Q&A - A Breakthrough Discovery

A BREAKTHROUGH DISCOVERY

One of the worst traits of cancer is how rapidly it grows. In 1984, a cancer research team led by Hal Moses, MD, ’56, discovered a protein our bodies naturally produce that helps slow that growth. It was a breakthrough discovery that changed the face of cancer research and treatment, opening the door to decades’ worth of related discoveries and giving doctors new ways to successfully combat this deadly disease.

Hal grew up in a poor family and attended Cumberlands back when it was only a 2-year school. He then completed his bachelor’s degree at Berea College and later graduated from Vanderbilt University School of Medicine. After 55 years of full-time work filled with globe-impacting cancer research, Hal officially retired in August 2017 as a nationally and internationally recognized physician-scientist, leader, and professor.

Why did you come to Cumberlands?

It was my only real choice. My family was very poor. Neither of my parents graduated from high school; my father was a coal miner and was unemployed during much of my college and medical school time. I was able to attend Cumberland College while living at home. With help from relatives, we were able to pay tuition. With encouragement from my professors, particularly Professor P.R. Jones in the Department of Chemistry, I was given self-confidence that I could succeed.

What did you do after graduating from Cumberlands?

During my second year at Cumberland, I learned about Berea College. They did not then and do not now charge tuition, and all students work for a minimum of ten hours per week for which they are paid. Dr. James Boswell, president of Cumberland College at the time, called me and a friend, George Ellis, ’56, into his office a couple of months before commencement and asked us what we were going to do after graduation. I had told George about Berea, and we both told Dr. Boswell that we would like to complete our college education there. He immediately turned around to his telephone and called Dr. Francis Hutchins, President of Berea College, and told him that he had two outstanding students that would like to come to his school. Dr. Hutchins responded that we were accepted to attend. After graduation from Berea, George went to medical school at the University of Louisville and has practiced family medicine in North Carolina since. I went to Vanderbilt University School of Medicine with two scholarships given to me by Dr. Hutchins.

When did you know you wanted to pursue a career in medicine? Why cancer research specifically?

When I was a junior in high school, my father and I visited the retired Gatliff coal company physician then living in Williamsburg, and he suggested that I consider a career in medicine because I could help people and make a good living while doing so. That resonated with me, so I decided to become a physician. Cancer research presented complex and challenging issues.

Tell us about the big discovery in 1984 with TGF-beta proteins.

I had been leading a research team at the Mayo Clinic for several years by then. We had co-discovered TGF-beta in the late 1970s, but that didn’t get much attention because we didn’t know the proteins had unique functions regarding the inhibition of cell proliferation. To explain, “proliferation” is when cells grow or multiply – often rapidly, in the case of cancer. When you “inhibit” that, it means you’re slowing or stopping that growth process. When we showed in 1984 that TGF-beta inhibits cell proliferation – that this small protein that’s already in our bodies helps keep cancer cells from growing and multiplying – that got a lot of attention. The implications were huge; if we could learn more about TGF-beta and figure out how to use it to help patients, it would change cancer treatment forever. The discovery was at that same time that a scientist at Genentech in San Francisco was able to demonstrate that TGF-beta was a unique growth factor, very different from all the others known at the time. It turned out to be a member of a large family, and, in short, there was a lot of research after that.

What are some other discoveries that your lab has made?

We have made many incremental discoveries which we’ve shared in more than 300 publications over the years. We were the first to get evidence from experimental animals that TGFbeta signaling was tumor-suppressive. It slows the growth of tumors. We also learned that it can help keep cells from becoming cancerous in the first place. Later, we showed that TGF-beta suppresses secretion by cells – particularly cancer cells – of factors that attract inflammatory cells that then promote tumor progression. It’s sort of a paradoxical effect. Essentially, early on in cancer formation, TGF-beta helps keep cancer from developing and progressing, but in later stages it does the opposite – it accelerates the growth. So, in the early stages, TGFbeta is helpful to the patient, but, later on, it’s harmful. Among other implications, that changes the timeline of when TGF-beta should be used in a patient’s treatment plan. We also discovered that later acceleration isn’t due to the effects of TGF-beta on the cancer cells, it’s due to the effects of TGF-beta on the host’s cells. Those are just a few of the many discoveries we’ve made in the lab, often in collaboration with many different groups.

What are some ways research has changed over the years?

Research has become very, very complex. You need to use different approaches and have people with different expertise involved to do the most competitive research. I’ve collaborated with many different groups over the years, both during my time at the Mayo Clinic and my years at Vanderbilt. We are getting better and more trustworthy results in research today than we did before. The amount we can learn in a matter of weeks used to take years in the early days of research. Additionally, technological developments have been key to the development of research for all different diseases.

Not only were you a researcher, but you were also a professor and a mentor. What did you enjoy most about teaching and mentoring?

One of the things I am most proud of is the success of individuals who received research training in my laboratory. Twenty-two people received Ph.D. degrees based on my mentoring and research conducted in my laboratory. Twice that many postdoctoral fellows and junior faculty received training in my laboratory. Many are now prominent scientists, administrators, and educators.

What does retirement look like for you?

Well, between August of 2017 and March of 2020, my wife and I took 10 trips. We went on cruises – small cruise ships with no more than 200 guests – and visited Iceland, Greenland, Germany to Hungary, Hawaii, Guam, Scotland, Sierra Leone, and the Greek Islands, among others. When COVID is under control, we look forward to traveling again. Until January 2021, I still had an office at Vanderbilt that I visited from time to time. I am currently an interviewer for prospective med school students. Some days I have an open schedule, other days I conduct several interviews. We also keep in touch with our family – we have three surviving children and 16 grandchildren who are all wonderful. For more than 20 years, we had grandkids come to “Grammy Camp” at our house and live there for a few weeks every summer. It’s great being a grandparent.

Cancer Research Achievements

Contributed to 350 Scientific Publications

Invited to present his work in 40 states and 22 countries

Founding director of the Vanderbilt-Ingram Cancer Center

Served as President of the American Association for Cancer Research and the Association of American Cancer Institutes

Founded and directed the Frances William Preston Laboratories

Founding chair of National Cancer Policy Forum for the National Academy of Medicine