PCOS, IVF and genetics in reproductive endocrinology: A chat with William E. Gibbons, MD

Since deciding in high school to become a physician, William E. Gibbons, MD, never had the desire to be anything other than who he is today, a self-proclaimed science nerd.

Gibbons, is a distinguished professor emeritus in the department of obstetrics and gynecology at Baylor College of Medicine. Outside of his work in reproductive endocrinology, he enjoys reading, music and caring for the dogs he owns and fosters with his wife who has done the lion’s share of work in keeping the family together while he worked. He said he wishes to spend more time with his family.

Gibbons is the recipient of the Lifetime Achievement Award presented during the ASRM Scientific Congress & Expo for his contributions to the field of reproductive medicine. Gibbons has served as the president of ASRM, the Society for Reproductive Endocrinology and Infertility and the Society for Assisted Reproductive Technology.

Healio spoke with Gibbons about how he got into his current field of research and what interests him most about reproductive endocrinology and the future of knowledge. He stated that he is very honored, but knows that there are others who are more accomplished than himself.

Healio: What was the defining moment that led you to your field? Why do you do what you do?

Gibbons: I was fortunate that the medical school I attended, Baylor College of Medicine, had a very good department of obstetrics and gynecology. The OB/GYN rotation at that time was 11 weeks, and I was able to read the entire Williams Obstetrics textbook during that time.

Also, one of the two largest obstetrical hospitals in America was there. The Jefferson Davis Hospital [now closed] alternated annually with the Los Angeles County Hospital for the greatest number of deliveries. There were more than 17,000 deliveries a year, or 42 deliveries per day. This meant that medical students had tremendous exposure to delivery. I performed more than 50 deliveries on the OB/GYN rotation. That is a very unusual experience and was unique from the standpoint of training people. If you ask why many people went into OB/GYN, they liked the fact that there was a mixture of surgery and medicine. This created a lifelong love for the kind of work that we do.

When I was a senior medical student, I was thinking about doing gynecologic oncology because Baylor was across the street from the MD Anderson Hospital and Tumor Institute, which is the largest in the country. However, in that last year, I did an elective rotation in the reproductive research lab. It exposed me to a wide variety of intellectually stimulating challenges. One of the individuals who was awarded the Nobel Prize for discovering and synthesizing gonadotropin-releasing hormone (GnRH) secreted by the pineal basal hypothalamus was at Baylor. At that time, we were doing GnRH simulation tests on women and studied their response. This meant I was exposed to the incredibly, intellectually interesting capacity of trying to evaluate how the cerebral cortex affects the hypothalamus, affects the secretion of hormones that affect the secretion of the pituitary hormones [luteinizing hormone] and [follicle-stimulating hormone] and how that then functions and change the way the ovary works and then the uterus.

It was that intellectual stimulation that made me realize that I was going to be more challenged by looking at reproductive endocrinology than being a gynecologic oncologist.

Healio: What area of research in women’s health most interests you right now and why?

Gibbons: If we want to talk about endocrinology, our current work developing the knowledge of polycystic ovary syndrome is very interesting to us right now. PCOS is one of the most common endocrine abnormalities that women develop. We know that it’s inherited, and we also know that it can be related to people who have insulin resistance.

Working with Dr. C. Selvanesan Blesson, a PhD researcher at Baylor, we’re currently looking at an animal model that recreates both the thin polycystic and the obese polycystic phenotypes. Typically, the most common PCOS phenotype is women who tend to be overweight, which affects or further worsens their insulin resistance, which further affects their ability to secrete the pituitary hormones, which then results in irregular menstrual cycles.

PCOS is usually associated with androgen excess and irregular cycles. We’re exposing pregnant rats to 4 or 5 days of androgens. When the female pups are born, they demonstrate evidence of PCOS, slight androgen excess, slight alterations in insulin sensitivity, but they’re not obese. This is important because another interesting population of women with PCOS is the thin phenotype and they act differently. We’re trying to understand the nature of the things that result in someone being thin polycystic. On the other hand, if the pups are born, and then you overfeed them adding androgens, you create an obese model, and these animals then develop PCOS.

The wonderful thing about our field is that every year there are more questions to answer and to ask. We’re not going to run out of things to study. I just hope that this will continue to challenge people to continue to look in this area.

Healio: Have you ever been fortunate enough to witness or to have been part of health care history in the making?

Gibbons: When I completed my reproductive endocrine fellowship at Baylor after completing my residency in OB/GYN, I was recruited to join the faculty at the University of Southern California by Daniel R. Mishell Jr., MD, the chairman of the department of OB/GYN. One of the things that Dr. Mishell wanted to explore was understand the growing concept of endocrinology from the standpoint of receptors, the small proteins within the cell that respond to hormones and change cell function. Fortunately for me, Baylor was one of the national centers studying hormone action and my research dealt with the effect of estrogen hormones on uterine function.

Dr. Mishell wanted to bring this type of research to USC, and he essentially gave me the resources to build the laboratory I needed to do that. In the meantime, joining the USC department at the same time was Richard Marrs, MD, who had completed his residency training at the University of Texas in Galveston. Upon completing his residency, Dr. Marrs went , and we interacted with the senior residents from both Baylor and Galveston. Dr. Marrs went to USC for his fellowship in reproductive endocrinology.

Dr. Mishell also wished to see the department produce an IVF program, which was now successful in England and Australia, but not yet in the U.S. He sent Dr. Marrs to Australia to study with the IVF groups there, and when he returned, initiated an IVF program at the University of Southern California. It was the perfect way to learn about the physiology, science, embryology of human reproduction and incorporate this into clinical reproductive medicine. He and I were the clinical team.

On Dec. 27, 1981, the first U.S. IVF pregnancy was born at the Eastern Virginia Medical School/Jones Institute. Our first pregnancy at USC was born 5 months later. Our first patient to produce a live birth delivered in May 1982. This was the third birth in America produced by IVF.

I returned to Baylor to establish an IVF program there soon after. At the end of the decade, I was contacted by one of the greatest reproductive biologists of that generation, Gary L. Hodgen, MD. Dr. Hodgen had been director of the pregnancy research branch at NIH. Dr. Hodgen wanted to learn more about IVF. This was a challenging time in the government, it was a politically charged area, and they indicated he would not be able to pursue his interest in the field of IVF. It’s very difficult to tell Dr. Hodgen, no, so he left and was offered a position at Harvard. However, he accepted the position to work with Dr. Howard Jones Jr., MD, at the Eastern Virginia Medical School, which was forming the Howard and Georgeanna Jones Institute of Reproductive Medicine. Gary called me and said, “I would like you to come to Eastern Virginia Medical School and be our chair.” No one turns Dr. Hodgen down, and it was an exciting, wonderful part of my growth.

Gary also was interested in looking at the ability to evaluate early embryos, to be able to biopsy a cell and be able to evaluate it for a genetic disease to prevent transmission of a disease, a process called Pre-Implantation Genetic Diagnosis. I became the clinical director of the Pre-Implantation Genetic Diagnosis program and recruited patients for this process, the first patient carried the genetic mutation for Tay-Sachs Disease, a lethal disease. Performing IVF, embryo biopsy and genetic analysis, embryos without the genetic disease were transferred into the patient. The couple conceived after the embryo transfer and gave birth to the first child in the world that had been screened for the disease Tay-Sachs.

Healio: What do you think will have the greatest influence on your field in the next 10 years?

Gibbons: We’re continuing to learn about the genetics of all cells. There may be 20,000 expressed genes, but these are produced from a very small percentage of the actual amount of DNA in the nucleus. One of the people first describing these non-expressed areas of DNA labelled it ‘junk DNA’. But this isn’t junk DNA. These areas allow DNA to communicate with other parts of the DNA in the same cell using this genetic material, and some of these very short bits of transcribed RNA, or microRNAs, perform important, varied actions. For instance, an embryo at the time of implantation creates and secretes into the uterine cavity a small bit of genetic microRNA that will be picked up by the endometrium. That changes the way the endometrium works. The endometrium communicates back to the embryo in a similar fashion thus aiding implantation. We are just beginning to understand this.

In 2017, the NIH announced that it was going to do the complete sequencing of the DNA of 1 million Americans! I can’t even put my mind around what we’re going to learn about reproduction, longevity, hypertension and other diseases.

People can sign up to be part of this 1 million at AllofUs.nih.gov. I hope that some of the people reading this will sign up to participate. I’ve been trying to make sure that as many of my patients with different conditions such as recurrent pregnancy wastage are part of that 1 million. You give them your information and they look at your history. They’re prioritizing the first DNA they’re going to sequence, so they may contact you and ask you to submit your DNA.

So, those of you reading this can participate in our evolution of understanding of genetic disease.

Healio: Do you have any good ideas? If you could make an app for something in your life, what would it be?

Gibbons: The wonderful thing about what we do is that there are always new ideas. But what is challenging for those within academic medicine is, how do we teach? There’s no question that, as a baby boomer, the way I learned is not the way current young people are learning. There are so many sources of information, so many inputs. The question is, how do we communicate and, essentially, infect people with the desire to know things? Not just, what’s the answer to the test question, but how does something work? Why does it work? We’re going to want the new group of physicians coming along in their career to ask and answer these questions.

If I had an opportunity to be able to create an app, it would be about how we can enhance learning. We’re going through this now in the reproductive endocrine specialty. We’re looking at how we can train reproductive endocrinologists for the future. A challenging point for us is to begin to understand the communication issues that will enhance connecting with this generation and the next generation of physicians.

Healio: Whom do you admire and what would you ask that person if you had 5 minutes them?

Gibbons: It would be Stephen Hawking. In about 1991, I read A Brief History of Time. All of this is going to sound strange. But as someone who had to type out every letter of every word with a stylus in his mouth and used a speech synthesizer to give voice to his words, Stephen Hawking was a great communicator. His ability to connect to all of us from the standpoint of looking at these super big things like galaxies and black holes, and super small things, the strong and weak nuclear forces, electromagnetism and gravity was astounding. The problem is that I’m pretty sure that I’m not smart enough that I should waste his time for the time it would take to ask everything. But he has helped change our ability to understand things and he made me want to know more, which is the desire of every educator.