December 2008
Volume 49, Issue 12
Lecture  |   December 2008
Introducing Lois E. H. Smith, the 2008 Recipient of the Friedenwald Award
Investigative Ophthalmology & Visual Science December 2008, Vol.49, 5175-5176. doi:10.1167/iovs.08-2585
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      Martin Friedlander; Introducing Lois E. H. Smith, the 2008 Recipient of the Friedenwald Award. Invest. Ophthalmol. Vis. Sci. 2008;49(12):5175-5176. doi: 10.1167/iovs.08-2585.

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      © ARVO (1962-2015); The Authors (2016-present)

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It is with immense personal pleasure and great professional pride that I introduce to you the recipient of this year’s Friedenwald Award, Lois Elaine Hodgson Smith. Lois is an outstanding example of a clinician scientist who has made highly significant and innovative contributions to both clinical ophthalmology and vision science while at the same time remaining one of the kindest, most generous individuals I have ever met. By maintaining her keen intellect, a passion for science, compassion for her patients, and a generosity of spirit and commitment to the Common Good, she is a great role model for the young clinician/scientist. She is an inspiring and devoted mother of Alexandra and Colin, as well as a great best friend and loving wife of her husband David. Professionally, we honor Professor Smith tonight for making not one, but several, seminal contributions to vision science. Her work has provided critical proof of concept in at least three major areas of study that have found therapeutic application to clinical ophthalmology. 
I first met Lois over a decade ago at a meeting where we were both speaking in Oxford, England. I arrived jet lagged and having just sent in a review of a paper Lois had submitted to Science. I was particularly agitated because I could find no significant flaws in her work. It was meticulously planned, flawlessly executed, and, most frustratingly, potentially broadly applicable and of very high significance…a typical story from the Smith laboratory. Just the sort of manuscript you hated to see come from the competition at Harvard. And here I was, heading to a meeting where I would almost certainly have to meet her. As fate would have it, I found myself sitting in the audience next to this very pleasant woman who chatted with me between talks. I was surprised when Dr. Lois Smith was summoned to the podium to give her talk, and the lovely woman next to me got up and gave the lecture. Now I was doubly agitated; not only was she smart, but she was extraordinarily nice. My wife and I spent several wonderful days in Oxford with Lois, and I have come to appreciate how wonderful it is to have colleagues who are not only smart, but most amiable and generous. All of you who know Lois realize that she is that rare individual who makes everyone feel comfortable and has an extraordinary intelligence and grace, as well as a highly developed generosity of spirit and gracious hospitality. 
But, on to her science. Lois graduated with a degree in chemistry from the UBC in Canada (Eh?). Being a masochist, she moved south to obtain a PhD in chemistry from Cal Tech. She relates that this was a real eye opener for her, but I suspect it was more of an eye opener for the “geeks” on campus at that time, since she was probably the first woman whom many of the Cal Tech graduate students had ever interacted with. 
Completing her degree on understanding the mechanism of lysozyme, Lois moved on to a more esoteric area: clinical medicine. She journeyed to the east coast to obtain her medical degree from BU School of Medicine and then went on to do her residency at MEEI. After suffering through her residency she completed a fellowship in pediatric ophthalmology at Children’s and then became an instructor at Harvard. Shortly after starting her own laboratory, Lois was engulfed by the excitement characteristic of the early days of investigating angiogenesis; VPF had been renamed VEGF (vascular endothelial growth factor), the cDNA cloned, the molecule characterized, and antagonists developed. As a clinically trained scientist, Lois recognized the need for a physiologically relevant model of pathologic angiogenesis that might share some of the characteristics of ROP, one of her key clinical interests. This led to her first seminal contribution to our field, the development of the mouse model of retinopathy. In 1994 she published a description of this model based on the principals of hypoxia-induced retinopathy. Its widespread application to the study of retinal vascular disease is a testament to its relevance and utility in ophthalmic (and other) vascular biology. This mouse model of retinopathy, coupled with the availability of different transgenic mice, is now widely used for elucidating basic mechanisms of diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration, the major causes of blindness in all age groups. The model has facilitated substantial progress in our understanding of the disease process and has allowed testing of new drugs to prevent and treat these diseases. 
With a good animal model in hand, she was now in a position to test hypotheses concerning the potential role of VEGF in experiment angiogenesis under normal and hypoxic conditions. She showed that inhibition of the VEGF pathway could inhibit changes similar to those observed in human ischemic retinopathies and thus was the first to define in the retina an association between ischemia-induced retinopathy and VEGF. She then went on to demonstrate that VEGF is necessary for ischemia-induced proliferative retinopathy by blocking VEGF in the mouse retina using soluble VEGF receptors and antisense oligonucleotides. Therapies based on these discoveries are now in clinical use and additional trials for age-related macular degeneration and diabetic retinopathy continue to provide hope for individuals suffering from these blinding disorders. 
Her next accomplishment was to define a role for growth hormone (GH) and insulin-like growth factor (IGF) in retinopathy. It had been long suspected that a pituitary hormone was involved in diabetic retinopathy, since patients with loss of the pituitary gland had regression of disease. But the specific involvement of growth hormone was neither proven nor understood. Dr. Smith, in another seminal paper published in Science in 1997, conclusively demonstrated that growth hormone, through IGF-1-mediated pathways, represents another pathway that can regulate proliferative retinopathy. She then went on to demonstrate, in an article published in Nature Medicine, that there is a functional interrelationship between VEGF and IGF-1 and that it correlates with changes observed in clinical ROP. This body of work has identified two separate pathways, VEGF and GH/IGF-1, as playing critical roles in regulating proliferative retinopathy. More recently, she has extended these laboratory observations into the clinics by demonstrating that phase I of ROP (associated with loss of vessels) correlates with IGF-1 deficiency, suggesting that IGF-1 replacement may prevent the disease. This deficiency also correlated with brain disease, suggesting that there are global consequences to loss of IGF-1 after birth. In collaboration with a group in Sweden, she is evaluating the use of IGF-1 to prevent ROP and the brain disease of prematurity, based on her ground-breaking work on IGF-1 in retinopathy. 
Lois, over the past 20 years, has consistently made outstanding contributions in all areas of ophthalmology; basic science, translational research, teaching, and clinical care. She has taught a generation of residents and fellows in pediatric ophthalmology. She is frequently sought for invited lectures and visiting professorships to teach medical students and residents as well as to educate clinicians and scientists world wide. She is a highly regarded clinical pediatric ophthalmologist caring for young children with eye diseases in a very active medical/surgical practice at Children’s Hospital, Boston. After a busy day that would exhaust even the most energetic person, she comes home to cook dinner for her husband David and tracks down Alexandra and Colin. She has been recognized for her remarkable professional record by receiving the Bressler Prize for Vision Science, the Alcon Research Institute Award, and the Don Gass Memorial Lecture Award from the MacTel Foundation. Most important, the high regard with which she is held by her peers is reflected in the her public service activities; the Advisory Council of the National Eye Institute, numerous NIH review and advisory committees and the scientific boards of The V. Kann Rassmussen Foundation, the Bressler Foundation, and The Lowy Medical Research Institute’s MacTel Foundation. 
Dr. Smith is well respected and highly regarded in the laboratory, clinic, classroom, and home. She is the quintessential example of the accomplished clinician scientist who has not only made seminal contributions to her chosen scientific and clinical fields, but is also a compassionate, extraordinarily talented pediatric ophthalmologist. The 2008 ARVO Friedenwald Award is an appropriate recognition of her remarkable accomplishments. 

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