Earlier this year, the international scientific and academic community lost a respected member and gifted vascular biologist with the death of Timothy Scott-Burden, PhD, on 19 April 2000 after a courageous, year-long battle with cancer. At the time of his death, Dr. Scott-Burden was 57 years old. Apparently, the predisposition to the disease that claimed him ran strongly in Dr. Scott-Burden's family, for he was preceded in death by both his father and his only sister from the same disease. Those of us who worked with Tim at the Texas Heart Institute have also lost a beloved colleague and family member.
Timothy Scott Burden was born in Oxford, England, on 4 April 1943, to Marjorie and Leslie Burden. In the 1970s, Tim changed his legal name to the hyphenated version that he used during his remaining professional career. This was done to honor his mother's familial roots, which were in a Scottish clan that had no male offspring to carry on the family name.
Tim's father, who was in the British military at the time of Tim's birth, had been stationed in North Africa. After spending a few years in Italy at the close of World War II, Mr. Burden, led by his fondness for Africa, moved his family to Navasha, Kenya. He wanted Tim to become a military man and follow in his footsteps: although young Timothy had received no formal schooling before the age of 11, he was sent to boarding school in the UK at the all-boys academy of St. Edward's in Oxford, where this type of training could be encouraged.
Upon graduating from the British primary and secondary education system, Tim returned to Africa and helped his father run a safari company from the family home. However, Tim's fondness for athletic competition, which had been fostered during his boarding school days, led him away from the family business. He enrolled in the agricultural studies program of Natal University in South Africa, where he participated in organized sports and coached several teams, in addition to receiving a BSc degree in 1966.
After graduating from Natal, Tim accepted a teaching position at the University of Rhodesia and soon enrolled in the graduate program there. Although Tim's PhD degree was granted in 1971 through King's College at the University of London (England), he performed his graduate studies in the lab of Dr. Arthur Hawtry in the Department of Biochemistry at University College of Rhodesia in Salisbury, Rhodesia (now Zimbabwe). As part of his doctoral studies in the field of biochemistry, Tim concentrated his efforts on the study of protein synthesis and the process of eukaryotic ribosome assembly and attachment to the endoplasmic reticulum. Together, he and Dr. Hawtry delineated a technique by which they could extract purified microsomal membranes from rat livers and study the reconstitution of membranes and ribosomes in an in vitro model that was elegant for the day.
After spending 2 years as a junior faculty member at the University of Rhodesia following his doctoral training, Dr. Scott-Burden was invited to move to Canada to work with Dr. David Canvin. As a postdoctoral fellow in Dr. Canvin's lab in the Department of Biology at Queen's University in Kingston, Ontario, Tim used his training in classical biochemistry to help develop more effective methods of separating various plant cell organelles from each other in order to better define the exact localization in plant cells where certain crucial metabolic processes take place.
Tim returned in 1974 to the University of Rhodesia and resumed his teaching duties in the Department of Biochemistry. Political unrest in Rhodesia grew worse during this time as several warring factions continued to fight for political control of the government; and the power balance within Rhodesia began to shift as some neighboring countries gained their independence. Soon, Tim found himself unwillingly conscripted into the Rhodesian Army. A brief and worrisome indoctrination into army life prompted Tim to move to neighboring South Africa in 1976.
For the next 10 years, Dr. Scott-Burden held a series of professional and tenured academic appointments at various hospitals, medical schools, and universities in South Africa. During this time, first as a Principal Professional Officer at Stellenbosch University Medical School, and later as a Chief Research Officer at the MRC Muscle Research Unit of the University of Cape Town, Tim became interested in the biology of vascular cells. He spent much of his time in South Africa studying the biochemical properties of the extracellular matrix. This interest was fostered by Tim's association with his colleagues at the time, notably Dr. Wieland Gevers, and it became one of Tim's enduring research interests.
While in South Africa, Tim also worked closely with his dear friend from graduate school days, Dr. Peter A. Jones, whom Tim had mentored as a graduate student at the University of Rhodesia, and who has since gone on to become director of the Norris Comprehensive Cancer Center at the University of Southern California. In the course of their studies, they developed a method of producing large amounts of extracellular matrix from cultured smooth muscle cells. This seminal work laid the foundation for the later development of such useful tissue-culture substratum material as Matrigel® and similar products, which are commercially available and commonly used in many laboratories around the world today.
Later, as a Senior Lecturer in the Department of Medical Biochemistry at the University of Cape Town, Dr. Scott-Burden would be instrumental in developing and teaching a series of courses that made advanced training in pharmacology and medicinal biochemistry available to many students from the local South African population who were denied entry into the state university's medical education program because of racial quotas. Tim was always proud of the caliber of students that his program graduated, especially when they would return to their respective townships and perform the work of caring for sick and injured patients under the substandard conditions often encountered in such places.
Spending 10 years in a country where he was unable to openly oppose the government's official apartheid policies, however, took its toll. Therefore, after a quick but limited search of scientific research positions available to him elsewhere in the world, Tim left most of what he owned and moved in 1986 with his wife Patricia to University Hospital in Basel, Switzerland. Tim and Patricia had married only recently, after meeting while Tim was on sabbatical at USC in Peter Jones's lab.
In Switzerland, Tim worked as a principal investigator in the Hypertension Laboratory of the Department of Research, headed by Dr. Fritz Bühler. During his tenure in Switzerland, and with the assistance of his colleagues, Tim initiated a brief but highly productive period of research into the growth regulation of vascular smooth muscle cells. Most of his research effort during this period was concentrated on the effects of various growth factors, heparinoids, and the extracellular matrix deposited by such cells, on the growth and inhibition of vascular cells isolated from animal models of normal and hypertensive subjects. These efforts yielded many insights into the cellular basis for the gross pathology long manifested to physicians and vascular biologists alike as visible structural changes within the vessel wall in the course of hypertension and atherosclerosis. In addition to these studies, and his early efforts to learn German at night school, Tim also found the time to help oversee the scientific studies that Patricia had initiated as part of her PhD thesis work at the university.
Dr. Scott-Burden's stay in Basel was short, due to Switzerland's stringent immigration and visa rules. This situation paved the way for him to come to the United States in the early 1990s, when he took a position as an assistant professor at Baylor College of Medicine in Houston. There had been brief visits to the States for various scientific meetings and short periods of work with Dr. Jones at USC, but this was the first time that his scientific research had been based at a U.S. institution. Throughout his life, however, Tim retained his British citizenship.
At Baylor, Tim worked in close collaboration with Dr. Paul Vanhoutte, director of the Center for Experimental Therapeutics, who had recruited him because of his expertise in the field of vascular cell growth regulation. Together, and with several of their Baylor colleagues, Tim and Dr. Vanhoutte made substantial contributions to the scientific literature and to our current understanding of the regulation of smooth muscle cell growth in the blood vessel wall by the endothelium-derived relaxing factor, nitric oxide (NO). Their studies helped to provide a biochemical basis for growth control of the normally “quiescent” smooth muscle cell population in the normal vessel wall and helped to explain the de-differentiation of such medial smooth muscle cells to the “synthetic” or proliferative state often encountered in areas of vessel where the endothelial function is impaired, as in cases of hypertension and atherosclerosis.
In 1993, Dr. Scott-Burden moved across the street from Baylor College of Medicine to accept the joint positions of Senior Scientist at the Texas Heart Institute and Associate Professor of Cardiology at the University of Texas Medical School at Houston. At THI, he helped establish the Department of Vascular Cell Biology, the Institute's first basic cell biology research-oriented laboratory devoted to studying the role of vascular cells in cardiovascular disease. Here, Tim combined his scientific interests in smooth muscle cell biology, extracellular matrix production, and nitric oxide chemistry into developing an enhanced biocompatible blood-contacting surface for cardiovascular prostheses.
Applying the knowledge he had gained in his 25 years of culturing and working with smooth muscle cells, Tim set about to create a tissue-engineered surface for left ventricular assist devices (LVADs) that could one day further improve the biocompatibility of such devices for long-term use. As part of this effort, he showed that autologous vascular smooth muscle cells obtained from animal models of patients could be genetically engineered to be pseudoendothelial in nature. These cells could be expanded in culture, and then be used to line the blood-contacting surfaces of LVADs, leading to the inhibition of platelet deposition on such surfaces when the LVAD was subsequently re-implanted in the same animal. Such tissue-engineered linings are expected to decrease the likelihood of acute postimplantation thrombocytopenia and chronic complications such as thromboembolic microevents that could lead to stroke. At the time of his death, Tim was planning to extend the use of genetically engineered smooth muscle cells beyond LVADs to other devices, such as vascular stents.
In addition to writing or co-writing over 80 peerreviewed scientific publications and 10 invited reviews or book chapters, Dr. Scott-Burden was a member of many national and international professional organizations and was serving on the editorial boards of 3 scientific journals at the time of his death (Journal of Vascular Research, Journal of Cardiovascular Pharmacology, and Circulation). During the course of his professional career, he directed the graduate studies of at least 13 different masters- and doctoral-level degree candidates, and he served on numerous scientific review panels and academic committees at the various institutions with which he was affiliated.
Tim will be remembered by his students as a consummate teacher and deeply caring mentor. His compassion for others, his subtle wit, and his ability to enthrall listeners with stories of his past, as well as his humor and magnanimous generosity, will be profoundly missed by those who were fortunate enough to have known him.
I will remember Tim as a dedicated and hardworking scientist whose dedication to the pursuit of knowledge about the biological processes that he had chosen to study was manifested in the logical progression of his scientific thought, his rigorous review of scientific data, and the exactness of his attention to experimental detail in his daily routine. Most of all, I will remember a kind and dear friend, one with whom I shared a deep passion for “hands on,” bench-level science. Those of us who knew Tim can count ourselves the richer for the experience.
Tim is survived by his beloved wife of 14 years, Patricia, and his 3 cherished Rhodesian Ridgeback dogs, fittingly named in honor of his beloved homeland of Africa—Mpani, Mkosa, and Nyanga.