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Wednesday, November 21, 2007




Nobel Laureates: Konrad Bloch and Feodor Lynen





 
The Nobel Prize in Physiology or Medicine 1964.
"for their discoveries concerning the mechanism and regulation of the cholesterol and fatty acid metabolism"


Konrad Bloch (1912-2000) and Feodor Lynen (1911-1979) received the Nobel Prize in Physiology or Medicine for their work in deciphering the cholesterol biosynthesis pathway. 

Feodor Lynen is mainly responsible for working out the pathway from acetate (acetyl CoA) to mevalonate [How Lipitor® Works] while Konrad Bloch worked mostly on the rest of the pathway [How to Make Cholesterol][Making Squalene].

Last week's Nobel Laureate, John Cornforth, was rewarded for discovering the exact mechanisms that give rise to a stereospecific product [Nobel Laureate: John Cornforth]. 

The 1964 presentation speech was given by Professor S. Bergström, member of the Nobel Committee for Physiology or Medicine of the Royal Caroline Institute.


Your Majesties, Your Royal Highnesses, Ladies and Gentlemen.

Since the start of the Nobel Foundation the professorial staff of the Karolinska Institute has chosen the prizewinners in Physiology or Medicine. This year the Karolinska Institute has been reorganized into a medical university and the duties of the professorial staff have been taken over by the medical faculty of the enlarged Karolinska Institute. As the last item on its agenda the professorial staff was to decide this year's Nobel Prizewinners in Physiology or Medicine and on October 15 Professors Konrad Bloch and Feodor Lynen were awarded the prize for their discoveries concerning the mechanism and regulation of the cholesterol and fatty acid metabolism.

The word cholesterol means gallstone and the reason for this name is that cholesterol was isolated almost 200 years ago from human gallstones. Another connection between cholesterol and human diseases has been established more recently. During the last decade there has been a lively discussion, also in the newspapers, about the correlation between atherosclerosis and the amount of cholesterol and other fats in diet and in blood. This discussion has perhaps concealed from many the fact that cholesterol is a necessary constituent of all our cells and that it fulfills important functions. The elucidation of its chemical structure is one of the foremost achievements in organic chemistry during the 1910's and 1920's. In 1928 the German chemists Windaus and Wieland received Nobel Prizes in Chemistry for their work on the structure of cholesterol and the closely related bile acids. The four-ring carbon skeleton characteristic of cholesterol was later found not only in a number of sterols of plant and animal origin but also in the precursors of vitamin D, in the male and female sex hormones, in the hormones from the adrenal cortex, etc.

Nothing was known about the way they were formed or about their interrelationships. When this year's prizewinners started their scientific career, Professor Hevesy had done his discoveries concerning the use of isotopes as tracers in the living organism. When first the stable and later the radioactive isotopes of hydrogen and carbon became available, they were first extensively used by a group at Columbia University that was headed by the late Rudolph Schoenheimer and in which Bloch played an important role. The work of the group with isotopically labeled compounds has laid the foundation of our general knowledge of the dynamic state in the living cell.

One of the fundamental discoveries was the elucidation of the role of acetic acid as a building block for cholesterol as well as fatty acids. Lynen, working in Wieland's laboratory on the metabolism of acetic acid, succeeded in isolating the so-called activated acetic acid, which is the precursor of all lipids in our body and the common denominator of a number of metabolic processes. With all possible refinements in the utilization of isotope techniques, Bloch and collaborators were able to show in a series of brilliant investigations how the two carbon atoms of acetic acid are used for the synthesis of a long hydrocarbon with thirty carbon atoms, squalene, which in turn is cyclized in a novel type of reaction to a steroid with thirty carbon atoms, lanosterol. This lanosterol is then transformed in a complicated series of reactions into cholesterol, which has twenty-seven carbon atoms. Of special interest are the reactions leading to the formation of the hydrocarbon squalene, and the elucidation of these reactions, which are common for the biosynthesis of many other lipids and natural products, is due not only to Bloch and Lynen and collaborators but also to Popjak and Cornforth in England and Folkers and co-workers in the U.S.A. In connection with this work Lynen made two other discoveries of great importance to our understanding of the mechanisms of cellular metabolism: the elucidation of the mechanism of action of the vitamin biotin and the determination of the structure of cytohemin.

At an early stage Bloch made another discovery of fundamental importance in showing that cholesterol is the precursor of bile acids and of one of the female sex hormones. These discoveries opened up a new field of research that has engaged a great number of scientists in different disciplines. We know now that all substances of steroid nature in our body are formed from cholesterol.

Mainly through the basic biochemical work of this year's prizewinners do we know today in detail how cholesterol and fatty acids are synthesized and metabolized in the body. These processes comprise series of reactions with a great number of individual steps. For instance, the formation of cholesterol from acetic acid is a process involving some thirty different steps. Derangements of this complicated mechanism of formation and metabolism of lipids are in many cases responsible for the genesis of some of our most important diseases, especially in the cardiovascular field. A detailed knowledge of the mechanisms of lipid metabolism is necessary to deal with these medical problems in a rational manner.

The importance of the work of Bloch and Lynen lies in the fact that we now know the reactions which have to be studied in relation to inherited and other factors. We can now predict that we, through further research in this field in the near future, can expect to be able to do individual specific therapy against the diseases that in the developed countries are the most common cause of death.

 

Professor Bloch, Professor Lynen. You have both started your research in Munich and you have proceeded the proud tradition of this town in a splendid way.

Feodor Lynen, you are now standing with dignity in the array of the earlier Munich Nobel Prizewinners, Adolf von Baeyer, Hans Fischer and Heinrich Wieland.

Konrad Bloch, you have like Emil Fischer and Richard Willstätter left Munich and continued your work in the New World.

I have made a very short summary of your successful research work in the field of lipids. You have provided us with detailed knowledge of many fundamental metabolic reactions. This knowledge forms the necessary basis for the study of the different medical problems in the field of lipid metabolism.

It can now be anticipated that in the near future we will learn how to deal with many of these diseases in a rational and successful way.

On behalf of the Caroline Institute I have the honour to congratulate you on your brilliant work and I now ask you to receive your prizes from the hands of His Majesty the King.


[Photo Credits: Konrad Bloch plaque is from Wikipedia. Restricted photos of Feodor Lynen are available on ViewImages]




Posted by Larry Moran at Wednesday, November 21, 2007
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Laurence A. Moran



Larry Moran is a Professor Emeritus in the Department of Biochemistry at the University of Toronto. You can contact him by looking up his email address on the University of Toronto website.


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The Sandwalk is the path behind the home of Charles Darwin where he used to walk every day, thinking about science. You can see the path in the woods in the upper left-hand corner of this image.


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Some readers of this blog may be under the impression that my personal opinions represent the official position of Canada, the Province of Ontario, the City of Toronto, the University of Toronto, the Faculty of Medicine, or the Department of Biochemistry. All of these institutions, plus every single one of my colleagues, students, friends, and relatives, want you to know that I do not speak for them. You should also know that they don't speak for me.



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Quotations

The old argument of design in nature, as given by Paley, which formerly seemed to me to be so conclusive, fails, now that the law of natural selection has been discovered. We can no longer argue that, for instance, the beautiful hinge of a bivalve shell must have been made by an intelligent being, like the hinge of a door by man. There seems to be no more design in the variability of organic beings and in the action of natural selection, than in the course which the wind blows.Charles Darwin (c1880)


Although I am fully convinced of the truth of the views given in this volume, I by no means expect to convince experienced naturalists whose minds are stocked with a multitude of facts all viewed, during a long course of years, from a point of view directly opposite to mine. It is so easy to hide our ignorance under such expressions as "plan of creation," "unity of design," etc., and to think that we give an explanation when we only restate a fact. Any one whose disposition leads him to attach more weight to unexplained difficulties than to the explanation of a certain number of facts will certainly reject the theory.

Charles Darwin (1859)


Science reveals where religion conceals. Where religion purports to explain, it actually resorts to tautology. To assert that "God did it" is no more than an admission of ignorance dressed deceitfully as an explanation...

Peter Atkins

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Quotations

The world is not inhabited exclusively by fools, and when a subject arouses intense interest, as this one has, something other than semantics is usually at stake. Stephen Jay Gould (1982)
I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory. Stephen Jay Gould (2002) p.1339
The essence of Darwinism lies in its claim that natural selection creates the fit. Variation is ubiquitous and random in direction. It supplies raw material only. Natural selection directs the course of evolutionary change. Stephen Jay Gould (1977)
Rudyard Kipling asked how the leopard got its spots, the rhino its wrinkled skin. He called his answers "just-so stories." When evolutionists try to explain form and behavior, they also tell just-so stories—and the agent is natural selection. Virtuosity in invention replaces testability as the criterion for acceptance. Stephen Jay Gould (1980)
Since 'change of gene frequencies in populations' is the 'official' definition of evolution, randomness has transgressed Darwin's border and asserted itself as an agent of evolutionary change. Stephen Jay Gould (1983) p.335
The first commandment for all versions of NOMA might be summarized by stating: "Thou shalt not mix the magisteria by claiming that God directly ordains important events in the history of nature by special interference knowable only through revelation and not accessible to science." In common parlance, we refer to such special interference as "miracle"—operationally defined as a unique and temporary suspension of natural law to reorder the facts of nature by divine fiat. Stephen Jay Gould (1999) p.84

Quotations

My own view is that conclusions about the evolution of human behavior should be based on research at least as rigorous as that used in studying nonhuman animals. And if you read the animal behavior journals, you'll see that this requirement sets the bar pretty high, so that many assertions about evolutionary psychology sink without a trace.

Jerry Coyne
Why Evolution Is True
I once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of them should be allowed to come back.

Sydney Brenner
TIBS Dec. 2000
It is naïve to think that if a species' environment changes the species must adapt or else become extinct.... Just as a changed environment need not set in motion selection for new adaptations, new adaptations may evolve in an unchanging environment if new mutations arise that are superior to any pre-existing variations

Douglas Futuyma
One of the most frightening things in the Western world, and in this country in particular, is the number of people who believe in things that are scientifically false. If someone tells me that the earth is less than 10,000 years old, in my opinion he should see a psychiatrist.

Francis Crick
There will be no difficulty in computers being adapted to biology. There will be luddites. But they will be buried.

Sydney Brenner
An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist

Richard Dawkins
Another curious aspect of the theory of evolution is that everybody thinks he understand it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology.

Jacques Monod
The false view of evolution as a process of global optimizing has been applied literally by engineers who, taken in by a mistaken metaphor, have attempted to find globally optimal solutions to design problems by writing programs that model evolution by natural selection.

Richard Lewontin

Principles of Biochemistry 5th edition

Principles of Biochemistry 5th edition
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Principles of Biochemistry: International Edition
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Biochemistry 2nd ed. (1994)

Biochemistry  2nd ed. (1994)
Moran, L.A.,
Scrimgeour, K.G. et al.