I am reading a pre-publication copy of Matthew Cobb’s new book about the genetic code, for he asked me if I could provide a blurb. Now, I never tout a book unless I’ve read the whole thing, but in this case it’s a labor of love. His book is called Life’s Greatest Secret: The Story of the Race to Crack the Genetic Code. It will be published in the UK by Profile on June 11, and in the US by Basic Books on July 7 (links go to the respective Amazon sites where you can pre-order it).
Here’s the Amazon UK description:
Life’s Greatest Secret is the story of the discovery and cracking of the genetic code. This great scientific breakthrough has had far-reaching consequences for how we understand ourselves and our place in the natural world. The code forms the most striking proof of Darwin’s hypothesis that all organisms are related, holds tremendous promise for improving human well-being, and has transformed the way we think about life.
Matthew Cobb interweaves science, biography and anecdote in a book that mixes remarkable insights, theoretical dead-ends and ingenious experiments with the pace of a thriller. He describes cooperation and competition among some of the twentieth-century’s most outstanding and eccentric minds, moves between biology, physics and chemistry, and shows the part played by computing and cybernetics. The story spans the globe, from Cambridge MA to Cambridge UK, New York to Paris, London to Moscow. It is both thrilling science and a fascinating story about how science is done.
This is a pretty accurate take on the book. I’m about halfway through it (it’s 320 pages long), and it’s very good, on par with Horace Freeland Judson’s The Eighth Day of Creation (which everyone should read), itself a superb account of the revolution in molecular biology in the twentieth century. While there is some overlap between the two books, Matthew’s story concentrates on the deciphering of the genetic code itself: how DNA can carry information that makes the molecule a blueprint for organisms’ bodies and behaviors.
Life’s Greatest Secret is a logical successor to Watson’s The Double Helix, and it would be a nice exercise to read them one after the other, though Watson’s is a memoir and Matthew’s a historical account. Most of us have read Watson’s book, but if you have you might not have realized that finding the structure of DNA was only the beginning of understanding how genes work. After Watson, Crick, Wilkins, and Franklin figured out that DNA was a double helix, and W&C elucidated its structure, geneticists still—as Hitchens might say—”had all their work before them.” For the structure, while telling us how DNA maintains its specificity through meiosis and mitosis, and how mutations might happen, tells us nothing about how the structure is translated into organisms. That depends on understanding the genetic code.
It took more than a decade to fully understand that code, and that’s the subject of most of Matthew’s book (he also describes the earlier work by Avery et al. on how they figured out that DNA rather than protein was the genetic material, and recounts the work of the four DNA sleuths mentioned above). While we know now how it all works, back then it was a complete mystery, and people like George Gamow—a fierce and eccentric intellect—bruited about erroneous suggestions like protein sequences being determined by amino acids fitting into the interstices of the DNA molecule. People were truly casting about for ideas on how the whole thing fitted together. Nothing was known about messenger RNA, about transfer RNA, or about the whole apparatus whereby DNA ultimately produces proteins. Figuring it out was a formidable task, requiring both theoretical insights and difficult experimental work. That story is gripping, as the blurb above says, and, at least for this biologist, Matthew’s book is a page-turner. I occasionally had to stop reading to digest and marvel at the detective work involved in gleaning what is now routine knowledge for high-school biology students.
One of my strongest impressions so far is that, in all of this tale, Francis Crick was a fricking genius. Yes, both he and Watson collaborated fairly equally in elucidating the structure of DNA. But Crick went on to help solve the problem of “translation,” and in so doing produced remarkable insights available only to someone with a brain qualitatively different from those of other scientists. I want to mention three of Crick’s intuitive leaps that were remarkably prescient, all turning out to be correct.
The first is the notion of transfer RNA: those small RNA molecules that latch onto amino acids and, moving to the ribosomes where the messenger RNA (the transcribed product of DNA) resides, assemble those amino acids into proteins. It was known that DNA remains in the nucleus, but that both RNA and proteins are found in the cytoplasm, the place where proteins appeared to be made. But it wasn’t obvious how an RNA product of DNA (and that product wasn’t known when Crick made his speculations) could get itself into the cytoplasm and act as a template for assembling proteins.
In 1957, only four years after he and Watson proposed the correct structure of DNA, and well before the genetic code was unraveled, Crick gave a lecture at University College London in which he speculated how DNA coded for proteins. In it, he took up the twin issues of how DNA was connected to RNA, and how RNA itself might help assemble proteins. His solution, which turned out to be right, was remarkably prescient. And here I’ll quote Matthew’s book (with permission):
In his lecture, Crick turned his brilliant mind to both these issues and publicly described the idea he had worked up with [Sydney] Brenner: there must be an unknown class of small molecule, which they called an adaptor, which would gather each of the twenty amino acids and take them to the ribosome, so that each protein could be assembled there. The most likely hypothesis was that there was one adaptor for each type of amino acid, and that it would contain a short stretch of nucleotides—a tiny bit of the genetic code that was able to bind to the RNA template in the ribosome, just like base pairing between the two strands of the DNA double helix. At the same time, on the other side of the Atlantic, Hoagland and Zamecnik were isolating what was later identified as Crick’s adaptor—eventually known as transfer RNA or tRNA—without knowing anything about Crick’s hypothesis.
Crick’s insight and Brenner’s contributions were remarkable, for at that time nobody knew about either messenger RNA or transfer RNA, much less how they worked. In all but trivial details—some amino acids can attach to more than a single tRNA molecule—Crick’s hypothesis was on the money. And yet it was a pure, blind stab in the dark.
Second, Crick realized, well before evolutionary biologists started even thinking about DNA and protein sequences, that these sequences could be of enormous value to our field. Here’s an excerpt Matthew gives from Crick’s 1957 talk—surely one of the most far-reaching scientific lectures of all time:
“Biologists should realize that before long we shall have a subject which might be called ‘protein taxonomy’—the study of the amino acid sequences of the proteins of an organism and the comparison of them between species. It can be argued that these sequences are the most delicate expression possible of the phenotype of an organism and that vast amounts of evolutionary information may be hidden away within them.”
That is an amazingly far-sighted statement, especially coming from someone who wasn’t even close to being an evolutionary biologist. It misses the mark only in that Crick didn’t mention that if DNA coded for proteins, then perhaps we could have the same kind of taxonomy based on DNA as on protein sequences. But here Crick was seeing proteins as part of the organism’s phenotype, and the “evolutionary information” as the way different phenotypes arose from different proteins.
Finally, a year earlier, Crick had already formulated the idea of the “central dogma”: “DNA makes RNA makes protein,” and the notion that no information could flow from protein structure back to the DNA. Below is Crick’s first recorded sketch of this idea in notes he made for himself. Note that Crick also allows both molecules to give information about themselves (i.e. the replication loops), as well as for information from RNA to be incorporated into DNA, which was later verified by the discovery of the enzyme reverse transcriptase.
Here are Crick’s notes from the NIH archive sketching the “central dogma,” which Crick called “The Doctrine of the Triad.” (See also the “Profiles in Science” page of The National Library of Medicine for information on lots of the principals in this story).
This is remarkable, and makes my heart beat a bit faster. Those were the days of the giants on whose shoulders we stand, and Crick was the biggest of them all. I won’t go on, as there is a lot more to this story that you can read in Life’s Greatest Secret. I’ll add only that if you have any interest in the history of genetics, or about the most amazing and informative discovery in biology of our time, you should read Matthew’s book. Here’s the cover; note the clever use of nucleotide bases:
Matthew also said that he’d be glad to answer readers’ questions about the book, or about the subject of the book, if you put them in the comments below.
Finally, here’s Francis Crick (1916-2004). Both he and Watson, by the way, were diehard atheists. Watson once told me that they were both partly driven to find the structure of DNA because showing that the “secret of life” was purely chemical would dispel notions that God had a hand in it:
Well, you’ve convinced me to read Matthew’s book and I look forward to it being released! I’d love to learn more about genetics and this seems to be the funnest way to do so!
I hope that the hard problem of consciousness (which Crick was also involved in) is solved in my lifetime and that high school students learn how consciousness works in the same way they learn about genetics today.
Which is to say for some of them that they check their iPhone for texts, then sleep through the lecture.
Amazing isn’t it? And yet they pass…
Well, does Cobb mention that Watson was a fricking idiot? Watson would have accomplished nothing without the shirt-tails of brilliant people around him.
I’m afraid I don’t say any such thing, because it’s not true. Quite the opposite. Watson realised the importance of DNA at a time when Crick was advising Maurice Wilkins to drop DNA and get himself a ‘decent protein’ to study.
He embraced the significance of Avery’s discovery of the genetic role of DNA at a time when his superiors in the ‘phage group’ (Delbrück, Hershey, Luria) were still either doubtful or ignored the issue.
It was this absolute focus, this obsessive certainty about the importance of DNA, which he eventually transmitted to Crick, with the results that we all know.That alone shows he was no ‘idiot’.
Even if Crick was almost certainly ‘smarter’ (whatever that is) than Watson, Watson amply deserved his Nobel for the double helix structure. It was a team effort.
After 1953, Watson could have won another Nobel prize, for the work he did isolating what we now call mRNA, in 1961. Two groups simultaneously made this decisive breakthrough: Brenner-Jacob-Meselsonon (with Crick as the catalyst) and the Harvard group led by Watson.
As it happens, for reasons that remain obscure, no one got the Nobel for mRNA, but Watson was the co-discoverer of this essential step in cracking the genetic code. Pretty good for a ‘frickin idiot’!
Watson was not riding on anyone’s coat tails. In both cases, he was driving forward an idea, part of a *team* that changed biology. He deserves our respect, not our scorn.
Now you might argue that Watson was ‘a frickin idiot’ because as a young man he was a complete jerk, spending his time thinking about how Rosalind Franklin was dressed, rather than the detail of her crystallographic data, in November 1951. Had he taken notes, the double helix structure might have been discovered earlier.
And you could equally argue – and many do – that Watson ‘stole’ the idea of the double helix when he was legitimately the famous Photo 51, originally taken by Franklin and her student, Gosling, but by early 1953 in the possession of Gosling’s new supervisor, Wilkins.
But think for a minute – what is the source for these tidbits? The Double Helix. A fantastic book, in which Watson succeeded in shaping all our views. He honestly portrayed himself as a jerk (no doubt he was – most young men are) and in the Epilogue he expresses contrition for his behaviour and shows a fulsome recognition of Franklin’s contribution.
As to the importance of photo 51, that’s another myth from The Double Helix. Similar photos were in the possession of the ace crystallographer Bill Astbury in Leeds, and he didn’t twig what it meant. Precise measurements were required, and that came not from photo 51 but from an MRC report that included data from Franklin.
Finally, your view of Watson in the 50s (and the 60s) might be coloured by his recent stupid comments about genetics and race. That would be grossly unfair to the younger man.
Do you know what stupidities you are going to come out with in your dotage? Criticise the man now, not the man he was.
And have a bit of respect for a man who changed the way we look at the world.
I love this website!
A sort of Marshall McLuhan moment.
It’s true that The Double Helix, while a highly entertaining read, gives the impression that Watson and Crick were dashing off in all directions, wasting time, and only came on the correct solution after they had tried everything else. (But then nobody else managed to beat them to it). Watson’s frank and unflattering impressions of the personae, which included Crick and himself, may not have been in the normal image of the dedicated scientist, but it would be inequitable to condemn him for his portrait of others while taking his self-judgement at face value.
The book is written in the style and from the viewpoint of a young man and his youthful enthusiasm maybe obscures the intellectual effort involved.
> Finally, your view of Watson in the 50s (and the 60s) might be coloured by his recent stupid comments about genetics and race.
Were they stupid because people reacted so strongly to them or because they were not backed by empirical data (and perhaps even contradicted by such data)?
Please state why you find them stupid.
Well said Matthew. That left a mark!
“Ditto.”
<sigh />
…another book for the pile….
b&
Yeah, my “to-read” pile of the physical books I buy is going to seriously break my bookshelf one night & scare the crap out of my dog (it won’t wake me up; I’m a light sleeper), which will cause her to wake me up.
Another really good book, about the origins of life, is The Carnegie Institution geologist Robert M. Hazen’s The Story of the Earth: the first 4.5 billion years, from stardust to living planet. ( blurbed by Neil Shubin among others).
Thanks for that tip Merilee. That goes on my stack.
You’re welcome, Rick. I’m a little more than halfway through. His main thesis is thst the geosphere and the biosphere have evolved together. Without the oxygen formed from photosynthesis we would not have many of the minerals we have today. The book is very readable.
Sounds great. I’m reading “Revolutions that made the Earth” – Tim Lenton. It discusses the 4 billion year set of Earth’s changes including photosynthesis. It claims that the idea of Lovecock’s ‘Gaia’ hypothesis is basically sound (although it was widely dissed) if understood correctly.
Oh, no. Another one to add to the giant pile of TBRs some friends and I call Mount Impossible (after Dawkins’ Mount Improbable.)
You will never be bored in an airport.
That is a fairly awesome Freudian Slip. 🙂
His main thesis is that the geosphere and the biosphere have evolved together.This is an argument posed by old earth creationists for the ‘fine-tuning’ necessary to support advanced life/human civilization.
There is absolutely NO godsplaining in Hagen’s book.
“Revolutions” (so far at ch 6)goes into the difficulty of evolving intelligent(observant species) life based on the probabilities of passing various critical phases such as the transition from simple bacteria to DNA, etc. The analysis is done in quite a bit of detail even though there is necessarily much speculation. The boundaries and error bars are refined to try to get a grip on the whole process. Of course the unspoken basis is that there was no need for interference from a supernatural chemist.
This looks fantastic!
And for contrasts, it might be noted that the progression of this work depended on use of centrifuges (for separating the different classes of RNAs) – the same devices that at least in concept are in use on the other side of human efforts to enrich uranium.
Dr. Cobb –
I notice that there only appears to be a hardcover version available for purchase on Amazon. Do you know if a kindle edition will be released?
Not sure – I will ask my publishers.
Perhaps you can ask if we can pre-order soon too?
Pre-ordering for the hardback is available on Amazon (other booksellers are available…). Or do you mean for a potential Kindle version?
I was thinking for amazon.ca – don’t see it when I search for it.
I just pre-ordered the hardcover from amazon.ca this morning!
Oh, found it now. I think I was looking for the cover and missed it. My excuse is I have a wicked migraine today so it makes cognition dodgy.
Well, there’s your problem. Make your cognition more catty and less dodgy and you’ll be able to think straight!
b&
That would be a catastrophe!
Only if you’re dogmatic about it.
b&
It didn’t show up when I looked under Matthew Cobb, but then it did under the title.
Yes, there will be a Kindle version in the US. It has an ISBN but no page for the moment, they’re waiting for the final proofs to whizz over from London.
Thanks for the info!
Watson, Crick, and Franklin also worked on the structure of viruses.
Franklin also was no one-hit-wonder. She determined the TMV virus’s helical structure.
The model is walking distance of Jerry at the Museum of Science and Industry. It was originally displayed at the 1958 World’s Fair.
Here is the model construction.
Yes, there’s a whole history to Franklin’s life after the double helix. And FWIW, I reckon had she lived, they’d have awarded two Nobels in 1962 (or 1963) for the double helix structure (one for chemistry, the other for Physiology/Medicine), with Watson-Crick getting one, and Franklin/Wilkins getting the other.
Can’t wait to read Matthew’s book, and I have had Judson’s on my shelves for years. Must get it out and put it right in the middle of the hall where I’ll trip on it!
Judson’s book is a masterpiece–one of the best biology books around.
Well my book list happily grows. Thanks!
His daughters book, Dr. Tatiana’s Sex Guide to All Creation, is pretty awesome, too. Loved both of the Judson books. Must be in the genes.
I’ve read some short pieces by the daughter – is it Olivia? – and she’s very good.
Brilliant, yes, but I think a theme for geniuses is to seek economy and simplicity in nature. Take what is known, which is that base sequences are linear information that can also form complementary pairs. It seems simple (in hindsight for the rest of us) to then say that these properties are used. Linear information that is stored also means that it is stable. Use complementary pairing to build a corresponding RNA. Use that stable RNA to carry the information to the cytoplasm for protein assembly in reference to that information.
Since the only known way to transfer base sequences was again by base pairing, use that once again to predict an adapter molecule with bases. That last bit was a stab in the dark, but it exploited what little was known.
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I have read Watson’s account(s), including one that reproduces an joke obituary notice for the double helix idea made by Franklin. I wish we could separate the revisionist history from the more realistic to get a proper handle on what Franklin actually did contribute, including, as it’s been suggested by Watson, she didn’t get along with anyone else, or at least with Wilkins. She has become a scientific standard-bearer for the feminists, claiming it was all her, and that her ideas were stolen by then men, but what I really want to know is the actual truth, not the political “truth”, if that makes any sense.
It sounds like this book spends a good bit of time on Crick, who seems to have also been overshadowed, like Wilkins and Franklin, by Watson’s personality and ego. From what I have read, Watson, intelligent and clever as he is, was and is pretty much an insufferable jerk much of the time.
Matthew’s book gives the most even-handed and concise account of Franklin’s contributions, which were considerable, of any account I’ve seen. But although I’m emphasizing Crick here, Matthew’s book, while seeing him as a major player in deciphering the code, pays more of its attention (in terms of space) to the other players in the search: Avery, Chargaff, Pauling, Franklin, etc.
A lot of scientists who made massive contributions were jerks. We have to be able to separate that out and judge their science apart from their personality. And, in my interactions with Watson, I haven’t found him nearly as bad as what you have “read.” And remember, most of the bad press about him is about the racist comments he made when he was quite old. Everybody admits that he can be abrasive, but he’s also known for extraordinary generosity, some of which included endowing our department with a lectureship after he stumbled into a molecular biology lab, was unrecognized, and one of our postdocs proceeded to tell Watson about DNA and how he was using a PCR machine to sequence it. Some scientists would have been huffy that they weren’t recognized and proceeded to pull rank, but he listened attentively, thanked the postdoc, walked away, and later we heard that he had been so touched by the kindness of the guy trying to explain science to someone he thought he was a layperson, that he gave us that endowed lectureship. He’s also been known for mentoring other scientists.
And, also the disagreements between him and E.O. Wilson recounted in Wilson’s book, “Naturalist”. In that book it was stated that he had a negative attitude towards “traditional” sciences, akin to Rutherford and the “stamp collecting” quote.
I had to go back and read up on the racist comments, they happened before I was aware of him and his contributions. Some seemed overblown, others seemed like the typical “casual racism” of old people, not that it makes it less bad, I guess?
I’ve also read, and absolutely loves Watson’s “Avoid Boring People”, and honestly, he comes across as a bit of a jerk there too, but then so am I, I suppose, but unlike Watson, I am without the benefit of genius! Scientist are human, with all the flaws that come with the package. Or, to put it another way, to mangle an old quote, all people are assholes, the question is to what degree.
and I agree about having to separate science from personality, the same goes for historical figures and holding them to modern morality. Feynman falls under this category for sure, as evidenced by the dust-up over a bl*g post about him a few months ago. and this is where I stop typing, and start singing the tv theme tune “you take the good, you take the bad, you take them both and there you have, the facts of life…” (sorry! couldn’t resist!)
Yes, to taking the good with the bad. I do not hold with some who say we should reject various people and their ginormous contributions b/c of a couple of stumbles that have no real effect on the world.
Now I have to find a way to replace that damn ‘ear worm’.
Such an interesting story. I am sure I will recognize his picture in a molecular biology book, but I very much doubt I would recognize him in any other context. Many of us find we do not recognize people we even know casually when in a different situation. I run into students all the time in, say, a local grocery store. They greet me warmly & start to chat with me, and i am thinking: ‘now, how does this person know me?’
How embarrassed that post-doc must have been whe he discovered thst it had been Watson!
There are worse ways for a young person to be embarrassed when interacting with a famous scientist. When I was a postdoc in the mid-80’s at the U of C, a grad student in our group came back to the lab after a trip to the restroom – he was visibly shaken. He said, “I almost killed Mulliken! (Robert Mulliken was a famous Nobel laureate in chemistry who is the ‘father of molecular orbital theory‘.) Apparently, he had quickly pushed open the bathroom door in a Searle Hall restroom and Mulliken, then in his late eighties, was knocked to the floor on the other side of the door. Imagine having to explain that to your advisor!
Me too. I remember when I stumbled on this (in a later formulation, so I didn’t know of “the Doctrine of the Triad” – thanks! … and maybe I need to buy the book …) and it was so brilliantly clear as opposed to the usual idea of showing the standard ad hoc duplication-transcription-translation loop-into-chain.
[Full disclosure: I happened to read molecular biology some time ago, way before I got interested in astrobiology. The text book, Watson’s “Molecular Biology of the Gene”, has the incomplete flow scheme of the DTT.]
So I surmised that Crick was a frickin’ genius in the way Newton, Darwin, Maxwell, Boltzmann, Einstein was of extracting valid information from sometimes scant data, but I didn’t know of his other visionary achievements.
You’ll be pleased to know that as well as Gamow, Norbert Wiener plays an important role. – MC
Remember the Alpher, Bethe, Gamov paper?
Whoops, Gamow
I used Watson’s Molecular Biology of the Gene for a class ( mid 70s), too. Excellent book I thought then.
yay! Another book to add to this physics teachers’s list of books to read.
Just an observation…. all the ‘stuff’ mentioned in the forthcoming book has happened in my lifetime, and I was taught the bare bones of DNA in ‘Biology’ in my high-school equivalent.
Sometimes the pace of change goes unrecognised until you do a retrospective review.
Good point. I enjoy reading about the history of invention and discovery for exactly this reason.
“Watson once told me that they were both partly driven to find the structure of DNA because showing that the “secret of life” was purely chemical would dispel notions that God had a hand in it.”
If only…
I can’t wait to read this book!
If I may offer one minor quibble with your phrasing (“It took more than a decade to fully understand that code…”), we’re of course still learning amazing new details even today.
I was fascinated by the suggestion (just published in this week’s Cell) that codons which code for the same amino acid may dramatically differ in their protein expression rates, due to their varying mRNA degradation rates.
phys.org/news/2015-03-hidden-limits-genetic-code.html
Fascinating about the different protein expression rates. The more we learn the more there is to learn.
Yes, that one has slipped through the net of the proofs, sadly. Although the bulk of the book deals with the cracking of the code and covers 1943-1967, the final four chapters bring the story up to date, including looking at artificial genetic codes, the evolution of the genetic code qne the RNA world (the subject of a post here a while back). One of the things that is dealt with is ‘codon bias’ – why some synonymous codons are more widely expressed in some lineages than others. There are genetic, evolutionary and protein-based explanations for this. The paper you cite would have been included, but came out too late. Science never stops!
Pre-ordered.
I was only able to locate on Amazon US using this phrase: “life’s greatest secret matthew cobb”
In a letter to Nature in 1882, in his last published work, Charles Darwin described a peculiar specimen: a water beetle onto which a small freshwater clam had attached itself. (This was relevant to the question of dispersal of populations over barriers.)
That particular specimen was sent to Darwin by a W. D. Crick, a shoe factory owner from Northhampton and the grandfather of Francis Crick.
Cool!
+1 Cool.
I love the cover: colorizing (or, I suppose in Matthew’s case, colourising) AGCT is brilliant!
Sounds like a promising read!
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