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Vol 24, No. 03, March 2020   |   Issue PDF view/purchase
SPOTLIGHTS
Pioneer in Cancer Immunoassay

A chat with the woman who invented the use of immunoassays for measuring chemical carcinogen-induced DNA damage.

1. I became a scientist because…

My Dad was a chemical engineer who worked in the pharmaceutical industry. He was involved in the manufacture of antibiotics in the very early days, and even met Sir Alexander Fleming, who discovered penicillin. I grew up listening to stories of successes and failures of biomedical research and was enthralled with the possibilities of research to make substantial positive contributions to the quality of human life.

2. I chose to work in cancer research because…

Cancer was a terrifying killer at the time I was applying to graduate schools, and furthermore it was something very hidden which nobody talked about. When I was accepted at one of the premier cancer research institutes in the country, the McArdle Institute at the University of Wisconsin, the choice was clear. You never know in advance if your research efforts will make a difference in the lives of patients, but I felt compelled to try.

3. My story of pioneering the use of immunoassays to determine chemical carcinogen-induced DNA damage in humans began with...

…a second term in graduate school. At Wisconsin I received a Master of Science degree in Oncology, after which I was married and had three children. In 1971 we moved the family to Bethesda where my husband and I began working at the National Cancer Institute, and I was given the opportunity to complete my PhD in Microbiology at Catholic University. One of the classes I took was Immunology, where I learned about radioimmunoassays, which were being used to determine low levels of human metabolites and hormones. My idea was to apply the same methodology to DNA adducts, not knowing if we could achieve sufficient sensitivity to measure them. The rest, as they say, is history. This was at a time when there were essentially no methods to measure DNA adducts in humans, and there was little known evidence linking DNA damage in humans and human cancer aetiology. The immunoassays, 32P-postlabelling, and mass spectrometry were the first non-invasive methods to measure DNA damage in humans and were all developed within about a 10-year period. Together these methods were applied widely, and the results have defined the role of DNA damage in human cancer aetiology.

4. Life as a retired professor is...

… still very busy. In the last couple of years, I have published a book and a study on whales, while participating in the leadership of a national society. In 2019, World Scientific Publishing Co. Pte Ltd published Carcinogens, DNA Damage and Cancer Risk, which I edited. This book contains chapters, written by experts in the field, describing situations where cancer risk was elevated due to specific exposures, and DNA adduct formation was an essential element in tumour aetiology. Also in 2019, we published a study showing that DNA adduct formation links exposure and cancer risk in beluga whales in the wild. The data indicated that marine mammals are susceptible to cancers caused by environmental pollution via mechanisms similar to those in humans. Finally, in 2018 and 2019 I served as Program Chair and President of the Environmental Mutagenesis and Genomics Society, an organization in the US dedicated to understanding and reducing DNA damage and mutagenesis in humans.

5. My work as Head of the Carcinogen-DNA Interactions (CDI) Section at the National Cancer Institute involved…

…different classes of carcinogens. We studied the chemotherapeutic agent cisplatin and showed that ovarian and testicular cancer patients with the highest levels of cisplatin-DNA damage had the most favourable therapy response. We showed that tamoxifen, used for adjuvant therapy of breast cancer, does indeed bind to DNA in human endometrium, supporting a genotoxic mechanism as one component in the aetiology of endometrial cancers occurring in women given tamoxifen. We studied the nucleoside reverse transcriptase inhibitors (NRTIs) used for antiretroviral therapy of HIV and showed that zidovudine caused DNA damage and tumours in mouse offspring born to dams given this drug while pregnant. Further studies, which showed both genotoxicity and mitochondrial toxicity in primate offspring exposed in utero to NRTIs, resulted in the long-term follow-up of children born to HIV-infected mothers receiving NRTIs during pregnancy to prevent maternal-foetal transmission of HIV. We have also had a long-term interest in carcinogenic polycyclic aromatic hydrocarbons (PAHs), components of environmental contamination. Besides animal models, we have evaluated PAH-DNA adducts in many human tissues and whales in the wild.

Over the years the CDI Section mentored many postdoctoral fellows, post-baccalaureate students, summer students, visiting scientists, and individuals coming to learn specific techniques. The success of all our students, most of whom have gone on to graduate school or medical school, is a great source of pride to myself and the other permanent staff members who participated in these efforts. One of the great joys of my career has been sharing the excitement of research with young people, and that is something I miss very much in retirement.

6. The biggest misconception about cancer is probably…

…that it is a single disease. I have often been asked “When are they going to cure cancer?” What many people do not realize is that cancer is many diseases. Most human organs have the potential to become cancerous, and in addition many organs can develop cancer of different cell types within that organ, so cancer is many hundreds of different diseases. Whereas in my lifetime great progress has been made against multiple cancers, and some we now have cures for, there are still many types of cancer that remain refractory to clinical therapies. Furthermore, some types of cancer will never be cured, but current therapies can be very effective in keeping a cancer in check long-term while maintaining a good quality of life for the patient.

7. A major challenge in treating cancer is…

…generating individualized therapy specific for a particular cancer. Normal cells and tumours accumulate cancer driver mutations over time, and these genetic changes, which can have different profiles in every tumour, dictate the capacity of a tumour for independent growth. Effective cancer treatment will require “personalized therapy”, that is drugs or protocols that target the specific growth pathways found in an individual tumour. We are in the early stages of understanding how to approach personalized therapy, but it is sure to play a major role in the future of cancer treatment.

8. The extra free time in retirement…

…has been valuable for me. I have young grandchildren whom I enjoy very much. I also have time to exercise more, which is critically important as we age. Other passions include playing guitar and singing, going to concerts, reading, and doing family genealogy.

9. I edited Carcinogens, DNA Damage and Cancer Risk because…

…at the present time we live in a world surrounded by carcinogens. Globally, we are just learning how to manage our waste, and in many countries carcinogen exposure will continue to be considerable, as the most economic approach to waste disposal often involves human exposure to carcinogens. This book comprises a series of chapters detailing DNA damage and cancer risk resulting from many types of exposures. Our hope is that the principles and examples presented in the book may be useful in guiding investigators worldwide who are learning to manage future chemical exposures and spills.

10. To aspiring young scientists who wish to pursue cancer research I would say…

…pick an important question to study, collaborate, and publish as much as possible. Always pay close attention to what your data is telling you, and don’t be afraid to think outside the box. Be aware that most novel findings have problems with initial acceptance, publication and obtaining grant support. The battles required for validation and acceptance are not for the faint of heart. The experience will teach you patience and persistence, both of which are worthwhile and necessary for the advancement of science.

About the Scientist

Miriam C. Poirier is currently a Scientist Emeritus at the National Cancer Institute (NCI), U.S. National Institutes of Health (NIH), where she worked since 1971. For the last 20 years of her career she was Head of the Carcinogen-DNA Interactions Section. Dr. Poirier and her associates pioneered the use of antibody-based assays for measurement of DNA damage in human tissues, and her studies fostered the development of molecular cancer epidemiology. Dr. Poirier is a recipient of the NIH Merit Award, the Marygrove College Distinguished Alumna Award, the NCI Leading Diversity Award, the NCI WSA Mentoring and Leadership Award, the Genetic Toxicology Society Excellence in Science award, and the Environmental Mutagenesis and Genomics Society Alexander Hollaender Award.

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