Daily Archives: March 7, 2017

Thomas Starzl (1926-2017) – The man who saved countless humans using animal research

Dr. Starzl, a pioneer in the field of surgery and the “father” of organ transplantation in humans, was the first surgeon to perform a human liver transplant.

The liver is a remarkable organ, although more specifically it is a gland. It is essential to the functioning of the human body and is involved in metabolism, the production of hormones, detoxification — to name a few of its many functions. Unlike some of the other organs in the human body — of which we have two, such as the kidneys — there is no redundancy for the liver. For example, if one kidney fails the other kidney can compensate for the loss of function, and in many cases people with one kidney can live a normal life. In contrast, in cases of liver failure the only way to continue living would be liver transplantation; although in the short term — usually while waiting for a liver transplant — liver dialysis may be used. However, the liver is quite remarkable, and unlike many other organs possesses the capacity to regenerate, even if as much as 50 to 75% of the organ is damaged. Chronic liver disease, lasting more than six months, is debilitating and if not assessed early and treated (where possible) leads to death. It is estimated that over 50 million people are impacted from chronic liver disease.

Dr. Starzl’s work on human organ transplants was based on his earlier fundamental (basic) research in dogs. Unaware then of the potential application to humans, Dr. Starzl was investigating the role of nutrient rich blood and its contribution to liver health. Dr. Starzl formulated this question based on a lecture by Dr. Stuart Welch in 1957, who described an experiment where he had grafted an extra liver into a dog. In this experiment, blood left the grafted liver via the same system as the original liver, while the system bringing blood to the liver was different. Dr. Starzl hypothesized that the reason Dr. Welch’s transplant failed was a consequence of the different blood supply which brought blood to the liver.

Image courtesy of the University of Pittsburgh

In his subsequent investigations, Dr. Starzl developed and refined several liver transplant procedures in dogs — with his first success (survival after the operation) occurring in 1958. Between then and 1963, when the first human liver transplantation occurred, much research was being performed into immunosuppression by Dr. Roy Calne — also in dogs. This research was integral to the organ transplant field. Without understanding immunosuppression, the body would reject the donor organ; rendering the transplant useless. This pioneering work, in conjunction with Dr. Starzl’s own work, led to the first attempt at a human liver transplant in 1963. This first transplant was not successful, with the patient dying during the operation. Subsequent operations also resulted in patient death within a few weeks. However, those deaths provided evidence that the donor liver was able to function in the recipient’s body.

Dr. Starzl continued to refine and update his method, later moving his investigations to pigs — grafts from pigs were better tolerated by the human recipient. Then in 1967, he reopened his program and performed the first successful human liver transplant. Mortality after the procedure decreased over time, and “more than half of the liver-transplant patients who underwent surgery in 1998 were alive ten years later, and in 2009, almost 50,000 Americans carried a transplanted liver” (Lasker Foundation).

In 2012, Dr. Starzl and Roy Calne were honoured with the Lasker Award for their pioneering work in liver transplantation – “an intervention that has restored normal life to thousands of patients with end-stage liver disease”.

Complete liver replacement in the dog. The fact that the recipient was a dog rather than a human is identifiable only by the multi-lobar appearance of the liver. Image from University of Pittsburgh

Dr. Starzl was a brilliant scientist with a prolific career; over 2200 articles, 26 honorary degrees, and thousands of lives helped/saved by his work. We have previously written about this here; discussing him receiving the Lasker award. Similar to that post, we recommend reading about Dr. Starzl and his remarkable life here. We also encourage our readers to reflect upon his work, and the remarkable progress that was made using non-human animals for research. In particular, much of his pioneering work was derived from fundamental research investigating surgical procedures in dogs and his later work, refining the method, involved other non-human animals: pigs and baboons. It is often difficult to estimate the prospective benefit of research performed in non-human animals — but Dr. Starzl’s work is a great example of the potential reach of such research.

Jeremy Bailoo