either obtuse or very obstinate not to think along helical lines. What Pauling did show us was that exact and careful model building could embody constraints that the final answer had in any case to satisfy. Sometimes this could lead to the correct structure, using only a minimum of the direct experimental evidence. This was the lesson that we learned and that Rosalind Franklin and Maurice Wilkins failed to appreciate in attempting to solve the structure of DNA. That, and the necessity for making no assumptions that could not be doubted from time to time. It should also be said that Jim and I were highly motivated to succeed, even if we approached problems in a relaxed manner, were quick to spot success when we saw it and to learn what lessons we could draw both from successes and from failures.
The α helix was an important milestone on the rocky path of molecular biology but it did not have the same impact as the DNA double helix did. We initially hoped that, given the basic folds of the α helix and β sheets, we might be able to solve the structure of a protein by straightforward model building. Unfortunately most proteins are too complex and too sophisticated for that. In short, these two structural cliches alerted us to what to expect in some parts of a protein but did not immediately reveal the secret of the specificity and catalytic activity of a particular protein. The structure of DNA, on the other hand, immediately gave the game away, suggesting only too vividly how nucleic acid could be replicated exactly. DNA is, at bottom, a much less sophisticated molecule than a highly evolved protein and for this reason reveals its secrets more easily. We were not to know this in advance—it was just good luck that we stumbled onto such a beautiful structure.
Pauling was a more important figure in molecular biology than is sometimes realized. Not only did he make certain key discoveries (that sickle cell anemia is a molecular disease, for example), but he had the correct theoretical approach to these biological problems. He believed that much that we needed to explain could be done using the well-established ideas of chemistry and, in particular, the chemistry of macromolecules and that our knowledge of the various kinds of atoms, especially carbon, and of the bonds that hold atoms together [the homopolar bond, electrostatic interactions, hydrogen bonds, and van der Waal’s forces] would be enough to crack the mysteries of life.
Max Delbrück, on the other hand, who started as a physicist, hoped that biology would enable us to discover new laws of physics. Delbrück also worked at Cal Tech, where Pauling was. He had pioneered important studies of certain viruses, called bacteriophage (“phage” for short), and was one of the leaders of the very influential Phage Group, of which Jim Watson was a more junior member. I don’t think Delbrück much cared for chemistry. Like most physicists, he regarded chemistry as a rather trivial application of quantum mechanics. He had not fully imagined what remarkable structures can be built by natural selection, nor just how many distinct types of proteins there might be.
Time has shown that, so far, Pauling was right and Delbrück was wrong, as indeed Delbrück acknowledged in his book, Mind into Matter. Everything we know about molecular biology appears to be explainable in a standard chemical way. We also now appreciate that molecular biology is not a trivial aspect of biological systems. It is at the heart of the matter. Almost all aspects of life are engineered at the molecular level, and without understanding molecules we can only have a very sketchy understanding of life itself. All approaches at a higher level are suspect until confirmed at the molecular level.
6
How to Live with
a Golden Helix
T HE DOUBLE HELIX is indeed a remarkable molecule. Modern man is perhaps 50, 000 years old, civilization has existed for scarcely 10, 000 years, and the United States for only just
The α helix was an important milestone on the rocky path of molecular biology but it did not have the same impact as the DNA double helix did. We initially hoped that, given the basic folds of the α helix and β sheets, we might be able to solve the structure of a protein by straightforward model building. Unfortunately most proteins are too complex and too sophisticated for that. In short, these two structural cliches alerted us to what to expect in some parts of a protein but did not immediately reveal the secret of the specificity and catalytic activity of a particular protein. The structure of DNA, on the other hand, immediately gave the game away, suggesting only too vividly how nucleic acid could be replicated exactly. DNA is, at bottom, a much less sophisticated molecule than a highly evolved protein and for this reason reveals its secrets more easily. We were not to know this in advance—it was just good luck that we stumbled onto such a beautiful structure.
Pauling was a more important figure in molecular biology than is sometimes realized. Not only did he make certain key discoveries (that sickle cell anemia is a molecular disease, for example), but he had the correct theoretical approach to these biological problems. He believed that much that we needed to explain could be done using the well-established ideas of chemistry and, in particular, the chemistry of macromolecules and that our knowledge of the various kinds of atoms, especially carbon, and of the bonds that hold atoms together [the homopolar bond, electrostatic interactions, hydrogen bonds, and van der Waal’s forces] would be enough to crack the mysteries of life.
Max Delbrück, on the other hand, who started as a physicist, hoped that biology would enable us to discover new laws of physics. Delbrück also worked at Cal Tech, where Pauling was. He had pioneered important studies of certain viruses, called bacteriophage (“phage” for short), and was one of the leaders of the very influential Phage Group, of which Jim Watson was a more junior member. I don’t think Delbrück much cared for chemistry. Like most physicists, he regarded chemistry as a rather trivial application of quantum mechanics. He had not fully imagined what remarkable structures can be built by natural selection, nor just how many distinct types of proteins there might be.
Time has shown that, so far, Pauling was right and Delbrück was wrong, as indeed Delbrück acknowledged in his book, Mind into Matter. Everything we know about molecular biology appears to be explainable in a standard chemical way. We also now appreciate that molecular biology is not a trivial aspect of biological systems. It is at the heart of the matter. Almost all aspects of life are engineered at the molecular level, and without understanding molecules we can only have a very sketchy understanding of life itself. All approaches at a higher level are suspect until confirmed at the molecular level.
6
How to Live with
a Golden Helix
T HE DOUBLE HELIX is indeed a remarkable molecule. Modern man is perhaps 50, 000 years old, civilization has existed for scarcely 10, 000 years, and the United States for only just
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