The First Five Pages: a Conversation With Matthew Cobb

“Now what you’ve got to do is get another paper like that Avery paper” is Matthew Cobb’s advice to Journal Experimental Medicine, referring to the series of JEM papers where Oswald Avery and his team demonstrated that genes were made of DNA. He’s just got one small, but pertinent, question: “What would it be on? What would be the topic?” Ay, there’s the rub…

Cobb’s own work focuses on olfaction in maggots, and somehow he also finds the time to write books on the Second World War. His latest book, Life’s Greatest Secret has been shortlisted for the Royal Society Winton Prize, and received rave reviews. Dr Cobb discussed with us the inspiration behind his books, how a scientist gets a book published, and the challenges of studying the history of science.

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Illustration by Madalena Parreira.

Why did you write a new history of the golden era of molecular biology?

Matthew Cobb: I could see there was a story there that I could explain to the general reader. By concentrating on the experimental detail, which is something I really know about, I could explain the story in a novel way. That was the motivation. When we learn about this period of scientific history, to the extent that we do learn about it, it’s generally confined to the first five pages in the textbook, that people probably skip over because they are not interested. It’s told in a very linear way, and of course history is only linear when you’re looking back. When things are happening, just like they are now, it’s really confused, and there are lots of interactions. It’s not clear where you’re going, and I wanted to recapture some of that confusion, and some of that groping, which you can see in the words that people use. I found myself using the word “information”, or the word “codon”—I didn’t allow myself to use that word until late 1961, by which point the word had been invented. This was really difficult, to force myself into this straightjacket. But at the same time it was essential to try to explain things in the right way and to show why what now seems obvious was once unknown.

So Life’s Greatest Secret focuses on the experimental work of cracking the code?

MC: As well as reading memoirs and so on, I read all the original papers—for every chapter. For the Jacob/Monod chapter, this was pretty heavy going, because I have no training in bacterial genetics at all, and their papers are very tough going, if you haven’t had someone take you by the hand and explain it all. I found that very difficult. But it was something I had to go through. I couldn’t explain it to the general reader if I couldn’t completely understand it myself. So the first task was to read the papers without knowing what was going to come next, just read them blank and imagine “OK, this is the frontier of knowledge now, how can I explain this, and what are the insights that are here, what’s novel, and where are the influences, where have these ideas about come from?”

You’re a working scientist, with a research group at Manchester University. How do you find the time to write about the history of science for a general audience?

MC: I don’t watch TV. That’s the simple answer.

Not even The Wire?

MC: [Laughs]  I watched The Wire. So, occasionally, boxsets.

Your first book was The Egg and Sperm Race. You mentioned in an interview with  American Scientist that what prompted the writing of that book was finding a copy of Swammerdam’s work in Paris.

MC: That’s right, that’s how that all started

The topics of the two books are separated by several centuries. Was there a common challenge in writing The Egg and Sperm Race (Generation in the US) and Life’s Greatest Secret?

The biggest challenge in writing the books, Life’s Greatest Secret and Generation, has been trying to put myself back in time, not to use words and concepts that weren’t appropriate for the time. So, in The Egg and Sperm Race, it was any idea of inheritance. I couldn’t write about inheritance because I was writing about the 17th century and although most people find this very surprising, the idea of there being something called heredity didn’t come about until the 1830s. So it was just this concept that didn’t exist. Yes, you could inherit debts, basically, or if you were lucky, a lot of money. But you couldn’t inherit a disease. ‘Heredity’ took on a biological meaning only in the 1830s.

Similarly, in Life’s Greatest Secret, the biggest difficulty was not talking about information, or code, at a time when those words weren’t appropriate. Genetic information, which is really the whole heart of the book, this idea that everybody shares today. If you explain to somebody what’s in a gene, if you explain to students, ultimately, it’s information. It’s information in the DNA sequence that’s going to produce a protein. That idea came about in a very particular time. In fact, we can date it very, very clearly to the end of May 1953, when Watson & Crick published their second paper in Nature. Not the one on the double helix structure, but another paper, published six weeks later, on what they called the genetical implications of that structure. That’s what the book is about. Where those ideas came from, how they sort of popped into Francis Crick’s mind, why he put them down on the page, and what happened to them once he set them into the wild.

Once you had a topic for your first book, how did you find a publisher? 

MC: It depends on what country you are in. If you’re in the UK, or the US, you need a literary agent, and simply by googling names, putting in “scientific literary agents” and your country, you’ll find various people who are appropriate. This wasn’t quite in the days before Google, but I started thinking about writing the book in about 1998…

So you went to AltaVista…

MC: [Laughs]  Not quite. I contacted Steve Jones, the UK science writer and Professor of Genetics at University College, because he’d published a lot of popular books and I wrote him a letter—or maybe an email… We had email. It wasn’t written with a quill pen. I sent him an email that said “who’s your agent?” He replied “Well, I’m not sure my agent is right for you, but this guy is just set up, he used to be the books editor at Nature, he’s called Peter Tallack.” So I sent an email to Peter basically describing what was going to be a rather boring book. I wanted to write a biography of Jan Swammerdam, this amazing 17th century anatomist and entomologist who was one of the men who could lay claim to having discovered that women have eggs. Peter was very nice about it, and he said he thought it was too academic. I said, OK, I’ll carry on writing and maybe I’ll get it published by one of the academic presses.

Then I suddenly came up with this idea of rather than write the biography, why not concentrate on this huge row that broke out in 1672 over who was the first to discover that women have eggs? This was a row that involved Swammerdam, Steno, who most people won’t have heard of, unless they’ve done Geology (he’s the guy that worked out that the different layers in rocks are looking back in time) and a third guy, who people may have heard of, who was Regnier de Graaf. de Graaf won the race in terms of history, because we now call the place where the eggs come from the Graafian follicles. So I sent Peter a paragraph focusing just on this row, this kind of men behaving badly in the middle of the 17th century, and that it happened at the same time as the Dutch Republic was being attacked by the French, so there was a war and a huge scientific row involving the Royal Society… I just sent this kind of sexed up pitch of one paragraph to him and in 10 minutes I got an email back saying “that’s really exciting, let’s do that”.

Then it was a matter of negotiating with various publishers and talking about a pitch. This is a very, very long process of writing a proposal and then the agent sends it round the publishers. You need to get an agent who is interested in your book, in your idea. Peter Tallack’s (my agent) website is Science Factory, and he’s got a very useful set of FAQs explaining what he needs to know about your idea, and why he’d be interested. The same applies to any literary agent, and they really act as a kind of quality control for the publishers. The publishers use them, and are much more likely to look through a book that comes through an agent than one that just turns up. That having been said, there is a very famous set of books about a boy wizard that was written by somebody who just sent it into a publishers and they all ignored it until about the 18th publisher picked it up. An intern had the job of going through what they call the slush pile, the rejected manuscripts, and she said “hey, Harry Potter is going to make a fortune,” and she was right. So, they don’t always know.

The final section of your book is a look at modern developments in Genetics. Where do you think the frontier is now?

MC: With the development of new sequencing techniques and new methods for looking at what the genome is doing in the cell, we can start to understand the incredibly complex network of repressors and activating molecules that are modulating the activity of genes. To really get a grip on this, we will need to build computer models of those processes, so in a way we’re going back to the ideas that Norbert Wiener came up with in the 1940s about control systems and cybernetics—which is another theme in my book. These ideas are informing systems biology and how genes and their products interact in the cell. I think ultimately it is going to be mind-bogglingly complicated. Which is kind of what we know, because the link between genotype and phenotype, unless it is something simple like eye color, is amazingly complicated. We know that it’s affected by environment and other genes and so on. We’re now beginning to understand how that occurs in molecular terms, and that’s where new models and computer models can be used and then tested by very delicate experimentation in a wide range of organisms, going beyond the traditional ‘models’ into organisms with interesting ecologies that illustrate important facets of evolution. That’s the future.

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