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Wednesday, July 23, 2008

Climbing Mount Improbable as Metaphor

 
One of my postings, Good Science Writers: Richard Dawkins, has been re-posted on RichardDawkins.net. This doesn't happen very often—in fact this may be the very first time. I can't imagine why they would have selected this particular posting.

I mentioned that some of the Dawkins metaphors are misleading and I suggested that Climbing Mount Improbable was one example. That prompted a comment from Richard Dawkins so I replied on his website. In case anyone is interested, I'm reproducing it here.



Richard Dawkins asks,

I am interested in the suggestion that Climbing Mount Improbable might not be an ideal title.

Richard, we've been over this ground before but for the benefit of the lurkers let me explain why I think the metaphor is inappropriate.

To begin with, you use the Mt. Improbable image as a metaphor for evolution. This is misleading since evolution encompasses more than just adaptation. It would be difficult to apply the "Climbing Mt. Improbable" metaphor to the organization of our genome, for example, since it's clearly not well-designed and could never be characterized as the peak of an adaptive landscape.

But even as a metaphor for adaptation the image is less than perfect. Most readers will see the peak of Mt. Improbable as a goal of adaptation, implying that evolution somehow recognizes that there is an ultimate perfection that all organisms seek to achieve by reaching the summit. As you well know (I hope) there are very few (any?) species that are perfectly adapted to their environment. If this were true, adaptation would cease because the species resides on the summit of Mt. Improbable.

Thus, in the real world, species tend to move about in the foothills rather than attempt to scale the highest peak. As long as they are good enough to survive and reproduce that's all that's required.

Yes, some individuals within the population might acquire a mutation that makes them a little more fit but in most cases the selective advantage will be too small to make much of a difference. I don't believe there's any great pressure to get to the top of Mt. Improbable. That's why we usually don't see perfection in nature. And it explains why most organisms do not look as though they have been designed by some intelligent being. If anything the "design" looks more like a Rube Goldberg creation, and I doubt that anyone would say that those creations represent the peak of perfection.

I prefer a different view of evolution, one that emphasizes chance and accident [Evolution by Accident]. For me, the metaphor of "Climbing Mt. Improbable" is quite wrong as a metaphor of evolution.

Now, I understand that you disagree about the role of chance and accident. You say, for example, on page 326 of Climbing Mt. Improbable, "It is all the product of an unconscious Darwinian fine-tuning, whose intricate perfection we should not believe if it were not before our eyes" (referring to the evolution of figs and fig wasps). For someone who believes that such a description is characteristic of most evolution (adaptation) the "Climbing" metaphor may seem quite appropriate.

BTW, I agree with you that your case for adaptationism is much stronger in Climbing Mt. Improbable than in The Blind Watchmaker. I especially like the chapter you mention, The Museum of All Shells, where you discuss - among other things - the contrast between your view of evolution and the mutationist view. Ironically, you begin that discussion by pointing out that this is a sophisticated controversy, "... and Mount Improbable, even in its multiple-peaked version, isn't a powerful enough metaphor to explore it."


Nobel Laureate: George de Hevesy

 

The Nobel Prize in Chemistry 1943.

"for his work on the use of isotopes as tracers in the study of chemical processes"


George de Hevesy (1885 - 1966) received the 1943 Nobel Prize in Chemistry for his work on tracing the synthesis of biological molecules using radioactive isotopes, such as 32P.

He was able to show, for example, that 32P is readily incorporated into phosphatides (lipids) in chickens and mammals (including humans) but that incorporation into nucleic acids was much slower unless the tissues were growing rapidly. de Hevesy also showed that 32P from labeled ATP could be incorporated into fructose-1,6-bisphosphate during glycolysis. This was the beginning of studies using radioisotopes to elucidate biochemical pathways.

The presentation speech was delivered by Professor A. Westgren, member of the Nobel Committee for Chemistry of the Royal Swedish Academy of Sciences in a radio address on December 10, 1943. The situation in Europe at the time made travel to Sweden quite difficult so there was no formal awards ceremony, even though de Hevesy was at Stockholm University.

When, in 1913, de Hevesy was working with Rutherford in Manchester, this young scientist had been commissioned to isolate radium D from radioactive lead. His efforts were unsuccessful. It had in fact become apparent that radioactive radium D differed so little from inactive radium G, the last of the series of descendants of radium, that all attempts to isolate them from each other seemed destined to failure. The reason for this was at the same time discovered. Radium D and radium G are isotopes and constitute different species of lead. They differ in their atomic weight whilst their atoms have the same nuclear charge. The shells of their electrons, shells which determine their chemical properties, are therefore more or less identical.

Although unsuccessful, de Hevesy's efforts were not wasted. They gave him the idea for a new method of chemical research.

If it is impossible to isolate chemically a radioactive isotope from an element of which it is part, it must be possible to use this peculiarity to follow in its details the behaviour of this element during chemical reactions and physical processes of different kinds. The active atoms are recognized by their radiation and, being faithful companions of the inactive atoms of an element, they serve as markers for them. Since the intensity of radiation can be determined with such precision that imponderable quantities can be measured in this way, extremely small quantities of a marker of this kind are sufficient.

By using radium D as a marker, de Hevesy determined the solubility of highly insoluble lead compounds. He succeeded in determining exactly the quantity of lead sulphide or of lead chromate taken up under different conditions from solvents of different types. He studied the exchangeability of lead atoms into the dissolved substances and was able to confirm that it corresponded to the behaviour of the lead atoms as ions. The movements of the atoms in solid lead, i.e. the self-diffusion which occurs in this metal, would be determined; it had previously been impossible to measure this process. By precipitating thorium B, a very active isotope of lead, on the surface of a lead crystal and by following the reduction in radiation intensity brought about by the changes in place of the active atoms with the inactive lead atoms of the lower layer, and hence with the penetrations which took place in the crystal, he was able to measure the energy needed to liberate an atom from the crystallised part of the lead, in other words the dissociation energy of the crystal lattice. This energy was found to be of the same order of magnitude as the heat of vaporisation of lead. This latter research is particularly interesting from the physico-chemical point of view.

The new method has also enabled biological processes to be studied. Beans placed in solutions containing lead salts with a mixture of active lead atoms absorbed a part of these salts but the distribution of the metal was not the same in the root, the stem and the leaves. Most of the lead, which does not favour natural biological development but on the contrary acts as a poison, stays in the root. Relatively more lead was extracted from dilute than from more concentrated solutions. Absorption and elimination of lead, bismuth and thallium salts by animal organisms was studied in this way. A knowledge of the distribution of bismuth compounds introduced into an animal organism is valuable from the medical point of view, since some of these compounds, as we know, are used therapeutically.

So long as natural radioactive elements only were used as markers, use of the new method was inevitably very limited. In fact the method could be applied only in the case of heavy metals - lead, thorium, bismuth and thallium - and their compounds. The situation was to be very different when Frédéric and Irène Joliot-Curie, and Fermi succeeded in producing radioactive isotopes from any element by bombarding it with particles. This discovery was made some ten years ago and the study of chemical processes by means of radioactive markers has since then been carried to such a point that it is now widely used in laboratories throughout the world. De Hevesy has remained the prime mover in this new field of activity and much first-class and important research has been carried out by him and his co-workers.

Exceptionally valuable results have thus been obtained in biology. An isotope of radioactive phosphorus, which can be obtained by exposing sulphur to neutron radiation or ordinary phosphorus to radiation from nuclei of heavy hydrogen, has mostly been used. This radioactive phosphorus is sufficiently long-lasting for tests of this nature. It has a half-life of approximately 14.8 days. De Hevesy produced physiological solutions of sodium phosphate containing this marker and injected them into animals and humans. The distribution of the phosphorus was determined at certain intervals. A study of blood samples showed that the phosphorus thus introduced quickly left the blood. In human blood the radio-phosphorus content had fallen after only 2 hours to a mere 2% of its initial value. It diffuses into the extra-cellular body fluid and gradually changes places with the phosphorus atoms of the tissues, organs and skeleton. After some time it can even be found, though in very small quantities, in the enamel of the teeth. Exchanges small and slow as they may be, therefore occur between the outer hard parts of the teeth and the inner tissues of the bones and the lymph. Most of the phosphorus introduced, finds its way into the skeleton, muscles, liver and gastro-intestinal organs. Elimination of phosphorus from living organisms has also been studied by this method.

Phosphorus is an extremely important element in biological processes. The knowledge of its functions in living organisms which has been acquired thanks to the use of radioactive markers is therefore of the very greatest interest. De Hevesy succeeded in detecting where and at what speed the various organic compounds of phosphorus are able to form and the paths which they take in the animal organism. In order to form from a phosphate which has been injected into the blood they must first penetrate into the cells. Acid-soluble compounds of phosphorus form rapidly, whereas phosphatides closely related to fatty substances are slower-forming. These latter form mainly in the liver, whence they are carried by the blood plasma to the places where they will be consumed. De Hevesy showed that the phosphatides of the chicken embryo are produced in the embryo itself and that they cannot be extracted from the egg yolk.

De Hevesy also carried out several investigations with radioactive sodium and potassium. He studied how physiological saline containing radioactive sodium which was injected into a human subject first spread into the blood and then slowly penetrated into the cells; he also studied the manner in which it is excreted. After 24 hours the blood corpuscles had lost approximately half their sodium content.

In addition to the above-mentioned markers, several other active isotopes, such as magnesium, sulphur, calcium, chlorine, manganese, iron, copper and zinc, have been used for this type of research. In the case of the lighter elements it has also been possible to use inactive isotopes such as heavy hydrogen, with an atomic weight of 2, nitrogen, with an atomic weight of 15, and oxygen, with an atomic weight of 18. It is of course less easy to determine the content of an inactive than of an active marker, but this can be done by determinations of density or mass-spectrographically. To determine the concentration of deuterium, or heavy hydrogen, which is twice as heavy as ordinary hydrogen, is a relatively easy matter. De Hevesy used deuterium as marker in many tests. He then noticed that a person who has drunk water containing heavy hydrogen excretes deuterium in the urine after only 26 minutes. Frogs and fishes swimming in water containing deuterium absorb it and, after about 4 hours, are in equilibrium with the medium as far as the deuterium is concerned. Heavy nitrogen and heavy oxygen have also been used in many investigations.


Tuesday, July 22, 2008

The Goal of a Science Education

We've recently been debating the purpose of our undergraduate program in biochemistry. There are some who think that the main goal is to teach students how to do biochemistry. Those biochemists want as many lab courses as possible and they want to provide plenty of opportunities for students to carry out research projects in a research lab. In some cases, they want to minimize the number of formal lectures. These are the biochemists who want undergraduates to read the primary literature instead of textbooks.

On the other hand, there are biochemists who want to emphasize the basic concepts and principles of biochemistry. They want to teach student about biochemistry. They believe that students need the latest knowledge of how cells work at the molecular level before they learn how to do research at the frontiers.

The first group wants to train students for a career in biochemistry while the second group tends to think that most students will not go on to be biochemists.

Eva Amsen, a graduate student in our department, has some comments. You should read her posting on her Nature Network blog [What will you be?]. Here's some of the interesting part ...
The problem is not that a science undergraduate degree is not a career-oriented degree. It shouldn’t be. History, English, Philosophy, and some of the social sciences aren’t career paths either. But for those fields people seem to know that, and yet people associate science with something that leads to a job. They picture a scientist in a lab somewhere, and don’t realize that the people at the bench are either lab techs with a degree from a technical college or university students or -graduates at some point in their training. It’s all training, it never ends. A select few will eventually have their own lab, and if their grandmother lives to experience this they can tell her that they now are a scientist. Finally, at the age of 35-40 they have what the family would consider a job. And then they spend the next few decades struggling to get grants and write papers just to be able to keep that job.

The problem is that science programs pretend to be career-oriented. They train you for the job of research scientist, but there are way more students than ever needed to fill these jobs. I’d guess that about 10% of PhD students end up with their own lab. Everyone else has to find an alternative career. But if 90% of the graduates of a science program need to find an alternative career, is it still alternative, or is that just what people do with their degrees?
I agree with Eva. Science programs often pretend to be career oriented but they should be knowledge oriented. The main goal should be to teach students how to think and not how to work at a bench. Thus, students who graduate from an undergraduate—or graduate—program will have valuable skills that they can use in any career they choose.


Good Science Writers: Richard Dawkins

 
Richard Dawkins was not included in Richard Dawkins' book: The Oxford Book of Modern Science Writing. The reason for the omission is obvious, so I rectify the "oversight" by including him in my list of good science writers.

I don't always agree with what Dawkins writes but there's no controversy about his ability to explain biology to the general public. He has a clear, crisp style that's easy to read and his arguments are well constructed. Part of his success is achieved by simplifying difficult concepts but this is also part of the problem since, in some cases, an over-simplification leads to misinterpretations.

Dawkins is also a master of metaphor but, sometimes the metaphors are misleading and can give an incorrect view of evolution (e.g. Climbing Mt. Improbable). I've chosen an excerpt from The Ancestor's Tale to illustrate Dawkins' skill at writing about science. This book is somewhat less polemical than his others, although it still has its fair share of strongly voiced personal opinions about evolution.

The passage below addresses "convergence," a favorite topic of theistic evolutionists such as Simon Conway Morris and Ken Miller. Dawkins has his own spin on the subject. He begins by addressing a question posed by Stuart Kauffman in 1985. Kauffman asked whether there are certain features of life that are easy to evolve. If so, we might expect these features to appear whenever life evolves. On the other hand ....
Those biologists who could be said to take their lead from the late Stephen Jay Gould regard all of evolution, including post-Cambrian evolution, as massively contingent—lucky, unlikely to be repeated in a Kauffman rerun. Calling it "rewinding the tape of evolution," Gould independently evolved Kauffman's thought experiment. The chance of anything remotely resembling humans on a second rerun is widely seen as vanishingly small, and Gould voiced it persuasively in Wonderful Life. It was this orthodoxy that led me to the cautious self-denying ordinance of my opening chapter; led me, indeed, to undertake my backwards pilgrimage, and now leads me to forsake my pilgrim companion at Canterbury and return alone. And yet ... I have long wondered whether the hectoring orthodoxy of contingency might have gone too far. My review of Gould's Full House (reprinted in The Devil's Chaplain) defended the unpopular notion of progress in evolution: not progress towards humanity—Darwin forfend!—but progress in directions that are at least predictable enough to justify the word. As I shall argue in a moment, the cumulative build-up of complex adaptations like eyes, strongly suggests a version of progress—especially when coupled in imagination with some of the wonderful products of convergent evolution.

Convergent evolution also inspired the Cambridge geologist Simon Conway Morris, whose provocative book Life's Solution: Inevitable Humans in a Lonely Universe presents exactly the opposite case to Gould's "contingency." Conway Morris means his subtitle in a sense which is not far from literal. He really thinks that a rerun of evolution would result in a second coming of man: or something extremely close to man. And, for such an unpopular thesis, he mounts a defiantly courageous case. The two witnesses he repeatedly calls are convergence and constraint.

Convergence we have met again and again in this book, including in this chapter. Similar problems call forth similar solutions, not just twice or three times but, in many cases, dozens of times. I thought I was pretty extreme in my enthusiasm for convergent evolution, but I have met my match in Conway Morris, who presents a stunning array of examples, many of which I had not met before. But whereas I usually explain convergence by invoking similar selection pressures, Conway Morris adds the testimony of his second witness, constraint. The materials of life, and the processes of embryonic development, allow only a limited range of solutions to a particular problem. Given any particular evolutionary starting situation, there is only a limited number of ways out of the box. So if two reruns of a Kauffman experiment encounter anything like similar selection pressures, developmental constraints will enhance the tendency to arrive at the same solution.

You can see how a skilled advocate could deploy these two witnesses in defence of the daring belief that a rerun of evolution would be positively likely to converge on a large-brained biped with two skilled hands, forward-pointing camera eyes and other human features. Unfortunately, it has only happened once on this planet, but I suppose there has to be a first time. I admit that I was impressed by Conway Morris's parallel case for the predictability of the evolution of insects.


Getting Rid of "Darwinism" in New Scientist

 
Last week, Olivia Judson published a controversial article on the New York Time website. She made the case for getting rid of terms like "Darwinism" and "Darwinian" to describe modern evolutionary biology [Let’s Get Rid of Darwinism]. I'm in complete agreement as I've stated on many occasions [see Why I'm Not a Darwinist]. The main point, as far as I'm concerned, is that modern evolutionary biology has gone way beyond Darwin's original ideas and it's no longer appropriate to describe the modern ideas as "Darwinian." In fact, it can be downright incorrect if you're a pluralist, like me.

Let's see how this might work in practice. The latest issue of New Scientist uses the term "Darwinian evolution" once in the lead editorial [Creationists launch cynical attack on school science]. Here's what it says ...
WHEN science education in the US has come under attack from religious critics, it has proved useful in the past to ask the question, what is science? This approach has been key to keeping public-school science lessons free from non-scientific alternatives to Darwinian evolution, such as creationism and intelligent design (ID) - the notion that life is so complex it could not have arisen without an intelligent agency, aka God.
Nothing is gained here by referring to biological evolution as "Darwinian evolution." As a matter of fact, in this context the term is bound to cause confusion. There are many scientists who think there really are legitimate alternatives to "Darwinian" evolution (e.g. random genetic drift) but the editorial implies that all such alternatives are simply attempts to sneak God into the equation.

Getting rid of "Darwinian" would be a good thing in this case since it is much more accurate to depict the conflict as a challenge to "biological evolution" and not just "Darwinian" evolution.

The lead article in the July 12-18th issue is New legal threat to teaching evolution in the US. The term "Darwininan evolution" is used a couple of times, as in ...
The new legislation is the latest manoeuvre in a long-running war to challenge the validity of Darwinian evolution as an accepted scientific fact in American classrooms.
Again, nothing is gained—and something is lost—by referring to biological evolution as "Darwinian evolution." It would be better to drop the term "Darwinian."

But there's a more serious problem with the article. It is accompanied by a photograph of a classroom with some writing on the blackboard. You can see the photo on the New Scientist website but you can't read what's written. Here's what it says on the blackboard ...
Darwin's Theory says:
Anyone who is familiar with the anatomy of man and the apes must admit that no hypothesis other than that of close kinship affords a reasonable ... explanation of the extraordinarily exact identity of structure in most parts of the bodies man and gorilla.
This is not Darwin's Theory. One of Darwin's main contributions was to show that evolution is the best explanation of life as we know it. We now think of this as the fact of evolution—demonstrated to such an extent that it would be perverse to entertain any other explanation. It's the fact of evolution that's described on the blackboard and this is not a theory, and it's certainly not Darwin's Theory.

The mechanisms of evolution are a different story. Darwin proposed that natural selection was an important mechanism of evolution. This is part of evolutionary theory and it can be referred to as Darwin's Theory of Natural Selection. There are other mechanisms (e.g. random genetic drift) that Darwin did not imagine because his understanding of genetics was incomplete. Those mechanisms are non-Darwinian mechanisms.

The blackboard photo in New Scientists is contributing to the general confusion among the public and thus, it is hurting the cause rather than helping it. This is another case were avoiding the terms "Darwin's Theory" and "Darwinian" would be a good idea.


Monday, July 21, 2008

Monday's Molecule #81

 
Today's molecule is not a specific molecule but rather a type of molecule. You have to identify the type of molecule shown here.

There's a connection between today's molecule and a Nobel Prize. The clue is the red "P" atom in the molecule. The Nobel Prize was awarded for discovering where that red "P" came from and how quickly this type of molecule was produced. Similar studies were done with many other "P"-containing molecules. This was the beginning of a whole new field of study in biochemistry.

The first person to correctly identify the type of molecule and name the Nobel Laureate(s), wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are four ineligible candidates for this week's reward. You know who you are.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Laureate(s) so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow. I may select multiple winners if several people get it right.

Comments will be blocked for 24 hours. Comments are now open.

UPDATE: The molecule is a phosphatidate. It's an intermediate in the synthesis of triacylglycerols or glycerophospholipids. The R1 and R2 groups represent strings of -CH2- groups, usually sixteen or eighteen carbons.

The phosphorus (P) atom is derived indirectly from inorganic phosphate and the incorporation of radioactive phosphorus as phosphate (32PO42-) into phosphatides was first studied by George de Hevesy. He received the Nobel Prize in 1943 for his work on using radioisotopes to study the synthesis of biological molecules such as phosphatides.

Lots of people knew that the molecule was a phosphatidate but nobody got the Nobel Laureate so there are no winners this week.


Gene Genie #34

 
The 34th edition of Gene Genie has been posted at ScienceRoll [Gene Genie 34: Summertime].
This is the first time I host Gene Genie since January. Gene Genie is the blog carnival of clinical genetics and personalized medicine. Enjoy the numerous posts and articles focusing on these interesting fields of medicine.
The beautiful logo was created by Ricardo at My Biotech Life.

The purpose of this carnival is to highlight the genetics of one particular species, Homo sapiens.

Here are all the previous editions .....
  1. Scienceroll
  2. Sciencesque
  3. Genetics and Health
  4. Sandwalk
  5. Neurophilosophy
  6. Scienceroll
  7. Gene Sherpa
  8. Eye on DNA
  9. DNA Direct Talk
  10. Genomicron
  11. Med Journal Watch
  12. My Biotech Life
  13. The Genetic Genealogist
  14. MicrobiologyBytes
  15. Cancer Genetics
  16. Neurophilosophy
  17. The Gene Sherpa
  18. Eye on DNA
  19. Scienceroll
  20. Bitesize Bio
  21. BabyLab
  22. Sandwalk
  23. Scienceroll
  24. biomarker-driven mental health 2.0
  25. The Gene Sherpa
  26. Sciencebase
  27. DNA Direct Talk
  28. Greg Laden’s Blog
  29. My Biotech Life
  30. Gene Expression
  31. Adaptive Complexity
  32. Highlight Health
  33. Neurophilosophy
  34. ScienceRoll



Sunday, July 20, 2008

Species-Scape

 
This is a snapshot of an animated picture of a "species-scape." The size of the organisms represent their relative abundance on Earth. See Species-Scape on the Cornell University website.

Another version is shown on Christopher Taylor's blog Catalogue of Organisms [The Species-Scape Picture].

Notice how insignificant mammals are, yet one particular species of mammal has the potential to ruin the entire planet for all other species.

Some groups seem to be missing, bryophytes (moss) for example. Can you find any others?


Wednesday, July 16, 2008

Nobel Laureate: George Palade

 

The Nobel Prize in Physiology or Medicine 1974.
"for their discoveries concerning the structural and functional organization of the cell"



George E. Palade (1912 - ) received the Nobel Prize in Physiology or Medicine for his contribution to understanding how proteins are synthesized and secreted in eukaryotic cells. He worked mostly on the secretory (exocrine) cells of guinea pig pancreas using a combination of cytological and cell fractionation techniques. As he says in his Nobel lecture, he was fascinated by the organization of these cells with their complex endoplasmic reticulum studded with ribosomes. Palade was among the first to get good electron micrographs of these structures [see below].

The idea was to track the route of newly synthesized proteins from the ribosomes to the exterior of the cell. Part of the solution came from developing techniques for EM autoradiography. This allowed Palade and his group to show that new proteins were first made by ribosomes sitting on the surface of the endoplasmic reticulum (ER). The labelled proteins were immediately seen to enter into the lumen of the ER. Subsequently they passed through internal vesicles and the Golgi until they reached the plasma membrane.

The photographs below show the results of a typical pulse-chase experiment. In the first panel (A) you can see that that with only a short pulse of radioactive amino acids the radioactive proteins—identified by the black squiggles—are localized to the endoplasmic reticulum. For a complete description of the photograph see The American Society for Cell Biology.

The pathway worked out in the 1950s and '60s is now known to be correct and it's a universal pathway found in all eukaryotes.

Palade is credited with being the first one to describe the small particles that later came to be known as ribosomes.

Palade was born in Romania where he obtained his M.D. degree in 1940. He joined the Rockefeller University shortly after World War II and remained there until he took up a position at Yale in 1973. In 1990 he moved to the University of California, San Diego.

Palade shared the 1974 prize with Albert Claude and Christian De Duve.

The presentation speech was delivered in Swedish by Professor Jan- Erik Edström of the Karolinska Medico-Chirurgical Institute


THEME:
Nobel Laureates
Your Majesty, Your Royal Highnesses, Ladies and Gentlemen,

The 1974 Nobel Prize in Physiology or Medicine concerns the fine structure and the function of the cell, a subject designated Cell Biology. There are no earlier Prize Winners in this field, simply because it is one that has been newly created, largely by the Prize Winners themselves. It is necessary to go back to 1906 to find Prize Winners who are to some extent forerunners. In that year Golgi and Cajal were awarded the Prize for studies of cells with the light microscope. Although the light microscope certainly opened a door to a new world during the 19th century, it had obvious limitations. The components of the cell are so small that it was not possible to study their inner structure, their mutual relations or their different roles. To take a metaphor from an earlier Prize Winner, the cell was like a mother's work basket, in that it contained objects strewn about in no discernible order and evidently, for him, with no recognizable functions.

But, if the cell is a work basket, it is one on a very tiny scale indeed, having a volume corresponding to a millionth of that of a pinshead. The various components responsible for the functions of the cell correspond in their turn to a millionth of this millionth, and are far below the resolving powers of the light microscope. Nor would it have helped if researchers had used larger experimental animals: the cells of the elephant are not larger than those of the mouse.

Progress was quite simply at a standstill during the first few decades of this century, but then in 1938, the electron microscope became available, an innovation that held out great promise. The difference between this microscope and the ordinary light microscope is enormous, like being able to read a book instead of just the title. With such an instrument it should now be possible to see components almost down to the dimensions of single molecules. But the early hopes were succeeded by disappointment. It was found impossible to prepare the cells in such a way that they could be used. The book remained obstinately shut, even though it would have been possible to read it.

Albert Claude and coworkers were the first to get a glance inside the book. In the mid-forties they made a break-through and succeeded in preparing cells for electron microscopy. I say a glance, because much technical development still remained to be done, and George Palade should be mentioned foremost among those who developed electron microscopy further, to the highest degree of artistry.

In addition to form and structure it is necessary to know the chemical composition of the cell components in order to understand their functions. It was hardly possible to analyse whole cells or tissues since these consist of so many different components, and so, one would get a confused picture. Each component has to be studied separately and obviously this is difficult when the components are so small. Here a new art was developed, and again Claude was the pioneer. He showed how one could first grind the cells into fragments and then sort out the different components on a large scale with the aid of the centrifuge. This was an important beginning. Palade made further contributions, but it was above all Christian de Duve who introduced brilliant developments within this field.

The functions of the cell could now be mapped with this armoury of methodology. Palade has taught us which components function when the cell grows and secretes. The Prize Winner of 1906, Camillo Golgi, discovered a cell component, the Golgi complex. Palade has demonstrated its role and he discovered the small bodies, ribosomes, in which cellular protein is produced.

Production of organic material must be balanced by scavenging and combustion of waste, even in the tiny world of the cell. de Duve discovered small components, lysosomes, which can engulf and dissolve, e.g., attacking bacteria or parts of the cell itself which are old and worn out. These are real acid baths, but the cell itself is normally protected by its surrounding membranes. Sometimes, however, the lysosomes are converted into veritable suicide pills for the cells. This occurs when the surrounding membranes are damaged, e.g. by ionizing radiation. The lysosomes play a role in many clinically important conditions and the foundations laid by de Duve are of the greatest significance for the interpretation of these states, and, thus, also for prophylactic and therapeutic measure.

To sum up, the 1974 Prize Winners have by their discoveries elucidated cellular functions that are of basic biological and clinical importance. Thus, they cover both aspects of the Prize, Physiology as well as Medicine.

Albert Claude, Christian de Duve and George Palade. During the last 30 years a new subject has been created, Cell Biology. You have been largely responsible for this development both by creating the basic methodology and by exploiting it to gain insight into the functional machinery of the cell. On behalf of the Karolinska Institute, I wish to convey to you our warmest congratulations, and I now ask you to receive the prize from the hands of his Majesty the King.


Monday, July 14, 2008

The Ethical Frontiers of Science

 
I'm at the Chautauqua Institution this week where the theme is The Ethical Frontiers of Science.

Today's speaker was Arthur Caplan Professor of Bioethics at the University of Pennsylvania. His topic was "Is it Immoral to Want to Live Longer, Be Smarter and Look Better?" The answer is no, it is not immoral. There's nothing wrong with wanting to take advantage of modern scientific advances to prolong life, enhance intelligence, and look better." I agreed with everything he said.

Caplan looked over the speakers for the rest of the week. Many of them are his friends and he's very familiar with their views. That's why he was able to congratulate us for coming to the first lecture. "It will be the highlight of the entire week," he said, "because all the other speakers are wrong." I suspect he's right but it will be fun, nevertheless, hearing what some of them have to say.




Monday's Molecule #80

 
Today's molecules are the little black blobs in the photograph. One of them is circled in the lower left-hand corner.

There's a direct connection between today's molecule and a Nobel Prize. In fact, the photograph was lifted directly from the Nobel lecture of the prize winner. The prize was awarded for determining the role of those little black blobs in the type of cell shown in the photo.

The first person to correctly identify the molecule and name the Nobel Laureate(s), wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are four ineligible candidates for this week's reward. You know who you are.


THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Laureate(s) so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow. I may select multiple winners if several people get it right.

Comments will be blocked for 24 hours. Comments are now open.

UPDATE: The photograph is rough ER and the black blobs are ribosomes. George Palade won the Nobel Prize for working out the pathway of protein secretion from the ribosomes on the surface of the ER to the plasma membrane. Many of you got it right but the first one was Charles Peterson of Hofstra University.


Sunday, July 13, 2008

Good Science Writers: Sean B. Carroll

 
Sean B. Carroll is Professor of Molecular Biology and Genetics at the University of Wisconsin in Madison, Wisconsin (USA).1 His research interests focus on evolution and development, mostly in fruit flies and other insect. Carroll is one of the leading advocates of a new approach to evolution arising out of what we have learned from animal development ("evo-devo"). (See the official Sean B. Caroll website.)

He is co-author on two textbooks: From DNA to Diversity: Molecular Genetics and the Evolution of Animal Design (2nd ed, 2005) with Jen Grenier and Scott Weatherbee; and Introduction to Genetic Analysis (9th ed., 2007) with Anthony Griffiths, Richard Lewontin, and Susan Wessler. Sean B. Carroll has written two trade books: Endless Forms Most Beautiful: The New Science of Evo Devo (2005) and The Making of the Fittest (2006).

Sean B. Carrol was not included in Richard Dawkins' book: The Oxford Book of Modern Science Writing

The excerpts below are from The Making of the Fittest. This is a book that emphasizes the role of natural selection in evolution.

It may be the most remote place on Earth.

Tiny Bouvet Island is a lone speck in the vast South Atlantic, some 1600 miles southwest of the Cape of Good Hope (Africa) and almost 3000 miles east of Cape Horn (South America). The great Captain James Cook, commanding the HMS Resolution, tried to find it on his voyages through the Southern Ocean in the 1770s, but failed both times. Covered by an ice sheet several hundred feet thick that ends in sheer cliffs, which in turn drop to black volcanic beaches, and with an average temperature below freezing, it still doesn't get many visitors.

Fortunately, for both my story and natural history, the Norwegian research ship Norvegia made it to Bouvet Island in 1928, with the principle purpose of establishing a shelter and a cache of provisions for shipwrecked sailors. While on Bouvet, the ship's biologist, Ditlef Rustad, a zoology student, caught some very curious-looking fish. They looked like any other fish in most respects—they had big eyes, large pectoral and tail fins, and a long protruding jaw full of teeth. But they were utterly pale, almost transparent. When examined more closely, Rustad noticed that what he called "white crocodile fish" had blood that was completely colorless.

Johan Ruud, a fellow student, traveled to the Antarctic two years later on the factory whaling ship Vikingen. He thought the crew was pulling his leg when one flenser (a man who stripped the blubber and skin from the whale) said to him, "Do you know there are fishes here that have no blood?"

Playing along, he replied, "Oh, yes? Please bring some back with you."

A good student of animal physiology, Ruud was perfectly sure that no such fish could exist, as textbooks stated firmly that all vertebrates (fish, amphibians, reptiles, birds, and mammals) possess red cells in their blood that contained the pigment hemoglobin. This is as fundamental as, well, breathing oxygen. So when the flenser and his friends returned from a day's efforts without any blodlaus-fisk, Ruud dismissed the idea as shipboard lore.

Of all the scientists in the world today, there is no one with whom Charles Darwin would rather spend an evening than Sean Carroll.

         Michael Ruse
He wasn't looking for a new kingdom.

Microbiologist Tom Brock and his student Hudson Freeze were prowling around the geysers and hot springs of Yellowstone National Park one day late in the summer of 1966. They were interested in finding out what kinds of microbes lived around the pools and were drawn to the orange mats that colored the outflows of several springs.

They collected samples of microbes from Mushroom Spring, a large pool in the Lower Geyser Basin whose source was exactly 163 degreed F, thought at the time to be the upper temperature limit for life. They were able to isolate a new bacterium from this site, a species that thrived in hot water. In fact, its optimal growth temperature was right around that of the hot spring. They dubbed this "thermophilic" creature Thermus aquaticus. Brock also noticed some pink filaments around some even hotter springs, which raised his suspicion that life might occur at even higher temperatures.

The next year, Brock tried a new approach to "fishing" for microbes in the hot springs of Yellowstone. His fishing tackle was simple: he tied one or two microscope slides to a piece of string, dropped it in the pool, and tied the other end to a log or a rock (don't try this on your own—you will be arrested and quite likely scalded or worse). Days later, upon retrieving the slides, he could see heavy growth, sometimes so much that the slides had a visible film. Brock was right that organisms were living at higher temperatures than had previously been thought, but he did not imagine that they were living in boiling water. And they weren't just tolerating 200 degrees F or more—these organisms were thriving in smoky, acidic, boiling pots such as Sulpur Cauldron, in the Mud Volcano area of the park. Brock's Yellowstone explorations opened eyes and minds to the extraordinary range of life's adaptability, identified bizarre but important new species such as Sulfolobus and Thermoplasma, and launched the scientific study of what he called "hyperthermophiles," lovers of superheat.


1. Sean B. Carroll is the biologist. Sean Carroll is the physicist at the California Institute of Technology and one of the authors on the blog Cosmic Variance.

Saturday, July 12, 2008

The Fluctuation Test

John Dennehy of The Evilutionary Biologist continues his almost perfect1 record of picking important papers for his Citation Classic.

This week's paper is the classic 1943 paper by Luria and Delbrück on the fluctuation test [The Fluctuation test]. This was the paper that proved that mutations arise randomly with respect to their phenotype. As John says, it is one of the most important experiments in biology.


1. For the exception see It Happens to all of Us Eventually.

Good Science Writers: Eugenie Scott

 
Eugenie C. Scott has been the Executive Director of the National Center for Science Education (NCSE) since 1987. She is a physical anthropologist who taught at several universities prior to becoming director of NCSE.

Scot has published dozens of articles on evolution and creationism in the popular press and she is a frequent guest on television and radio broadcasts. She is one of the world's leading experts on explaining evolution to the general public (and to other scientists).

Although she meets all the qualifications, she was not included in Richard Dawkins' book: The Oxford Book of Modern Science Writing.

The following excepts are taken from her latest book Evolution vs. Creationism: An Introduction.

If a population at the end of a geographic range of a species is cut off from the rest of the species, through time it may become different from other populations. Perhaps natural selection is operating differently in its environment than it is in the rest of the species range, or perhaps the population has a somewhat different set of genes than other populations of the species. Just by the rules of probability, a small, peripheral population is not likely to have all the variants of genes that are present in the whole species, which might result in its future evolution taking a different turn.

No longer exchanging genes with other populations of the species, and diverging genetically through time from them, members of a peripheral, isolated population might reach the stage where, were they to have the opportunity to mate with a member of the "parent" species, they would not be able to produce offspring. Isolating mechanisms, most of which are genetic but some of which are behavioral, can arise to prevent reproduction between organisms from different populations. Some isolating mechanisms prevent two individuals from mating at all: in some insects, for example, the sexual parts of males and females of related species are so different in shape and size that copulation can't take place. Other isolating mechanisms come into effect when sperm and egg cannot fuse for biochemical or structural reasons. An isolating mechanism could take the form of the prevention of implantation of the egg or of disruption of the growth of the embryo after a few divisions. Or the isolating mechanism could kick in later: mules, which result from crossing horses and donkeys are healthy but sterile. Donkey genes thus are inhibited from entering into the horse species and vice versa. When member of two groups aren't able to share genes because of isolating mechanisms, we can say that speciation between them has occurred. (Outside of the laboratory, it may be difficult to determine whether two species that no longer live in the same environment are reproductively isolated.)

The new species would of course be very similar to the old one—in fact, it might not be possible to tell them apart. Over time, though, if the new species manages successfully to adapt to its environment, it might also expand and bud off new species, which would be yet more different from the parent—now "grandparent"—species. This branching and splitting has, through time, given us the variety of species that we see today.
... common to all ID [intelligent design] proponents is the rejection of "Darwinism." In ID literature, "Darwinism" becomes an epithet, though it is not always clear in any given passage exactly what is meant by "Darwinism." In evolutionary biology, "Darwinism" usually refers to the ideas held by Darwin in the nineteenth century. Usually the term is not used for modern evolutionary theory, which, because it goes well beyond Darwin to include subsequent discoveries and understandings, is more frequently referred to as "neo-Darwinism," or just "evolutionary theory." Evolutionary biologists hardly ever use "Darwinism" as a synonym for evolution, though it occasionally is used this way by historians and philosophers of science. In ID literature, however, "Darwinism" can mean Darwin's ideas, natural selection, neo-Darwinism, post-neo-Darwinian evolutionary theory, evolution itself, or materialist ideology inspired by "Godless evolution."

The public, on the other hand, is unlikely to make these distinctions, instead equating "Darwinism" with evolution (common descent). For decades, Creation Science proponents have cited the controversies among scientist over how evolution occured—including the specific role of natural selection—in their attempts to persuade the public that evolution itself—the thesis of common ancestry—was not accepted by scientists, or at least was in dispute. Within the scientific community, of course, there are lively controversies, including over how much of evolution is explained by natural selection and how much by additional mechanisms such as those being discovered in evolutionary developmental biology ("evo-devo"). No one says natural selection is unimportant; no one says that additional mechanisms are categorically ruled out. But these technical arguments go well beyond the understanding of laypeople and are easily used to promote confusion over whether evolution occurred. Intelligent Design proponents similarly exploit public confusion about "Darwinism" to promote doubt about evolution.



Friday, July 11, 2008

Was Charles Darwin a Good Science Writer?

 
Olivia Judson is a research fellow at Imperial College in London (UK). She studies evolution. Judson is a former pupil of W.D. Hamilton. She is also the daughter of Horace Freeland Judson.1

Judson writes a weekly article for the New York Times website. This week she tackles the heretical question of whether Charles Darwin was a good science writer [An Original Confession]. Here's a treaser ...
It always happens the same way. A glance around the room to make sure no one else is listening. A clearing of the throat. A lowering of the voice to a conspiratorial tone. Then, the confession.

“I’ve never read ‘On the Origin of Species.’ I tried, but I thought it was boring.”

Thus, a number of eminent scientists — biologists all — have spoken. Or rather, whispered.

1. Author of The Eighth Day of Creation, the definitive history of the early days of molecular biology.

[Hat Tip: RichardDawkins.net]