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"The Impact of Linus Pauling on Molecular Biology."

"The Impact of Linus Pauling on Molecular Biology." February 28, 1995.
Talk delivered at the Pauling Symposium, Oregon State University.

Excitement Over Pauling's Nature Article. (3:53)

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Transcript

Francis Crick: I came across an article in Nature about sickle-cell hemoglobin, by Linus Pauling, in which he said it was a molecular disease. It had been shown quite recently by geneticists that indeed the gene for it was inherited in a Mendelian manner. I will not go into the details, but it looked as if it were caused by a single gene. What Linus and his co-workers had shown was that there was a change in the hemoglobin molecule, so that under electrophoresis it moved at a different rate. In other words, one of the charge residues had been changed.

And I remember how excited I was at this idea, because this was the sort of thing I was very interested in. I was very interested in genes. Here was presumably a gene product. It looked much the same, as far as one could tell, in many of its properties, but there clearly had been some change. As a result of that article, when Vernon Ingram came to join us at the lab, he and I wanted to find out what happened when there was a mutation in a gene. Did it affect that particular protein which we believed was controlled by that gene? We did not make any progress on that. We tried working on lysozymes and various other things, but Vernon received a specimen, I think through Perutz, of sickle cell anemia hemoglobin, and he was able to show that Linus was right. There was a change in a single amino acid. Here we had a very dramatic case of a disease where, if you have two bad copies of the gene, you probably at least in those days would not live much beyond your teens. And yet it is a change, as we know now, of just one base pair in the DNA, one amino acid in the protein.

You may ask "how it is possible that a small molecular change can do something which will kill you?" But you realize that in the red cell, first of all, there are many copies made of the gene onto the messenger RNAs, so there is amplification there. But there is amplification before that, because from the fertilized egg there come many, many red cells. There are an enormous number of red cells being made by a stem cell, because the cell is dividing, so you have got a lot of red cells in your blood which carry the hemoglobin. Then the messenger RNAs produce many copies of the molecule. Thus, in fact, you get a large mass of not very good molecule, even though it is a very tiny change in the egg and the sperm. Just one or two atoms here and there is enough to make a change which is potentially lethal.

Nowadays, of course, these ideas are commonplace, but in those days that was not the case. You may be surprised to know that most people who worked on protein chemistry wanted to know merely what the composition was. Fred Sanger had just been doing the sequence of the first protein to be sequenced, which was insulin. Protein biochemists really had no idea their subject had anything to do with genetics. Those of you who are in the field may find this absolutely astonishing, because now it is commonplace. One of the major functions of genes is for each one to code for a particular protein. That was not known in those days, so this was a very dramatic case. In fact, as a result of it, Sydney Brenner, Seymour Benzer, and I gave lectures to Fred Sanger's group on the elements of genetics. It was the first time they realized that they had to learn something about the subject. Nowadays, of course, all of you who go into these things learn it right from the beginning and take it as a matter of course. And it was very much sparked off by this discovery of Linus that sickle cell hemoglobin was, as he said, a molecular disease.

Clip

Creator: Francis Crick
Associated: Linus Pauling, Max Perutz, Frederick Sanger, Sydney Brenner, Seymour Benzer, Vernon M. Ingram
Clip ID: 1995v.1-article

Full Work

Creator: Francis Crick
Associated: Linus Pauling, Oregon State University

Date: February 28, 1995
Genre: video
ID: 1995v.1
Copyright: More Information


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