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An all-too-familiar story among researchers is the failure to get grant support for innovative ideas—good ideas, some even great ideas. Sometimes the ideas pan out despite the lack of funding. Such a scenario took place in the early '80s when Lee Hood and his associates at the California Institute of Technology (Pasadena) were working on an idea to automate DNA sequencing. And in this case, panning out is an understatement. The invention of the automatic DNA sequencer is largely what enabled the human genome project to be what it is today—a multi-million dollar effort, engaging thousands of researchers worldwide, and leading arguably to the most massive collection of information the world of science has ever seen.

Now 20 years and some billions of DNA sequences later, the federal government is trying to take credit for supporting the invention and thereby recoup millions of dollars of federal money spent to purchase instruments for the Human Genome Project and other federally funded sequencing projects. While universities are allowed to patent inventions made with federal funds under the terms of the 1980 Baye-Dole act, the government retains the rights to use such inventions without having to pay royalties. At issue is the $300,000 price tag on the DNA sequencers that came into being as a direct result of the pioneering work at Caltech (for background, see related article).

Two investigative reporters from the Los Angeles Times reported in last Sunday's edition on their efforts to get to the truth, and presented what on the surface appears to be damning evidence against the Caltech claim that federal funds were not used during the invention phase of the work. Specifically, the reporters found:

• Grants written by Hood's group and submitted to the NSF in the mid 1980s to "devise and improve" the DNA sequencer, including a $2.5 million grant explicitly "to automate DNA sequencing."
  
• A 1988 licensing agreement with a company started by the inventors that contains provisions for discounting purchases of the technology to the federal government.
  
• Letters and memos among the inventors that show that the sequencer was not working when the NSF grant was funded.
  
• Different opinions on whether those named on the patent include the true inventors.

On the first point, while current officials at the NSF feel that the language of the grants clearly show that the machine had not been invented at the time the grant was submitted, the person who headed the unit at that time has a different view. John Wooley, who is now an associate vice chancellor at the University of California, San Diego (UCSD; La Jolla), visited the Hood lab six months prior to the grant start date and was shown a prototype of the DNA sequencer and a large amount of data. Caltech's lawyers have obtained an affidavit from Wooley to this effect.

The Times reporters, on the other hand, say that their own review of lab notebooks from that time clearly show that the machine was not working, nor did it produce the four-color data that was the crux of the invention.

On the second point, the language in the licensing agreement granting provisions to the federal government has since been removed, and was the result of bad legal advice, according to statements attributed to Caltech and PE officials in the Times report.

And on the last point, the inclusion of certain individuals on the patent that was filed for the automated DNA sequencer and the exclusion of others—much of the information on this point comes from a single source—an interview with Robert Cook-Deegan, now an official at the National Academy of Sciences, who wrote an account of this work called "The Gene Wars." Cook-Deegan told the Times that the inventors disagree on crucial aspects, such as who actually came up with the chief contribution of using four fluorescent dyes to mark the four bases. According to his account, Henry Huang, now a professor at Washington University in St. Louis, may have been the one to do so, but he is not named on the patent.

What do the principals have to say? Lee Hood is quoted as saying that this is someone just trying to make trouble. Michael Hunkapillar, whose name appears on the patent and is now the CEO of PE Biosystems, said it's Cal Tech's problem. And Caltech, through a statement by Provost Steven Koonan, maintains that everything was done properly.

Stay tuned.

By Laura DeFrancesco