Decoding the genesis of the "génie génétique" - Irene Hussels Maumenee.

“Genetic code is a divine writing.” – Toba Beta

This very quote has been exemplified by Dr. Irene Hussels Maumenee who has been a founder of ophthalmic genetics and an asset to the clinicians struggling to find a solution for their patients suffering from rare genetic disorders. She is a legend who envisioned a fusion of ophthalmology and medical genetics. She took several fellows under her wings, provided extensive training in ophthalmic genetics, and created a well-designed network worldwide.

Born in Germany at the beginning of World War II to parents from the medical fraternity, Irene Hussels was always encouraged to excel. With a deep-rooted belief that “the only thing nobody can take away from you is your education,” her parents instilled in her the urge to achieve the highest level of education and reach the zenith.

As a child, alongside her siblings, she had keen interest in studying the minute details of the plants and animals around her, which included lamb’s lettuce in the fields, white button mushrooms in the meadows, birch boletes, porcini, and chanterelles under the trees. Nature’s beauty caught the attention of her curious mind, and she was fascinated by the colorful land snails and the captivating stages of development of various animals.[1] This way, she explored and comprehended her interest in genetics. Her strong sense of self-realization was the greatest service she could render to the world, as she found her life’s work in the process.

As she began studying French, she not only learnt the language, but also immersed herself in the unique French culture by spending her time with a French family. This not only enabled her to read and speak French at school, but also helped her in graduating from Göttingen Medical School in Germany.[1] By virtue of her love for nature and genetics, she wrote her thesis on X-linked retinitis pigmentosa at the University of Geneva Medical School, Switzerland. Due to the high number of cases of genetic blindness in Switzerland, Professor Adolphe Franceschetti, chair of ophthalmology at the University of Geneva, initiated a medical genetics program in their curriculum,[1] supporting her commitment to genetics and ophthalmology.

Dr. Newton E. Morton, one of the founders of genetic epidemiology and a population geneticist from the University of Hawaii, was impressed by her abilities, talent, and observations on the increased frequency of rare diseases in areas with higher rates of consanguinity.[1] Dr. Hussels moved to Hawaii to work with Dr. Morton on his data in his population genetics laboratory. Meanwhile, she studied the rare genetic eye disease, achromatopsia, on the island of Pingelap in the Pacific region.[1]

Popularly known as the father of medical genetics, Dr. Victor A. McKusick laid down the foundation of clinical genetics at the Johns Hopkins University in Baltimore. Dr. Hussels visited him for 2 months in 1969 and developed a special interest in inherited disorders of connective tissue, including Marfan syndrome. Her short pause evolved into a long journey of a postdoctoral fellowship in medical genetics at the Johns Hopkins University School of Medicine followed by a preceptorship at the Wilmer Eye Institute.[1] There she learnt the art of integrating mathematical principles into medical genetics.

Dr. Hussels revers Dr. McKusick for selflessly showing her the right direction and considers him as her primary mentor. In her words, “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.” This not only shows her dedication to her mentor, but also underscores her clinical skills.[1]

She joined the Department of Ophthalmology under Dr. A. Edward Maumenee, where she was successful in building a bridge between genetic eye diseases and laboratory research. Dr. A. Edward Maumenee and Dr. Irene Hussels married and were blessed with two sons.

Dr. Irene Hussels Maumenee [Fig. 1] founded and directed the Johns Hopkins Centre for Hereditary Eye Diseases, an international referral center, and, under her supervision, more than 30,000 patients with rare eye disorders were diagnosed and managed.[1] She became the Ort Professor of Ophthalmology at the Johns Hopkins University, and she trained several legends including Dr. A. Lin Murphree, who contributed tremendously to the world of ocular oncology [Fig. 2a]. Every rare disease was a piece of mysterious puzzle to her. Her skill of putting the pieces together, by remembering and recalling the cases individually, was par excellence and unparalleled, allowing her to solve the puzzle and unravel the mystery.

Figure 1

Dr. Irene Hussels Maumenee[14]

Figure 2

(a) A priceless capture of Dr. Maumenee with one of her sons, Niels K. Maumenee (on the left) and her first ever fellow Prof. A. Linn Murphree (on the right), who was a tremendous force in ocular oncology known for decoding the retinoblastoma genetics (courtesy: Dr. Emily Chew). (b) Dr. Maumenee with Dr. Stephen H. Tsang (standing) and Dr. Peter M. J. Quinn (sitting) at the Columbia University, Vagelos College of Physicians and Surgeons in New York city (courtesy: Dr. Stephen H. Tsang)

The Ophthalmic Genetics Study Club founded by Dr. Maumenee in 1976[1] gave opportunities for enthusiasts from the genetic world to discuss their respective cases and broaden their knowledge horizon. In 1978, a small meeting of Drs Ed Cotlier, N. Ohba, and Maumenee at a restaurant in Tokyo led to a grant by the International Council of Ophthalmology and the inception of the International Society for Genetic Eye Diseases and Retinoblastoma (ISGEDR).[1] The now biennial meetings have promoted the spread of the knowledge of genetics across the international borders and have built interest in curious minds with a strong inclination toward ophthalmic genetics.

Her caring nature and curiosity enabled her to work for decades as a consultant at the John F. Kennedy Institute for Visually and Mentally Handicapped Children and with the Maryland School for the Blind. Her desire to add more to the pool of available knowledge was always evident. In 2008, Dr. Maumenee joined the faculty of the Illinois Eye and Ear Infirmary and is currently a Professor of Ophthalmology at Columbia University, Vagelos College of Physicians and Surgeons in New York city [Fig. 2b].[12]

Dr. Maumenee initiated a chain reaction of understanding genetics in ophthalmology and trained many fellows, instilling the same thirst for knowledge in them. Her contagious energy and abilities have created a strong sense of loyalty, love, and affection among her fellows, which have been acknowledged by many over the years with utmost respect [Fig. 3]. She is a calm, encouraging, and forgiving source of knowledge, radiating positivity all around, and those who have come in touch with her, even if only for a short while, have been inspired. She believes in dual board certification in both genetics (American Board of Medical Genetics) and ophthalmology (American Board of Ophthalmology) to serve patients and society.[3]

Figure 3

(a) A precious keepsake - Dr. Maumenee with her fellows. From left to right – Drs Yasuhiko Tanaka, Jane D. Kivlin, Irene H. Maumenee, James Richard, Bronwyn Bateman, Shakur Hamidi Toosi (courtesy: Dr. Jane D. Kivlin). (b) Dr. Irene Hussels Maumenee with her proud former fellows at the American Academy of Ophthalmology Laureate Recognition Award ceremony in 2017. From left to right – Drs Emily Chew, Marilyn Miller (a friend), Irene Hussels Maumenee, Marilyn Mets, Bronwyn Bateman, Terri Young (courtesy – Dr. Emily Chew).

Although there have been major advances in genetics over the span of her career, she still believes that the manpower required for discovering the world of genetics is sparse. “We have an estimated 22,000 genes and we know over 6000 single gene disorders and complex diseases, but causative mutations have been identified in fewer than 4000 genes. The complexity of gene function for most genes remains unknown,” she said.[1] Her curiosity and urge to explore the unsolved mysteries of several rare diseases continues. She has encouraged collaborations between private practices and universities. She understands the issues of government funding for rare diseases and has included support groups and foundations to develop a strong funding for research and development for these diseases.

Out of her innumerable contributions, a few of the landmark impacts are as follows:

Marfan syndrome and other connective tissue disorders – diagnosis and management of ocular manifestations[4567]

Genetic aspects of congenital cataract and their management[89]

Ocular and genetic manifestations of mucopolysaccharidosis[1011]

Leber’s congenital amaurosis and hereditary optic neuropathy[1213]

Identified the first gene for achromatopsia, CNGB3, among the Pingelapese Islanders.[1]

In 2017, 13 years following Dr. Danièle S. Aron Rosa, Dr. Maumenee received the American Academy of Ophthalmology (AAO) Laureate Recognition Award.[1415] She mentioned in an interview that people considered her inclination toward genetics equivalent to “collecting butterflies,” but she saw it as “a new opportunity in life and in the world.” Despite making the impossible become possible, she feels she could have pursued more if it were not for responsibilities toward family. However, she quoted, “It’s hard to know if I would have done anything really differently. I certainly would not want to be without a family.”

As she put it, “My knowledge of French had opened the door.” We have all the reasons to believe that her knowledge of French opened the doors of genetics to the entire world.

We are forever indebted to her for her accomplishments. Her life-long dedication to ophthalmic genetics to identify and understand rare hereditary ophthalmic disorders has revolutionized the management of such cases due to her grit, inventiveness, optimism, generosity, and imagination.

“Heredity provides for the modification of its own machinery.” – James Mark Baldwin