Thoughts From a Research Career by William Slikker Jr,the ATS 2019 Mildred S. Christian Career Achievement Award Winner

One of the most important aspects of the ATS 2019 Mildred S. Christian Career Achievement Award, besides the recognition and honor of joining an amazing list of previous recipients, is the name sake of the award itself. As a recipient of the award named in Millie’s honor, I deem it a welcomed responsibility to keep in mind her accomplishments and impact on the practice of toxicology. Millie was a dynamic and charismatic scientific leader and visionary. Her educational background was excellent, culminating in a doctorate in developmental anatomy from Thomas Jefferson University. Her lifelong interest in reproductive and developmental toxicology resulted in numerous peer-reviewed journal publications and books including Assessment of Reproductive and Teratogenic Hazards (Advances in Modern Environmental Toxicology, Vol 3).

Millie had many virtues that provided the basis for her outstanding leadership and resulted in her ability to organize scientific societies, mentor students and colleagues of all ages, and promote team and collaborative science. In addition to Millie’s training and keen business sense in advancing Argus International, Inc, and other industry-based entities, she helped establish not 1 but 2 well-recognized scientific societies. Millie was a founding member of the Society, American College of Toxicology (ACT) and founding editor of the Journal of the American College of Toxicology. American College of Toxicology was founded in 1979 and originally established to provide an organization for scientists in the field of toxicology with the goals of advancing the field and acting as a forum for scientific exchange. American College of Toxicology membership includes more than 1000 toxicologists from over 15 countries who work in academia, industry, government regulatory agencies, or as private consultants.

In addition to her ACT leadership, Millie was also fully involved in supporting the development and maintenance of the Academy of Toxicological Sciences (ATS). Since 1981, ATS has awarded the title of “Fellow” to toxicologists worldwide who are recognized by their peers for their expertise and sound scientific judgment. The purpose of ATS is to ensure, through peer review of member credentials, the competence and experience of professionals whose work affects public health. Currently, there are over 300 toxicologists worldwide who are certified as ATS Fellows or Emeritus Fellows. Dr Christian encouraged and mentored many trainees and coworkers over the years. She believed in team work and collaborative studies. Her leadership in the Teratology Society exemplified these capabilities where she served on Council and was elected president for the 1988-1989 year. So, Millie has left us with many important accomplishments for which to remember her: as a leader, organizer, and mentor in the field of toxicology.

As a young person, who (or what) inspired you to pursue a career in science?

The first scientific question I remember encountering was in my kindergarten class at Fruitvale Grammar School, just west of Bakersfield, California. My teacher, Mrs Powers, placed a glass of water on the mantel of the classroom fireplace and over the next few weeks my classmates and I monitored the water level in the glass. Well, the level kept going down and if we discounted the possibility that the janitors were drinking it, we had to accept the hypothesis that the water was evaporating and changing state from liquid to vapor. I did not really understand this until I took physical chemistry while at UC Santa Barbara (UCSB), and even then, not very well. But that simple experiment setup by Mrs Powers got me thinking that there may be other things to test.

In my early teens my Uncle Leonard got me interested in racing pigeons. The obvious question was “How did these homing pigeons find their way home?,” a question that at the time was not fully answerable. But my interest stemmed from my desire to find a way to get them to come home faster. The prevailing theories were 2-fold: good genes and environmental training (sound familiar?).

My uncle had provided me with pairs of pigeons that had come from good blood lines, so I decided to work on the training issue: how to manipulate the environment to improve performance. In reading about different methods, 2 seemed relevant and feasible: the widowhood method and single toss training. Now pigeons generally mate for life, but if you separate them by sex early in their lives, you can determine the timing of their breeding and, thus, precisely schedule the classic behaviors of mate determination and nest building. During this early nest building activity, the male drives his selected mate to the nest box and proceeds to help her build a nest. The hypothesis of the widowhood method was that at this time in the breeding cycle, the male is most motivated to return to the pigeon coup to complete the mission of nest building with his mate. So, one could compare widowhood pigeons’ flight performance with other males who were not in this stage of the reproductive cycle.

The single toss training routine was simpler in that most pigeons were trained by taking them to a point in the desired flight path and releasing them all at one time from a holding cage located in the trunk of your car (my parent’s car, they were very understanding), say 25 miles from home. While another group of pigeons was taken to the same location for release but tossed one at a time making sure that the previously released bird was way ahead of the next subject to be released. The hypothesis was that those that were trained by the single toss method would learn the way home better than those that were merely following the flock. This was thought especially important in that huge numbers of pigeons (in the thousands) were released on race day and my birds that resided in Greenacres (yes, my little farming village; and no, Eddy Albert did not live next door) needed to peel off to reach their home destination and not stay with the masses headed to the south, toward Los Angeles.

While I am sure I did not include all the proper controls and use a 2-arm cross-over design, I will say that as a novice and youngest member of the Bakersfield Pigeon club, I did win the young bird best average speed title that year, much to the disgust of the senior membership.

Please tell us about your early scientific training.

My early training was like that of most others in the science: long, 3-hour labs 2 times per week and 1-hour lectures 3 times per week for chemistry, biology, and physics. Sounds like a drag now but I enjoyed it! But the real learning came when I was a senior undergraduate student at UCSB and volunteered to work/study for Dr Neal Holmes, a UK trained physiologist and head of the university’s vivarium. I did not realize at the time that I would mainly work for his postdoctoral fellow, Dr Edward Helton, but that worked out OK because later, Ed recruited me to the National Center for Toxicological Research/ Food and Drug Administration. Anyway, I not only became quite proficient at paper chromatographic isolation of glucocorticoids but also landed a job caring for the animals in the vivarium. I was raised in a farming community and my father was a dairy farmer, so I was responsible from a very young age for caring for and feeding animals. Now, the diversity of animals in the UCSB vivarium was far greater than in my backyard, including boa constrictors, Xenopus frogs, and orangutans, but the important principles of animal care and responsibility for animal well-being were the same. As low man on the seniority list, I had the opportunity to work holidays and fondly remember the responsibility and the pride I experienced in maintaining all the animals in the vivarium by myself on Christmas day.

I entered the master’s program in Biological Sciences at UCSB, and while I was earning my degree performing class work and research, 2 important life lessons were realized. One, that you must remain focused on the project at hand if you want to bring your studies to a fruitful conclusion. I came close to being thrown out of the lab on one occasion because my mentor thought, and rightly so, I was spending too much time thinking about molecular biology experiments and not focusing on glucocorticoid physiology, the study for which he had funding. Second, I realized that even with all its virtues, physiology was not as interesting to me as pharmacology and toxicology. So, with my mentors help, I finished my master’s degree and was admitted into the PhD program in Pharm/Tox at UC Davis, a welcomed outcome for all concerned. So, I learned that my early scientific training was dramatically influenced by my family and work experiences and that mentors were critical to one’s development even if one did not always see eye-to-eye with them.

Who had the biggest impact on your career, and why?

Without a doubt I would say that Dr Keith Killam, my PhD advisor, had the biggest impact on my career. He provided research opportunities and encouraged novel ideas and new approaches but was always there with a steady hand and support. His own training was diverse, with support and summer jobs from the pharmaceutical industry, excellent postdoctoral fellowship training at UCLA’s Brain Research Institute, and an initial faculty position at Stanford University before becoming the founding chair of the Department of Pharmacology at the UC Davis School of Medicine. He encouraged students to express their views and to be involved in as many topics as they could handle. Dr Killam stressed excellent animal care and high ethical values. He also trained his many students on how to put on a scientific meeting by taking on a last minute request from American Society Pharmacology Experimental Therapeutics to host an annual meeting that had to be rescheduled from another campus. We learned in real time that there was more to a successful meeting than just the well-planned scientific presentations. The audiovisual equipment, the coffee breaks, and the airport transportation all had to be coordinated, not to mention the hosting of the attendees’ reception complete with donated wine from some of Napa/Sonoma’s best.

Dr Killam supplied a novel research environment for his graduate students and postdoctoral fellows. There were a variety of animal models including strobe-light-induced epilepsy and drug self-administration paradigms. The unique capabilities included continuous recording of electroencephalographic (EEG) signals from both cortical and deep brain structures. The analysis of the vast amount of data collected in this fashion was conducted in a state-of-the-art computer laboratory including some of the first in-laboratory computers (predecessors to the PDP-12) and fast Fourier transformations so 4-second epochs of power spectra could be visualized and quantified. The raw analog EEG data were captured from over a dozen brain sites on 16-channel Ampex tape recorders, digitized and then converted to power spectra for analysis. So, Keith Killam’s students were exposed to big data collection and analysis in the 1970s, long before the current terminology and turn-key instruments were available.

Any advice for young scientists?

Those coming into the field of toxicological sciences have many more opportunities of focus than ever before. This is both a blessing and a distraction. The narrow path of earning a PhD and completing one or more postdoctoral fellowships and then moving into an assistant professorship at a university is not the path most traveled any longer. Additional opportunities in industry, government, and not-for-profits are also not the only choices. One of the fastest growing demographics within the SOT membership is the consultant category. Another is the PhD jurisprudence combination. There are just so many more options and that is a good thing because funding for focused toxicology is not necessarily growing. Multidisciplinary team approaches are on the rise and multidisciplinary training is in demand. So, the advice to those moving into toxicology is to have a strong research focus but also to maintain a multidisciplinary background to ensure flexibility in pursuing job opportunities and to foster the ability to work productively in a team environment.

One way to network and build multidisciplinary team spirit is to be active in scientific societies and take on leadership roles as often as practicable. This networking will help to broaden your exposure and make it possible to become an active practitioner of the team approach. Several funding opportunities are now focused on supporting these multidisciplinary team approaches including toxicologists, bioengineers, and bioinformatics experts. So, my advice is to publish your work in peer-reviewed journals with long track records, train broadly, and use societies and networking to help you build collaborative, team approaches to solving important issues in toxicology.

If you had not decided on a career in science, what would you have done with your life?

If not a career in science, well, I never really considered anything else. But perhaps farming or ranching. These are challenging careers that my uncles, cousins, and father pursued. To be successful as a farmer or rancher, you must be independent, self-initiated, thoughtful, and informed. You have to take risks, but usually very educated ones. You must be dedicated and self-reliant and probably optimistic about the future.

All these traits are important for a successful career in science as well. One of the lead veterinarians at the California Primate Research Center once told me that his most sought-after graduate students were daughters or sons of farmers. They had the initiative and drive to complete the rigorous graduate program and the practical sense to push through the rough spots, and there are always rough spots when completing a clinical or graduate degree. So, the successful scientist and farmer likely share common traits that allow them to plow through the challenges, and both are accustomed to waiting for that next drop of rain or research dollars to keep their entrepreneurial spirit moving forward.

How would you like to be remembered in 20 years?

Twenty years is like a blink of the eye, it all happens rather quickly so one must be careful answering this question. I would like to be remembered by my students and collaborators as someone who helped them achieve their scientific goals and stirred in them the love of science and quality research. Someone who sees the glass as half full and always expects the best from his coworkers and collaborators. Someone who appreciates and expects diligent work but is also able to celebrate the successes. Thanking colleagues for good effort and results is an easy thing to do, but it is also the right thing to do. Team work and collaboration are wonderful things and I hope that my collaborators appreciate how much that means to me. So, I hope to be remembered as a team player with an occasional good idea that kept the science of toxicology moving forward.

Finally, and most importantly, I want to thank those who supported me in receiving the ATS 2019 Mildred S. Christian Career Achievement Award and my many coworkers and collaborators who made it possible. Without the mentorship I received, the opportunities availed to me by a variety of scientific societies, and the team approach embraced by my coworkers, this recognition would not have been possible. And last but not least, recognition to my spouse, Cristine, for supporting me and making the innumerable meetings and travel possible as well as my two now grown children, Annamarie and William, and their families including my grandchildren for understanding and putting up with their scientist Dad.

Thank you so much for sharing your story, and congratulations on your award!

William Slikker Jr. NCTR, Jefferson, AR, USA