An Interview with Dr. David DeMarini

When did you first become involved with GEMS?

I worked with Tom Hughes, Larry Claxton, and others to found GEMS in 1984; I became the Vice-president in 1987 and President in 1988.

What were you doing when you first became involved with GEMS and what are you doing now?

When we founded GEMS, I was completing my 2nd and final year at the NTP/NIEHS doing research with Lynn Ripley on the mutation spectra induced by topoisomerase poisons; it was an exciting time because I was learning to do cloning, probe hybridization, and DNA sequencing in 1984—very early days!  I was also working with Mike Shelby to help write the genetic toxicology and discussion sections of the NTP carcinogenesis reports.

How have you contributed to GEMS?

Besides helping to found and incorporate GEMS in the State of North Carolina, I served as Vice-president in 1987 and President in 1988 and helped behind the scenes for many years to organize the meetings and handle various administrative aspects of the society.  I have also brought many of my technical staff, students, and postdocs to GEMS, where they have presented their work.

What aspect of genetic and environmental mutagenesis research and/or application has had the most impact, in your opinion?

Having served on 8 IARC panels (chairing one of them), I think that environmental mutagenesis has had an enormous impact on the ability of risk assessors, such as IARC, to do their work.  The literature from our colleagues over the past 40 years has helped IARC declare as Group 1 (known) Human Carcinogens the following agents:  Indoor Air, Outdoor Air, Cigarette Smoke, Arsenic, and Diesel Exhaust.  The mechanistic data, largely mutagenesis data, provided strong (overwhelming) support for these evaluations by IARC, and a significant portion of the mutagenesis work on these agents was done by GEMS members.  The IARC evaluations have influenced regulatory decision-making among all the WHO member nations, including the U.S.

What advice do you have for early career scientists?

It is incredibly important to network right from the beginning of graduate school and throughout your professional career.  Hopefully one has professors, colleagues, and even other students who can help you be connected to the people in your field.  Attendance at various meetings is a critical aspect of this.  Another important thing to do is to read widely; stay informed of developments in your field (and even unrelated fields)—you never know what information may be helpful to you as your career develops.

 An Interview with Dr. Jef French

When did you first become involved with GEMS?  What were you doing when you first became involved with GEMS, and what are you doing now?

As an NIEHS investigator, I became involved with GEMS in 1991 after spending a sabbatical year at the Finnish Institute of Occupational Health in Helsinki on a NIH USPHS work-study fellowship.  I had become interested in both in vitro and in vivo mutagenesis assays and tools and their use in identifying and estimating exposures in high-risk occupations. In Helsinki, I worked with Marja Sorsa, Hannu Norpaa, and Kirsti Husgavel-Pursiainen.  Our mutual interest morphed into investigations of mutations and mutation rates in tumors suppressor genes like TP53, which had just become to be studied. My goal was to identifying tumor suppressor gene mutations in workers exposed to asbestos and smoked tobacco.  In Helsinki, I learned to take human lung cancer (mesothelioma and squamous cell carcinoma) biopsies, primary culture cancer cells for DNA isolation and genotyping using Southern blot analysis. GEMS meetings and interactions with local and national scientists involved in mutagenicity and carcinogenicity research were instrumental in further developing my interests and research activities at the NIEHS. This work led to development of research projects in the Laboratory of Environmental Carcinogenesis and Mutagenesis with Ray Tennant and colleagues using Hras overexpression and/or Trp53 haploinsufficient (genetically altered through the introduction of random or targeted mutations into inbred or hybrid mouse and rat models for in vivo short term mutagenesis and carcinogenesis studies focusing on the mechanisms of loss or gain of function in proto-oncogenes and tumor suppressor genes. At the time, mutations in these two genes were overrepresented in human cancers likely due to environmental or occupational exposures and, thus, represented likely targets associated with increase risk for cancer. We were the first to validate and test short-term mutagenesis and carcinogenesis protocols and assays for identifying mutagenic versus non-mutagenic xenobiotics. Using the “precautionary principle” approach, we worked to develop protocols to identify potential human mutagenic carcinogens requiring in-depth investigation for establishing exposure and risk to human populations.

 Currently, I am interested in developing in vivo research models in outbred randomized populations of mice that treat toxicity, including mutagenicity as a quantitative trait.  Most disease is an outcome of the interaction between the differences in our genomes and epigenomes that affect susceptibility to toxicity and disease. Beginning in the early 2000s I became involved with the Complex Traits Consortium (now the Complex Traits Community) to aid development of population based mouse models (eight-way multiparental advanced generation intercross or MAGIC) like the Collaborative Cross and their randomized outcross relatives, the Diversity Outbred mice.  With these models we can treat chemical toxicity and mutagenicity as quantitative traits and determine the individual genetic variants of genes and their proteins (forward genetics) that contribute to the observed heritable traits without and a priori hypothesis. Once the relative genetic or epigenetic contribution is statistically determined, we can employ reverse genetics using the new tools of genetic engineering to test hypotheses and develop a better understanding of the mechanistic basis for quantitative trait loci. We recently demonstrated the power of this approach in a paper on benzene mutagenicity in DO mice in Environmental Health Perspectives in 2015. These models may better approximate the heritable traits and outcomes from exposure to mutagens and carcinogens in a manner similar to that observed in human populations.

How have you contributed to GEMS?

I was honored to serve as Vice-President Elect in 2008-2009 and to organize both the Spring and Fall meetings in 2009. We focused on the 1) Implications and Sources of Genome Variability and 2) Genome Structure, Genetic Traits and the Basis for Complex Diseases, respectively, in 2009.  Subsequently, I served as President of GEMS in 2009-2010. Since my term as Treasurer began in 2012 I have been fortunate to serve on the GEMS Board of Directors and observe the BOD and its members to build and invigorate this dynamic and innovative local scientific society.

What aspect of genetic and environmental mutagenesis research and/or application has had the most impact, in your opinion?

Each era of scientific research can be landmarked to innovative new technologies and the elegant questions and answers that have followed.  I have been fortunate to observe the major advances in both testing and research. Both in vitro and in vivo screening of putative genetic toxicants have been critical to public health research as well as the developments in both DNA damage and repair mechanisms led by Tomas Lindahl, Paul Modrich, and Aziz Sancar, who received Nobel laureates in 2016, as well as the insertion of targeted sequences of  genetic DNA with loss or gain of function using embryonic stem cells into mice (Mario R. Capecchi, Sir Martin J. Evans,  and Oliver Smithies, 2007) that greatly influenced biology, including toxicology and genetic toxicology. I was fortunate at NIEHS/NTP to help Ray Tennant and others develop both transgenic and genetically engineered mouse models for testing and research to identify environmental toxicants and assess potential risk from human exposures.    

What advice do you have for early career scientists?

Be curious, follow what stimulates your interest and the questions, yes, and ask questions, lots of questions and “dig deep” into the literature – both the old and the new.

Is there anything else that you would like to add?

It has been my privilege to participate as a member and officer in GEMS. As a local society, we have had a great impact in the development and career focus on our next generation of leaders in the environmental sciences in RTP region, the United States, and the international community.

 An Interview with Ms. RoseAnne McGee

When did you first become involved with GEMS?

In 1984.

What were you doing when you first became involved with GEMS and what are you doing now?

I was a laboratory technician in Dr. Martha Moore’s laboratory at the Environmental Protection Agency, as a stay-in-school student.  I am currently a Scientific Review Officer at NIEHS.

How have you contributed to GEMS?

I have served as Corporate Sponsor Coordinator, Councilor, President-elect, President, and Treasurer.

What aspect of genetic and environmental mutagenesis research and/or application has had the most impact, in your opinion?

A number of research areas supported the NIEHS had a significant impact, and will continue to inform the areas of genetic toxicology and mutagenesis. Both intramural and extramural scientists supported by the NIEHS have discovered and characterized trans-lesion synthesis polymerases (in humans and in model systems). These specialized polymerases can be error-prone, but also can accurately replicate DNA opposite DNA lesions such as UV-induced DNA damage.

Other broad programs supported by the NIEHS include environmental epigenetics, the application of the Exposome concept, and support for new methods for detecting gene-environment interactions have the potential to significantly expand the area of genetic toxicology and risks to human health in the next decade.

What advice do you have for early career scientists?

Actively participate in local and regional scientific societies and organizations.  This gives you the opportunity of learning about the latest research, affords you the opportunity of networking and meeting other scientists and policy makers, may give you the opportunity of presenting your own research and prepares you for participating in national/international meetings. 

Is there anything else that you would like to add?

I am humbled by this award; there are so many people who have done so much more for GEMS and to be counted among them is an honor.

Photographs of Ms. Kristine Witt and Dr. Errol Zeiger were taken by Steven R. McCaw, NIEHS Multimedia Services