This year’s honorees tell us how far we have come in the cell death field. Both started their careers studying cell death, but it has always been obvious that, even in the narrowest definition that cell death could be programmed, the program had to be initiated somehow; even if cell death proved to be a clock ticking down from some starting point, that starting point had to be defined, and it was extremely unlikely that the point of initiation would be the last telophase or other step in the life cycle of a cell. Even in Caenorhabditis, in which some cells are born only to die before differentiating into a neuron or other identifiable cell type, one had to assume that the death would result from some sort of internal metabolic failure. For metamorphosis, part of the definition of programming included recognition that cell death was triggered in amphibia by hormones and in insects by hormones and neural signals.
Gabriel Nuñez has followed that logic to the extent that they now can be considered to work more on cell signaling. Gabriel writes, in submitting his abstract, “No cell death in the abstract!!”. Thus, while there are many secrets still to be understood concerning the internal workings of how cells die, by apoptosis, necroptosis, pyroptosis, ferroptosis, or other means, we are now also focused on what extracellular and intracellular signals determine the point at which a cell turns down an increasingly irreversible path toward death.
Our first awardee, Gabriel Nuñez, comes to us from a large family in Seville, Spain and is a man of very broad interests, including moviemaking and cooking paella for charities. Accepting an invitation from Peter Stastny to work in a rheumatology laboratory in Texas, he sought a career that would combine clinical medicine and research, and so he next moved to Washington University in St. Louis where, working with Stanley Korsmeyer, they identified BCL2 as an important gene in B-cell lymphoma. Moving to the University of Michigan, he met Craig Thompson. Their collaboration led to exploration of how Apaf-1 activates caspase-9; and shortly thereafter along with his postdoctoral fellow Naohiro Inohara Gabriel published the structure of an Apaf-1 homolog, Nod1.
Nod1, however, is not a regulator of apoptosis. A mutation of Nod1—Nod2—turned out to be a sensor of bacteria and highly linked to Crohn’s Disease, an inflammatory disease of the intestine. This led to exploration of the role of the intestinal biome in establishing intestinal homeostasis or, when the microbial balance is deranged, diseases such as Crohn’s disease.
And so, he has pursued a career moving from topic to topic, identifying at each step something important and interesting. As he notes, “I think you have to be passionate about it…” He also has said, “So I think this is one of the perks, if you can call it that way, to be a scientist, that you get invited to give talks. You can also spend time all over the world and talk about science, but also talk about other things, human activity in those countries. And I think that sort of perspective makes you, I think, a better scientist and also a better human being. That’s my view.”
I would most certainly and most enthusiastically agree. Perhaps we will even get to taste his paella one day. In the meantime, we have the privilege of hearing his thoughts on his current interests, “Host-Microbiota Interactions in Health and Disease”.
For his work, he has rightly been awarded many prizes. He is a member of the U.S. National Academy of Medicine and is the Paul de Kruif Endowed Professor of Pathology at the University of Michigan. (Paul de Kruif was fired from a post at Rockefeller for describing the practice of medicine as “medical Ga-Ga-ism”, wherein doctors provided only a “mélange of religious ritual, more or less accurate folk-lore, and commercial cunning”. He went on to write Microbe Hunters, still worth reading today. He would have been proud to see Gabriel in a post bearing his name. We are pleased to add another honor, the ICDS award, to his collection.