Scientist Spotlight, 7th Edition, June 2016
From Our Field…
Scientist Spotlight: Hans Rollema, PhD
Dr. Hans Rollema received his PhD in Pharmaceutical Chemistry at the University of Groningen, The Netherlands in 1976. He then became an Associate Professor in the School of Pharmacy at the University of Groningen, where he taught pharmacy students and conducted research on the mechanisms of action of centrally acting agents focused on anti-Parkinson and antipsychotics drugs. He was part of a group that pioneered novel methods for the bioanalysis of neurotransmitters, and the use of in vivo microdialysis for pharmacodynamics and pharmacokinetic studies in drug research. During a sabbatical year at University of California, San Francisco, he worked on the Parkinsonian neurotoxin MPTP with Professor Neal Castagnoli. Their collaboration on structure-activity relationships of related neurotoxins continued for several years. In 1992, he was recruited by Pfizer to set up a microdialysis lab in the neuroscience research laboratories in Groton, Connecticut. His team studied the neurotransmitter release induced by novel compounds for treating different mental disorders, including three marketed drugs – sertraline (Zoloft), ziprasidone (Geodon) and varenicline (Chantix). From 1993 to 1998, he was a member of the nicotinic partial agonist project team that discovered varenicline (Chantix, Champix), and later became the point of contact for the preclinical pharmacology of varenicline. Since 2005, he has been working with several Chantix teams on the efficacy and safety regulatory aspects of this smoking cessation aid. For further characterization and understanding of the mechanism of action of this class of compounds, he has set up several collaborations with outside investigators and contract research organizations. In December 2010 he retired from Pfizer and started a biomedical consulting business in 2011. He has been consulting for Pfizer on preclinical aspects related to the safety of varenicline, and for other pharmaceutical companies, small biotechs and academia on nAChR ligands as therapeutics. Dr. Rollema has published about 100 scientific papers in peer-reviewed journals. He has extensive research experience in both the academic and industrial environment, which he is going to share with us in this spotlight interview.
1. Why did you choose to become a scientist?
That choice was only made when I was studying at the University. In high school, I had better grades in languages than in science and math, but enjoyed chemistry and biology and decided to study Pharmacy, which offered an attractive combination of chemistry and biology applied to medicines. After the first 2 years, I became more and more interested in pharmaceutical and analytical chemistry, and realized that I would rather do research in these areas than becoming a pharmacist. That idea was strengthened after I had several teaching assistant jobs and started my ‘scientist career’ by accepting a PhD student position in the Department of Pharmaceutical and Analytical Chemistry, where I later got a PhD in Medicinal chemistry.
2. How have your research interests evolved over the course of your career?
My interests did change with time. At the University of Groningen, my focus was on medicinal chemistry and pharmacology of antipsychotics and anti-Parkinson agents. An additional interest of mine became measuring the effects of CNS drugs on neurotransmitter release, as well as brain levels of the drug itself, using in vivo microdialysis. Later, when I was at Pfizer, and had set up an in vivo microdialysis lab that supported several CNS projects, the use of in vivo microdialysis in drug discovery became my main interest. After I joined Pfizer’s ‘partial nicotinic agonist’ project team (that discovered varenicline) and became the preclinical contact for the varenicline development teams, nAChR ligands as therapeutics became - and still is - my main scientific interest.
3. What do you view as the main challenges for your field? From your perspective, what do you view will be the next biggest breakthrough(s)?
Although not an expert and without deep knowledge in these areas, I think that advances on one hand in the analysis of big data bases (estimated n=1012-18 bytes), and on the other hand in personalized medicine (in principle n=100) are some of the main challenges.
‘Big data bioinformatics’ requires the development of novel approaches for collecting, mining and interpreting the incredible amount of biomedical information on compounds, systems pharmacology, protein networks, clinical data, etc. Breakthroughs in this field are expected to enhance our knowledge of drug interactions with multiple targets, which impact several networks and can mediate therapeutic as well as side effects. This would enable the rational design of novel drugs with good efficacy and minimal side effects.
At the same time, developments in ‘big data bioinformatics’ could enable breakthroughs in personalized medicine, i.e. tailored medicines for individuals by selecting the optimal treatment for individual patients. A current example is prescribing either nicotine replacement therapy or non-nicotinic medications for smoking cessation, based on the rate of nicotine metabolism. The challenge here is to find biomarkers that can help to select the best pharmacotherapy for an individual – based not only on metabolic markers, but also on biomarkers that can predict efficacy and risk of side effects.
4. What do you see as your main career milestones?
First, becoming a staff member at the School of Pharmacy in Groningen, where I combined teaching with research for about 20 years. Second, becoming a scientist doing drug research in the pharmaceutical industry (Pfizer) for the next 20 years of my career. Lastly, I had the fantastic opportunity to spend a sabbatical year at UCSF in the late 80’s, and that milestone had a big impact on my life and on my decision to move to the USA.
5. What career choices do you feel have been the most beneficial to result in your success?
In hindsight, the 3 key career choices (pharmacy study, sabbatical at UCSF, moving to a job in the USA) worked out very well, but for a large part I had ‘good luck’. Throughout my career, I ended up working with many outstanding scientists and colleagues, both in academia and industry, who were very helpful, supportive and excellent collaborators. I learned a lot from all of them, which has greatly benefitted my career. Also, being part of a team that discovers a novel drug that ends up in the clinic can be good luck rather than a choice: the majority of projects does great science and discovers excellent compounds that for different reasons never become an approved drug.
6. Based on your experience, what are the differences of doing research in an academic and industrial environment?
I found doing research in a pharmaceutical company was actually not that different from academia: in both settings, a scientist works on projects with similarly enthusiastic and curious colleagues. For me, a key difference in industry was the close scientific collaboration in projects across several disciplines with the same goal in mind – design the best compound for a novel therapeutic target within a reasonable timeline, but without the pressure of publication or writing grants to fund projects. In addition, in industry it is (at least was….) generally easier to get additional resources, personnel or equipment, if you can make the case that it is needed to advance a project or to increase productivity.
One obvious difference is that a research-based industry is still a business, so that decisions regarding initiating, funding or halting projects are not only based on scientific rationale, excellence and do-ability, but also on competitive and market analyses. These decisions are ultimately made by industry management. And the same is true for staffing of projects and changes in someone’s role and function in the company – as the saying goes ‘the only constant is change’.
7. What qualities do you think the companies are looking for when recruiting people?
Besides a curious and a good scientific mind, collaboration and teamwork skills are very important, since in discovery projects, a multitude of disciplines will all come together to continuously discuss data and decide on what the ‘next step’ should be. Being open to other opinions, to be able to clearly formulate ideas and comments and to give and to receive criticism are important.
8. What advice would you have for postdoctoral trainees seeking to transition into industry?
If you start in industry as a scientist at the bench, keep in mind that good and critical scientific thinking, integrity, and meticulous notebook keeping are key. If you are a lab head, you are likely also to be a supervisor, with responsibilities of mentoring people, keeping career opportunities of your reports in mind, solving problems in your team, performing mid-year progress and annual performance evaluations, etc.
Attending (the often very frequent) general and project team meetings in a company can be time consuming: a good rule to go by is to only attend a meeting if you can either learn or contribute something. If not, it may be better to spend your time on reading the literature or generating scientific data….
If you have an idea for a new therapeutic target/pharmacological approach that you think is worth pursuing, you will need to ‘champion’ that project yourself to try to move it forward, since your colleagues might find it a great idea, but are often already very busy with ongoing projects.
Finally, anticipate scientific disappointments (e.g. chances are that the candidate compound from your great scientific project will not make it to market, due to unexpected toxicity, lack of efficacy, not being better than an existing drug, etc.). In that context a sense of humor can be helpful to realize that these are usually relatively minor matters in life and that there will be a next project or other opportunities.
9. What is the best advice that you ever received from your mentor or given to/received from your mentees?
One of my mentors said to me after I expressed my admiration for a very self-confident researcher during a presentation and scientific discussion: “I don’t think that was very good: Dr. X. knows all the answers…”. In other words, remain critical – it is unlikely that anybody really knows all the answers; and don’t be afraid to ask ‘simple and naïve’ questions (it’s a cliché, but ‘there are no stupid questions, only stupid answers’…).
Interview conducted by Dr. Luyi Zhou, June, 2016.