Decades ago, unbeknownst to each other, two chemists were independently working on a screening approach to identify new potential drugs. Both published papers about the technique around the same time. So now, when scientists write papers that cite the technique, who should get credit for discovering it?
Decades later, that question still hasn’t been answered — and the researchers continue to argue, this time over one’s decision not to cite the other’s work.
More than 30 years ago, Árpád Furka—now retired from Eötvös Loránd University in Budapest—developed an approach he says has had “outstanding importance” in drug development. The technique, called split-mix synthesis, made it possible to synthesize and screen millions of peptides at once, instead of one by one. Furka patented the method in 1982, presented an abstract in 1988, and published a paper in 1991.
But Kit Lam—chair of the Department of Biochemistry and Molecular Medicine at the University of California Davis Cancer Center in Sacramento—told us that, unaware of Furka’s discovery, he “independently came up with the idea” for split-mix synthesis in 1989 and published a 1991 letter in Nature , shortly before Furka’s paper appeared, describing the technique. From there, Lam developed the “one-bead one-compound” (OBOC) approach, which allowed researchers to create libraries of small molecules, not just peptides.
Now, decades later, the two researchers are still arguing over who should get credit for the technique. Furka claims Lam took credit for his discovery and has repeatedly failed to cite his work and contribution to the field. Lam told Retraction Watch that he does not dispute that Furka was the first to report the split-mix technique, but claims he took the concept an important step beyond what Furka had reported.
Furka, however, contends that split-mix synthesis and OBOC are essentially the same:
It is the intrinsic feature of the split-mix method that produces OBOC compound libraries.
This debate is described in Brent Stockwell’s 2013 book, “The Quest for the Cure,” which explores the history of drug development. In the book, Stockwell—a professor of Biological Sciences and Chemistry at Columbia University in New York City—notes the “bitter feelings between Lam and Furka” and concludes:
Ultimately, it is fair to say that both Lam and Furka were instrumental in bringing this powerful new technology to the world of synthesis and drug discovery.
Last year, Lam published two reviews that describe the split-mix method but do not cite Furka’s work. Furka wrote to both two journals to complain about the omission.
The journals had different approaches to resolving the complaint. Current Opinion in Chemical Biology allowed Lam to rebut Furka’s letter regarding “Combinatorial chemistry in drug discovery.” Advanced Drug Delivery Review published a corrigendum to Lam’s review, “Tumor-targeting peptides from combinatorial libraries,” which now includes a reference to Furka’s 1991 paper on the history of split-mix strategies.
Ben Davis, the editor-in-chief of Current Opinion in Chemical Biology, explained that the decision to publish the letters to the editor “hinged on fact that Current Opinion is an opinion journal:”
I believe science should be as transparent as possible, and by publishing the letters, we hoped to minimize any filtering of the authors’ views and allow readers to make their own judgment.
(We asked Hamid Ghandehari, the editor-in-chief of Advanced Drug Delivery Reviews, why the journal decided to publish a correction in this case, but did not hear back.)
This is not the first time Lam has published an erratum for failing to cite Furka’s work. Lam corrected his 1991 letter in Nature for “inadvertently” omitting a citation to Furka’s 1988 abstract that “independently described a similar synthetic method.”
Given that Lam could likely predict how Furka would react if his work wasn’t cited, we asked Lam why he didn’t consistently cite Furka’s work:
I did cite Furka’s paper in a lot of my early papers. It has been over 25 years, OBOC is now a standard procedure and I have published over 100 papers on the subjects. Our original Nature article has had over 1000 citations. I do not see the need for citing Furka’s paper on every OBOC paper, unless the focus is on synthetic methods and on history of combinatorial chemistry. This is particularly true when there is a limit in number of citations one may use. That was indeed the case for our mini-review article in Current Opinion in Drug Discovery.”
I have not heard [from Furka] for years until recently, relating to his complaint about my two articles.
We asked Furka why, after 30 years, he continues to pursue this issue:
Imagine that the best article of your life is advertised by another person … I wish [to] restore my reputation as the inventor of the first published combinatorial synthesis.
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