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Hydrophilicity Analysis of Proteins

While most molecular biologists are familiar with the hydropathic plotting procedure of Kyte and Doolittle, they are less well aware that the Kyte and Doolittle method is nearly identical to the Hopp and Woods hydrophilicity plotting procedure published more than a year earlier.

Furthermore, strong evidence suggests San Diego scientists Kyte and Doolittle obtained the inspiration for their concept via a backdoor peek into Tom's unpublished studies, provided to them by Richard Lerner, Director of the Scripps Institute in La Jolla.

If you're more interested in Tom's long record of hydrophilic/hydrophobic publications, than in the scientific intrigues that surround them, click here for a listing. Otherwise, read on.

While it is unlikely any direct proof exists that Kyte and Doolittle's method was lifted from Tom while he was postdocing in the New York laboratory of Nobel Prize winner Gerald Edelman, the circumstantial evidence is strong, and available in the public domain.

Most notably, a controversy broke out between Lerner and Doolittle, regarding which of the eminent men had truly originated the idea of hydropathic plotting. As was reported in Science Magazine, Lerner insisted that he came up with the idea while strolling in New York's Central Park in May, 1979, and he wrote it on a napkin. He claims he told Doolittle about the idea later, in the course of discussions about influenza virus antigens. Doolittle claims to have thought up the idea in October, 1978. Neither man claims a date as early as Tom's inspiration, in 1975.

However, there is another key fact yet to consider. Richard Lerner was in New York City on that day in 1979 to meet with Tom's boss, Gerald Edelman. Edelman even introduced Lerner and Tom, briefly, in the hallway on a chance meeting. Although there was no discussion of Tom's method at that moment, it seems all too coincidental that Lerner had his postprandial inspiration later on that same day.

It doesn't take a rocket scientist (or even a molecular biologist) to put two and two together. The route from Tom's boss, Edelman, to Lerner, to Doolittle is a very short loop. Why would Edelman give away Tom's unpublished work? Perhaps because he never had any enthusiasm for Tom's efforts, and never supported the development of the idea.

In fact, Tom had originated the idea in his PhD thesis work at Cornell Medical College four years earlier, in 1975, in discussions with his thesis advisor, Kenneth Woods. A primitive version of the method was even described as part of Tom's PhD thesis, published in February of 1977. When Tom joined the Edelman lab and gave a seminar on the hydrophilicity method in March of 1977, it was roundly criticized and shot down. Tom did three years of protein chemistry work for Edelman, then moved on to the New York Blood Center, where he immediately finished his long-suppressed hydrophilicity study and published it, still beating Doolittle to publication.

To their credit, Kyte and Doolittle made reference to Tom's paper in a note added in proof at the end of their paper, stating that it was a closely similar method (an understatement of fact, since the methods are virtually identical). However, this afterthought placement of the citation is highly irregular. The common place for such citations is in the introduction to the paper. If Kyte and Doolittle had cited Tom up front, it seems unlikely that peer reviewers would have considered Kyte and Doolittle's paper to be sufficiently innovative to warrant publication in a first-line scientific journal.

Tom has continued to contribute to this interesting field of science, writing papers and articles that further the development of hydropathic analysis. Details, and some rare and unrecognized but ground-breaking papers on membrane protein analysis and identification of protein-protein interaction sites can be found among these articles. More.