Monday, November 17, 2008

Plague on Both Houses? Biopure vs. Natanson

Nature, in its November 13 issue, reported on the lawsuit filed by the firm Biopure against Charles Natanson, an NIH scientist and author of a study published in JAMA that questioned the safety of one of the firm's products.

At issue is the blood substitute Hemopure, a hemoglobin-based blood substitute. Natanson and colleagues looked at clinical trials of five blood substitutes, one of which was Hemopure. They claimed that these products were associated with a 30 percent increase in death, primarily due to heart attack risk. Biopure then sued, claiming that Natanson had made "false and defamatory statements" about Hemopure both in the JAMA article and also in letters he then sent to health officials in the United Kingdom, Greece, and South Africa (countries in which some of the blood substitutes had been approved for sale). Hemopure was initially approved only in South Africa, where the HIV epidemic has seriously restricted the human blood supply; subsequent to the controversy, South Africa withdrew its approval.

In an editorial, Nature attacked Biopure for this attempt to conduct "science by litigation," and noted that however unlikely the suit was to succeed in court, the clear intention was to intimidate scientists from speaking out against commercial products. (As explained in HOOKED, such a suit is sometimes termed a SLAPP suit, designed to have a chilling effect even it it never goes to court at all--in part because of the disparity in financial power between a large firm that can keep a bevy of lawyers on retainer, and the individual scientist who can barely afford legal counsel if named in such a suit.)

And, as the news account in Nature explained, if you want to measure corporate behavior on the Sleaz-o-meter, Biopure wins hands down. Its previous achievements include: the FDA halting a human trial of Hemopure because of safety concerns; three of its executives and the company sued by the US Securities and Exchange Commission for misrepresenting Hemopure's FDA status to investors; and criminal indictment of the company's former head of regulatory affairs for lying about his own health to avoid testifying before the grand jury.

But the main point that I want to make here is that Natanson, very sadly, appears to have invited some of this treatment through his own conflicts of interest. Natanson (who refused requests to be interviewed by the Nature reporter) failed to disclose that he was involved in a provisional patent application for a new technique to make hemoglobin-based blood substitutes safer. He has since amended his conflict-of-interest statement and has withdrawn his name from the final patent application. But one could not blame Biopure if they saw him more as a business competitor and less as a disinterested NIH scientist. Based on the old adage "it takes one to know one," they might well have concluded that Natanson's research methodology in his meta-analysis in JAMA was just as unreliable as their reports of their own research.

So, while I completely concur with Nature's condemnation of Biopure's resorting to a lawsuit to settle what ought to be a scientific question of drug safety, I must also note that scientists need to cleanse themselves of financial conflicts of interest if they wish their findings to be taken seriously.

Ledford H. Company sues researcher over unfavourable review. Nature doi: 10.1038/news.2008.1219

Science by litigation [editorial]. Nature 456:142, 13 November 2008.

Natanson C, Kern SJ, Lurie P, et al. Cell-free hemoglobin-based blood substitutes and risk of myocardial infarction and death: a meta-analysis. JAMA 299:2304-12, May 21, 2008.


Anonymous said...


I think we should bear in mind that Natanson says he simply forgot to disclose that his name was on that patent application. In addition, I see nothing wrong with NIH and Natanson trying to come up with an improved and safer blood substitute. To me, the fact that he initially failed to disclose the patent does not call his research into question at all.

I think what Biopure is doing is intimidation pure and simple. Notice that they only sued Natanson, not his co-authors or the journal. All this talk about the patent is an attack-the-messinger tactic to divert attention from the real issue here: hemoglobin-based blood substitutes are dangerous and should not be used.

The tobacco industry used similar tactics for years to sow doubt about the work of scientists who were doing work on the health effects of smoking. David Michaels discusses the history of this tactic in his book Doubt is Their Product.

Roy M. Poses MD said...

Note that Biopure is apparently close to fading away. It recently laid off nearly all its employees. See:

Anonymous said...

Um, let us review the facts here. Natanson failed to disclose that his name was one of 16 government employees listed on US Government Provisional Patent Application relating to hemoglobin-based oxygen carriers (HBOCs) that was filed in August of 2007. The Provisional Application related to a method of using nitrite bound to methemoglobin to reduce the deleterious effects associated with HBOC use as blood substitutes. Although some of the preclinical work underlying this application was performed in Natanson's laboratory, that work did not involve HBOCs and Natanson did not participate in the preparation of the provisional filing. Further, when the final patent application was filed in August of 2008, Natanson's name was no longer on it (!) -- he was not deemed to have made a material contribution to the work. (Provisional applications are merely placeholders for patents and often they list many more people than actually made a significant contribution. Patent lawyers review the inventor names and independently decide which work was material to the patent before they file the final application.)

While it's true that he should have disclosed his name on the provisional application, it's absurd to argue that this represented a significant financial incentive of any kind. Natanson has argued that HBOCs should NOT be tested at all in humans until less toxic products can be developed and FULLY vetted in animal models - the only way he could have benefitted financially from the issued patent (on which his name no longer appears and which is held by the U.S. government) is if the current crop of HBOCs ARE tested and used extensively in humans.

This is a clear case of a company trying to harass a scientist out of publishing his findings - Biopure should have published a peer-reviewed article which argued convincingly and with solid data against Natanson's conclusions rather than suing him. Apparently, they were unwilling or unable to do so.

Anonymous said...

Wheter one or 1/16 he should know he was a part of it and it should be stated that he has tried to "sell" his invention to solve the problem--I'd call it conflict and selective memory loss. His letter with that of Wolfe is harassment of the company since the work he relies on for his "facts" has not been validated. What he calls "toxicity" is to many a treatable 'side effect"; the MI issue has not been related to the product use after finite analysis...

Anonymous said...

So, by Natanson's logic, ALL automobile manufacturers should be shut down because the Ford Pinto had exploding gas tanks in the 70's. Science by litigation my ass.

This is nothing more than monumental self-aggrandizement by an insecure doctor.