Bridging the gaps from discovery to medicine

In biomedical research, the gaps between basic science, translational research and medical progress are often significant. Historically, the path from scientific discovery to clinical implementation has been long and circuitous.

Basic science is vital for expanding knowledge and understanding in ways that are based on open exploration, not effort toward a defined goal. Its contributions are frequently unexpected and may be difficult to track, but they are profound. Nonetheless, there is a growing emphasis on more applied, translational research, which includes the formation of the new National Center for Advancing Translational Research at the NIH. The trend is leading to some important debates, and it may put pressure on the research community to streamline the road from discovery to medicine.

The Jackson Laboratory's history provides an excellent example of how basic research can lead, eventually, to clinical progress. Its future, however, provides an important opportunity to establish a better path to progress and accelerate the translation of its discoveries to improve patient care.

A surgeon and a scientist

The recent death of Joseph Murray at age 93 and accompanying media coverage brought to mind an important medical breakthrough that illustrates both success and disjunction in the historical biomedical research continuum.

Murray, who shared the 1990 Nobel Prize for Physiology or Medicine, was a pioneering surgeon who performed the first successful kidney transplant in 1954, between identical twins. It was a decade later, however, in the mid-1960s, that organ transplants began to help more than a select few patients. It took that long for Dr. Murray and his collaborators to overcome the body's immune response, which leads to transplant rejection. Only then was it possible for an organ to be transplanted into a recipient from an unrelated donor.

In the widespread coverage of his death, there was a notable absence. What basic research led to the immunosuppressive drugs Murray needed for successful transplants? Who did the work?

Looming large in the answers to both questions is George Snell, an immunologist who worked at The Jackson Laboratory for decades, starting in 1935. Snell is credited with essentially creating a field of study, immunogenetics. He also identified the genes that comprise the major histocompatibility complex (MHC), which mediates the immune response to foreign proteins, which of course are present on a massive scale in transplanted tissue.

Snell worked with mice and transplanted tumor tissue, and he created many of what are known as congenic strains of mice. These mice, which involve crossing many generations in a specific way to study a specific trait (in this case immune response), took years to establish, and many strains remain important to research today. The difficult, exacting work paid off, however, and Snell's research into the genetic basis of immune response to foreign tissue revealed a common mechanism between mice and humans. His contributions to science and medicine led to his receiving the 1980 Nobel Prize in Physiology or Medicine, which he shared with two fellow immunology pioneers.

Snell did much of his most important work before Murray performed his first kidney transplant between the twins. The gulf between basic science and medicine was large, however, and the application of the knowledge—in this case through Murray's skilled surgeon's hands—lagged far behind. What he knew about Snell's contributions one can only speculate, but it's probable that the development of Imuran, the immunosuppressive drug tailored by Murray for transplants, would have been greatly accelerated if the two had been in contact. Unfortunately, however, Snell and Murray were and remain unlinked, and the recent passing of the man who applied the knowledge was feted with no mention of those before him who teased out the workings of the immune system.

Establishing a continuum

The Murray and Snell story illustrates a disconnect between basic science and applied medicine that is longstanding and usually slows the movement of important discoveries to practical clinical use. There are other valid factors at play, of course, with ensuring patient safety topping the list. The pace of clinical progress also depends on the different perspectives, goals, work styles, and even locations of basic and translational research. The handoff points are rarely clear.

The disconnect persists, even in genomics. Moving genomics research into the clinic is far from easy, and much remains in flux. It is, as Lisa Lee, executive director of the Presidential Commission for the Study of Bioethical Issues, says, "a period of intense transition with respect to integrating whole-genome sequencing into clinical care." During this time of transition, it is important to find better ways to integrate findings from basic genome research data with human patient care.

The Jackson Laboratory for Genomic Medicine in Connecticut presents a tremendous opportunity in this area. There will be a natural continuum between the basic mammalian genetics/genomics findings for which the Laboratory is known and clinical progress in Connecticut. It's an exciting time of "intense transition" for the genomic medicine field as a whole, but could it also be a time of transition away from the twisty old basic-to-translational-research-to-patient benefit pathway? JAX Genomic Medicine may well provide an important new model for accelerating clinical translation.

Legacy of genetic discovery

Legacy of genetic discovery

Eight decades of genetics research at The Jackson Laboratory has improved countless lives.
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JAX Genomic Medicine

Researchers at our new Connecticut institute investigate how each piece of the genome contributes to health and disease.

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