Tangled Bank #110

 
The latest issue of Tangled Bank was supposed to appear on Blue Collar Scientist but circumstances intervened¹ and PZ Myers has kindly filled the gap on Pharyngula [Tangled Bank #110].

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If you want to submit an article to Tangled Bank send an email message to host@tangledbank.net. Be sure to include the words "Tangled Bank" in the subject line. Remember that this carnival only accepts one submission per week from each blogger. For some of you that's going to be a serious problem. You have to pick your best article on biology.

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1. The blog owner was recently diagnosed with cancer.

Good Science Writers: Douglas J. Futuyma

 
Douglas J. Futuyma is Distinguished Professor in the Department of Ecology and Evolution at the State University of New York at Stony Brook [Douglas Futuyma]. He is best known for his textbooks on evolution, Evolutionary Biology, beginning with the first edition in 1979. The latest version is a shorter textbook entitled Evolution (2005).

Futuyma has also published a trade book on the evolution/creation controversy. The first edition of Science on Trial: The Case for Evolution was published in 1983 and the second edition was published in 1995. Since Futuyma is a professional scientist, he meets all the qualifications for inclusion in Richard Dawkins' book: The Oxford Book of Modern Science Writing. But he is not there.

Douglas Futuyma is a brilliant textbook author. This kind of science writing is not usually recognized, but it should be. Futuyma's ability to accurately explain complex ideas is head-and-shoulders above that of most other textbook authors—no matter what their subject. I've chosen two excerpts from Evolution (2005) to illustrate this ability. You may find them familiar—that's because they have been widely quoted and paraphrased to the point where they seem trivial. Let's not forget that it is Futuyma who first began to explain evolution in this manner.

What Is Evolution?
The word evolution comes from the Latin evolvere, "to unfold or unroll"—to reveal or manifest hidden potentialities. Today "evolution" has come to mean, simply, "change." It is sometimes used to describe changes in individual objects such as stars. Biological (or organic) evolution, however, is change in the properties of groups or organisms over the course of generations. The development or ONTOGENY, or individual organisms is not considered evolution: individual organisms do not evolve. Groups of organisms, which we may call populations, undergo descent with modification. Populations may become subdivided, so that several populations are derived from a common ancestral population. If different changes transpire in the several populations, the populations diverge.

The changes in populations that are considered evolutionary are those that are passed via the genetic material from one generation to the next. Biological evolution may be slight or substantial: it embraces everything from slight changes in the proportions of different forms of a gene within a population to the alterations that led from the earliest organism to dinosaurs, bees, oaks, and humans. (p. 2)

Good Science Writers

Good Science Writing
David Suzuki
Helena Curtis
David Raup
Niles Eldridge
Richard Lewontin
Steven Vogel
Jacques Monod
G. Brent Dalrymple
Eugenie Scott
Sean B. Carroll
Richard Dawkins

Evolution as Fact and Theory
In The Origin of Species, Darwin propounded two major hypotheses: that organisms have descended, with modification, from common ancestors; and that the chief cause of modification is natural selection acting on hereditary variation. Darwin provided abundant evidence for descent with modification, and hundreds of thousands of observations from paleontology, geographic distributions of species, comparative anatomy, embryology, genetics, biochemistry, and molecular biology have confirmed this hypothesis since Darwin's time. Thus the hypothesis of descent with modification from common ancestors has long had the status of a scientific fact.

The explanation of how modification occurs and how ancestors gave rise to diverse descendants constitutes the theory of evolution. We now know that Darwin's hypothesis of natural selection on hereditary variation was correct, but we also know that there are more causes of evolution than Darwin realized, and that natural selection and hereditary variation themselves are more complex than he imagined. A body of ideas about the causes of evolution, including mutation, recombination, gene flow, isolation, random genetic drift, the many forms of natural selection, and other factors, constitute our current theory of evolution or "evolutionary theory." Like all theories in science, it is incomplete, for we do not yet know the causes of all of evolution, and some details may turn out to be wrong. But the main tenets of the theory are well supported, and most biologists accept them with confidence. (pp. 13-14)

I've also chosen an excerpt from Science on Trial (1995). In order to appreciate it, you will need a bit of background. The passage below comes from a chapter on "Chance and Mutation." The chapter opens with a brief description of a play by Tom Stoppard celled Rosencrantz and Guildenstern Are Dead. For those of you not intimately familiar with Shakespeare's Hamlet, Rosencrantz and Guildenstern are two minor characters who are tricked by Hamlet and end up sailing to England where, contrary to their expectations, they will be executed. Stoppard's play is about fate and inevitability.

But just as gravity and Brownian movement may both affect the motion of an airborne particle, chance and natural selection often work simultaneously, and certain evolutionary phenomena can be understood only if we take both into account. Many populations of houseflies throughout the world have evolved a resistance to DDT—an adaptation that has come about by natural selection. In some populations, however, the adaptation is provided by a dominant gene; in some by a recessive gene; in some by a number of genes, each with a small effect. The physiological mechanism by which the genes act also varies: flies can be resistant, for example, either by having developed an enzyme that degrades DDT or by having altered the cell membrane so that DDT is less able to penetrate the tissues. These are alternative adaptive mechanisms. Which one developed in a particular population must have depended on which mutations happened to be present in the population when it became exposed to DDT—and this is very much a matter of chance. Thus, chance initially determines what genetic variations will be acted on by natural selection to develop an adaptation.

When we extrapolate this principle of indeterminacy to long-term evolution, we can understand why different organisms have evolved different "solutions" to similar adaptive "problems." By chance, they had different genetic raw materials to work with. It is doubtless adaptive for male frogs to have a vocal sac that enables them to produce resonant calls that attract females. But whether a frog developed a single sac in the middle of the throat, as in the bullfrog, or a pair of sacs on either side, as in the leopard frog, may have been affected by what mutations first occurred by chance in the ancestor of each species.

If chance is a name for the unpredictable, them almost any historical event is affected by chance. Would Hamlet's mother, watching him stab Polonius through the arras, have predicted that this would be one in a chain of events leading to the death of Rosencrantz and Guildenstern? If you had been on the island of Mauritius in the mid-Tertiary, would you have predicted that the pigeons there would evolve into flightless dodos and then become extinct in the seventeenth century because they were easy prey for sailors? If you had seen a bipedal ape on the plains of Africa in the Pliocene, could you have predicted that this feature would prove crucial in the evolution of a larger brain and the development of human culture? Probably not; for in all such instances, the event that we recognize in hindsight as a "cause" might have been followed by other events leading to a different outcome. All of evolution, like all of history, seems to involve chance, in that very little of what has happened was determined from the beginning.

The mind that cannot abide uncertainty is troubled by the idea that the human species developed by "chance." But whether we evolved by chance or not depends on what the word means. We did not arise by a fortuitous aggregation of molecules, but rather by a nonrandom process—natural selection favoring some genes over others. But we are indeed a product of chance in that we were not predestined, from the beginning of the world, to come into existence. Like the extinction of the dodo, the death of Rosencrantz and Guildenstern, or the outbreak of World War I, we are a product of a history that might have been different. (pp. 146-147)

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WikiPathways

Find a website with a correct citric acid cycle and win $1,000,000 or equivalent!NatureNews has an article on the growth of biological Wikis as a way of involving the molecular biology community in annotating genes, proteins, etc. [Molecular biology gets wikified]. I strongly support the work of Huss et al. (2008) as I described in a previous posting [A Gene Wiki].

Now Pico et al. (2008) have tried to do for metabolic pathways what Huss et al. did for genes. Unfortunately, WikiPathways isn't going to be successful for a number of reasons.

The idea is to create a Wiki for various pathways and allow the biological community to update and comment on the various entries. However, whereas Gene Wiki did the right thing by adding the human genes to Wikipedia, WikiPathways creates its own separate database. This makes it much less accessible since not only do you have to make an effort to find the Wiki, you also have to create an account to make changes.


That's not the only problem. Let's look at a familiar metabolic pathway on WikiPathways, the citric acid cycle. Right away you can see that there are no visible chemical reactions. Instead, you just see a pathway created by lines between boxes with the names of molecules. You don't even see that CO₂ and reducing equivalents are produced by this pathway! That's not going to be very useful.

Contrast the WikiPathways entry with the existing entry on Wikipedia [citric acdi cycle]. The Wikipedia entry is much more useful and, as it turns out, reasonably accurate. I'd be tempted to correct the Wikipedia entry but I'm not interested in doing all the work required to make the WikiPathways entry useful.

Speaking of corrections, when I teach my biochemistry course in the winter I challenge my students to find a single website that shows the citric acid cycle correctly. By that I mean a website where every single reaction is correctly balanced and all reactants and products are shown. The Wikipedia reactions are not correct and the sum of all reactions is incorrect, although in this case the only errors are in balancing the number of hydrogen atoms. Can anyone find the mistakes? Can anyone find a website that's correct? (You can't count any website that shows a figure from my textbook and you can't count the IUBMB website (e.g., citrate synthase). (The most serious error is in getting the products of the succinate dehydrogenase reaction wrong.)

The prize for finding a correct website is seeing your name in print on Sandwalk or $1,000,000 (one million dollars), whichever I think is the most valuable.

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Huss III, J.W., Orozco, C., Goodale, J., Wu, C., Batalov, S., Vickers, T.J., Valafar, F., and Su, A.I. (2008) A Gene Wiki for Community Annotation of Gene Function. PLoS Biol 6(7): e175 [doi:10.1371/journal.pbio.0060175]

Pico, A.R., Kelder, T., van Iersel, M.P., Hanspers, K., Conklin, B.R., and Evelo, C. (2008) WikiPathways: Pathway Editing for the People. PLoS Biology, 6(7), e184. [DOI: 10.1371/journal.pbio.0060184]

Epigenetics

Epigenetics is one of those words that means entirely different things to different people. P.Z. Myers has put up a nice description of the term on his blog [Epigenetics]. Here's how he defines epigenetics ...

Epigenetics is the study of heritable traits that are not dependent on the primary sequence of DNA.

In fairness, he then goes on to explain that this is an unsatisfactory definition. That's an understatement.

Now, as it turns out, those scientists who work on animal development employ a definition of epigenetics that looks very much like what we used to call developmental regulation of gene expression. That's why PZ can say ...

... developmental biology basically takes epigenetics entirely for granted — development is epigenetics in action! Compare an epidermal keratinocyte and a pancreatic acinar cell, and you will discover that they have exactly the same genome, and that their profound morphological, physiological, and biochemical differences are entirely the product of epigenetic modification. Development is a hierarchical process, with progressive epigenetic restriction of the fates of cells in a lineage — a dividing population of cells proceeds from totipotency to pluripotency to multipotency to a commitment to a specific cell type by heritable changes in gene expression; those cases where there is modification of the DNA, as in the immune system, are the exception.

Here's the problem. If this is epigenetics then what's the point? When I was growing up we had a perfectly good term for these phenomena—it was regulation of gene expression. Why is there a movement among animal developmental biologists to use "epigenetics" to refer to a well-understood phenomenon?

I've been bugging my colleagues today by asking them to tell me whether certain examples of gene regulation are epigenetic or not.¹ The answers are mixed so I thought I'd submit the questions to Sandwalk readers. Which of the following are "epigenetic"?

1. Consider an E. coli cell that grows and divides for hundreds of generations in the absence of any exogenous β-galactosides (e.g. lactose). Under those conditions the lac operon is repressed and this state is heritable from generation to generation due to the presence of lac repressor.
2. Consider mating type in yeast. In an α cell the a gene is suppressed from generation to generation. This is heritable regulation of gene expression. All daughter cells inherit the ability to express the α gene and suppress the a gene.
3. During a bacteriophage infection certain genes are turned on in a definite sequence. In the simplest cases there is a set of "early" genes that are expressed as soon as the 'phage DNA enters the cell. After a few minutes the expression of the "early" genes triggers the expression of the "late" genes. Note that the "late" genes are not transcribed initially even though they are present.
4. Right now your major heat shock genes (e.g. Hsp70 genes) are transcriptionally silent. However, if you are stressed by heat those genes will become active and will be transcribed at a very high rate.
5. During oogenesis in fruit flies the bicoid gene is expressed in nurse cells and bicoid mRNA is deposited in the egg. In males, the bicoid gene is never expressed.
6. One of the nucleotides at an EcoR1 restriction endonuclease site in E. coli is methylated. This blocks cleavage at that site, thus protecting the bacteria from degrading its own genome. The methylation pattern is inherited from generation to generation by the action of a methylase enzyme.
7. Globin genes are expressed in erythroblasts but not in brain cells. During development the globin genes are activated in erythroblast stem cells because certain activator proteins are synthesized. The globin genes are not activated in any other tissues.
8. During development in mammalian females one of the X-chromosomes is randomly inactivated [Calico Cats]. Once this occurs the pattern is inherited in (almost) all cells that descend from the initial embryonic cell where the inactivation first occurred. The same X-chromosome is inactivated in all daughter cells.

I'm interested in two questions. First, is it possible to define epigenetics in a rigorous manner so that we can decide whether certain cases are "epigenetic" or not? Second, what, if anything, is the difference between "epigenetics" and "developmental regulation of gene expression"?

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1. And they are quite annoyed about it. Many of them are avoiding me because they don't know how to answer the questions.

[Image Credit: The cartoon is from Mark Hill's website at the University of New South Wales, Australia. It appeared originally in Nature. The figure represents a different definition of "epigenetics"—one that focuses on modifications to DNA and histones.]

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.

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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."

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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.

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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.

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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.

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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.

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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 (³²PO₄^2-) 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.

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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

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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?

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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.

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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.

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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.

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