So the Mitchell Report is out, casting steroids and human growth hormone (HGH) into day-to-day discourse. Although it would be interesting to talk about what HGH does and how it can enhance athletic performance, I’m willing to bet there are others out there who are already doing that. Instead I thought I’d talk a little bit about another dark side of HGH that you probably haven’t heard about – the patent dispute between the University of California, San Francisco (UCSF), and Genentech, Inc.
Before I begin, I should disclose that I am a graduate student at UCSF and have heard various versions of this story in different amounts of detail from faculty and other potentially biased sources, but I have attempted to research the issue as best I can, and everything here is based entirely on reporting in Science, The Washington Post, and publications of equivalent believability. This is, to the best of my knowledge, the history of HGH.
Growth hormone is essentially a protein which acts as a signaling molecule – HGH is the human version of this hormone. When the protein binds its receptor, signaling pathways are activated that stimulate the growth of the cell (this is, of course, a vast oversimplification, but should serve for the purposes of this story) Because of its ability to trigger these pathways, growth hormone has many therapeutic uses including treatment of multiple sclerosis.
Recall from my earlier posts that the central dogma of biology is that protein is encoded by RNA which is in turn encoded by DNA. Thus there is a DNA sequence which tells a cell to build growth hormone. One common technique in molecular biology is to “copy” a specific piece of DNA (in this case the DNA coding for HGH) and place it into bacteria. The rationale for this is that you can grow lots and lots of bacteria and then extract and purify the protein, cheaply and quickly.
In 1977, Dr. Peter Seeburg, then in a postdoctoral position in Dr. Howard Goodman’s lab at UCSF successfully copied the DNA that coded for HGH and UCSF was awarded the patent for the gene. Incidentally, UCSF’s version of the copied DNA included the DNA sequence that encodes for HGH but with an additional 48 nucleotides (i.e. 48 more characters) added on at the end (these nucleotides are present in the human genome, but don’t actually serve any purpose in producing the protein) – an unimportant scientific distinction, but one which would be important legally years later.
In 1987, Seeburg left UCSF for Genentech where his job would focus on expressing that DNA in bacteria, so that Genentech could grow lots and lots of the bacteria, which would then make lots and lots of HGH, which Genentech would then use to make lots and lots of money. In fact Genentech eventually did just that, producing the drug Protropin which went on to produce over $2 billion in sales.
In 1990, UCSF sued Genentech for $400 million for infringing their HGH patent. Genentech’s response was that they had developed their HGH from DNA that was independent from the original UCSF DNA. This could have actually been entirely possible, except that, at trial, Seeburg would testify that he actually HAD copied the UCSF DNA.
When Seeburg left UCSF, Robert Swanson, then president of Genentech, sent a letter to Seeburg’s old boss, Dr. Goodman asking for the DNA that Seeburg had worked on. Goodman apparently refused so Seeburg, fresh out of his postdoc, visited his old lab on midnight of New Year’s Eve, and took copies of the DNA with him. Seeburg justified this “midnight raid” claiming that it was customary for scientists to take work they had produced with them to their next positions (it is actually quite common, if not quite proper, to do so within academia), and that he had gone at the late hour merely to avoid Dr. Goodman with whom he was no longer on friendly terms. UC later found out about this incident and in 1980 settled for $2 million with Genentech, but still retained full patent rights over their DNA construct.
Genentech, not wishing to use any of UC’s intellectual property, decided to duplicate the old work and isolate the DNA for HGH themselves and then introduce it into bacteria. Except that they couldn’t get it to work. So Seeburg, with, allegedly, the knowledge of his Genentech coworker Dr. David Goeddel, decided to just use the UC construct to make their bacteria. They even published a Nature paper with results from their supposedly novel construct. At trial, Seeburg, no longer with Genentech and testifying on behalf of UC, stated that much of the data from the Nature paper with all new “UC free construct” was fudged. Goeddel denied knowing that Seeburg had cheated, and Seeburg’s coauthors on the Nature paper denied Seeburg’s account of falsified data (although the “midnight raid” and lifting of UC property was corroborated).
In the legal battle, Genentech argued that because the UC sequence contained those extra base pairs, the Genentech DNA, which contained only the HGH DNA, was substantially different, and an entirely new invention (many patent lawyers actually thought Genentech had a decent case, and that Seeburg’s testimony, although indicative of intent to copy, had no bearing on the final legal issue of whether the Genentech construct was sufficiently different). In 1999, a nine member jury ruled 8 to 1 in favor of UC, however the split decision saved Genentech from damages that could have been as high as $1.2 billion. Rather than risk losing on appeal, and with UC having already invested $20 million in legal fees, the two sides settled for $200 million. $50 million went to building my home away from home, Genentech Hall, – the first building at the new UCSF Mission Bay campus:

Picture taken from (http://www.pbase.com/klaorman/image/11306539)
$30 million went to the UC general fund, $35 million went to research at UCSF and the remaining $85 million was split amongst the original inventors and collaborators, including Dr. Seedburg, whose individual share ended up as $17 million.
I’ve glossed over a lot of the science and legal issues involved here, partly because I’m no lawyer and I don’t know enough to say what really happened here, but it’s clear that HGH has had a colorful history that continues today.