In Memoriam: Michael Phillip Waalkes

By Peter Goering posted 10-13-2022 14:06


Co-authored with Donald Fox, Curtis Klaassen, and Erik Tokar

Michael Phillip Waalkes

Michael Phillip Waalkes was born August 6, 1953, and passed away on July 27, 2022, at age 68 from glioblastoma. Mike was a scientific giant in metals toxicology and carcinogenicity.

Mike started his post–high school education at Hope College in Holland, Michigan, where he earned a BS, majoring in biology and chemistry. He received his PhD in pharmacology and toxicology in 1983 from West Virginia University studying the perinatal toxicity of cadmium in John Thomas’s laboratory. With a wry sense of humor, he would specify that for postdoctoral training, he was looking for a mentor with common attributes, including a double a in their last name, as well as having a mustache. Thus, from 1981 to 1983, he settled in Curtis Klaassen’s laboratory at the Kansas University Medical Center, studying the biochemical and metal-inducing/metal-binding properties of metallothionein and other high affinity metal-binding proteins localized in various tissues. Although many researchers had studied these proteins in tissues where these proteins were abundant, such as liver and kidney, Mike elucidated their localization and properties in testes and placenta.

In 1983, Mike obtained a position at the National Cancer Institute (NCI) in Frederick, Maryland. After a few years, he was promoted to Chief of the Inorganic Carcinogenesis Section. The NCI and the National Institute of Environmental Health Sciences (NIEHS) decided it would be mutually beneficial to have an NCI scientist located on the NIEHS campus, so in 1996, Mike was recruited for this position and moved his laboratory of 13 years from Maryland to North Carolina with NCI providing the salary and NIEHS the laboratory and support facilities. From 2010 to 2014, he served as Chief of the National Toxicology Program Laboratory and Head of the Inorganic Toxicology Group in the Division of the National Toxicology Program (NTP) at NIEHS. Mike retired from NIEHS in 2014.

Mike’s research primarily centered on arsenic- and cadmium-induced carcinogenesis. His comprehensive scientific approaches spanned the gamut of research models and tools, from mechanistic in vitro studies and studies in different strains of mice, pregnant mice, and genetically modified mice to two-year carcinogenicity studies from which hypotheses for subsequent mechanistic in vitro studies were generated. Mike’s early career focused heavily on tackling cadmium carcinogenesis in both in vitro and in vivo models, elucidating several mechanisms and adverse outcome pathways following cadmium exposure.

In the final 15 years of his outstanding career, Mike pioneered innovative approaches for studying arsenic carcinogenesis that involved the development of transplacental and whole-life models of arsenic carcinogenesis in multiple strains of mice. Before these studies, rodent models with clear and repeatable evidence of inorganic arsenic as a complete carcinogen were not available, though highly sought. His seminal studies led to countless important contributions to understanding the mechanisms of arsenic carcinogenesis and identifying the key role that stem cells and cancer stem cells play in this process.

These accomplishments were made possible by the numerous in vitro chronic exposure models of arsenic and cadmium cellular transformation in nearly every human-relevant target tissue that his program developed. Each of these areas—transplacental and whole-life exposures, stem cells, and model development—have clearly influenced a great number of other groups working in and beyond inorganic carcinogenesis. These critical contributions from Mike’s laboratory continue to profoundly reverberate in the metals carcinogenesis scientific and public health communities and influence many groups who use transplacental/whole-life exposure models and stem cells for understanding toxicology of metals.

Such impactful and encompassing research made Mike a prolific writer and sought-after speaker. He published 325 peer-reviewed articles; many of which have been highly cited. Mike had an h-index of 80 when an h-value of 20 is considered good, 40 is great, and 60 is remarkable. Mike also published 59 reviews and book chapters. He was invited to present more than 90 lectures in the US and around the world.

Mike’s sense of humor served him well when communicating with colleagues and friends. When occasionally asked about his career path and next steps, he would casually reply that once he figured out cadmium carcinogenesis, he’d move on to working on arsenic. And when he figured out arsenic carcinogenesis, he’d retire—and he did. This description of his career trajectory was followed with one of his hearty laughs that would make all listeners laugh, too.

SOT was Mike’s scientific home. He organized and co-chaired numerous Continuing Education courses and Symposia for SOT Annual Meetings. In 1990, Mike received the SOT Achievement Award for outstanding contributions to the science of toxicology by an individual within 15 years of their highest earned degree. He held all elected positions in the SOT Metals Specialty Section, including the 1999–2000 President, and co-founded and served as the 2010–2011 President of the SOT Stem Cells Specialty Section. Mike was Editor-in-Chief of Toxicology and Applied Pharmacology (TAPP) from 2000 to 2010 and was elected as an SOT Councilor in 2010.

Mike’s scientific citizenship extended beyond his service to SOT. He was an author, reviewer, and advisor for numerous monographs for the International Agency for Research on Cancer. For numerous years, he was a member of the NIEHS/NTP internal review committee for the Report on Carcinogens and held various editorial positions for the journal Environmental Health Perspectives (EHP), including Associate Editor and Deputy Editor. He was also on the editorial board of another half-dozen journals. Mike also gave of his time to review grants, documents, and programs for many organizations, universities, and agencies, including the US Environmental Protection Agency, National Institutes of Health, US Department of Defense, and National Research Council. He also held leadership roles in the organization of numerous international meetings on metals toxicology. People realized that if you wanted something done well, you went to Mike Waalkes.

Mike had a strong commitment and desire to help educate the next generation of toxicologists. He was author of the “Toxicity of Metals” chapter for Casarett and Doull’s Toxicology textbook. He mentored over 20 PhD candidates and postdoctoral fellows and actively prepared them for presentations at regional and national scientific meetings where they received numerous awards. He helped his students find support for their salaries and funds to go to national meetings. Mike also promoted the careers of early career scientists by inviting them to participate in scientific meetings that he organized, and sometimes he stepped back to allow colleagues to receive recognition by having them take a prominent role organizing a meeting or lead in writing an invited review article.

While Mike was a great contributor to our knowledge of the toxicology and carcinogenicity of metals, we will remember him most for his character: his impeccable honesty, his self-deprecating personality, his low-bass laugh, and his abiding dedication to his wife Michelle (Mickey) and three sons, Phillip, Joseph, and Thomas.

Here are personal tributes from some of the many colleagues who were lucky enough to count Mike as a friend.

Betzabet Quintanilla‐Vega, PhD, Cinvestav, Mexico City, Mexico

Dr. Waalkes was always very empathetic and shared with our institution, Cinvestav in Mexico. He kindly agreed to be part of the inauguration of the new facilities of our department in 2014 with an excellent talk and was always willing to collaborate and support us. His example has inspired several members of the Mexican community. Personally, I will always be grateful to him, as he had a very positive influence on my career. We will remember him as a generous scientist and a wonderful and gentle person.

Eduardo Brambila, PhD, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico

Thanks to Dr. Mike Waalkes for his professionalism and above all his humanity that allowed him to leave a mark on many of us who had the honor of being part of and trained in his laboratory. We thank him for visiting us at my university in Puebla, Mexico, and for being an inspiration to those of us who had the pleasure of meeting him as a great researcher and as a beautiful person. He will always be in our hearts.

Erik Tokar, PhD, NIEHS, Research Triangle Park, North Carolina

One of my favorite memories with Mike is driving with him to Frederick, Maryland, from NIEHS when we were still part of NCI. It was a five- to six-hour trip that we made multiple times a year. During the first trip, I mentioned that I had the Tom Petty CD boxset, and after that, Mike wanted me to bring those CDs on each trip. That is all we would listen to every trip, and we would tell the same stories about the same songs. It’s a memory that makes me smile every time I hear a Tom Petty song.

Dori Germolec, PhD, NIEHS, Durham, North Carolina

I have so many wonderful memories of Mike as a mentor, a colleague, and a friend. We shared a passion for investigating the mechanism of arsenic-induced cancer and one of the earliest, if not the first, speaking invitations that I received as an early career scientist was to discuss proposed revisions to allowable limits for arsenic in drinking water at an arsenic meeting that Mike organized. It was my first real exposure to how impactful our science can be and the competing pressures from diverse sectors (regulatory, utilities, public health) that encompass the science of toxicology. While I will always remember the beautiful rolling hills of the meeting venue in Mike’s beloved Maryland, the understanding that I gained of risk assessment has remained with me to this day.

Jerry Hjelle, PhD, Hjelle Advisors, St. Louis, Missouri

During our postdoctoral years with Curt Klaassen, the heavy metals folks and the metabolism-biliary folks would have an ongoing, playful back-and-forth on the merits of these projects. Mike had a very strong serve and great backhand during these mindless discussions. Finally, one of us liver guys said to Mike that “the only way someone would die from cadmium was from a cadmium bullet.” His retort was, “We can arrange that!” Luckily, he missed—and he will be missed!

Peter Goering, PhD, DABT ATS, US FDA, Silver Spring, Maryland

Mike Waalkes was a postdoc when I was a graduate student in Curt Klaassen’s lab. Like Curt, Mike was an excellent mentor, and we discussed aspects of experiments on a weekly basis. He would share ideas of potential future experiments on notebook paper and when we concluded would crush it, pitch it in the trashcan, and invariably retort, “You know what to do!” Apparently, many of his future trainees recall the same phrase. After we finished in the lab on Fridays, we’d gather with our spouses for some beers and listen to John Prine records while our newborn sons snoozed nearby. I felt fortunate that we continued our research collaborations and family gatherings when we both ended up in Maryland.

William Achanzar, PhD, DABT, Bristol-Myers Squibb Company, New Brunswick, New Jersey

I have an amusing anecdote about when Mike hired me as a postdoc. It started as an introductory phone call that ended with Mike offering me a postdoc position 30 minutes later and me accepting, sight unseen. I never met Mike in person until I visited NIEHS after I had already agreed to join his lab. However, Mike made such an impression during that call that there was no way I could refuse. I’m so glad I accepted, as Mike was an excellent mentor and talented scientist role model. To this day, I am proud to say that I came out of the Waalkes lab!

Donald A. Fox, PhD, ATS, FARVO, Retired Professor, Austin, Texas

I have several wonderful and varied scientific and personal memories of my friend Michael over the past 25+ years.

Scientifically, I served on the TAAP editorial board and frequently chatted with Mike not only about papers under my purview but those that Mike felt problematic or borderline for sending for review. He endeavored to treat all authors equally and with respect. We also served together on the EHP editorial board and as Associate Editors and Deputy Editors helping Hugh Tilson and the NIEHS. Mike had insightful and forward-thinking comments that expanded the local, national, and global reach of EHP.

None of this is surprising to those that knew Michael, as he was a righteous religious, spiritual, and family/community person. He deeply loved his wife, his three boys, and his siblings. In addition to these and many more memories, Mike and I shared several whiskey drinks at SOT Council meetings and at SOT Annual Meetings, as well as at his home. We laughed a lot and told lots of stories. In addition, Michael was a skilled wood craftsman with a shop in his garage. He applied the same meticulous approach to this skill as he did to his research. Following Michael’s retirement, we still maintained contact and shared our love of life, family, and science. I miss you, my dear friend. RIP.