You'd Prefer An Argonaute

Give this man a Nobel Prize. Give it to him.

I know before I’ve made clear my affection for Harry Noller, and that affection still remains strong like a peptide bond, but lately I’m head over heels (head over sneakers) for Venki Ramakrishnan. Last week in his lecture for the MIT Biology Colloquium, Venki Ramakrishnan charmed me and several hundred other people with his humor, smarts, and beautiful structural work.

The scene of Venki’s lecture, titled “How the ribosome facilitates selection of the right tRNA during decoding of the message,” was quite a spectacle. There was an electricity in the air. Never had I seen room 32-123 so packed. Every seat was taken, of course, and there were at least one-hundred other people huddled in the back of the lecture hall, down the stair aisles, in front, everywhere. Some professors were seated on the concrete floor.

Venki’s faculty host had warned the audience before the lecture began that the aisles had to be clear (for fire safety reasons), and so they were cleared. But sure enough, ~10 minutes into Venki’s lecture, the honorable MIT campus police unkindly entered the room and, temporarily, ruined some beautiful science.

It was quite funny: Venki was captivating us from the lectern, as he faced a projection screen to his left. To his right, a plump MIT police officer sauntered in, unbeknownest to Venki, but knownest to everyone else in the room. The copper reached his arm out to the lectern to capture Venki’s attention, Venki stopped talking, and the officer motioned to follow him outside the lecture hall. Totally perplexed, Venki obliged and left the room, to a chorus of boo’s directed at the police. Moments later, Venki emerged calm as a clam, and succinctly directed movement of his audience into a fire-escape safe arrangement so that his lecture could continue.

Imagine what Venki’s story could sound like: “I won the Nobel Prize, went to MIT, and was accosted by the campus police at my own lecture!”

Venki gave a beautiful introduction, even making a jab at Jim Watson (Watson the man, not Watson the scientist). (He also later hilariously and appropriately mocked Tom Steitz.) He then proceeded to give the best structural biology talk I have ever seen.

He described how proper base pairing between the tRNA anticodon to the mRNA codon induces subtle structural movements between that end of the tRNA and small subunit RNA that are transmitted up through the tRNA toward its aminoacyl end, inducing residue movement in EF-Tu leading to GTP hydrolysis–a cascade of events leading to EF-Tu release and aa-tRNA incorporation. (For more, see Venki’s recent review.)

He ended by narrating an incredibly cool animated movie of all the ribosome structural movements he had just described in detail, and then reprised the movie with a version set to a soundtrack of snippets of classic pop tunes (e.g. by The Clash, David Bowie, etc.), arranged by his lab. The lyrics spoke to the molecular movements spotlighted in the movie. It was very entertaining.

I realize I could have proclaimed Venki the “Rolls-Royce” of ribosome investigators, since he’s at the MRC. But no. He’s American; he’s a Caddy.

A few days ago I attended an informal talk by the cancer biologist Bob Weinberg, who discussed some of his family history, upbringing, and early career, peppering many chunks of wisdom onto the attentive audience throughout. While introducing him, a colleague mentioned that Bob has received 62 awards for his scientific pursuits. Among these are the National Medal of Science (1997), and the Wolf Prize in Medicine (2004). He has also written the reference textbook on cancer, The Biology of Cancer. So as a scientist and educator, this man is solid gold.

Weinberg recounted one story about how, in the early 70’s, he crossed paths with a fraud who had shared his intense interest in the mechanisms by which infection with DNA tumor viruses could lead to transformation of mammalian cells. Weinberg had thought of several experiments to address the question, only to find out soon after that another investigator in Toronto had beat him to it, becoming a minor celebrity while giving talks up and down the east coast. However, the unthinkable quantity of data this investigator had amassed would soon end his career. (This outcome is assumed as Bob did not provide a name.) The data was fabricated. The first hint resulted from a back of the envelope calculation by a journal editor showing that the number of petri dishes required to generate the data far exceeded the number available to all scientists in the Toronto area during the relevant period.

Hot fields are of course vulnerable to fraud. Recently there was Woo Suk Hwang in the stem cell field, and Luk Van Parijs ran a lab studying RNAi technologies and immunology. Back in the late 80’s/early 90’s there was the notorious Imanishi-Kari/Baltimore affair. I suppose it’s possible that immunology was hot back then. Stranger things happened.

So how ’bout the small RNA field? No big scandals I can recall, (although I’m fairly new to the field). A search for the terms “miRNA” and “retraction” in Pubmed yields 3 results: one Science paper and a couple Nature papers. However, retracted papers and scientific fraud are not one and the same.

The controversies in the small RNA field seem to encompass smaller battles, say a partially disputed and highly visible paper with data that is not totally rebuked by others, but where the authors make overly great leaps in their interpretations. And as a colleague of mine pointed out, the field is so new and moves so quickly that there hasn’t been enough time for researchers to confirm all previously published results.

A paper claiming miRNAs can up-regulate translation under certain cellular conditions generated a lot of controversy. A recent presentation of this work by Joan Steitz at the Keystone meeting in April, more than a year after its initial publication, was still met with some underlying skepticism in the questions that were asked.

Bob Weinberg himself published a miRNA paper that generated some discussion in journals (1), and at conferences (2). But these last two examples are really cases of a healthy scientific discourse, openly discussing results and interpretations.

While in the literature I regularly encounter dubious data, it’s more often the dubiousness of some of the interpretations that bothers me. For novel published data I think it is beneficial to temper skepticism with belief. Considering alternative explanations for what one may consider questionable data is a much better intellectual exercise than discounting an entire paper, and just ragging on it.

But hey, what do I know. Listen to a guy like Bob Weinberg. He said he doesn’t even read the literature. He just talks to people.

(1) http://www.nature.com/nature/journal/v455/n7216/full/nature07362.html; http://www.nature.com/nature/journal/v455/n7216/full/nature07363.html

(2) Witnessed at Keystone RNAi, MicroRNA, and Non-Coding RNA 2008 meeting