Cells as "Programmable Messengers," 1981-1994

As a direct result of Martin Rodbell's discovery of the G-proteins, scientists have adopted signal transduction as the preeminent paradigm for cellular communication. "Since those discoveries more than 20 [years] ago," wrote Rodbell in 1991, "transduction has become a key concept for explaining the actions of hormones and drugs on membrane processes."

Beginning in the late 1980s, Rodbell became more philosophical about the G-proteins and their potential in biomedical research, especially after he saw a new generation of scientists applying his discoveries in their laboratory experiments. In the 1970s, for example, Alfred Gilman of the University of Texas Southwestern Medical Center refined and expanded Rodbell's work when he isolated and identified the biochemical structure of the G-proteins. During that same period, the Israeli molecular biochemist Zvi Selinger demonstrated that diarrhea associated with cholera was the consequence of G-protein transducers that could not be "turned off" once activated. Perhaps, Rodbell envisioned, scientists might be able to re-engineer transducers and thus normalize cellular metabolism. Cells could be modified at the transducer level, which might open up an extraordinary range of scientific and biomedical possibilities.

Until his retirement in 1994, Rodbell continued to describe G-proteins in the language of computer science, further exploring through metaphor the idea of working cells as "programmable messengers," a phrase first suggested to him by Danish physiologist Torben Clausen. As Rodbell asserted in 1992, "The living cell is in essence a communicating device, built primarily of organic matter rather than the silicon of today's computers. Pliable in structure with multiple types of storage forms that have infinite possibilities for change and adaptation, the natural process evolved essentially passively into states of complexity that no human could have imagined." The concept of G-proteins as "programmable messengers" has led to advanced research in signal transduction, especially in contemporary disciplines such as epidemiology, neuropharmacology, oncology, and gene therapy.