Life and Death Decisions by Cells, Investigated Under Life-threatening Conditions During WWII

I am using this posting to call attention to a moving and important blog about Nobel Laureate Rita Levi-Montalcini's life and research (A Tale of Centenarians, posted February 25, 2013).

My fellow student from the mid-1960s at the Cambridge University Genetics Department, Claudio Scazzocchio, originally wrote the article in Spanish for the Montevideo, Uruguay, magazine Brecha, where it was published January 25. Moselio Schaechter, a retired Tufts microbiologist, posted the story in English on his American Society of Microbiology blog page.

Like Claudio, Elio was born in Italy, but spent much of his youth in Ecuador because of WWII. Claudio had grown up in Uruguay for similar reasons. Among other things, Claudio's blog tells us about the toughness, resilience and dedication to science of Jewish biologists in Italy during the war. Several were tough enough to become centenarians.

The scientific content of Claudio's piece is just as fascinating as its human and humane interest. It describes how Levi-Montalcini discovered the first peptide signaling molecule, Nerve Growth Factor (NGF). Her initial research on NGF was done while in hiding from Mussolini's Fascist government.

Viktor Hamburger, also a WWII refugee, had published a paper on spinal nerve depletion in chicken embryos with injured wing primordia. Clandestinely, Levi-Montalcini and her teacher, Giuseppe Levi, repeated and perfected the experiments. Hamburger had proposed that the peripheral wing tissue stimulated the development of nerves from the spinal column.

In contrast to Hamburger's interpretation, Levi-Montalcini and Levi proposed that the damaged tissue acted to block the death of nerve cell precursors in the developing spinal column. They may well have been the first to suggest the now well-documented phenomenon of programmed cell death (apoptosis) in animal development. It was certainly the first time anyone suggested that one kind of cell could signal to another kind of cell what its survival fate should be.

After the war, Hamburger invited Levi-Montalcini to join him and work together at Washington University in St. Louis. There they confirmed her interpretation. Together with Stanley Cohen of Vanderbilt University, they isolated NGF and showed how it prevented neuronal death by transfer from peripheral tissue cells to developing nerve cell axons.

NGF was the vanguard of a host of peptide growth and death factors that influence the outcome of programmed cell death decisions. The ability of cells to make signal-based life and death choices is not just basic to animal development. It turns out to be a very fundamental aspect of cell existence, extending to single-celled eukaryotes and even to bacteria.

Although we now have a great deal of information about the complex biochemical events involved in executing programmed cell death, the nature of the existential decision-making process remains mysterious. How cells make these signal-influenced choices is a major focus of contemporary, 21st Century research. The truly heroic story of Rita Levi-Montalcini illustrates how dedicated and inspired scientists can address advanced questions in the most difficult of circumstances.