Patent and Penicillin

Apparently the discovery of penicillin is often trotted out as a classic case showing the importance of having the innovation-incentives of a patent system in place. The following post from Greg Aharonian’s PatNews is a letter from a medical specialist debunking some urban legends about this, including one repeated by then-US Patent Office Director Q. Todd Dickinson:

Greg,

Thought you and your readers might enjoy this comment on the twisted history of patenting and penicillin. Lots of urban myths about this story, and Q. Todd Dickinson took it to the top — citing a nonexistent patent in congressional testimony, and saying it made the world a safer place. He could have used the streptomycin example legitimately, although the success of commercializing penicillin without a patent on the penicillin molecule does detract from the drama of his (obviously suspect) point.

We have three success stories of innovation in this early antibiotic history, with penicillin driven by forced cooperation among firms with government grants for manufacturing capacity and guaranteed market through purchase contracts for successful manufacture, while streptomycin and cephalosporins are more like what we have come to see as the normal model of patenting the therapeutic and licensing to a pharma firm. This came up in review of a manuscript we sent to a journal, and one reviewer made some assertions about the role of patenting in the development of polio vaccine and penicillin. Many paths to innovation. Anyway, this is an excerpt from our cover letter in response, which I thought might be of interest to some of your readers:

“A couple of reviewer comments about the role of patents in both the polio vaccine and penicillin stories bear some attention. We have been reviewing the histories of intellectual property in some classic cases of biomedical innovation, including penicillin and other antibiotics, polio, thyroid hormone, insulin, and growth hormone. There is a good deal of misinformation — and urban legend — that has grown up around some of those cases. One of the reviewers makes two statements that seem to indicate he or she has some erroneous information about the role of patents in polio vaccine and penicillin.

When Jonas Salk asked rhetorically “Would you patent the sun?” during his famous television interview with Edward R. Murrow, he did not mention that the lawyers from the National Foundation for Infantile Paralysis had looked into patenting the Salk Vaccine and concluded that it could not be patented because of prior art — that it would not be considered a patentable invention by standards of the day. Salk implied that the decision was a moral one, but Jane Smith, in her history of the Salk Vaccine, Patenting the Sun, notes that whether or not Salk himself believed what he said to Murrow, the idea of patenting the vaccine had been directly analyzed and the decision was made not to apply for a patent mainly because it would not result in one. We will never know whether the National Foundation on Infantile Paralysis or the University of Pittsburgh would have patented the vaccine if they could, but the simple moral interpretation often applied to this case is simply wrong.

The reviewer also asserts that penicillin ‘didn’t move for 14 years due to absence of a patent.’ This is far off the mark, and a clear case of misattribution of cause. Fleming discovered penicillin in 1928 and found it could be used as an adjunct to diagnosis of H. influenza infection. He never tried to do clinical tests of penicillin as a human antibiotic. It was indeed not patented, but it was also not fully characterized and it is not clear it was described with sufficient precision to warrant a patent. Moreover, for the limited utility that Fleming wrote about in his papers, there was little reason to patent penicillin. In any event, the patent would nearly have expired by the time Florey and Chain did their crucial clinical experiments in mice and then humans in 1941, and would have had only a few years left when production was sufficient to lead to broader clinical use in 1944 and 1945. Moreover, the inducement to produce penicillin during World War II was largely driven by the War Production Board, and far from encouraging proprietary exclusive property rights, the U.S. Government basically forced various pharmaceutical manufacturers to share technology, including various manufacturing patents. It is crystal clear that the missing element in the 1928 to 1941 gap was not absence of patent incentive. There were four other factors much more important in this story:

1. It took Florey and Chain to demonstrate the clinical potential.

2. It was very hard to manufacture penicillin in sufficient quantity, and the scientific groups funding R&D strongly favored trying to chemically synthesize penicillin, rather than producing it through fermentation. That never became the preferred method, although it was eventually synthesized in 1959, 30 years after Fleming’s discovery (penicillin is made by fermentation even today). Immense sums were wasted in the organic chemistry, when in fact it was a biological production method that proved key to success.

3. It was a USDA government laboratory that increased yield of penicillin and made it feasible to go to large-scale production. USDA had real expertise in fermentation. USDA increased yield enormously by developing vat fermentation instead of surface fermentation, and hired out work to find mutant strains of the fungus that produced more drug. This is what proved to be the hard work that mattered most for penicillin — making enough of it — not the chemical structure or chemical synthesis.

4. Government grants to build fermentation capacity proved crucial to getting companies involved, not the absence of patent incentive on the chemical structure. The armed forces agreed to fixed contracts to buy penicillin as it was produced. The government thus induced innovation by supply-push (subsidy for manufacture) and demand-pull (guaranteed market).

Another option for government action — patenting the chemical structure and backing up exclusive property rights — was not used in this case. This is actually quite common in defense goods, although often forgotten as a way to get drugs or vaccines to market. But it is simply wrong to say that absence of a patent had much to do with why it took from 1928 to 1944 for penicillin to see widespread clinical use.

It is interesting that this reviewer apparently believes that penicillin languished for lack of patent incentive for 14 years. A US Patent Commissioner, Q. Todd Dickinson, testified to precisely the opposite interpretation of events in his testimony before Congress in July 2000, when he said “When Dr. Fleming discovered that mold in his Petri dish had killed bacteria nearby, and then isolated penicillin from that mold, that drug was patented, and the world was a safer place.” It appears that penicillin is something of a Rorschach Test for one’s underlying belief in = patents: some (such as our reviewer) say lack of patenting explains why penicillin was not developed earlier and others see it as a fabulous success story of patenting (e.g., Dickinson). Both interpretations are demonstrably wrong, at odds with the history, which has been pretty well laid out by William Kingston (Research Policy 29 (2000): 679-710) and Peter Neushul (Journal of the History of Medicine and Allied Sciences 48 (1993): 371-395).

I go on at some length here, because we believe that case studies (such as penicillin and polio vaccine) are actually quite important, as nearly everyone is thinking of one case or another when arguing for a preferred policy regarding intellectual property…”

Robert Cook-Deegan, MD Director, Center for Genome Ethics, Law, and Policy Institute for Genome Sciences and Policy Duke University Durham,

NC

http

://genomics.duke.edu/