The next paper selected for me was by Adrian and Bronk. They demonstrated that nerve impulses were sharp, single-pulse phenomena. They had done experiments with cats in which they had measured voltages on nerves.
I began to read the paper. It kept talking about extensors and flexors, the gastrocnemius muscle, and so on. This and that muscle were named, but I hadn’t the foggiest idea of where they were located in relation to the nerves or to the cat. So I went to the librarian in the biology section and asked her if she could find me a map of the cat.
“A map of the cat, sir?” she asked, horrified. “You mean a zoological chart!” From then on there were rumors about some dumb biology graduate student who was looking for a “map of the cat.”
When it came time for me to give my talk on the subject, I started off by drawing an outline of the cat and began to name the various muscles.
The other students in the class interrupt me: “We know all that!”
“Oh,” I say, “you do? Then no wonder I can catch up with you so fast after you’ve had four years of biology.” They had wasted all their time memorizing stuff like that, when it could be looked up in fifteen minutes.
After the war, every summer I would go traveling by car somewhere in the United States. One year, after I was at Caltech, I thought, “This summer, instead of going to a different place, I’ll go to a different field.”
It was right after Watson and Crick’s discovery of the DNA spiral. There were some very good biologists at Caltech because Delbrück had his lab there, and Watson came to Caltech to give some lectures on the coding systems of DNA. I went to his lectures and to seminars in the biology department and got full of enthusiasm. It was a very exciting time in biology, and Caltech was a wonderful place to be.
I didn’t think I was up to doing actual research in biology, so for my summer visit to the field of biology I thought I would just hang around the biology lab and “wash dishes,” while I watched what they were doing. I went over to the biology lab to tell them my desire, and Bob Edgar, a young post-doc who was sort of in charge there, said he wouldn’t let me do that. He said, “You’ll have to really do some research, just like a graduate student, and we’ll give you a problem to work on.” That suited me fine.
I took a phage course, which told us how to do research with bacteriophages (a phage is a virus that contains DNA and attacks bacteria). Right away I found that I was saved a lot of trouble because I knew some physics and mathematics. I knew how atoms worked in liquids, so there was nothing mysterious about how the centrifuge worked. I knew enough statistics to understand the statistical errors in counting little spots in a dish. So while all the biology guys were trying to understand these “new” things, I could spend my time learning the biology part.
There was one useful lab technique I learned in that course which I still use today. They taught us how to hold a test tube and take its cap off with one hand (you use your middle and index fingers), while leaving the other hand free to do something else (like hold a pipette that you’re sucking cyanide up into). Now, I can hold my toothbrush in one hand, and with the other hand, hold the tube of toothpaste, twist the cap off, and put it back on.
It had been discovered that phages could have mutations which would affect their ability to attack bacteria, and we were supposed to study those mutations. There were also some phages that would have a second mutation which would reconstitute their ability to attack bacteria. Some phages which mutated back were exactly the same as they were before. Others were not: There was a slight difference in their effect on bacteria—they would act faster or slower than normal, and the bacteria would grow slower or faster than normal. In other words, there were “back mutations, but they weren’t always perfect; sometimes the phage would recover only part of the ability it had lost.
Bob Edgar suggested that I do an experiment which would try to find out if the back mutations occurred in the same place on the DNA spiral. With great care and a lot of tedious work I was able to find three examples of back mutations which had occurred very close together—closer than anything they had ever seen so far—and which partially restored the phage’s ability to function. It was a slow job. It was sort of accidentaclass="underline" You had to wait around until von got a double mutation, which was very rare.
I kept trying to think of ways to make a phage mutate more often and how to detect mutations more quickly, but before I could come up with a good technique the summer was over, and I didn’t feel like continuing on that problem.
However, my sabbatical year was coming up, so I decided to work in the same biology lab but on a different subject. I worked with Matt Meselson to some extent, and then with a nice fella from England named J. D. Smith. The problem had to do with ribosomes, the “machinery” in the cell that makes protein from what we now call messenger RNA. Using radioactive substances, we demonstrated that the RNA could come out of ribosomes and could be put back in.
I did a very careful job in measuring and trying to control everything, but it took me eight months to realize that there was one step that was sloppy. In preparing the bacteria, to get the ribosomes out, in those days you ground it up with alumina in a mortar. Everything else was chemical and all under control, but you could never repeat the way you pushed the pestle around when you were grinding the bacteria. So nothing ever came of the experiment.
Then I guess I have to tell about the time I tried with Hildegarde Lamfrom to discover whether peas could use the same ribosomes as bacteria. The question was whether the ribosomes of bacteria can manufacture the proteins of humans or other organisms, She had just developed a scheme for getting the ribosomes out of peas and giving them messenger RNA so that they would make pea proteins. We realized that a very dramatic and important question was whether ribosomes from bacteria, when given the peas’ messenger RNA, would make pea protein or bacteria protein. It was to be a very dramatic and fundamental experiment.
Hildegarde said, “I’ll need a lot of ribosomes from bacteria.”
Meselson and I had extracted enormous quantities of ribosomes from E. coli for some other experiment. I said, “Hell, I’ll just give you the ribosomes we’ve got. We have plenty of them in my refrigerator at the lab.”
It would have been a fantastic and vital discovery if I had been a good biologist. But I wasn’t a good biologist. We had a good idea, a good experiment, the right equipment, but I screwed it up: I gave her infected ribosomes—the grossest possible error that you could make in an experiment like that. My ribosomes had been in the refrigerator for almost a month, and had become contaminated with some other living things. Had I prepared those ribosomes promptly over again and given them to her in a serious and careful way, with everything under control, that experiment would have worked, and we would have been the first to demonstrate the uniformity of life: the machinery of making proteins, the ribosomes, is the same in every creature. We were there at the right place, we were doing the right things, but I was doing things as an amateur—stupid and sloppy.
You know what it reminds me of? The husband of Madame Bovary in Flaubert’s book, a dull country doctor who had some idea of how to fix club feet, and all he did was screw people up. I was similar to that unpracticed surgeon.
The other work on the phage I never wrote up—Edgar kept asking me to write it up, but I never got around to it. That’s the trouble with not being in your own field: You don’t take it seriously.
I did write something informally on it. I sent it to Edgar, who laughed when he read it. It wasn’t in the standard form that biologists use—first, procedures, and so forth. I spent a lot of time explaining things that all the biologists knew. Edgar made a shortened version, but I couldn’t understand it. I don’t think they ever published it. I never published it directly.