Russell From Gene to Protein: Information Transfer in Normal and Abnormal Cells

1. Auflage 2012
ISBN: 978-0-323-14370-7
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 668 Seiten

Miami Winter Symposia, Volume 16: From Gene to Protein: Information Transfer in Normal and Abnormal Cells presents the expression and processing of genetic information at the levels of both proteins and nucleic acids. This book deals with the reassembly and mobilization of genetic information. Organized into 105 chapters, this volume begins with an overview of the discovery of the double helix and the search for the genetic code and the three-dimensional structure of protein. This text then examines the molecular mechanism by which steroid hormones regulate specific gene expression. Other chapters consider the possible hazards inherent to hybrid DNA technology. This book discusses as well the various problems of gene control in higher organisms, which are illustrated by the changes that occur in the hemoglobin of mammals. The final chapter deals with the characterization of adenovirus-2 mRNAs. This book is a valuable resource for biochemists, genetic engineers, enzymologists, scientists, geneticists, and molecular biologists.

Autoren/Hrsg.

Russell, Thomas

Leseproben

HOW TO LIVE WITH A GOLDEN HELIX

Francis Crick1,     The Salk Institute, La Jolla, California

Publisher Summary

This chapter focuses on the discovery of the structure of DNA. RNA can form a double helix similar in its base-pairing rules to DNA. Both nucleic acids can form triple helices and some DNA molecules, having the purines and pyrimidines segregated on different chains, may even be able to form a four-stranded structure. Poly I also appears to be four stranded. Double helices with parallel chains—rather than anti-parallel—can be formed by special molecules such as poly A; however, whether such a structure has any biological significance remains to be seen. In transfer RNA unusual base-pairs and base-triples abound. DNA molecules—both single- and double-stranded—can be circular. Intact circular double-stranded DNA is often found supercoiled. There appear to be many mechanisms for DNA addition, translocation, and multiplication. If these processes are at least partly random, then in an organism where most DNA is not exon DNA, the commonest sequences to be moved around are likely to be those of introns and intergenic spacers. Thus, intron size in evolution may be a dynamic balance between additions and deletions.

The Lynen Lecture is traditionally an occasion for a broad overview of one’s life and scientific interests, or at least some part of them; an occasion for reminiscences of the past together with a few speculations about the future. I shall try to conform to this agreeable format as far as I can but I have a difficulty. I can hardly avoid saying something about the discovery of the structure of DNA, if only because audiences invariably show such a keen interest in it, although I notice that they are usually less concerned with the scientific aspects than the psychological ones. “What did it feel like?” they ask. An embarrassing question, since after almost 25 years I have some difficulty in recalling in detail the curious combination of excitement, euphoria, and skepticism which we experienced at the time.

My main problem is that the discovery has been described in print several times already, not only by Jim Watson in that rather breathless fragment of his autobiography he called “The Double Helix” (perhaps “Lucky Jim” would have been a better title), but also, in a more sober, detailed and scholarly way by Bob Olby (“The Path to the Double Helix”). At least one TV documentary has been made about it. Leaving more ephemeral effusions, whether girlish or soured, on one side we shall soon have an excellent account by Horace Judson. His book, “The Eighth Day of Creation,” to be published in the spring of 1979, covers not only the discovery of the double helix but also the search for the genetic code and the three-dimensional structure of proteins. Very well researched, scientifically accurate and written in a lively and readable style, it reveals more about the way molecular biology was done and about the people who did it than any other account I know.

Some of you may have already seen three extracts from it which appeared last year in the New Yorker. If you enjoyed these, I think you will like the more extended account in the book itself.

What more can I add? Before the whole thing gets out of hand and becomes an academic cottage industry I think a dose of cold water would do no harm. No doubt it is fascinating to read just how a scientific discovery is made; the misleading experimental data, the false starts, the long hours spent chewing the cud, the darkest hour before the dawn, and then the moment of illumination, followed by the final run down the home straight to the winning post.

And what a cast of characters! The Brash Young Man from the Middle West, the Englishman who talks too much (and therefore must be a genius since geniuses either talk all the time or say nothing at all), the older generation, replete with Nobel Prizes, and best of all, a Liberated Woman who appears to be unfairly treated. And in addition, what bliss, some of the characters actually quarrel, in fact almost come to blows. The reader is delighted to learn that after all, in spite of science being so impossibly difficult to understand, SCIENTISTS ARE HUMAN, even though the word “human” more accurately describes the behavior of mammals rather than anything peculiar to our own species, such as mathematics. Surely the script must have been written, not in heaven, but in Hollywood.

Unfortunately a closer study shows that real life is not always exactly like a soap opera. Not everybody was competing madly, with one eye on Stockholm. In actual fact there was a considerable amount of cooperation mixed in with the inevitable competition. The major opposition Rosalind Franklin had to cope with was not from her scientific colleagues, nor even from King’s College, London (an Anglican foundation, it should be noted, and therefore inherently biased against women) but from her affluent, educated and sympathetic family who felt that scientific research was not the proper thing for a normal girl. Rosalind’s difficulties and her failures were mainly of her own making. Underneath her brisk manner she was oversensitive and, ironically, too determined to be scientifically sound and to avoid short cuts. She was rather too set on succeeding all by herself and rather too stubborn to accept advice easily from others when it ran counter to her own ideas. She was proffered help but she would not take it. The soap opera has many other distortions and simplifications. I need not elaborate further. The plain fact that science is largely an intellectual pursuit, that it involves an enormous amount of hard, often grinding, work (both theoretical and experimental), that it is based upon an immense body of closely interlocking facts and theories, much of which must be thoroughly mastered before any progress at all can be made — all this tends to be submerged in the popular mind beneath those personal aspects which ordinary people relate to more easily. It is certainly an excellent idea to kill the stereotype of the cold, impersonal scientist in the white coat — such people do exist but they are as dull in science as they are in life — but we must not let the public think that because they understand some of our motives they thereby understand what science is about. The most surprising characteristic of modern western society is that in spite of being largely based on science and technology, the average citizen understands so little about the scientific enterprise. It is not only that elementary scientific facts are not known (the shape of H2O, for example) but there is an almost complete lack of any scientific overview, a lack of any description, even in outline, of what is well established, what we still have to discover, and how we hope to go about discovering it.

Let me return for a moment to the discovery of the double helix. I think what needs to be emphasized is that the path to the discovery was, scientifically speaking, fairly commonplace. What was important was not the way it was discovered but the object discovered — the structure of DNA itself. One can see this by comparing it with almost any other scientific discovery. Misleading data, false ideas, problems of personal interrelationships occur in much if not all scientific work. Consider, for example, the discovery of the basic structure of collagen. It will be found to have all these elements. The characters are just as colorful and diverse. The facts were just as confused and the false solutions just as misleading. Competition and friendliness also played a part in the story. Yet nobody has written even one book about “The Race for the Triple Helix.” This is surely because, in a very real sense, collagen is not as important a molecule as DNA.

Of course this probably depends upon what you consider important. Before Alex Rich and I worked (quite by accident, incidentally) on collagen we tended to be rather patronizing about it. “After all,” we said, “there’s no collagen in plants.” After we got interested in the molecule we found ourselves saying, “Do you realize that one-third of all the protein in your body is collagen?” But however you look at it, DNA is more important than collagen, more central to biology, and more significant for further research. So, as I have said before: it is the molecule which has the glamor, not the scientists.

There was in the early fifties a small, somewhat exclusive biophysics club at Cambridge, called the Hardy Club, named after a Cambridge zoologist of a previous generation who had turned physical chemist. The list of those early members now has an illustrious ring, replete with Nobel Laureates and Fellows of the Royal Society, but in those days we were all fairly young and most of us not particularly well-known. We boasted only one F.R.S. — Alan Hodgkin — and one member of the House of Lords — Victor Rothschild. Jim was asked to give an evening talk to this select gathering. The speaker was customarily given dinner first at Peterhouse. The food there was always good but the speaker was also plied with sherry before dinner, wine with it, and, if he was so rash as to accept it, drinks after dinner as well. I have seen more than one speaker struggling to find his way into his topic through a haze of alcohol. Jim was no exception. In spite of it all he managed to give a...