By JOSIAH TAKANG (@jtakang22_7)
Photo credit goes to the LA Times.
On a typically frigid October morning in the Norwegian capital of Oslo, the Nobel Prize in Physiology or Medicine was awarded to Japanese biologist Yoshinori Ohsumi.
His groundbreaking work on the basic cell process called autophagy, which literally means “self-eating,” was enough for the Nobel committee to make that phone call every scientist dreams of.
Autophagy, a mechanism discovered in the 1960s by Canadian-American cell biologist Keith Porter, allows cells to recycle their contents rather than simply dispose of proteins and other molecules they have already used. The process helps cells destroy invading bacteria and viruses, eliminate damaged proteins and respond to stresses such as starvation. Disruptions in autophagy have been linked to diseases including Parkinson’s, cancer and type 2 diabetes.
Ohsumi pointed out the key genes that drive autophagy and demonstrated that the process is controlled by an avalanche of proteins. His landmark experiments actually were done in the mid-1990s, making this another Nobel in which the prize committee has reached back decades for work to honor. The prize money totals ¥95 million Japanese yen, or about $936,000, a pretty penny for anyone, let alone a scientist.
"Ohsumi’s discoveries led to a new paradigm in our understanding of how the cell recycles its content,” said the Nobel committee In its official announcement. “His discoveries opened the path to understanding the fundamental importance of autophagy in many physiological processes, such as in the adaptation to starvation or response to infection [and] … conditions including cancer and neurological disease.”
There is no dispute that autophagy is a key cellular process, deserving of a Nobel.
But the committee’s decision to award the prize to Ohsumi as an individual may cause at least a modicum of discontent in the scientific community.
In 2013, Reuters made predictions as to who would receive the honor for the autophagy process, and came up with three candidates:Ohsumi, of the Tokyo Institute of Technology; Daniel J. Klionsky, of the University of Michigan; and fellow Japanese Noboru Mizushima, of the University of Tokyo.
Ohsumi’s work builds upon the 1950s discovery that vesicles ensconced inside cells — called autophagosomes — would engulf burnt-out structures such as mitochondria or globs of cytoplasm and convey them to what had been considered the cell’s "garbage disposal,” a structure called the lysosome. In 1988, Ohsumi began studying autophagy in brewer’s yeast, a one-celled organism that is a favorite of researchers because of its fairly simple genetic structure.
He discovered that autophagy seemed to occur when the yeast was running out of nutrients: The yeast cells were essentially cannibalizing their own parts and recycling them to stay alive, allowing them to survive a month or more with little outside sustenance.
He also discovered that some mutant yeast were actually garbage at autophagy and died within only days of generation. He identified the mutant genes, from a family called Atg’s, in 1992; as he told Thomson Reuters, “identification of these genes evoked a revolutionary change in the research field of autophagy.”
Later, mutant mice that were deficient in autophagy were created in the Ohsumi lab. That helped reveal the key role autophagy plays in normal development: In very early embryos, for instance, autophagy recycles maternal proteins into its own. And when cells are deprived of nutrition, they cannibalize themselves in order to survive.
Mice whose mutations keep them from autophagy, Ohsumi and others also discovered, develop way more tumors than normal mice. Additionally, in Parkinson’s disease, cells fail to clear out and recycle defective mitochondria.
That process — autophagy of mitochondria — was the focus of the aforementioned Daniel Klionsky, to the point where in 2009, Science Watchers called him one of the “leaders of this autophagy revolution.”
Under the terms of Alfred Nobel’s will, up to three laureates can be named for each of the science prizes. Unfortunately for Klionsky, the committee went with Ohsumi — and Ohsumi alone.
According to David Pendlebury of Thomson Reuters, who helps make Nobel forecasts, Ohsumi was "the pioneer and senior figure, even if Mizushima extended the work in important ways, as did Klionsky to a lesser degree in confirming [their] discoveries.
“The Thomson Reuters selection is meant to recognize the important contributions of individuals even if they are not selected in the end for the Nobel Prize, and this is a good example,” Pendlebury said.