know
all that; otherwise I wouldn't be in the course. What is
lecithin
?"
"I don't know."
I had to report on papers along with everyone else, and the first one I was assigned was on the effect of pressure on cells--Harvey chose that
topic for me because it had something that had to do with physics. Although I understood what I was doing, I mispronounced everything when I read
my paper, and the class was always laughing hysterically when I'd talk about "blastospheres" instead of "blastomeres," or some other such thing.
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 exact ly 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 accidental: 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, hut 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, hut I couldn't understand
it. I don't think they ever published it. I never published it directly.
Watson thought the stuff I had done with phages was of some interest, so he invited me to go to Harvard. I gave a talk to the biology department
about the double mutations which occurred so close together. I told them my guess was that one mutation made a change in the protein, such as
changing the pH of an amino acid, while the other mutation made the opposite change on a different amino acid in the same protein, so that it
partially balanced the first imitation-- not perfectly, but enough to let the phage operate again. I thought they were two changes in the same protein,
which chemically compensated each other.
That turned out not to be the case. It was found out a few years later by people who undoubtedly developed a technique for producing and
detecting the mutations faster, that what happened was, the first mutation was a mutation in which an entire DNA base was missing. Now the "code"
was shifted and could not be read any more. The second mutation was either one in which an extra base was put back in, or two more were taken out.
Now the code could be read again. The closer the second mutation occurred to the first, the less message would he altered by the double mutation,
and the more completely the phage would recover its lost abilities. The fact that there are three "letters" to code each amino acid was thus
demonstrated.
While I was at Harvard that week, Watson suggested something and we did an experiment together for a few days. It was an incomplete
experiment, but I learned some new lab techniques from one of the best men in the field.
But that was my big moment: I gave a seminar in the biology department of Harvard! I always do that, get into something and see how far I can
go.
I learned a lot of things in biology, and I gained a lot of experience. I got better at pronouncing the words, knowing what not to include in a paper
or a seminar, and detecting a weak technique in an experiment. But I love physics, and I love to go back to it.
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