John B. Fenn dies at 93; shared Nobel Prize in chemistry

Chemist John B. Fenn, who shared the 2002 Nobel Prize in chemistry for work that made possible the rapid analysis of the structure of proteins and other biomolecules through mass spectrometry, died Friday in Richmond, Va. He was 93 and died of complications from a fall suffered Oct. 12.

“The possibility of analyzing proteins in detail has led to increased understanding of the processes of life,” the Swedish Royal Academy of Sciences said in its citation for the 2002 prize. “John Fenn was one of those scientists whose discovery opened up an entirely new field to investigation; in his case, proteomics — the hallmark science of the post-genomic era,” Thomas Huff, vice provost of Virginia Commonwealth University, said in a statement. Fenn’s work made it possible to identify proteins in seconds or minutes as opposed to days or weeks, greatly speeding biological research.

Mass spectrometry is a tool that has been widely used in chemistry laboratories throughout the world for rapidly determining the identities of small molecules. By vaporizing a molecule, giving it an electrical charge and subjecting it to an electromagnetic field, researchers can determine its mass-to-charge ratio. By analyzing both that and the mass/charge ratios of various breakdown products, it is possible to determine the original molecule’s identity.

But the procedure would not work for proteins and other biological molecules because they tended to clump together, making it impossible to vaporize them.

Fenn’s approach was conceptually quite simple. He sprayed a solution of the sample into the mass spectrometer while simultaneously applying an electrical field to charge the droplets. As the water evaporated from the droplets in the vacuum of the instrument, freely hovering charged molecules remained behind. The technique came to be called electrospray ionization, and the mass/charge ratio became small enough that the molecules could be analyzed successfully in the mass spectrometer.

The 2002 Nobel Prize in chemistry was divided among three researchers. Fenn and Koichi Tanaka of Japan, who developed an alternative way of getting large biomolecules into a mass spectrometer, shared half the prize. Kurt Wuthrich of Switzerland received half the prize for using nuclear magnetic resonance for determining the structure of biomolecules.

In 1988, Fenn published two papers: one showing that his technique would work with molecules of polyethylene glycol and a second showing that it would work on proteins.

In an interview in 2002, Fenn said, “We learned to make elephants fly…. There’s an awful lot of luck in this. In fact, there’s an awful lot of luck in science.”

Fenn was then on the faculty at Yale University but was not happy with the school. Yale at the time required a 70/30 split of profits from patents, with the university getting the bulk, and he thought that was unfair. Moreover, he had recently reached mandatory retirement age and could not take on new graduate students and his research was otherwise impaired. He thus chose to patent electrospray ionization in his own name and licensed the patent to a company he co-founded.

Yale ultimately sued, and in 2005 a federal judge found Fenn guilty of “civil theft” and ordered him to pay Yale more than $1 million.

John Bennett Fenn was born June 15, 1917 in New York City. During the Depression, his father lost his job in New Jersey but obtained a new one at the Berea Academy in Berea, Ky. Young Fenn attended the academy, then received his bachelor’s degree in chemistry from Berea College in 1937 and a doctorate in 1940 from Yale.

He found academic life very boring, however, and determined to go into industry. During the war, he worked for the Monsanto chemical company in Anniston, Ala., and Sharples Chemicals Inc. in Wyandotte, Mich. After the war, he co-founded Experiment Inc., an R&D company in Richmond, Va., developing a ramjet propulsion system. From 1959 to 1967 he was at Princeton University, where he worked on the Navy’s Project SQUID, which developed a superconducting quantum interference device. Many details of that project are still secret.

After his retirement from Yale, he joined the staff of Virginia Commonwealth University, where he was an active researcher until very recently.

Fenn’s first wife, the former Margaret Wilson, died in an automobile accident in New Zealand, where the couple were traveling in 1992. He is survived by his second wife, Frederica Mullen; a son, John Jr. of West Hills; two daughters, Marianne Steinberg of New York and Barbara Reif of Branford, Conn.; two stepdaughters; seven grandchildren; seven great-grandchildren; three stepgrandchildren; and seven stepgrandchildren.

thomas.maugh@latimes.com