Is there anything that stands out as a career highlight for you? I think one of my most exciting moments came when I was part of the team of scientists working on the question of terfenadine’s potential for cardiac toxicity, specifically TdP. I am proud of our research that identified fexofenadine (Allegra) as a much safer alternative to terfenadine (Seldane). A single clinical case made us, and eventually the world, realize that drugs in any therapeutic class might have the potential to cause cardiac arrhythmias and sudden death. The ‘ah-ha moment’ quickly became ‘oh my goodness’ as we realized the magnitude of the harm that had resulted from a lethal drug–drug interaction involving terfenadine, which we mistakenkly thought was the safest nonsedating antihistamine ever developed. We were stunned as other drugs such as astemizole, cisapride, gatifloxacin, cisapride, probucol, and levomethadyl were removed from the market due to the same toxicity, TdP. Furthermore, as drugs like methadone, which had been used for over four decades under close observation in addiction-treatment centers, were found to have the same problem, we worried ‘will we ever know the full extent of this problem and how will this affect the industry’s future ability to develop safe medicines?’ Screening tests have been developed to detect drugs that have this TdP risk, but I fear that many good medicines are being needlessly scrapped because of their effects on imperfect surrogates, such as ion channels and QT intervals in normal subjects. If we better understood why certain patients develop this toxicity, I have no doubt that many important medicines that prolong the QT interval could be used safely. However, my greatest pride comes from joining Dr Janet Woodcock (at that time Deputy Commissioner of the FDA) to launch C-Path. C-Path has become all that we had
Trends in Pharmacological Sciences xxx xxxx, Vol. xxx, No. x
envisioned; that is, a trusted third party that united over 60 pharmaceutical companies and foundations including the Bill and Melinda Gates Foundation together with FDA scientists to review and reach consensus on best methods to use in drug development. The five consortia formed by CPath have over 1000 scientists sharing data and knowledge that improve the speed, efficiency, and accuracy of drug development for the public health. 5. What do you think is the most rewarding part of a life in science? The most challenging? Clearly the most rewarding experience for me was the opportunity to work with graduate students and research fellows who are some of the brightest minds and the most dedicated people I have ever known. I have lectured to thousands of medical students and trained dozens of clinician scientists who are enjoying very productive and rewarding careers in medicine and biomedical research. I am very proud of every one of them and their impact on the safe use of medicines. The most challenging part of my life in science has been dealing with the inertia and bureaucracy of government and the politics of academia. 6. What’s the best piece of advice you have ever been given? ‘Stay in school as long as you can.’ Over the years I’ve come to better understand what my father really meant. At that time, I thought ‘what does he, a farmer and grocer, know about the importance of staying in school?’ However, when it came time for me to begin grade school, he moved our family from the farm to live in a nearby college town, Bowling Green, KY, just so my brother and I could get a better education. I later learned that when he was 12 his father sent him to Louisville to live with an uncle so he could graduate from the best high school in the state. My father’s advice and his example as a lifelong learner had its impact on how I spent my career continually learning about the exciting interface between medicine and pharmacology.
3
Scientific Life: TrendsTalk
An interview with Raymond L. Woosley [email protected]
Raymond L. Woosley, MD, PhD is the founding President of the Arizona Center for Education and Research on Therapeutics (AZCERT), a nonprofit organization dedicated to the safe use of medications. He is Emeritus Professor of Medicine and Pharmacology at the University of Arizona and Visiting Scholar at the College of Medicine in Phoenix. Dr Woosley received his medical degree from the University of Miami, his doctorate in pharmacology from the University of Louisville, and his bachelor’s degree from Western Kentucky University. After an internship and residency in internal medicine at Vanderbilt University, he completed a fellowship in clinical pharmacology before joining the faculty and rising to the rank of Professor of Medicine and Pharmacology. In 1988, Dr Woosley was appointed Chairman of the Department of Pharmacology at Georgetown University Medical Center in Washington, DC. In 2001, Dr Woosley joined the faculty at the University of Arizona as Vice President of the Arizona Health Sciences Center and the Dean of the College of Medicine. In 2005, he founded the Critical Path Institute (C-Path), an independent, nonprofit organization created jointly by the US FDA and the University of Arizona to help implement the FDA’s Critical Path Initiative. Dr Woosley’s research has been published in more than 280 peer-reviewed publications and in 11 patents. For his contributions to medicine, Dr Woosley has received numerous awards from academic institutions, government agencies, and professional organizations. 1. How did you first become interested in pharmacology? It was simply by accident that I chose a career in pharmacology. I was a chemistry/biology double major planning for a career in chemistry when my advisor told me of a new National Institutes of Health (NIH) training program in pharmacologic sciences at the University of Louisville. After grabbing a dictionary to look up the definition of pharmacology (this is before Google or Wikipedia), I realized that this discipline was the blend of chemistry, biology, physiology, and medicine that I sought. My mentor in pharmacology at the University of Louisville, Kee Chiang Huang, MD, PhD, was one of the medical school’s most gifted teachers and one of the few physicians in the basic sciences. He always emphasized the clinical context for my research and in doing so had a major influence on how I approached biological questions. He 0165-6147/ ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tips.2014.05.002
stressed scientific rigor in our research but also taught me to ask ‘is the answer to this question likely to be relevant to human health?’ I have no doubt that his early influence led me to later apply to the University of Miami’s school of medicine and eventually train in internal medicine and clinical pharmacology at Vanderbilt. I was attracted to Vanderbilt because of its excellent program in clinical pharmacology that, still today, bridges the departments of medicine and pharmacology, a model created in the 1970s by Alan Bass, MD and Grant Liddle, MD, chairs of pharmacology and medicine, respectively. After training and spending 13 exciting years as a member of the faculty at Vanderbilt, I left to become Chairman of Pharmacology at Georgetown University. I found it difficult to leave Vanderbilt but I was excited about the opportunity to recreate the ‘Vanderbilt model’ by working closely with my new colleague and subsequent good friend John Eisenberg, MD, who was Chairman of Medicine at Georgetown. At the time, we didn’t refer to our efforts as ‘translational’, but, in retrospect, that was our goal. We sought to have a clinical pharmacologist in every division of the Department of Medicine to stimulate collaborations between the clinical and basic scientists in the Medical School. We had a lot of success but our work was cut short by John’s untimely death due to brain cancer. I’ve never felt that pharmacology was just another of the basic biomedical sciences. Over the years, I have become convinced that biomedical scientists generally fall into only one of four categories. Some study structure (anatomists), function (physiologists), or dysfunction (pathologists), and some want to perturb biology (pharmacologists). So I’m proud to be a pharmacologist and able to perturb the system, hopefully for the better. Unfortunately drugs are not always medicines. Nor are they always as safe as their inventors would have liked. Too often, I and my colleagues in clinical pharmacology find ourselves studying toxicology. 2. You are currently the President and Chairman of the Board of AZCERT. What can you tell us about AZCERT’s mission and your role within it? I am very proud that I had the opportunity to serve as director of one of the nation’s Centers for Education and Research on Therapeutics (CERTs). They are home to a lot of pharmacologists working under many other labels as agents for change. The idea for CERTs began in the early 1990s when it became clear to many of us in medicine that there was an unmet need for independent research and educational programs that focused on the safe use of medicines. I published a series of papers calling for an Trends in Pharmacological Sciences xx (2014) 1–3
1
TIPS-1141; No. of Pages 3
Scientific Life: TrendsTalk independent network of CERTs. I had recently moved to Georgetown, and living in DC you quickly become aware of the opportunity to work with members of Congress (yes, lobby). My former Vanderbilt colleague and surgeon Bill Frist, MD had just been elected to the Senate and he became our congressional champion for CERTs. In 1997, the Food and Drug Modernization Act (FDAMA) was being enacted and Senator Frist included legislation authorizing the Agency for Healthcare Research on Quality (AHRQ), working with the FDA, to establish a network of centers that conduct research and educational programs to foster the safe use of medicines and other therapeutics. In 1999, Georgetown University applied for and was awarded one of four center grants and AHRQ launched the network of CERTs. At its peak, the CERTs network had 14 centers and a coordinating center, each located at one of the nation’s leading universities. The importance of federal funding for the CERTs was to enable them to remain independent of market forces (not just independent of pharmaceutical companies, but all commercial influence such as health insurers). Independence was an essential characteristic of these centers, one that has been difficult to sustain due to limited federal funding. In 2001, the Georgetown CERT moved with me to the University of Arizona and became AZCERT. In 2005, it moved with me again to the C-Path. After 12 great years, the AHRQ funding for AZCERT and seven other centers was not renewed and today there are only six federally funded CERTs. However, all 14 continue to perform essential research and educational programs on the safe use of medicine. Since 2012, AZCERT has been a free-standing 501(c)3 nonprofit organization supported by volunteer efforts, research grants, and charitable contributions. AZCERT has become the internationally trusted source for information on drug interactions and a particular form of drug toxicity; that is, drug-induced QT prolongation and the potentially lethal arrhythmia torsades de pointes (TdP). AZCERT analyzes evidence and maintains lists of drugs that are categorized according to their risk of causing TdP. These lists are regularly accessed by thousands of researchers and healthcare providers. Originally termed the QTdrugs.org website, it is now branded as CredibleMeds.org to emphasize the goal of providing credible, independent assessment of evidence that can improve the safe use of medicines. The site has three portals, especially designed for the public, healthcare providers, and research scientists. In the last 9 months, the site has had over 150 000 unique users from 174 countries, and 8200 are registered users who have requested that they be notified as the drug lists are revised. The lists have been used in at least 14 research publications and cited as valuable resources on drug safety in three clinical practice guidelines. 3. Given that all drugs will have side effects, how do you think we should approach the concept of drug safety from a societal standpoint? (That is, how should we decide if a particular drug is ‘safe’ or ‘unsafe’? Who should decide?) The essential caveat to this question is ‘for what purpose’. No medicine is completely safe under all conditions of 2
Trends in Pharmacological Sciences xxx xxxx, Vol. xxx, No. x
use. As prescription of a medicine – old, new, or investigational – is being considered for a patient, it is essential to ask ‘why is it being prescribed?’ and ‘how will it most likely be taken?’ Our current drug-regulatory system requires that drug sponsors submit data demonstrating that a new drug is effective and relatively safe when used as directed. Unfortunately, drugs are often not used as directed and the FDA lacks the authority and the means to ensure that they are. Until recently, our society lacked the technology to monitor effectively how medicines are being used and to assess their relative impact on patients (both for safety or effectiveness). In the USA, we still rely on a voluntary reporting system of adverse events and rarely do we have adequate data to assess the comparative effectiveness or safety of medicines. To select the optimal therapy for a specific patient (i.e., personalized medicine), healthcare providers need a reliable assessment of the potential benefits and relative risks of therapeutic alternatives. Today we have the technology but we still lack the data or, more precisely, we lack the investment to obtain the data. In 2007, Congress mandated the FDA to create (without sufficient funding) the ‘Sentinel’ system. Sentinel was expected to monitor drug safety by active surveillance of the health records of at least 100 million Americans by 2012. It is still in the pilot phase and has only limited funding. I have come to believe that drug safety and prevention of adverse drug reactions (ADRs) are not the sole purview of the FDA. Because medications are the fifth leading cause of death in the USA, drug safety science should be a major focus for NIH-funded biomedical research. NIH research could examine and enable better understanding of the mechanisms of drug toxicity and the biological and clinical risk factors for individual patients who develop ADRs. Furthermore, prevention of drug-induced illness (ADRs) should be a leading public health goal and, for that reason, I believe the responsibility for surveillance and quantification of ADRs should include the Centers for Disease Control and Prevention (CDC), just as does surveillance for other illnesses. Ideally, the FDA could work with the NIH and CDC to set priorities for research and surveillance and still retain the responsibility to make the regulatory decisions regarding whether a drug should carry special warnings or if it should be marketed. New technologies are also creating the opportunity for us to rethink our nation‘s regulatory approach to drug development and approval. As our nation finally develops the technology to have integrated electronic health records, we will have an opportunity to develop a ‘learning healthcare system’. We should no longer be forced to rely on outdated and inefficient methods such as randomized controlled trials to learn about the benefits or risks of medical interventions. Having timely and accurate outcome data available would enable the FDA to approve drugs earlier for carefully evaluated and defined populations. Later, as the sponsor obtains post-market data from the learning healthcare system, the agency could consider allowing the expansion (or constriction) of a drug‘s indications for use. I have termed this concept ‘rolling approval’ and others have called it ‘adaptive licensing’, but it will require a rapid learning environment to monitor how drugs are used and
TIPS-1141; No. of Pages 3
Scientific Life: TrendsTalk how they perform. Adaptive licensing is now being piloted in Europe, where more advanced and uniform healthcare data systems are available. 4. You’ve served in so many different aspects of pharmacology, publishing hundreds of papers and receiving numerous awards. Is there anything that stands out as a career highlight for you? I think one of my most exciting moments came when I was part of the team of scientists working on the question of terfenadine’s potential for cardiac toxicity, specifically TdP. I am proud of our research that identified fexofenadine (Allegra) as a much safer alternative to terfenadine (Seldane). A single clinical case made us, and eventually the world, realize that drugs in any therapeutic class might have the potential to cause cardiac arrhythmias and sudden death. The ‘ah-ha moment’ quickly became ‘oh my goodness’ as we realized the magnitude of the harm that had resulted from a lethal drug–drug interaction involving terfenadine, which we mistakenkly thought was the safest nonsedating antihistamine ever developed. We were stunned as other drugs such as astemizole, cisapride, gatifloxacin, cisapride, probucol, and levomethadyl were removed from the market due to the same toxicity, TdP. Furthermore, as drugs like methadone, which had been used for over four decades under close observation in addiction-treatment centers, were found to have the same problem, we worried ‘will we ever know the full extent of this problem and how will this affect the industry’s future ability to develop safe medicines?’ Screening tests have been developed to detect drugs that have this TdP risk, but I fear that many good medicines are being needlessly scrapped because of their effects on imperfect surrogates, such as ion channels and QT intervals in normal subjects. If we better understood why certain patients develop this toxicity, I have no doubt that many important medicines that prolong the QT interval could be used safely. However, my greatest pride comes from joining Dr Janet Woodcock (at that time Deputy Commissioner of the FDA) to launch C-Path. C-Path has become all that we had
Trends in Pharmacological Sciences xxx xxxx, Vol. xxx, No. x
envisioned; that is, a trusted third party that united over 60 pharmaceutical companies and foundations including the Bill and Melinda Gates Foundation together with FDA scientists to review and reach consensus on best methods to use in drug development. The five consortia formed by CPath have over 1000 scientists sharing data and knowledge that improve the speed, efficiency, and accuracy of drug development for the public health. 5. What do you think is the most rewarding part of a life in science? The most challenging? Clearly the most rewarding experience for me was the opportunity to work with graduate students and research fellows who are some of the brightest minds and the most dedicated people I have ever known. I have lectured to thousands of medical students and trained dozens of clinician scientists who are enjoying very productive and rewarding careers in medicine and biomedical research. I am very proud of every one of them and their impact on the safe use of medicines. The most challenging part of my life in science has been dealing with the inertia and bureaucracy of government and the politics of academia. 6. What’s the best piece of advice you have ever been given? ‘Stay in school as long as you can.’ Over the years I’ve come to better understand what my father really meant. At that time, I thought ‘what does he, a farmer and grocer, know about the importance of staying in school?’ However, when it came time for me to begin grade school, he moved our family from the farm to live in a nearby college town, Bowling Green, KY, just so my brother and I could get a better education. I later learned that when he was 12 his father sent him to Louisville to live with an uncle so he could graduate from the best high school in the state. My father’s advice and his example as a lifelong learner had its impact on how I spent my career continually learning about the exciting interface between medicine and pharmacology.
3