• Bringing Genetics to the Forefront: The 2017 Academy Laureate, Irene H. Maumenee, MD

    Written By: Catherine Morris, Associate Editor, EyeNet Magazine

    Irene H. Maumenee, MD, is one of the world’s leading experts in genetic eye diseases and is unanimously regarded as the founder of genetics as an ophthalmic subspecialty in the United States. “Dr. Maumenee’s contributions include the description of the ocular manifestations of numerous inherited disorders, such as Marfan syndrome and others, and the utilization of molecular biol­ogy techniques to map and identify the genetic basis of inherited eye disorders,” said Elias I. Traboulsi, MD, MEd. “More importantly, she is a compassionate physician and patient advocate who is adored by her patients young and old, and a dedicated educator who has trained many specialists in the field.”

    Early Life

    Dr. Maumenee was born in Germany at the beginning of World War II. Her mother was a general practitioner, and her father was a dentist. Her parents were insistent that their children earn advanced degrees. “The question was whether I would go into medicine, biology, or biochemistry, but my mother was very adamant about me going through medicine first before settling on a field,” she said. She believes that her parents’ childhood during World War I had a lot to do with their stance on education. “They wanted their children to have a fulfilling career. We learned that the only thing nobody can take away from you is your education.”

    Genetics captivated her from the very beginning. “It was always genetics, first and foremost. I did not go to school until third grade, given the chaos of the postwar years, but even when we were as young as 5 or 6, my siblings, cousins, and I were involved in studying the plants and animals around us. We looked for lamb’s lettuce in the fields; white button mush­rooms in the meadows; and birch boletes, porcini, and chanterelles under trees. We saw salamanders shed their tails and take off. We were fascinated by the varied col­oring of the shells of the abundant small land snails, which lived in the bushes close to home. We kept colonies on our balcony and fed them religiously, but we did not know how to find the answers to our questions about the development of their coloring. From that age, I knew that I was going to be a geneticist.”

    Even so, her first area of study con­cerned languages. “I worked hard to learn French, initially school French, daily French, French literature, and, later, medical French. My parents organized an exchange with a French family, which was a wonderful opportunity to learn about a different culture.” 

    The transition to medicine soon followed. After obtaining her MD from Göttingen Medi­cal School in Germany, Dr. Maumenee moved to Switzerland to write a the­sis in ophthalmology and genetics at the University of Geneva Medical School. “My knowledge of French had opened the door,” she said. It was there that her path to ophthalmic genet­ics solidified. “There were many cases of genetic blindness in Switzerland, so Professor A. France­schetti, chair of ophthal­mology, had developed the medical genetics program of the University of Geneva—that is how genetics merged with ophthalmology for me.” During this time, Newton E. Morton, PhD, a popula­tion geneticist from the University of Ha­waii (now known as one of the founders of genetic epidemiology), visited Geneva to look at the singular data on genetic blindness that Dr. Maumenee had been accumulating in Switzerland. Switzerland has many geographic isolates with high rates of inbreeding: the higher and nar­rower the mountain valley, the higher the rate of consanguinity and the higher the frequency of rare diseases. Dr. Morton suggested that she move to Hawaii to analyze the Swiss data in his population genetics laboratory. She stayed for a year; during this time, she also studied genetic eye disease in the Pacific region, which later led to identification of the first gene for achromatopsia, CNGB3, among the Pingelapese Islanders.

     

    GENETIC EYE DISEASE IN THE PACIFIC. Lemwuel Ohri, a Pingelapese teacher, organizing data, drawing blood samples, and establishing the genetic pedigree on Pingelapese in Micronesia. Dr. Maumenee’s group was searching for the gene for achromatopsia (present in the woman holding the child in the back row). They later identified the gene as CNGB3.

    Buoyed by Curiousity

    Before she returned to Germany from Hawaii, Dr. Maumenee decided to visit the genetics clinic at Johns Hopkins Hospital in Baltimore, which had been founded by Victor A. McKusick, MD (now recognized as the father of medi­cal genetics). He had a special interest in inherited disorders of connective tissue, including Marfan syndrome, which led to Dr. Maumenee’s lifelong commitment to the ocular features of this disease group. What began as a 2-month visit turned into a postdoctoral fellowship in medi­cal genetics at Johns Hopkins University School of Medicine, then a preceptorship at the Wilmer Eye Institute, and a family and career in Baltimore. “It was a tre­mendously exciting and productive time in genetic disease—I really loved those years,” she said. Dr. Maumenee considers Dr. McKusick to have been her primary mentor during that time. She said, “To him, it didn’t matter whether somebody was male or female, where they came from, or who they were—just whether the person had a passion for the field and could move it forward. He was singularly directed in his pursuit and tremendously knowledgeable. He would help you and foster your growth, and he was very gen­erous with his time, input, and teaching. He was an extraordinary mentor.”

    Catapulting the study of ophthalmic genetics. As the field of molecular genet­ics evolved in the 1980s, Dr. Maumenee successfully merged clinical studies of genetic eye diseases with lab research, among the first of such efforts. While she was on the Wilmer faculty, she founded and directed the Johns Hopkins Center for Hereditary Eye Diseases, an interna­tional referral program that has evalu­ated, diagnosed, and treated more than 30,000 patients with rare eye diseases. Despite this vast number, she maintains a striking ability to remember individual cases. “Her recall and synthesis of the puzzle of each patient over time as more discoveries are made is unparalleled,” said Marilyn Baird Mets, MD.

    Dr. Maumenee also served as an active consultant to the John F. Kennedy Insti­tute for Visually and Mentally Handi­capped Children since its inception, and she worked extensively with the Mary­land School for the Blind. “These experi­ences were definitely gratifying in a hu­manitarian respect, but a lot of it was just pure curiosity,” she said. “It was to learn about the diseases and all their possible manifestations. I enjoyed seeing patients, and I realize more and more how much I enjoyed the interaction. The motivation lay in increasing the understanding of the underlying pathology, and I did the work primarily to move things forward—there was so much to be done.” Dr. Maumenee joined the Faculty of the Illinois Eye and Ear Infirmary in 2008 and is currently the director of ocular genetics as well as a research professor of ophthalmology at the University of Illinois College of Medicine at Chicago. 

    “We Decided to Get Something Started"

    In order to gain momentum toward her goals to spread knowledge, Dr. Maumenee created the Ophthalmic Genetics Study Club in 1976. She invited people who had published articles on genetic eye disease to come to an annual meeting to share cases, give each other feedback, and discuss knowledge gained. The organiza­tion still meets annually. In 1978, along with E.F. Cotlier, MD, and N. Ohba, MD, Dr. Maumenee started the International Society for Genetic Eye Diseases and Retinoblastoma (ISGEDR). “Our first meeting was at a restaurant in Tokyo; then I applied to the International Council of Ophthalmology to give the organization legitimacy. We were accepted, and from then on, we had meetings every 2 years worldwide to pass the knowledge around to different countries. These meetings were really very focused on getting people interested in and learning about genetic eye disease.” ISGEDR still meets every 2 years internationally. “Dr. Maumenee’s leadership in organizations such as the ISGEDR has provided the opportunities needed for fellowship and collaboration between individuals interested in oph­thalmic genetics and the education and sharing of information between them,” said Dr. Traboulsi.

    A Passion for Training

    Dr. Maumenee believes strongly that more people need to be trained in both ophthalmology and genetics. “There are not enough people who can train the present generation and the next genera­tion, so a big effort should be made to educate people in order to facilitate this,” she said. “Treatment gets developed when there is understanding of the correlation between the gene and the disease.” She has trained more than 60 fellows herself, and “her loyalty to and support of her trainees is unfailing,” said Dr. Mets.

    Tim Stout MD, PhD, MBA, recalled a story from his student days. “I had just finished my PhD and was interested in going into ophthalmology, so I went to Wilmer Eye Institute, where Irene was on faculty. I spent about half of my day doing research in her lab, and the other half in the clinic and in the OR with her. This was my first ophthalmic rotation, so I didn’t know very much, that’s for sure. “One day we went to the OR, and there was a child who was asleep. Irene was interested in refracting the child, so she looked at me and asked if I would mind handing her the loose lenses from across the room. I went over and got the box, but I opened it the wrong way and the lenses scattered all over the floor. After about a half a second, Irene looked at me and said, ‘Oh my gosh, I’m so glad somebody else does that—I do it all the time.’ Mortified, I gathered up the lenses and put them back, and we finished the case. When Irene left, the nurse looked at me and said, ‘She’s just trying to make you feel good. That’s never happened in here—she’s never done that in her entire life.’
     
    “It was such an instantaneously graceful thing for her to do, and she made me feel so much better. I’m this lowly medical student who knows nothing, and here’s this faculty member that’s working hard to try to make me feel more comfortable. It was my first experience in ophthalmology, and I thought that if all faculty are like this, this is definitely a field I could go into. So you could say Irene is a big reason I went into ophthalmology.”

    Looking Ahead

    “The genetic basis of human diseases needs to be recognized—there is no place for taking that component lighthearted­ly,” said Dr. Maumenee. “If somebody has a blind child and they ask if the disease will appear in their next child and you say, ‘Oh, no. I have never seen it come back,’ that is just irresponsible. There has to be a totally different level of recogni­tion of the significance of the genetic component in blindness and eye diseases in the United States and worldwide than there currently is.” To this end, she is tak­ing action toward the following goals.

    Dual board certification. Ophthal­mologists currently cannot order a DNA analysis through a lab; they have to send patients to a geneticist, who may not know eye diseases. To mitigate this, Dr. Maumenee and her colleagues want to create a pathway for people to become board certified in both genetics and ophthalmology.

    Funding gene sequencing. There is still a large gap between identification of genes through the Human Genome Project and determination of their func­tion and impact on disease. Dr. Maumenee would like to see more work on gene sequencing in human eye diseases. “We have an estimated 22,000 genes and we know over 6,000 single gene disorders and complex diseases, but causative muta­tions have been identified in fewer than 4,000 genes. The complexity of gene function for most genes remains un­known,” she said. Much information is needed to establish the correlation between genes and their mutations and a specific genetic disease. She said, “Not all genes may harbor mutations that lead to disease, because many of them may lead to benign variants. We are still unable to identify causative mutations for many patients, even though the technology is available to do so. The manpower is largely missing.”

    Joining forces. Dr. Maumenee believes that it is key to create collaborations be­tween private practices and universities. “What I want to do is basically help every ophthalmologist who sees an unusual case establish a research project with an institution. This way, patients with genetic issues will be better positioned to find an investigator who can work toward solving the problem and possibly even develop a treatment. The flow needs to go from the private practice to the universities.”

    Finding treatment. “I would like to bring at least one disease to treatment,” she said. “That is very high up on my list. If you look at genetic eye diseases, they are individually rare. The government’s function is not to address diseases that affect maybe 1 in 100,000 people or 1 in 30,000 but rather to take care of the com­mon problems. So there is a tremendous power in organizing patient support groups and foundations that bring patients in the United States and world­wide together to work on a given disease. Patient support groups are very impor­tant in the development of treatment. 

    Women in Ophthalmology

    Dr. Maumenee joins Danièle S. Aron Rosa, MD, PhD, as the only women to receive the Academy’s Laureate Recogni­tion Award. “The biggest challenge lies in combining family and work life, and that continues to be a large issue for women. Women still get paid less and usually need to hire help to manage responsibili­ties at home. Men are parents too, but their time is often considered more valu­able than a woman’s time. It is a difficult position to be in,” Dr. Maumenee said. She believes that if she did not have fam­ily obligations, she might have pursued more field research in inbred populations in other countries. “It’s hard to know if I would have done anything really differ­ently. I certainly would not want to be without a family.” She hopes the next generation will do a better job of figuring out a balance.

    In any event, those who have worked with her see no deficits. “Dr. Maumenee has embraced and mentored multiple individuals worldwide, and now all are disciples of her lessons and persever­ance,” said Terri L. Young, MD, MBA. “She truly is a visionary, and her pio­neering work has forever changed the landscape of ophthalmic genetics.”