Tom Maniatis on Writing and Science: Molecular Cloning
  Tom Maniatis     Biography    
Recorded: 22 Mar 2003

So, the history of that book is that I was asked by Jim, it must have been in 1980, to teach a course on molecular cloning, a summer course at Cold Spring Harbor. And I look back at that and can’t imagine how I agreed to do that because I was a young professor at Caltech. I had a big lab. I was on the study section. I had all sorts of things to do and these courses take a huge effort because you have to plan all the experiments and the lectures beforehand. But anyway I did that.

And at the time at Caltech, as I said, we had developed cDNA cloning, we had developed genomic cloning, and we really had, basically, all the tools of recombinant DNA working in our lab. We were applying them to understand gene regulation. And I had a number of really exceptional people at the lab who were technically amazing. And so we taught this course and in order to teach it we had to put together a list of protocols, or I mean a volume of protocols. So in the six months prior to that first course we actually wrote a rough draft of a manual for this course. And it was just, at first just throwing protocols together. We gave it to the students in that first year.

And at the end of the course Jim approached me and said, you know, I think it would really be great to turn this, you know, this list of protocols into a manual that could be—you know, Cold Spring Harbor Press would publish. Of course, that’s the last thing I wanted to hear at the time because of all these other things. And at first I was very reluctant and I actually was so focused on what I was doing that I couldn’t really even imagine the value of this, you know. In fact what I thought was that, well, maybe it could be used by labs that do this work and have new students come in. But, of course, it turns out that the big impact was not on that but on people in entirely different fields, medicine, plant biology, and so on.

But anyway, so I was reluctant and then he said, well, you know there’s a guy here that’s really a superb writer and you know—that could be involved in it. And I was wondering who that would be and he said, Joe Sambrook. And it was funny because, as I told you earlier, Joe’s initial reaction to me was quite negative, but over the two years that I was there we became much closer because I was—worked very closely with Mike Botchan who was his postdoc. And at the end of that time there was, developed some mutual respect between us. But there was no real personal friendship or anything. So again at first I thought, well I’m not sure that that’s the best thing. But I realized that if it was going to happen that would be the best way to do it because Joe would be at Cold Spring Harbor. He could work with the people there. He, you know, he was known as an extremely good writer and so on. So we started this. And it was Ed Fritsch, who was the postdoc that put the initial collection of protocols together in my lab, and Joe and I.

And we started writing this and it really evolved in an amazing way because as we wrote it we realized that if it was going to be useful there had to be a lot of sort of conceptual information. And at the time it was really important because no one knew, I mean this technology was known to very few people and there weren’t kits. You couldn’t just, you know, call your favorite biotech company and get a kit for this and that. And so it meant that if people were going to use this technology successfully they had to know how to troubleshoot. And the only way they could troubleshoot is if they understood the conceptual basis behind the techniques. So the way we organized it was to write introductory pieces to each of the chapters outlining, you know for example, bacteriophage Lambda, genetics and so on.

And as it came together it became clearer and clearer that that was going to work. And so it was a huge labor. I mean we put in an enormous amount of time in this. And Joe fulfilled a number of important functions. One is that he was a terrific editor; secondly, he was very critical and we had a lot of very difficult critical interactions and finally he kept it going. Because Ed, at that point, left for a faculty position in Michigan. I was deeply involved in my lab and in all these other things, a study section. And so I could always find reasons not to work on it. But there would be a phone call from Joe, have you got this chapter. And, you know, Joe didn’t mince words when he called: “Have you got that chapter ready?” and so on. And so he kept the pressure on. And I think that was really important for me because I had all these other things to do. And so it finally came together. And what we found is that the more we wrote the more we would have to go back and change it because things were moving so fast and so finally we had to call an end to it.

And, of course, you know; now it turns out to be extremely important. What it did was to introduce this technology to the broadest possible biological community at a time in which there was nothing out there. And so it had a huge impact. And it was translated into many different languages. In fact, actually, I was giving a talk last week at Rutgers and a Russian came up to me and he had this little blue book which was the translation of the manual into Russian. And he asked if I would sign it for him.

And, you know, and actually what the funny thing that happened was that Taiwan had a—they pirated it. So they actually published it in huge numbers and sold it in China. And so there are enormous numbers of it. And somebody told me that when they visited China they would go in and every student would have on their lab bench, you know, this pirated copy of the cloning manual.

So that, you know, the bottom line is that this is just another one of the amazing things that Jim does, you know. He could see before any of us that there was a need for us because, you know, we were so focused on our careers and all that stuff and Jim was standing back and realized that this was—the timing was right. And it was really important to do. And so it was his idea.

Tom Maniatis, molecular biologist, is a leader in the field of recombinant DNA. At Vanderbilt University he completed his Ph.D. studying DNA wide-angle scattering. He became a postdoctoral fellow and professor at Harvard University and met Jim Watson just before he became director of Cold Spring Harbor Laboratory.

While Maniatis was beginning experimentation with cDNA cloning and gene regulation of higher cells, the controversy over recombinant DNA in Cambridge stunted his progression. Watson offered Maniatis a position at CSHL where he could work more efficiently to understand the methods of recombinant DNA. At CSHL, Maniatis completed full-length synthesis of double stranded DNA and actual cloning of cDNA.

He is currently a professor of molecular and cellular biology at Harvard University studying the mechanisms involved in the regulation of RNA transciption and pre-messenger RNA splicing. He studies transcription to understand how eukaryotic genes are activated by viral infection and extracellular signals.