When I first knew Bruce Ames he had just arrived as a new junior professor in the Berkeley biochemistry department. At the time, he was widely celebrated in molecular biology circles as the senior author of the Roth, Hartman and Ames triumvirate that had elucidated the basic control circuits for the histidine biosynthetic genes of Salmonella typhimurium, and showed that they were also organized as an operon [Cold Spring Harb Symp Quant Biol. 1966, 31:383–392]. The John Roth of that trio joined the molecular biology dept. at the same time, and became my second thesis advisor (Don Glaser was the first), but that is a long and very, different story.
Some years later Bruce became really famous (and perhaps a little wealthy as well) by inventing the "Ames Test" to accompany his new mantra "Carcinogens are Mutagens". There are some who are not completely convinced of the efficacy of this mantra, although its acceptance is nearly as universal as "HIV causes AIDS". One of those is my friend Peter Duesberg, who recently presented his reasons for challenging this dogma at the (now combined) departmental winter retreat early last month.
A few weeks after the seminar, Peter received an email from his colleague Ames taking umbrage with some of his characterizations of certain well known, highly carcinogenic substances, like asbestos fibers, as non-mutagenic. While he did not argue that such chemically inert substances are direct mutagens, he did contend that they can cause "numerous mutations" via secondary pathways, such as the generation of "mutagenic free radicals" that were released as a result of tissue irritation.
In the same email he urged Peter to do a "literature search" and discover, as he did, that there are "61,000" entries for "asbestos mutagen". There was, however, one odd thing about the request, and I believe it was the reason Peter sent me the brief exchange.
I remember Bruce as being as obsessive a millimole counter as Peter, yet the letter recommending a literature review read: "Do a search on Google for "asbestos mutagen". There are ~61,000 entries. it has been long known to be both a mutagen and human carcinogen."
The Duesberg reply was typical, and unchanged in tone and temperament in 40 years.
"As per your advise I have also searched PubMed for "asbestos + mutation". Surprisingly the third entry on that query was: Cell Motil Cytoskeleton. 2006 Oct;63(10):646-57. Intracellular protein binding to asbestos induces aneuploidy in human lung fibroblasts. by MacCorkle RA, Slattery SD, Nash DR, Brinkley BR - and thus a useful reference for the chromosomal cancer theory."
Which returns us by a less than "commodious vicus of recirculation" to the subject of citation.
One of the most frequently heard remarks in scientific circles when discussing the Duesberg critiques of the HIV/AIDS literature is that Peter "abuses" it in two contradictory sounding ways. He either cites so many papers that no one could possibly read them all, or he misquotes and takes out of context data from papers he cites making his apparent scholarship worthless.
Until recently both of these charges were impossible to refute, but last year the Rethinking AIDS group was able to mount a CD on its server that contains the full text of Duesberg's apparently definitive, Pharmacology and Therapeutics review of 1992, hyperlinked to full texts of almost all of the hundreds of references (many containing Peter's handwritten notes and markings). Using this tool to decide for oneself the merits of the Duesberg analysis requires both a certain amount of technical knowledge and a significant amount of perseverance. "Informing oneself is tiresome", as Ignacio Ramonet concluded in his book The Tyranny of Communication.
But as an inducement, allow me to present one example of a kind of conundrum the use of this tool can clarify.
Peter writes in the review the following: "Other studies have also found that AZT inhibits T-cells and other hemopoietic cells in vitro at 1–8 μM (Balzarini et al., 1989 ...)". The reference is to this paper: Balzarini, J., Herdewijn, P. and De Clercq, E. (1989) Differential patterns of intracellular metabolism of 2',3'-didehydro-2',3'-dideoxythymidine and 3'-azido-2',3'-dideoxythymidine, two potent anti-human immunodeficiency virus compounds. J. biol. Chem. 264: 6127-6133.
The paper is an excellent piece of biochemistry except for three misleading words in the title, and Peter's citation of it is 100% accurate, even though the title and abstract make it appear one of those imagined "abuses". [For those not technically up to this challenge, a readable (if slightly long, although amusing) explanation can be found here.
Harvey Bialy is the founding scientific editor of Nature Biotechnology, and the editor of "You Bet Your Life".