The Physics of DNA: And of Eyebrows

       Which brings us (as you might guess) to Francis Crick, an intellectual giant with the eyebrows to match, and perhaps the greatest biophysicist ever.  Unless you live under a rock, you've already heard of Crick as part of the famous pair "Watson & Crick" whom you vaguely remember had something to do with DNA, and whom you also think won best Country Duo Grammy in '87.  I happened to see him in person at a seminar at UC San Diego a few years ago, and he was clearly the smartest, most well-respected guy in the room (which was full of other esteemed, famous professors).  He was the prototype hard-nosed scientist, essentially a walking & breathing personification of the physics hubris.  He also had eyebrows that I could feel 30 rows back in the seminar auditorium.

       So exactly what did he do?  50 years before "biophysics" was a trendy college major, he approached DNA as a physics problem.  What he and James Watson did was to piece together just exactly what DNA looks like physically, the spiral-staircase shape that we now all know and love and build mock-ups of from toothpicks and marshmallows while everyone else is at the prom.  (Whoops, did I type that out loud?)  So why exactly is this such a big deal?   In a nutshell, you've got to know what it looks like to understand what it does, and understanding what it does was the holy grail in all of biology at the time.  For my money this accomplishment isn't even as important as another of his accomplishments, his work in figuring out the "genetic code".  The genetic code is, to put it succinctly for once, the scheme of how a particular string of DNA letters is read by a cell to manufacture a particular protein.  Say, "AGGAGTTACCAGATTA" might code for the protein in those giant kegs of powdered protein drink that your roommate drinks every morning to get "yoked".  Crick was instrumental in figuring out the code, which like his work on the structure of DNA, really needed a physicist's perspective to solve.  Not that he used physics equations in his work ("assume the DNA is a sphere..."), but he had the quantitative problem-solving skills that were needed in this new era of biology. 

       Later in life Crick switched fields to the study of consciousness, figuring that with his tenure and Nobel prize, if anyone could work on something as outlandish as consciousness without being fired, it would be him.  Today, mainly because of him (and Schrodinger before him), consciousness is now a proper field of study in biology departments across the country.  For more on the fascinating way preeminent scientists are drawn to the study of human consciousness like a moth to a bug-zapper, often to find their reputations vaporized the same way, see our article "I've Got an Idea..." -- but for now, let's get back to the hunt for the genetic code, which was the hot-button issue of the 1950's and was about to attract another physics bigshot.

       Everyone in science felt the intoxicating thrill of rapid advances in understanding DNA being pushed forward in part by Francis Crick and Max Delbruck.  George Gamow, one of the most highly-respected theoretical physicists of the day, became enamored with the excitement surrounding DNA at the time, and decided to try his hand at solving the problem of the genetic code.  Gamow would later become famous for his theoretical prediction of the cosmic microwave background (the afterglow of the Big Bang), a prediction so far ahead of the curve that everyone forgot he made it when the glow was actually detected experimentally.  In probably the very last example of a pure amateur contributing to the frontiers of important research, Gamow worked out an elegant scheme for how DNA makes proteins, a scheme that fit the observed data so well, was so simple, that it must have been quite a disappointment to discover was completely and utterly wrong. 

       Gamow noted that amino acids (the building blocks of proteins) just about fit perfectly in the gaps between the rungs of the DNA ladder, specifically in little diamond-shaped holes with four adjacent DNA bases at the corners.  What's more, since there are four kinds of bases (A, G, C, and T), there turn out to be twenty different unique diamonds made by all possible combinations of bases at the corners.  And there just so happens to be twenty different amino acids that chain together to form any possible protein.  It's tempting to envision each of the twenty little diamonds permitting one (and only one) of the twenty amino acids to drop neatly into the slot in the DNA ladder -- so if you need to make yourself a particular protein, just go get yourself the corresponding stretch of DNA, throw it into an amino acid soup, and let the little guys find their matching holes to line up in the right order.  Theories that fit together this neatly just aren't wrong.  Ever.  There have been much uglier theories that won Nobel Prizes.  But no, we now know this idea is completely wrong, is not even close to how nature actually accomplishes protein formation -- Crick and others in fact pointed out subtle problems in Gamow's idea almost immediately.  Still, it was a good try, and it got him published in the prestigious journal Nature -- not a bad consolation for one of the great wrong ideas of this century.