Six degrees of science

Little did Andy Johnson know that when he started working in Ronald Schwartz’s lab at the National Institutes of Health, he was entering a race against several other investigators all working independently (and secretly) on the same protein.

Johnson came to the lab with a mouse model with an apparent immune defect. Using T-cell proliferation assays, Schwartz’s team traced the problem back to the thymus. With the help of Johnson’s co-mentor, Richard Cornall at the University of Oxford, they found that the mouse was unable to express a thymic protein that appeared critical to T-cell development. Find this mysterious protein’s function, and Johnson would have a nice publication for his thesis defense.

But Johnson didn’t realize that just a few buildings away, Paul Love’s group at the NIH had been studying the same protein for several years, using different approaches. While Johnson was working on characterizing...

Like a bad romantic comedy, Schwartz and Love continued to miss chance opportunities to learn about each other’s work for several years, until finally a mutual colleague made the introductions.

Johnson and Schwartz had recruited the help of a skilled NIH bioinformaticist, L. Aravind, to see if he could discover a chemical motif that might suggest the protein’s function. Not long after, Love decided he also wanted to answer the same question, and went to the NIH’s expert: Aravind. Although the two groups had given the protein a different name, it didn’t take long for Aravind to realize he was looking at the same protein. He informed both investigators. Love remembers thinking, “Gee, isn’t this quirky!” (While he couldn’t figure out its function, Aravind did see that the protein had a cysteine domain conserved throughout almost all animal lineages, suggesting it played a role outside adaptive immunology, since not all animals have T cells.)

Shortly thereafter, Love and Schwartz met and cagily discussed their projects. It was clear that they had come at the problem from different angles. Schwartz’s group was focused on microarray searches for homologues of the protein’s key chemical motif that Aravind investigated, while Love had done more of the typical cellular assays used in developmental biology to find the proteins or factors that would rescue the knocked-out phenotype. It was also clear that neither group had quite nailed it. “We were both frustrated because we couldn’t find function,” recalls Love. They agreed to continue to work independently until one group was ready to publish.

Several groups, all working independently (and secretly) on the same protein.

Then, shortly before Love presented his results at the American Association for Immunologists 2009 annual meeting in Seattle, he got a call from Nick Gascoigne at Scripps Research Institute in LaJolla, who had read the title for Love’s talk on the meeting website. Gascoigne said he had been working on the same protein for 10 years. “Paul called me and said, ‘you aren’t going to believe this, there’s someone else and he’s been working on this longer than we have!’,” says Schwartz. Gascoigne had joined forces with another researcher, Oreste Acuto, based at the University of Oxford, when both discovered they were working on the same project after sharing a cab to the airport. Gascoigne was aware of at least two other groups who were getting ready to publish. “I didn’t think it was statistically possible,” says Love.

Love and Schwartz (with Cornall) decided that they were far enough along in their research and manuscript preparation to each publish a paper describing the protein, and told Gascoigne that they planned to submit their articles to Nature Immunology. Gascoigne and Acuto submitted the same week.

The journal accepted all three papers. Then there was only one thing left to discuss: the protein’s name. Each group was quite attached to the name each had chosen for the protein. After a round of vetoes, they selected “Themis,” which contains an acronym for “thymocyte-expressed-molecule.” Themis was also the name of a Titan in Greek mythology who weighed the moral fates of man—a fitting choice, since the protein was important in deciding the fate of the T cell during development (Nat Immunol, 10:831–56, 2009).

It may seem strange to have three papers published on the same topic, but it’s “not as uncommon as you may think,” says Jamie Wilson, an editor at Nature Immunology, in an email. What made the protein rack up so many researchers was its clear importance in development and its elusive function, which remains unsolved. “It was so surprising that so many people were able to keep it secret,” says Gascoigne.

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