Nobel Laureates: Bergström, Samuelsson, and Vane

The Nobel Prize in Physiology or Medicine 1982.

"for their discoveries concerning prostaglandins and related biologically active substances"

Sune K. Bergström (1916-2004), Bengt I. Samuelsson (1934-), and John R. Vane (1927-2004) received the Nobel Prize for discovering prostaglandins and working out their structure. In additon, Vane discovered the role of aspirin in inhibiting prostaglandin synthesis.

Prostaglandins are homones that mediate pain, inflamation and swelling. They also control blood clotting and and arterial constriction. See Why You need Linoleate and tomorrow's articles ("Prostaglandin Synthesis", "How Painkillers Work") for more information.

Why You Need Linoleate

Polyunsaturated fatty acids (PUFAs) are long chain fatty acids with multiple double bonds. Monday's molecule was linoleate or cis, cis -Δ^9,12- octadecadienate. It's an 18-carbon fatty acid with double bonds at positions 9 and 12. PUFA's are essential components of many biochemical pathways. (Note that this fatty acid is a normal cis fatty acid and not a trans fatty acid.)

The standard route for synthesis of PUFAs requires specific enzymes that create the double bonds at fixed positions. These enzymes are called desaturases. Other enzymes can extend the fatty acid chain from 18 carbons (18 carbons are the longest chains made by the normal fatty acid synthesis pathway). These enzymes are called elongases.

The combination of various desaturases and elongases will result in the synthesis of a wide variety of complex polyunsaturated fatty acids. One of these, arachidonate, is the precursor for synthesis of many eicosanoids—a class of compounds that includes the hormones prostaglandins, leukotrienes, and thromboxane.

Arachidonate is made from linoleate.

The first step in the pathway is activation of linoleate by attaching a cofactor called coenzyme A. The result is linoleoyl CoA, which is then converted to arachidonoyl CoA by the action of two desaturases and an elongase.


Now, here's the catch. Most eukaryotes contain a variety of desaturases that can create double bonds as far as 15 carbons away from the the carboxyl end of a fatty acid (i.e., at position 15). Mammals have lost some of these desaturase enzymes so they can't make any PUFA with a double bond beyond position 9. They (we) can't make linoleate even though it is absolutely required for life. We need to get it from our diet.

Tomorrow we'll learn how arachidonoyl-CoA is converted to prostaglandins and how aspirin, ibuprofen, acetaminophen, and other NSAIDS block the synthesis.

Shelley Batts in Toronto on New Years Eve

Shelley Batts of Restrospectacle describes her Toronto New Years and a Sad Rose Bowl. Apparently it went pretty good except that she couldn't get a cab at 3:30 am on Sunday night/Monday morning and she didn't like the Rose Bowl game.

Shelley, I can't do anything about the Rose Bowl but next time you need a cab in Toronto give me a call.

Edge Question for 2007

John Brockman runs an interesting "blog" called the Edge. He has assembled a cadre of intellectuals, and people who aspire to be intellectuals. Most of them are authors and Brockman is their agent.

This year's question is ...

The Edge Annual Question — 2007
WHAT ARE YOU OPTIMISTIC ABOUT? WHY?

As an activity, as a state of mind, science is fundamentally optimistic. Science figures out how things work and thus can make them work better. Much of the news is either good news or news that can be made good, thanks to ever deepening knowledge and ever more efficient and powerful tools and techniques. Science, on its frontiers, poses more and ever better questions, ever better put.

What are you optimistic about? Why? Surprise us!

The results are fascinating [THE WORLD'S LEADING THINKERS SEE GOOD NEWS AHEAD]. I haven't picked a favorite 'cause there are so many good ones. Many of them focus on issues that we have been discussing here: issues such as the fight between rationalism and superstition, the meaning of science, and science education.

Do you have a favorite?

Why European Countries Don't Have the Death Penalty

The recent discussion of capital punishment in another thread prompted me to look for opinion polls to see what kind of support for the death penalty there was in Europe and Canada. It turns out that a majority of citizens in those countries actually favor the death penalty in spite of the fact that their governments have abolished it.

Death penalty proponents make a big deal of this contrast. They claim that European societies are just as barbaric as American societies—although they don't actually put it in those words.

Are you interested to know how some American websites interpret this result? If so, read on, but before clicking on the "Read more" link I want to warn all Europeans that you may not like what you read. If you have high blood pressure you'd better skip it.

Here's an explanation written by Wesley Lowe on the Pro Death Penalty Webpage. Remember, he's trying to explain why European governments have abolished the death penalty in spite of the fact that a majority of Europeans support it.

Differences between European parliamentary government and the American separation-of-powers system also play a role. Parliamentary government may provide voters with more ideological variety, but it is much more resistant to political newcomers and fresh ideals which may support different political views. In parliamentary systems, people tend to vote for parties, not individuals; and party committees choose which candidates stand for election. As a result, parties are less influenced by the will of the people. In countries like Britain and France, so long as elite opinion remains sufficiently united (which, in the case of the death penalty, it has), public support cannot translate into legislative action. Since American candidates are largely independent and self-selected, they serve as a much more direct conduit between public opinion and actual political action.

Basically, then, Europe doesn't have the death penalty because its political systems are less democratic, or at least more insulated from public opinion, than the U.S. government.

This is so astonishingly ignorant that it leaves me speechless. Let's hear from other Americans on this point. Do you really believe that the government of the USA is more democratic and more open to fresh ideas than governments in Europe? Do you really believe that the US Congress is more responsive to public opinion than governments that have a parliamentary system? (While replying, keep in mind the frequency with which incumbent American politicians are turfed out of office. Contrast this with parliamentary systems where it's not uncommon for 50% of the seats to change hands in a general election.)

Brits Losing After American Invasion

According to recent reports red squirrels in Britain are facing extinction. There may be only 30,000 left in England, 10,000 in Wales, 10,000 in Northern Ireland, and 121,000 in Scotland [Red Squirrel Facts]. The European Red squirrels (Sciurus vulgaris) are being out-competed by American or Eastern gray squirrels (Sciurus carolinensis) introduced into Great Britain in 1876.

Human Brits are banding together to help the red squirrels fight off the foreign invasion [Friends of the Red Squirrel] but the prospects are dim. It looks like curtains for the reds.

This clearly has something to do with evolution. When one species out competes another and drives it to extinction we think of this as part of the process of evolution. But which process is it? It doesn't really count as natural selection, strictly defined, since that process involves differential success of individuals within a population. What do we call it when two species go head-to-head and only one survives?

Monday's Molecule #7

Name this molecule. The common name will do but there will be bonus points for finding the correct scientific name. This compound is essential in human diets. You will die if you don't get it in your food. Comments will be blocked for 24 hours. You can post your answer in the comments.

Appeaser Ed Brayton Asks Dawkins to Back Off

There's been a bit of trouble over the fact that Richard Dawkins signed a petition he shouldn't have signed. Ed Brayton attacked Dawkins and Dawkins explained that it was all a mistake.

Now, Ed Brayton has published his letter of apology to Dawkins. In that letter Brayton criticizes Dawkins for making it more difficult to oppose American creationists. This is the classic appeasement position and I'm delighted that Brayton has made his position clear. I reject it entirely. Writing to Dawkins to ask him to tone down his criticism of religion is a really, really stupid thing to do. Among other things, it shows us that Brayton doesn't understand the fight between rationalism and superstition.

It shows us something else as well. Ed Brayton needs to learn that the world does not revolve around the USA. People who live in other countries don't react well when they're told to put a muzzle on because their ideas might not play well in America.

Here's what Brayton says,

Let me address, as well, a more general subject. You and I agree on a great many things and disagree on a few. We are both staunch defenders of evolution against the ignorant attacks of creationists of every stripe, but I genuinely do believe that your aggressive anti-theism makes it more difficult for those of us engaged in the daily fight to protect science education to make our case. I hope that you understand what I believe to be the single most important aspect of this dispute, which is that the vast, vast majority of those who reject evolution do so solely because they believe it disproves their religion. The average person knows as little about evolutionary biology as I know about Sumerian architecture, which is to say virtually nothing. The only thing they know, on an almost reactive level, is that evolution = no god = no morality. Now, I think it's important to attack this misconception at the levels you do as well, by pointing out that atheism does not lead to immorality, and I make that argument loudly and often. But I assure you that for those of us "on the ground" in the battle, so to speak, every anti-theistic statement you make is amplified by our opponents and used as a sort of prophylactic to guard against the infiltration of not only evolution but of virtually all scientific thought.

I am in full agreement with Dr. Tyson, in his admonition to you at the recent Beyond Belief conference, that if you would just be more circumspect in your hostility toward religion, at least in regards to those who are largely on our side in the evolution conflict, it would help a great deal. I hope you will accept that criticism from me as graciously as you accepted it from him at the time ( and I say that with full recognition that I could also learn a thing or two about being more reserved and less bombastic from time to time). I can tell you with no hesitation that it would make my work in this regard a good deal easier and would help avoid the kinds of emotional distractions that are fed and amplified by the anti-evolution movement.

I'd like to make one more point. I find it very offensive for Ed Brayton to state that he is "on the ground" in the fight against creationism, implying that Richard Dawkins isn't. Brayton is not a scientist and he is not an expert on evolution. Yet Brayton is lecturing Dawkins on the proper strategy to pursue in order to defeat the forces of superstition and anti-science. That's hubris.

Old Professors

Jonah Lehrer is an editor for Seed magazine. On his blog, The Frontal Cortex, he has resuscitated an old argument that I though we had settled. The issue is whether Professors over 60 should be put out on an ice flow to make room for, presumably smarter, young scientists [Old Professors].

The article defines old Professors as those over 60. I'm going to assume that young Professors are under 40. Since I'm 60 years old, that makes me still middle-aged and in a good position to present a totally unbiased opinion concerning the stupidity and naivety of youth.

It might be helpful to have some examples of old dotty Professors who clearly lost all ability to contribute to science once they turned 61. In the field of evolutionary biology we have; Ernst Mayr (101 when he died last year), Jared Diamond (69), E.O. Wilson (77), Richard Dawkins (65), and Stephen Jay Gould (61 when he died in 2002).


My faculty union and the University of Toronto recently concluded an agreement to abolish mandatory retirement at age 65 and the Province of Ontario has recently passed legislation abolishing mandatory retirement in the public sector. Let's not argue about whether Professors should be forced to leave their jobs on their 65th birthday. This is a rights issue. It is ethically wrong to discriminate on the basis of age. There is no justification for such discrimination in this day and age and it's about time that we did away with it. (Most American schools abolished mandatory retirement many years ago.)

Are there any conceivable arguments for reinstating mandatory retirement that meet the test of rationality? No there aren't. So why is there still a debate?

Lehrer quotes from an article in the Boston Globe on the Graying of US Academia. The article points out that since the abolition of forced retirement, the average age of Professors is increasing (duh!) and this is a bad thing.

Why is it a bad thing? The perceived wisdom is that old Professors are taking up space that should be going to younger faculty. Well, it turns out that this isn't very significant. It will always be the case that a new faculty member will be hired every time a Professor retires. Assuming a steady state, the rate of new hires won't be much different if some of the Professors stay on past 65 or 70. (Less than 25% of Professors continue to work after they turn 65.) That argument doesn't really cut the mustard. The real problem is that the number of Professors is not expanding very much so that new opportunities for junior faculty aren't being created. In our department, for example, budget cuts are forcing us to cut back on the number of Professors.

But even if the argument were true there is no ethical way to improve the situation by getting rid of old Professors. You can't just knock on the door of Professor Dawkins and tell him to get the hell out of Oxford because there's some 32 year old post-doc who wants his job. Be reasonable, people.

There's an underlying assumption in these discussions that I find troubling. If you read John Lehrer's posting and the comments that follow, you'll see lots of discussion about whether old Professors can still do their job. Lots' of people think that young Professors are better teachers, for example. That's nonsense. I've not seen any evidence to support that assumption in my forty years of experience in universities. Some young Professors are excellent teachers and some aren't. Some old Professors are excellent teachers and some aren't.

I can tell you one thing that seems to be a general rule. Whenever we sit down as a group to discuss teaching, the older Professors bring a great deal more to the table than the younger ones. I was reminded of this last month when we discussed changes to our undergraduate and graduate programs. This is a time when wisdom counts. My older colleagues know how to effect real change and they know how to avoid fads that will get us into trouble later on. They know how to work the system for maximum benefit.

(I should point out that in science departments teaching is a minor part of the job so it doesn't play a big role in deciding whether old Professors are better than young ones.)

Administrative tasks are a major part of the average Professor's job. There's no question about the fact that the longer you've been at a university the more capable you are of handling administrative tasks. This applies to local jobs like departmental chair, associate chair, and managing undergraduate and graduate programs. It also applies to higher level jobs like chairing university committees and becoming a Dean or assistant Dean.

Research is the big bogeyman. There's this persistent myth out there that young people are ever so much better at it that the old fuddy-duddys who already have one foot in the grave. There is no evidence to support this myth, even in mathematics where it originated. If you want to maximize research productivity in a department you don't do it by forcing out highly productive scientists just because they turn 65.

Please don't misinterpret me. Of course there are old Professors who are not being productive. There are ways of encouraging them to retire and if they don't take the hint there are ways of firing them even if they have tenure. This won't be required nearly as often as people imagine, but it will happen and it should probably happen more often. On the other hand, let's not forget that there are lots of younger people who don't make the cut. It's not a direct function of age.

This is an issue that demands more sensitivity than it gets. I find it very unsettling to hear people calling for the firing of old Professors just because we need to make room for younger ones. What do you imagine those old Professors are going to do when they are fired? In many cases they have been working for much lower wages than they could have gotten in the private sector and they still have mortgages to pay and kids to put through college. They often have decent pensions but still not enough to maintain their lifestyle. (I'm not talking about Harvard, I'm talking about state schools.) Do we really want to move to a cut-throat corporate model where youth and lower wages trump wisdom and maturity? Is that the kind of university we want?

The Three Domain Hypothesis (part 6)

[Part 1][Part 2][Part 3][Part 4][Part 5]
Evolving Biological Organization
Carl Woese discovered archaebacteria and he made them fit into a separate super-kingdom, or “domain.” He is the man behind the claim that archaebacteria are so different from other bacteria that they deserve equal taxonomic status with eukaryotes. Woese is the father of the Three Domain Hypothesis, which not only claims domain-level recognition for archaebacteria, but also claims that eukaryotes descend from a primitive archaebacterium.

Back in 1995, when evidence against the Three Domain Hypothesis was mounting, I made a bet with Steven LaBonne that Woese would recant by January 1997.

I lost that bet, but eight years later Woese has finally come to his senses ... at least partly ....

I’m reviewing articles that appeared in Microbial Phylogeny and Evolution edited by Jan Sapp. Carl Woese’s contribution (“Evolving Biological Organization”) describes his current thoughts about the emergence of defined species from the pool of primitive gene-swapping cells that characterized the early history of life.

Woese’s idea, which has been evolving of a period of ten years, is that primitive life existed as a community of cells that freely exchanged genes. They shared a basic translation system for making proteins, but had little else in common. These cells evolved as a community and not as distinct lineages.

Woese refers to this time as the “progenote era” where the word “progenote” refers to a cell that has not yet established a definite link between a stable genotype and a heritable phenotype. At some point in time, certain cells make the transition from progenote to the founders of a stable lineage. The transition point is known as the “Darwinian threshold.”

The real mystery, however, is how this incredibly simple, unsophisticated, imprecise communal progenote—cells with only ephemeral genealogical traces—evolved to become the complex, precise, integrated, individualized modern cells, which have stable genealogical records. This shift from a primitive genetic free-for-all to modern organisms must by all acounts have been one of the most profound happenings in the whole of evolutionary history. Although we do not yet understand it, the transition needs to be appropriately marked and named. “Darwinian threshold” (or “Darwinian Transition”) seems appropriate: crossing that threshold means entering a new stage, where organismal lineages and genealogies have meaning. where evolutionary descent is largely vertical, and where the evolutionary course can begin to be described by tree representation. (p. 109)

According to Woese, bacteria were the first species to emerge from the pool. From that point onwards, the evolution of bacteria was “Darwinian” and could be represented by a bifurcating tree.

What about archaebacteria and eukaryotes? They emerged later ...

At that point, though, both the archaeal and eukaryotic designs remain in the pre-Darwin progenote, condition: still heavily immersed in the universal HGT field, still in the throes of shaping major features of their representative designs; and so, their evolutions cannot be represented in tree form. In other words, the node in the conventional phylogenetic tree that denotes a common ancestor of the archaea and eukaryotes does not actually exist. The two cell designs are not specifically related; it is just that the tree representation made them “sisters by default.” (p.111)

Woese suggests that the archaebacteria were the next to cross the Darwinian threshold followed by eukaryotes. This explains why archaebacteria have simpler cell components and eukaryotes are more complex. (The precursors of the eukaryote lineage spent more time in the progenote era and accumulated more innovative structures, such as nuclear membranes.)

The progenote community may have spawned other “domains” but these are now extinct, although Woese suggests there are some clues pointing to their previous existence. I assume that the progenote community itself petered out shortly after the emergence of eukaryotes.

This new theory of Woese is not very satisfying. I find the explanation somewhat confusing. Woese is trying to preserve the distinctiveness of the Three Domains while denying that their relationship can be discerned. In other words, he wants to have his cake and eat it too.

In order to defend the monophyletic domains, especially archaebacteria, he has to postulate that each one descends from a single cell, or lineage, that pops out of the progenote community. That’s why each domain has a defined root (i.e. monophyletic). But in order to account for the massive amounts of data that show eukaryotes closer to bacteria than to archaebacteria, he postulates an extended period of evolution where cells exchanged genes in a communal pool. This is not unlike the ideas of many other workers in the field except that for Woese it represents a denial of one of the basic tenets of the original Three Domain Hypothesis.

Woese is very clear about this. He makes the case that the branches at the base of the ribosomal RNA tree are not meaningful. It is wrong to assume that archaebacteria and eukaryotes share a common ancestor. I’ll close this part with an extended quote from Woese to show you just how far he’s willing to go to make the case. (Note how much he has come to agree with people like Ford Doolittle [Part 5] who have been challenging the Three Domain Hypothesis for over a decade.)

Classical biology has also saddled us with the phylogenetic tree, an image the biologist invests with a deep and totally unwarranted significance. The tree is no more than a representational device, but to the biologist it is some God-given truth. Thus, for example, we agonize over how the tree can accommodate horizontal gene transfer events, when it should simply be a matter of when (and to what extent) the evolution course can be usefully represented by a tree diagram. Evolution defines the tree, not the reverse. Tree imagery has locked the biologist into a restricted way of looking at ancestors. It is the tree image, almost certainly, that has caused us to turn Darwin’s conjecture that all organisms might have descended from a simple primordial form into doctrine: the doctrine of common descent. As we shall discuss below, it is also the tree image that has caused biologists (incorrectly) to take the archaea and the eukaryotes to be sister lineages. Much of the current “discussion/debate” about the evolutionary course is couched in the shallow but colorful and cathected rhetoric of “shaking,” “rerooting,” “uprooting,” or “chopping down” the universal phylogenetic tree. (p.102)

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Microbobial Phylogeny and Evolution: Concepts and Controversies Jan Sapp, ed., Oxford University Press, Oxford UK (2005)

Jan Sapp The Bacterium’s Place in Nature

Norman Pace The Large-Scale Structure of the Tree of Life.

Woflgang Ludwig and Karl-Heinz Schleifer The Molecular Phylogeny of Bacteria Based on Conserved Genes.

Carl Woese Evolving Biological Organization.

W. Ford Doolittle If the Tree of Life Fell, Would it Make a Sound?.

William Martin Woe Is the Tree of Life.

Radhey Gupta Molecular Sequences and the Early History of Life.

C. G. Kurland Paradigm Lost.

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Creation Sunday

 Looking for some entertainment in February? Check out Creation Sunday in Orangeville, Ontario (north of Toronto). On Sunday Feb. 11th and Monday Feb. 12th you can hear three of the leading IDiots from Creation Ministries International speaking on "Authority Begins With Genesis," "Genesis and the Gospel Connection," "Codes and Creation," and "What the Bible and Science say about the Age of the Earth."

It ought to be a barrel of laughs. Bring lots of popcorn.

Capital Punishment Is Barbaric

 With the hanging of Saddam Hussein, Iraq affirms its membership in the group of nations that don't deserve to be called civilized.

New But Not New

 
Another major breakthrough in molecular biology has just been reported [Jefferson researchers discover new way nature turns genes on and off]. (I've lost track of how many times traditional molecular biology has been overturned in 2006—has anyone kept a list?)

Here's the startling news,

Peering deep within the cells of fruit flies, developmental biologists at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia may have discovered a new way that genes are turned on and off during development.

Reading a bit further, we find,

According to Dr. Mazo, the researchers found that one of the likely mechanisms behind ncRNAs' ability to regulate essential coding genes is through a "transcription interference" mechanism. "Such mechanisms are known in bacteria and yeast, but not much is known in higher organisms," he explains.

In other words, it's not new at all. I've been teaching transcriptional interference during bacteriophage lambda development since 1979 and it's in many textbooks, including mine (1994).

Question: What the heck is a "higher organism?"
Answer: It's a term we look for in order to identify people who don't understand evolution.

Can You Be a Theist and Believe In Evolution?

 
John Wilkins wonders about this in God, evolution and variation. I think it all boils down to purpose. Science doesn't reveal purpose but most religions demand it. (We're talking about interventionist Gods here.) Real evolution incorporates a large degree of accident and randomness and that's just not consistent with a God who has a plan. (Yes, I'm aware of the confused rationalizations of some theistic evolutionists.)

A Challenge to Denyse O'Leary

 
Denyse O'Leary writes in Thoughts on recent books on the intelligent design controversy: Some ways to spend your holiday cash.

Case in point: North American mainstream media report that the vast majority of Americans do not believe Darwinism, with the clear implication that there must be something wrong with them. It is almost inconceivable that media boffins, for whom materialism is the normal way of thinking, would actually be interested in knowing why so many who are at liberty to doubt take up that option. And the media boffins are not likely to change. The media they govern are more likely to simply decline in importance as a source of information.

Denyse, you claim to be a journalist. I challenge you to come up with a reasonable explanation. Keep in mind that you also have to explain one additional fact; the majority of Canadians and Europeans believe in evolution and they have just as much freedom to doubt as Americans. Possibly, more.

So, give it your best shot. If you think the "media" aren't interested in knowing why so many Americans are fooled by the IDiots then here's your chance to get them interested. More importantly, here's your big chance to do what nobody else has been able to do—explain why so many people in the USA are anti-science. You could be famous.

P.S. Why are you still using the term "Darwinism" to describe acceptance of the scientific facts of evolution? You haven't been paying attention, have you?