Interview by David Grech, Commissioning Editor
Welcome, readers, to our first ever Expert Interview. Today, I am talking with Professor David Janero, the Editor-in-Chief of Expert Opinion on Drug Discovery (EODC) and the Guest Editor of EODC’s up-and-coming themed issue on “Opportunities and Challenges in Substance Abuse Drug Discovery”. Professor Janero is the Deputy Director of the Centre for Drug Discovery and is a faculty member in the Centre and in the Department of Pharmaceutical Sciences based at Northeastern University in Boston, Massachusetts, USA.
David Janero received his B.A. (biology/chemistry) summa cum laude and Phi Beta Kappa with honours in molecular genetics from Boston University and his Ph.D. in cell biology from the Biomedical Sciences Program, Yale University School of Medicine. After completing a National Institutes of Health (NIH) Postdoctoral Fellowship in physiological chemistry at the Johns Hopkins University School of Medicine, Dr. Janero held senior R&D positions with international “big pharma” concerns. During that time, he established and directed innovative R&D programs that resulted in the identification of novel drug targets and clinical development candidates and supported commercialization and post-marketing studies of therapeutics for varied indications, including key brand experience with drugs for obesity/metabolic syndrome, dermatology, hypertension, heart failure, dyslipidaemias, microbial infection and cancer. He then helped launch a private, start-up biotechnology company and lead its R&D for proprietary drug and device applications, culminating in an initial public offering, an FDA product approval, and a high-profile market launch in the cardiovascular space. Dr. Janero and his colleagues have addressed fundamental questions on signal transduction, disease mechanisms, preclinical disease models, drug targeting and distribution, pharmacology profiling, systems biology, structural biology, molecular medicine, biomarkers and biomediators, particularly as applied to translational science. The results of this work have been presented in numerous peer-reviewed publications and at international biomedical and business-development meetings. Dr. Janero currently holds faculty and administrative appointments in Northeastern University’s Department of Pharmaceutical Sciences and Centre for Drug Discovery in Boston, Massachusetts, and serves as a reviewer and an adviser for several biomedical journals and government and private funding agencies. He holds positions on various advisory, planning and education committees at Northeastern University and extramurally and has contributed to several graduate-level courses and funded grants. Dr. Janero is also active as an independent consultant to academia, the pharmaceutical and biotechnology industries, VC/investment firms and the legal profession. His scientific, commercial and entrepreneurial accomplishments have been recognized by appointment as Editor-in-Chief of the journal Expert Opinion on Drug Discovery and memberships in Northeastern University’s Health Sciences Entrepreneurs and Massachusetts Institute of Technology’s Venture Mentoring Service.
Question 1: Firstly, what led you to the field of Drug Discovery?
I was trained as a biomedical scientist within research-intensive medical schools, principally by clinician-scientists who continually challenged colleagues (students included) to think beyond their own (and others’) discoveries and relate experimental findings to medical problems, especially regarding how data obtained in the laboratory could inform our understanding of disease mechanisms and the hunt for therapies. My mentors also maintained ties with the pharmaceutical industry through activities including consultancies and board memberships that I also engage in, as well as through clinical research. This environment and tenor of mentoring kindled my interest in and commitment to drug discovery – specifically, using my (still-accumulating!) scientific and business experiences to improve patient health through translational R&D. I also recognized early on that the field of drug discovery offers the attraction of a dynamic, evolving landscape encompassing multiple diseases, indications, constituencies and business models – a vast terrain that has kept me continually engaged and excited over some three decades.
Question 2: Are there any particular people in the field that have influenced your career or research?
I have been extraordinarily fortunate to have worked in discovery-related endeavours with many talented people who have taught me much. They fall into two main groups: those whom I have trained, mentored and advised either as a scientist, a businessman and/or an entrepreneur; and those who mentored me, especially during my formative years as burgeoning independent investigator. In the latter group, I risk naming four people: Drs. Russell Barrnett and George Palade, my principal Ph.D. advisors at Yale; Dr. M. Daniel Lane, my postdoctoral advisor at Hopkins; Dr. Leo Sternbach at Roche; and Dr. William Lands, formerly with the National Institute on Alcohol Abuse and Alcoholism at the US National Institutes of Health. I attribute mainly to them the curisoity, passion and entrepreneurial instinct I have for opportunities within the discovery arena and for my active commitment to the foundational R&D upon which the art and science of therapeutics invention rest. Since four of these five gentlemen are no longer with us, I particularly enjoy passing on what I have learned from them to my mentees.
Question 3: You’ve had a long career in research and development. What would you class as the current highlight of your career?
I have been a member of talented scientific and business teams through whose efforts commercially successful and medically useful drugs were introduced into the clinic for various indications. I have also had the experience of helping develop a biotech start-up from idea through initial public offering along with a Food and Drug Administration-approved medication. But to single out one activity or accomplishment as a career highlight might diminish the satisfaction I have derived from wearing several different professional hats – often simultaneously – and meeting diverse challenges and constituencies in an evolving and increasingly variegated discovery environment. Perhaps this state of affairs offers the ultimate highlight in itself: an accumulation of varied experiences and associations that allows me to evolve productively, and not devolve, in addressing whatever discovery-related tasks I undertake across both public and private sectors.
Question 4: You have a very broad range of research interests. When did you first develop an interest in substance-abuse drug discovery?
A main discovery R&D focus of mine has been therapeutics for complex diseases whose pathogenesis involves an appetitive component for non-drug substances (e.g., food intake/metabolism as related to cardiometabolic syndromes such as obesity and diabetes). In 2007, I assumed faculty and administrative appointments in an academic institution having a critical mass of neurobiologists and scientists investigating proteins and signalling pathways implicated in both non-drug and drug substance-use disorders. They – and the intriguing deficits in our understanding of substance abuse and its therapy – sparked my interest in drug addiction, its treatment and its relationship to non-drug substance-use disorders and overall human health.
Question 5: Out of all the substance-abuse illnesses, would you say smoking is the biggest issue of all?
Whereas the well-recognized negative public health impact of smoking has spurred the invention of some useful smoking-cessation treatments and modalities, I suggest that the lack of effective pharmacotherapy associated with recreational psychostimulant abuse represents a more pressing issue in the drug-addiction field, especially given the rise of street substances such as designer cathinones.
Question 6: Cigarette smoking has been associated with a number of potential health risks for a long time but is addiction considered a major one? What are your views on e-cigarettes?
There is no question that nicotine and other substances in cigarettes (e.g., menthol) promote continued smoking behaviour and are associated with tobacco harm, although tobacco combustion products are responsible for most of smoking’s harmful physical effects and are a source of secondary toxin exposure. Essentially atomizers for delivering aerosolized nicotine, e-cigarettes do not generate tobacco combustion products and, thus, may offer a harm-reduction alternative to the many cigarette smokers who find it difficult to quit. Yet our understanding of the underlying pathobiology supporting the smoker’s behavioural phenotype and the tobacco/nicotine-associated physiological changes remains far from complete. Further research regarding the safety, toxicant exposure, and efficacy of e-cigarettes is required before they can be regarded as therapeutic tobacco-cigarette substitutes. Appropriate quality control and manufacturing standards also need to be established, likely with regulatory guidance and oversight.
Question 7: How big of a deal is addiction to prescription medications? Could the Pharma Industry be doing more?
Arguably, the major concern today in this area is the growing illicit, non-medical use of (long-acting) prescription painkillers and the resultant epidemic of opioid-use disorders and opioid overdoses. Some success in this area has been achieved, e.g. buprenorphine-naloxone for substitution treatment and opioid detoxification. From a pharmacological perspective, though, the neurobiological and therapeutic interconnections between chronic pain and addiction impede separating one from the other operationally and often confront patients and their healthcare providers with complex therapeutic needs – a situation that can deter physicians from treating such patients in the first place. Prescription and drug monitoring programs on a national scale, wider recognition by healthcare providers and the pharmaceutical industry of the need for simultaneous treatment of both chronic pain and opioid-use disorders, and introduction of improved deterrent standards within the drug-development process are forecast to help reduce inappropriate opioid prescribing and use.
Question 8: The US Food and Drug Administration have recently rejected a petition to force drug makers to reformulate CNS-acting drugs including painkillers and drugs like Ritalin to prevent illegal use. Do you feel that this is something that could happen in the future?
I consider that drug reformulation will become well-accepted by the pharmaceutical industry and regulatory agencies as a component of a more comprehensive strategy to deter non-medical use of CNS-accessible therapeutics having demonstrated abuse potential.
Question 9: Finally, what would you say you are most excited about in the future of this field?
The field of substance-use disorders holds unlimited scope and opportunities to make meaningful therapeutic advances and at the same time satisfy urgent medical needs with new and improved treatments whose introduction into the clinic may also shed much-needed light on substance-abuse pathology and the addiction phenotype.
Declaration of interest
D Janero has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Disclaimer
The opinions expressed in this interview are those of the Interviewee and do not necessarily reflect the views of the Expert Collection.