“Life imitates art far more than art imitates Life.” Oscar Wilde
Dr Lorenz Zimmerman was born on November 15, 1920 in Washington DC. Early in his life, he learnt the importance of a disciplined life while working in the bakery his parents owned and being a sports enthusiast. He played football, baseball, and tennis, which he took up when he was 40 years old. He would often get into trouble, getting caught watching a game during social gatherings!
Dr Zimmerman graduated from the George Washington University in 1945. During medical school, he entered the US Army Reserves in 1943. While an intern at the Gallinger Memorial Hospital, his interest in internal medicine waned as he realized that it was, “an overlay of psychosomatic medicine and that, if I did not want to see patients whose problems were more in their heads than in their bodies, I ought to stick with genuine pathology.” He served as a general medical officer at the Pentagon and completed his residency in Pathology at Walter Reed Hospital in 1950. During the Korean War, he was the pathologist in charge of a mobile medical laboratory. He was awarded the Bronze Star and the Legion of Merit for his service during the war.
On his return to America in 1952, he was posted in Armed Forces Institute of Pathology (AFIP). AFIP was born of the Army Medical Museum. In the 1920s, most enucleated eyes were simply discarded in the absence of any trained ophthalmic pathologist. It was Dr George Callendae, the then Director of AFIP, who began examining the enucleated eyes from the military hospitals. By World War II, all ophthalmic specimens started being sent to AFIP for histopathology. This lead to the development of the American Registry of Pathology, and Ophthalmic Pathology was the first in this registry. Zimmerman was rotated through different specialities, till he settled in ophthalmic pathology. He had no experience in this field, but neither did anyone else in AFIP in the early 1950s. The war had lead many civilian institutions to stop subspeciality pathology and he inherited a backlog of over 5000 cases. He confessed, “I thought it was a stroke of real good fortune for me personally, not because I had any preconceived notions or interest in pathology of the eye, but I just knew that it was a gold mine … in the figurative sense … in terms of having a wealth of material available and having this tremendous inflow of material, not only from military institutions all over the world, but from the civilian sector. My entrance into the field was made comparatively easy by the fact that I hardly had any competitors. There were very, very few people who were well-trained who were in the field of ophthalmic pathology, and really none of them doing ophthalmic pathology on a full-time basis.” He was mentored and introduced to the key people in ophthalmology and eye pathology clubs by Helenor Wilder, ophthalmic pathology technician who ran the department during war. He had many military ophthalmologists assigned to him and they also taught him some clinical ophthalmology as they together learnt about eye pathology. He always considered himself fortunate for these associations. With the tremendous backlog, it was usually 5–6 years before he could actually give a final report, but at the end of each report, he would add a note – “We would appreciate your providing follow up information.” This basically formed his foundation of clinicopathological information with a long follow up.
He went on to become the Chairman of the Department of Ophthalmic Pathology in 1954 and developed ophthalmic pathology as an important subspeciality. He was the recipient of some of the highest awards, including the Jackson Lecture, Ernst Jung Prize in Medicine, Donders Medal, Jules Stein Award, Helen Keller Prize for Vision Research (ARVO), Howe Medal (AOS), the Academy’s Laureate Award and was declared one of the ten most influential ophthalmologists of the 20th century (ASCRS). Dr Zimmerman was a founding member of the Verhoeff Society for Ophthalmic Pathology. The Society, in 1998, changed the name to Verhoeff-Zimmerman Society in recognition of his immense contributions. The American Academy of Ophthalmology’s annual Lorenz E. Zimmerman Lecture is held in his honor.
In the first 15 years at AFIP, he published more than 50 articles on ocular oncology. For almost 50 years, he made landmark contributions to ocular pathology, oncology, and ophthalmology with his work on ocular neoplasia, their classification, retinoblastoma (RB), uveal and conjunctival melanoma, corneal dystrophies, inflammation, degenerations, and congenital abnormalities. He was the coauthor of the original book Hogan and Zimmerman Ophthalmic Pathology published in 1962 and continued to contribute to the subsequent editions.
He worked on the review of specimen and reclassification of the uveal melanoma from the original Callendar classification. This new classification correlated better with the prognosis of the patients. The follow up of patients enucleated for uveal melanoma from the Pathology Registry lead his team to find out that there was an increase in mortality from metastasis in the first two years following enucleation as compared to no surgery at all. They hypothesized that manipulation during the surgery and associated increase in intraocular pressure leads to dissemination of tumor cells. The numbers start rising after the metastatic cells set in and start producing their effect. This is followed by the body’s response to fight against these cells. Thus, a peak of 8% mortality is seen in the second year from the time of surgery. This observation was termed as the Zimmerman effect and the iatrogenic role in tumor dissemination was called the Zimmerman hypothesis. This happened around the same time as plaque brachytherapy was being developed and refined as a treatment for uveal melanoma. Both these lead to surgeons trying to find better techniques of enucleation with minimal manipulation and adjunctive prophylactic radiation as well as the Collaborative Ocular Melanoma Study (COMS), the first multicentric, prospective, randomized control trial to look into the outcomes of patients with uveal melanoma. The COMS on medium-sized melanoma showed that survival statistics were similar in patients who underwent enucleation and those who were treated with plaque brachytherapy, thereby disproving the Zimmerman hypothesis that enucleation facilitated metastasis. For large melanomas, EBRT before enucleation did not have any survival benefit as compared to enucleation alone. The mortality peak was at 3 years for both plaque brachytherapy and enucleation groups, proving the Zimmerman effect.
Zimmerman met his wife Anastasia in the Korean War where she served as an Army nurse. Together they had six children, 14 grandchildren, and ten great-grandchildren. Zimmerman and retinoblastoma were entwined in an ironical twist of fate, a story of tragedy, strength, and determination to overcome challenges. He was one of the pioneers in RB research. He published his first paper on RB in 1967, co-authored with Dr Marshall Parks. His last child, Larry, was born in the same year. Around the time of Larry’s birth, Dr Zimmerman was reviewing all the cases of RB at AFIP. When Larry was 4 months of age, Dr Parks diagnosed him with bilateral RB, a large macular tumor in the right eye and three small perimacular tumors in the left. At that time, the standard treatment was enucleation for the worse eye and external beam radiation (EBRT) for the better. Larry was the first baby to be treated with intracarotid chemotherapy under Drs Reese and Ellsworth followed by bilateral EBRT. Both these were in the experimental stage at that time. Today, bilateral EBRT has been replaced by better means of treatment because of high risk of secondary malignancies. Zimmerman coined the term, “trilateral retinoblastoma” along with his son Brian and Dr Mark Tso. He proposed pinealoblastoma to be a second primary neoplasia rather than distant metastasis in patients with bilateral retinoblastoma. When Larry’s wife was pregnant with their daughter, Perry, an amniocentesis revealed that the child had the inherited RB mutation. Perry was examined from the day she was born. From 7 weeks to 9 months of age, she was treated by Dr David Abramson for bilateral RB with laser therapy and both the tumors were regressed. When Perry was two, she started showing symptoms of neurological disease and was diagnosed with pinealoblastoma. Back then, trilateral retinoblastoma had a survival rate of only 5–6%. The child underwent two surgeries and five cycles of chemotherapy. The parents made a plea to the hospital tumor board to develop a protocol and attempt intrathecal chemotherapy for the first time for Perry. She also underwent a stem cell transplant and treatment for osteosarcoma of the femur which she developed when she was 11. Larry’s second daughter, Lizzie, was born of pre-implantation genetic diagnosis (PGD) to prevent the transmission of RB gene and was the first child to be born of PGD for any cancer-related genetic disease. It was probably the challenges that Zimmerman faced in his personal life that he was so dedicated in his work of pursuing research with the hope that even others could overcome this potentially fatal illness.
“Zim”, as he was lovingly called by his friends, and “Cool Papa” by his grandchildren, was a great teacher and a loving husband, father, and grandfather. He mentored a generation of ophthalmic pathologists. Daniel Albert observed, “Zim had the ability to look at slides from diseases that had been studied for over a century and make new observations and correlations. His vast knowledge and insight into the pathology of eye diseases, backed by his total mastery of the basics of pathology, made him a uniquely qualified mentor. This knowledge was combined with his gifts as a clear and precise teacher, patience, intellectual honesty, and humility.” Fred Jakobiec recalled, “While some leaders in their fields are threatened by the most talented young people they have trained, Zim has exhibited the trait of promoting their careers at every turn. His personal and professional lives have been a parable of strength, decency, and accomplishment”
Lorenz Zimmerman died on March 16, 2013, 10 days before his wife. A man of humility despite all his accomplishments, an epitome of courage and dedication, Dr Zimmerman is a legend by all means. Having received multiple awards, once when his granddaughter asked him, “Cool Papa, I forgot, what made you so famous?” he replied, “Because I’m your grandfather, Lauren.”
“What would life be if we had no courage to attempt anything?” Vincent van Gogh
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3. Collins ML. Retinoblastoma:The Zimmerman family story JAMA Ophthalmol. 2014;132:519–20
4. Tso MO. In Memoriam:Lorenz E. Zimmerman, MD (1920-2013), and Anastasia U. Zimmerman (1923-2013) JAMA Ophthalmol. 2013;131:1104–5
5. Jakobiec FA, Tso MO, Zimmerman LE, Danis P. Retinoblastoma and intracranial malignancy Cancer. 1977;39:2048–58
6. McLean IW, Foster WD, Zimmerman LE, Gamel JW. Modifications of callender's classification of uveal melanoma at the Armed forces institute of pathology Am J Ophthalmol. 1983;96:502–9
7. Zimmerman LE, McLean IW. The natural course of untreated uveal melanomas Doc Ophthalmol. 1980;50:75–82
8. Zimmerman LE, McLean IW, Foster WD. Does enucleation of the eye containing a malignant melanoma prevent or accelerate the dissemination of tumour cells Br J Ophthalmol. 1978;62:420–5
9. Grossniklaus HE. Understanding uveal melanoma metastasis to the liver:The Zimmerman effect and the Zimmerman hypothesis Ophthalmology. 2019;126:483–7