Tuesday, May 25, 2021

Matt Meselson Needs a Biographer!

Yesterday was Matt Meselson's 91st birthday.  I have only met him a few times and he wouldn't know me from Adam, but he is a particularly interesting individual I've had the good fortune to converse with.  I'm putting out a plea now for a skilled biographer to write his life, because it certainly has been an interesting and impactful one, with scientific work stretching from the early beginnings of molecular genetics to a preprint just recently posted on BioRxiv.

Given the breadth of his work, which I will outline below, he certainly deserves a full blown biography.  But I'd also suggest he would be an excellent center of a "Surely You're Joking Mr. Feynman" style approach.  Meselson is a gifted storyteller and also has a wonderful speaking style -- one of my fellow grad students joked he would pay to hear Meselson read from a phone book.

He is of course best known for the the Meselson-Stahl experiment, in which he and Franklin Stahl used density gradient centrifugation to show that DNA replication is semi-conservative.  I learned of it as a freshman, but I suspect these days it is covered in advanced high school classes.  The analytical technique may have fallen by the wayside, but it is simple to explain, enables simple graphics and lends itself to myriad test question constructions.  Meselson claims they had a title all lined up if it disproved the Watson-Crick model - "CalTech Trickery Defeats Watson-Crickery".  He doesn't lack for humor!

His Wikipedia entry is incomplete but shows more interesting threads for a biographer to follow.  For example, he had a two part Ph.D. thesis.  The second part involved X-ray crystallography of N,N-dimethylmalonamide, which must have been technically challenging but has hardly set the world on fire.  What was the first part?  Only inventing density gradient centrifugation!  I haven't quite plowed through the thesis to see if Meselson-Stahl is in there (and it is interesting to note that his thesis advisor, Linus Pauling, didn't put himself on the paper either), but it was around the same time.  

Meselson would use the centrifugation trick again to analyze recombination in phage lambda.  When Sydney Brenner and Francois Jacob wanted to prove the existence of mRNA, they converged on Meselson to again use centrifugation to prove its existence.  Not bad company!

Meselson moved to Harvard and continued to work on recombination, mismatch repair and restriction -- his group purified the first restriction enzyme though it was a type I enzyme.

Meselson also became very worried about chemical and biological weapons -- he had toured Europe soon after World War II and seen the lasting effects of conventional war.  Wikipedia credits him with helping get the U.S. to pull back in these areas during the Nixon Administration.  His efforts in CBW would become very controversial when he put forth the proposal that the alleged "yellow rain" chemical weapon attacks on the Hmong in Laos were actually mass in flight bee defecations -- an opinion he reiterated when I was at Harvard using a less than lofty term for the effect.  This earned him the enmity of many political conservatives.  His efforts here led to one famous reversal of position -- based on a trip minded by Soviet authorities he had concluded that the 1976 Sverdlosk anthrax outbreak was not a weapons factory accident, but after Glastnost a brave pathologist came forward with formalin fixed slides showing it was weaponized anthrax and Meselson was a co-author on a publication contradicting his prior position.

A pretty impressive resume for someone who never finished high school!  Apparently lacked enough physical education credits.  The Wikipedia entry also shows a rather messy undergraduate curriculum, bouncing around between University of Chicago and CalTech and a bit of graduate work in physics at Berkeley.  Meselson tells the story of his admittance to graduate school at CalTech - he was at a pool party with CalTech friends and Pauling showed up, dressed in his trademark suit.  If I recall correctly, Meselson claims to have been in the pool when Pauling asked what he was doing next and Meselson mentioned graduate work in some lab at University of Chicago. Pauling asked "why don't you come work with me?" and that was it.  Having just gone through GRE's and such the first time I heard this tale, I was rather jealous!

What may be the capstone of his career may be his work on reproduction in the bdelloid rotifers.  These ubiquitous pond and puddle dwellers had long been thought to not engage in sex, which might be a lens on why sex exists.  If a numerous and ancient creature didn't need it, why do we?  Meselson is one of the originators of an idea that asexual diploid species will over time experience divergence in its homologous chromosome pairs so that they would eventually little resemble each other.   When I was at Harvard, he had set out to use the growing ability to analyze DNA at scale to test this -- as he told it then he expected to prove that bdelloids did have sex.  But his group thought they had found the genetic evidence that they had indeed been long celibate.  But further work by his group and others -- I haven't followed it closely -- led to the recent BioRxiv preprint concluding that bdelloids rarely engage in sex -- but rarely isn't never! 

I'm sure I've done a thin job of covering him -- a proper biographer would do a lot more research.  Even reading a whole book on the Meselson-Stahl experiment, which I think I ordered in a mid-pandemic book spree, would be a good idea.  But perhaps my slapdash treatment can inspire a proper one -- I can only hope!

1 comment:

Unknown said...

You say 'the experimental technique may have fallen by the wayside', but I used it during my PhD in the early 2000s to measure the replication timing of specific genomic regions in yeast. I'm not sure if it's still being used extensively, and short-read sequencing approaches have filled that niche to some extent, but I've found at least one publication from a couple of years ago that used it. The original experiment was so elegant, it's nice to know that a modified version is still being used to answer research questions.