Aldrichimica Acta Woodward Memoirs

I was not aware of this splendid 1977 issue of Aldrichimica Acta dedicated to RB. It has an insightful article by David Dolphin containing memories I have not heard recounted elsewhere. One of the more curious part of the article narrates the story of a horoscope that was prepared for Woodward! Read on...probably his most important piece of advice was:
"There is not time to worry over what others think of us..."

Also, I was hoping that someone who stumbles upon this blog would have a personal photograph of Woodward to contribute to our Wikipedia article on him. I have contributed considerably to this article and in fact was the first to expand it from a two sentence piece to a bonafide article, but could never locate a photo that didn't have a copyright.

Thanks for all the fish

The LHC begins crashing protons tomorrow. The following from Stephen Hawking captures it the most accurately:

"It is a tribute to how far we have come in theoretical physics that it now takes enormous machines and a great deal of money to perform an experiment whose results we cannot predict"

Since one of those unpredictable results is the end of the world, we might as well depart with song and dance:



But as imbibed with levity as this matter is, it reminds me a very similar matter brought up during the making of the atomic bomb; the suspicion by Edward Teller that the atmosphere might go up in flames. Teller first brought up the topic during a secret 1942 Berkeley summer study headed by Oppenheimer. Oppenheimer was concerned enough to go to Michigan and discuss it with Arthur Compton, one of the administrative heads of the project. The two actually decided to stop work on the project if this scenario posed a non-trivial risk. But the resourceful Hans Bethe by then had worked out the energy balances of the reactions involved and concluded that there was a "vanishingly small" possibility that this might happen...

Fast forward to 16 July 1945 at the site of the world's first atomic bomb detonation. Enrico Fermi was cheerfully taking bets on whether the bomb would ignite the entire planet or just the state of New Mexico...

Gernot Frenking is not happy...not at all

Stable is simply "able" with a "st"



Wow. This is a first for me. Three of the heavyweights in theoretical and computational chemistry have published a set of prescriptions in Angewandte Chemie for theoretical chemists claiming to have discovered new, "stable" molecules. In response, Gernot Frenking who is a well-known chemist himself has not just published a piercing and trenchant critique in reply to this article, but they actually seem to have reproduced the text of his referee's comments as a reply. This is a lively and extremely readable debate.

In an article asking for more "realism" from theory, the three heavyweights- Roald Hoffmann, Paul von Schleyer and Henry Shaefer III- have basically come up with a roster of suggestions in response to what they see as the rather flippant declarations by theoretical chemists of molecules as "stable". One of the annoying things about theoreticians is that they regularly analyze molecules and proclaim them as stable. Experimentalists then have to sweat it out for years to actually try to make these molecules. Frequently such molecules are stable under rather extreme conditions, for example in gas phase at 4 degrees kelvin. To address the animosity that experimentalists feel against such carefree theoretical predictions, the three chemists have come up with suggestions for publication.

They make some interesting points about criteria that should be satisfied when declaring molecules as stable. In fact they think that one must do away with the word "stable" and replace it by the words "viable" and "fleeting". For example for "viable" molecules, one has to be clear about the difference between thermodynamic and kinetic stability. Molecules described as viable by theoreticians must have half lives of about a day, must be isolable in condensed phases at room temperature and pressure, and must not react easily with oxygen, nitrogen and ozone (?). Molecules with more than +1 positive or negative charge must also be included with "realistic" counterions. Molecules must even be stable under conditions of some humidity. The authors then also make suggestions about reporting accuracy and precision, and about the well-known fact that theoretically reported precision cannot be more than experimentally measured precision.

If theoreticians think these suggestions are asking for too much, they have a friend in Gernot Frenking.

Frenking batters these suggestions down by basically launching two criticisms:
1. The suggestions are too obvious and well-known to be published in Angewandte Chemie
2. The suggestions are heavily biased towards experimentalists' preferences
As Frenking puts it, he expected to walk into a "gourmet restaurant", and was served a "thin soup" instead. Ouch.

I have to say that while the suggestions made by the three prominent scientists are quite sound, Frenking's points are also well-taken. He lambasts the suggestions that realistic counterions should be included in the calculation of a molecule with multiple charges; there are already molecules with multiple charges predicted to be theoretically stable which were then isolated by experiment. Ionic molecules with charges more than + or -1 are easily isolated in condensed phases. And one of the central questions Frenking asks is; why does a molecule need to be so experimentally stable in order to justify the publication of its theoretical existence. After all there are many molecules present in interstellar space which cannot be isolated under average Joe lab conditions. Under these circumstances, Frenking is of the opinion that the distinction between "viable" and "fleeting" is "eyewash" (it's the European way of euphemism)

I resoundingly agree especially with this contention, harsh as it sounds. Why should experimentalists get an easy pass? The whole point of theory is to push the boundaries of what's experimentally possible. To suggest that one should only publish a theoretical prediction if it can easily be verified by experiment is to do disservice to the frontiers of science. While I can understand the angst that an experimentalist may feel when he sees an unusual molecule stable only under extreme conditions declared by a theoretician as "stable", that's exactly the challenge experimentalists should be up to, to devise conditions under which they can observe these short-lived molecules. If they do this they are the ones who carry the day. Since stability as is well-known is a relative term anyway, why insist on calling something "stable" only if it satisfies the everyday lab conditions of the experimentalist. I believe that it is precisely by testing the extreme frontiers of stability that chemistry progresses. And this can be done only by making things hard for experimentalists, not easy. Theoreticians pushing experimentalists and vice versa is how science itself progresses, and there is no reason for either one of them to quit questioning the boundaries of the others' domain.

There are other points and criticisms worth reading, include other referee comments which endorse the article and are also quite interesting. In the end however, I cannot answer Frenking's central question; should this article have been published in Angewandte Chemie? We should leave it for readers to judge.

Roald Hoffmann, Paul von Ragué Schleyer, Henry F. Schaefer III (2008). Predicting Molecules - More Realism, Please! Angewandte Chemie International Edition, 47 (38), 7164-7167 DOI: 10.1002/anie.200801206

Gernot Frenking (2008). No Important Suggestions Angewandte Chemie International Edition, 47 (38), 7168-7169 DOI: 10.1002/anie.200802500

Vytorin: New Problems for a New Era

The NYT has a piece today in which it describes the problems riddling Vytorin, a combination of ezetimibe and simvastatin, which is taken by 3 million around the world and makes 5 billion for its owners, Schering-Plough and Merck. The piece says that in spite of such widespread usage, there is apparently no clinical trial data that demonstrates that the second piece of the cocktail- ezetimibe- is efficacious. Much more concerning is the fact that there may be a link between ezetimibe and cancer, although the link looks fragile at best right now.

Statins have been the wonder drugs of our time, with Atorvastatin (Lipitor) being the best-selling drug in the world. Their efficacy in reducing heart attacks has been demonstrated in large-scale trials. Ezetimibe which blocks cholesterol absorption in the intestine and reduces LDL has much more tenuous effects. Recent large-scale studies found that while ezetimibe does reduce LDL, it's effect on the variables that actually matter are far less certain; there was no evidence that it actually reduces heart attacks. Yet it continues to be prescribed by thousands of doctors around the country, with patients shelling out considerable amounts for it.

However, the article raises the much bigger issue of knowing exactly when a drug is efficacious. According to the article, utility of a drug is usually gauged by "surrogate endpoints", that is, endpoints which indicate reductionist type effects rather than an actual increase in life-span or quality of lives. Take cancer for example. For most cancer drugs, tumor shrinkage is a convincing endpoint, not an actual increase in life-span. Or take cholesterol medications. The causal link between LDL cholesterol lowering and reduced heart attacks is apparently well-proven. Yet the body is complex enough for this causal link to be questioned; such questions arise most often in truly large sample studies, when the drug is on the market. Clearly the only true indication of side-effects or efficacy will come from such large-scale studies.

But there's a dilemma here as far as I can see it. The reason why surrogate endpoints are used seems clear to me; it's simply much more easy to look for such effects and ascribe them to drug action than effects like "increase in life-span" which can be controlled by multiple factors. Let's say two men who are the same age have been prescribed the same cancer medication. Both show shrinkage in tumors. Apparently the medicine works. But can this be translated into an observation about the difference in their life-spans, which can be attributed to so many different factors. Especially if the general health of one of the patients is worse than the other, then the cancer medicine can basically be an adjuvant and not the primary cause for his prolonged survival. How do we know that it's the cancer medicine and not his general health condition that actually increased his life-span? Naturally a reduced incidence of heart attacks is much easier to analyze than an increase in life-span. But even there it seems that so many factors can be responsible for a heart attack that it would be a problem trying to attribute specific effects to the medication, or especially the lack thereof of its effects.

The article also says that the FDA has become stringent about medications that address chronic problems like heart disease. The stringent bar set for a true study of efficacy seems to be about 10,000 patients over about four or five years. If every pharmaceutical company needs to do such a study to get approval, they might as well start digging their grave right away. Drug development is already so risky and expensive that putting a drug through 10,000 patients over five years and having the FDA almost certainly reject it after that would spell doom for all drug makers. Yet it is clearly unethical for doctors to keep on prescribing medication whose efficacy has not been demonstrated.

There does not seem to be an easy way out of this problem. To me right now it seems that, with all the compromises and problems it entails, the best bet might be to set such a stringent bar for medications for which good alternatives exist (and medications for chronic heart disease seem to fall into that category now) but relax the need for such large-scale trials for unmet and critical needs for which no good drugs exist. I am pretty sure the FDA is not going to set the bar for cancer so high.

So what's the way out for companies? To me the soundest scheme for now seems to be for doctors to provide information on the label saying that the drug did not show efficacy in a fair number of patients, and let the patient decide for himself or herself. It would be ridiculous in my opinion for the FDA to demand that the company withdraw the drug. Also, as a general thought, I think that both the FDA and public opinion need to get over their obsession of approving drugs only if they show efficacy in 100% or even 90% patients. What if a drug shows efficacy in 50% of patients? The rational thing would be for doctors and companies to explicitly say this on their label and let the consumer decide. That's the kind of thing that should happen in a liberal society.

Note: Over at The Pipeline, Derek has quite a few posts on this

Tipping Point

The Revenge of Gaia: Earth's Climate Crisis and the Fate of Humanity
By James Lovelock
Basic Books (2007)

In this clarion call to arms, eminent scientist James Lovelock warns us cogently and eloquently of the impending doom that we have forced upon our planet by global warming. Lovelock is well-qualified to offer such gloomy predictions; it was this extremely versatile scientist who in the 1960s and 70s proposed the idea of Gaia, the notion that the earth is a self-regulating organism whose regulatory mechanisms are intimately coupled to the activities of species in its biosphere. One species- man- has tilted the balance of these mechanisms and thrown them into disarray. The species that will pay the biggest price for this deed is also man himself. Through careful speculation and excellent scientific arguments about details, he rationalized this notion until it has now become widely accepted.

Lovelock's premier argument is that global warming (which he amusingly always refers to as "global heating") has already rendered our planet incapable of the self-regulation that it has admirably demonstrated for millennia. The temperature rises which global warming are going to bring about are beyond those which the earth can endure in a homeostatic manner, and its catastrophic effects are likely going to manifest within decades. There is a horrific precedent for believing this; the same kinds of temperature rises fifty five million years ago led to catastrophic mass extinctions and sea-level rises, inducing an ice age that lasted 200,000 years. We are in danger of inducing such a global pandemic by our efforts right now. The most serious manifestation of man-made global warming is in positive feedback. Two examples suffice; the well-known melting of ice which leads to less reflection of sunlight which leads to more melting, and the heating of the upper layers of the ocean that kills algae. These algae are crucial players in maintaining cooling by the emission of sulfur compounds that serve to reflect sunlight from clouds. Lovelock documents both these effects well as well as others that are resulting from the 'double whammy' that we are serving our planet; simultaneously emitting CO2 and depriving the earth of biomass that normally absorbs it.

While the first part of the book describes Gaia and how it's been affected irreversibly by global warming, the second part basically deals with the muddle headed perceptions of energy, food sources and environmentalism that affect many in the political establishment and media, most prominently environmentalists themselves.

There is clearly a rift between environmentalists that threatens to slow down action against climate change. One section, unfortunately the bigger one, is the more vocal one consisting of organizations like Greenpeace, who have a wrong-headed and irrational perception of environmentalism. They tout phrases like "sustainable development" and "renewables" without really understanding their limitations. They participate in emotion-laden protests and demonstrations just to prove their point. Their environmentalism mainly deals with trying to save cuddly creatures and colorful birds in remote parts of the world, while there are organisms much more in need of saving, including the microorganisms and algae which play extremely crucial roles in maintaining the homeostasis of Gaia.

The second group of environmentalists is a minority, and Lovelock is one of them. They understand that global warming has already done its damage and our goal now should not be mainly "sustainable development" but "sustainable retreat". They understand that much more important than saving a few endangered species in New Guinea is to prevent deforestation and use of more landmass even in developing countries. They know that debate about saving the environment cannot be dictated by emotion. Most importantly they understand that nuclear energy is the best short-term and perhaps long-term solution for our energy needs.

When it comes to energy sources that we should pursue, Lovelock's thesis is clear and rational. Renewables (solar, wind, biofuels) may sometime make a dent in the energy equation, but renewables are not going to save us soon enough. The phrase soon enough is important here. Lovelock is a reasonable man and does not discard renewables entirely. The problem is in trying to find good energy sources as fast as we can. But each one of the renewables is currently fraught with problems of inefficiency, environmental unfriendliness and lack of scale-up plans. Solar panels are expensive and inefficient. Wind farms consume huge tracts of land, land on which forestation usually soaks up carbon dioxide, and in addition need back up from fossil fuel generators when the wind is not blowing. Biofuels struggle with maintaining energy balances and pose similar land-use problems. It will be at least 50 years before renewables make a significant contribution to our energy needs and their use becomes cheap and widespread. But by that time it will be too late. The single-most important factor here is time.

The answer is clear and rational; especially for the short term future, nuclear power is the most efficient, readily available, widely-implementable, environment-friendly and safe source of power. Even if the problem of waste disposal is not trivial, it pales in comparison with the benefits we will incur, and especially the catastrophe that we will find ourselves in if we don't do it.

While Lovelock hopes fusion will become important soon, fission is currently our best bet. We already have the technology unlike that for renewables. Its efficiency is marvelous- a good numerical argument to keep in mind is this; global CO2 emissions for a year make up a mountain that is a mile in diameter and sixteen miles in height, a behemoth. In contrast all the nuclear fuel providing power for a year will constitute a cube that is sixteen meters on a side. It was Lovelock's espousal for nuclear power that represented a break from the 'green' party line. But now, nuclear is going to be as green as we can think of. To stave off fears of nuclear waste, Lovelock has even offered to bury the waste from a nuclear reactor in his backyard and use its energy for heating his house. In addition to these facts, Lovelock also clearly describes the paranoia that the public has for nuclear power, while all the time they face risks and dangers much more damaging and insidious.

One very cogent point that Lovelock makes is about how religious faith has caused problems in enabling our stewardship of the planet. He correctly points out that all religious texts were written at a time when man and his life were the focus. At very few places in the Bible or the Koran or even the Eastern texts is there an emphasis on the planet. None of the major world religions put nature before man. Now however, emphasizing man is going to be meaningless unless we emphasize Gaia, because without Gaia we won't be around. There need to be new "religious" principles, infusing the care and stewardship of the planet into children's minds, instead of the narrow self-serving interests of man that will become irrelevant once the sea-levels rise or the North Atlantic current slows down.

The same factor- time- that makes a good argument against renewables, also makes the strongest argument against libertarian "solutions" to climate change. Libertarians argue that the free market will eventually find solutions to the climate change problem without government intervention. But even if this solution might work in principle, 'eventually' is not going to be soon enough, good enough for us. We may have a little more than 20 years to beat a respectable retreat. For that we need legislation against carbon emissions, against use of oil for transportation, against land use right now. The libertarian approach may have worked 50 years ago when we had time. Thinking about renewable sources could have saved us if we had begun 200 years ago. But now even if these solutions work, they almost certainly will come too late to save us. As they say, "operation successful, but the patient is dead". To save the patient in time, we are going to inevitably have to make compromises, sacrifice at least some of our freedom to large scale government actions. We have to operate now in a manner reminiscent of how we operate in wartime. In times of legitimate (and in these times I stress the word 'legitimate') war, citizens don't complain about sacrificing freedom because they know their lives depend on it. Now Lovelock says we face a similar scenario.

On the downside. Lovelock makes some statements which I think should be better referenced. For example, I would not completely trust his contention that most of the cancers that we are going to die from are caused by our breathing oxygen. While oxygen certainly can produce free radicals and cause damage, such a significant role should be more firmly supported by evidence.

It is very difficult to find wholesome solutions to climate change. We seem to have now done a good job of recognizing the problem in the first place. But unfortunately it's too late to implement quick fixes that will wake us up from this nightmare when we will find that everything is all right. In an age where politicians are pushing for more oil drilling, rapid action and awareness is essential. We have to beat a retreat and live to fight another day, unlike Napoleon in Russia in 1812. For that we need coherent and rational thinking and global fixes, with all the compromises that they might entail. Going nuclear, and perhaps even indulging in grandiose fixes like "space reflectors" which reflect sunlight from miles-wide arrays, may be possibilities. Lovelock sounds an alarm in his book that is backed up by evidence and grim prognostication. Gaia will do whatever it takes to establish her equilibrium, equilibrium that's inherent in the laws of her physics and chemistry, equilibrium that will be established even if it means the loss of humanity. As a pithy line in an X-Files episode once put it, "You can't turn your back on nature, or nature will turn her back on you". It's simple.

The End of Industrial Productivity?

A long time ago when I was a fledgling student studying college physics and chemistry, I ventured into the haunting, dark recesses of our library which housed science classics. As I browsed through those classic volumes by Kelvin, Einstein, Raleigh and Medawar and as the dust gathered on to my clothes, I saw a 1930s book titled "Electronics" by Bill Shockley, the Bill Shockley of the legendary Bell Labs who had played a key part in the invention of the transistor. As I eagerly opened the pages of the book in a cloud of dust, I was surprised to see equations covering the pages. Almost no diagrams of circuits and components found in modern electronic texts, but reams and reams of quantum mechanics detailing calculations of current density and electron transport. It was then that I realised that that singular device, the transistor, had its conceptual roots in fundamental physics. Without quantum mechanics and the basic physics of electron flow the transistor may never have been possible. The experience drove home a fundamental point for me; without the roots of basic research that nourish and inspire, there are no fruits of applications possible.

Sadly, the same Bell Labs which exemplified all that basic research stood for and which for a long time was the greatest industrial basic research laboratory in the world, is now getting divorced from its roots. An article in Nature documents the sad case of the once scientific giant whose basic physics research team has dwindled to four scientists, an extremely sad state of affairs. The division that generated six Nobel Prizes for basic and breakthrough research has now shrunk to basically non-existence. Unfortunately similar trends are seen elsewhere. The consequences for future technology cannot be anything but dire. In the last fifty years almost every one of the technological innovations that we take for granted, including the computer, laser, transistor and digital memory to name a few have come from research in basic science. Nobel Prizes have been gathered in the dozens by scientists who worked on these discoveries. Where Bell Labs scientists won Nobels for the laser and the transistor, IBM researchers in a grand encore performance won two Nobels in the 1980s- one for the invention of the Scanning Tunneling Microscope (STM) and one for high-temperature superconductors. Most recently it was academic scientists who won the Nobel for discovering Giant Magnetoresistance, the phenomenon that powers our iPods and computers.

This trend is hardly surprising however. As companies move increasingly towards satisfying the bottom line for the next quarter and pleasing shareholders, they are having scant patience and even more scant funding for basic research. While product development may diversify in the short term, it's like water flowing over a long distance which is slowly cut off at the source; while the flow of water will persist and even appear normal for some time, it is undoubtedly going to shut down after a while. With their current policies of downsizing even applied departments, let alone ones doing basic research, companies are headed for a downfall in new product innovation in the long term. And when I mean "new", I don't mean just another version of Windows or another MP3 player. I am talking about the kind of innovation that leads to a paradigm shift, an outburst of raw data resulting from a single discovery that drives ideas, applications and services for many future decades. Transistors, lasers and STMs all revolutionized the practice of science and technology.

Such innovation can be possible only if we go back to the roots of technology. After all, every technological invention that we are aware of is ultimately based on the laws of physics and chemistry. It is only by exploring these laws that we can discover new applications for them. Consider organic semiconductors and quantum computing that will promise untold increases in computer power that will overcome Moore's Law, or number theory and quantum entanglement that will allow for foolproof data encryption. If the history of basic industrial research has taught us anything, it is that only by pushing the frontiers of the fundamental laws of science can one achieve windfalls of industrial innovation. And yet it is precisely this kind of research that industry is ignoring, at its own and our great peril.

Sadly, science is not like cocaine, promising instant rewards. It treads a risky path, strewn with blind alleys and failures. And yet treading this path is an essential series of steps to achieve the few gems scattered on it. Only in the uncertainty of scientific discovery lies great opportunity. But companies, whether they are hardware developers or pharmaceutical innovators, want the gems without having to vet the stones. Pipe dreams. The greatest entrepreneurs of our time, Warren Buffet and Bill Gates, became who they are by engaging in a philosophy of investment. Invest now, reap the rewards tomorrow. Industry seems to have forgotten this essential philosophy of promising productivity. If this trend continues for long, the verdant branches of the tree that we see today, already divorced from their roots, will wither away to nothingness. And Bell Labs will be the star at the top that first toppled.

P.S. Excimer fumes too

Water and Amyloid Self-Assembly

One of the most significant, interesting and yet poorly understood effect in chemistry and biology is the hydrophobic effect. An important manifestation of its role in biology is invoked by the picture of two parallel hydrophobic plates with water between them that are slowly brought close to each other. At a certain distance called the 'dewetting distance', dewetting is observed and the water suddenly gets expelled out from them. Since nature abhors the resulting vacuum, the two hydrophobic surfaces collapse and 'stick' to each other.

Bruce Berne and his colleagues at Columbia had hypothesized that such dewetting could be observed in biological systems. A remarkable dewetting transition in the protein mellitin and in other proteins in the PDB provided evidence. Now they and others investigate such possible roles of water in the formation of amyloid by molecular dynamics simulations. They focus on the central core peptide of the Alzheimer's Aß (1-42) peptide consisting of the 16-22 region. Since one of my projects involves investigation of the self-assembly of this segment, it is of particular interest to me. This oligopeptide is interesting because it seemingly is the smallest stretch of the bigger parent that also forms the characteristic cross-beta sheet structure of amyloid. Importantly, it is also soluble which means it is more amenable to structural characterization compared to the bigger peptide.

Berne's group investigates the role that water plays between two sheets of 16-22 consisting of nine peptides each. The MD simulations were run for 1 ns, a typical time for such systems. The dewetting critical distance was found to be 12.8 A. Compare this with the classic repeat distance between amyloid beta-sheets which is 9.9 A. Basically two types of phenomena were observed depending on different trajectories and conditions; dewetting, which means that water expulsion was followed by hydrophobic 'collapse', and the simultaneous occurence of expulsion and collapse. The latter phenomena can be interpreted as a kind of 'lubrication' effect that water has been hypothesized to play in the folding of proteins. They haven't been able to put a finger on which is the phenomenon in the 'real' system, but it at least seems plausible that dewetting could be observed in such systems. In the cases where dewetting is not the driving force for assembly, they dissect the interaction energies of different amino acid residues that contribute to the total energy, and find that the Phe-Phe energy contributes to the most.

From a methodological standpoint, the investigation is complicated by the fact that, as in other such studies, the results seem to depend on the methods used. This is a common characteristic of modeling and theoretical investigations. In this case, turning off the protein-water Van der Waals forces causes dewetting in every instant, perhaps not a surprising conclusion since there is now no attraction at all between the water and protein. Also, turning off the electrostatic forces caused no changes, which means that electrostatic attraction plays a small role in the system. Again probably not too surprising. A third observation is that the choice between the two phenomena depends on rather small changes in temperature.

The interpretations are also rendered ambiguous by the fact that amyloid surfaces and indeed most 'hydrophobic' protein surfaces are a poor approximation to two parallel hydrophobic plates. It should be noted that the attractive energy of interaction between two flat plates separated by a distance R is inversely proportional to the square of R. Compare this with the case of two spheres of radius R whose classical Van der Waals attractive energy is proportional to the sixth power of R. That means that in the case of the plates the attraction falls off much more slowly which can lead to significant dispersion forces even at relatively long separation.

This paper, while not leading to very novel or practical results, sheds light through detailed investigation of the possible role water can play between amyloid sheets. It again demonstrates the important effect that choice of methods and parameters can have on observations.

Krone, M.G., Hua, L., Soto, P., Zhou, R., Berne, B.J., Shea, J. (2008). Role of Water in Mediating the Assembly of Alzheimer Amyloid Aß (16-22) Protofilaments. Journal of the American Chemical Society, 130(33), 11066-11072. DOI: 10.1021/ja8017303

I exist

But I had to inevitably be away. I will reemerge very soon. Put it in the bank.

I am full of piety

Or so the Blog Cuss-o-Meter says. Only 0.1% of pages on my blog have "cuss words", less than the average of 10%. I wonder how they are defining these though. Does "creationist" count? How did you do?


OnePlusYou Quizzes and Widgets

Why is body temperature 36 degrees celsius?

While I was doing an unrelated search on the Nature website, I came across this intriguing debate about why body temperature is maintained around 36 degrees and not some other value. (Nature, Vol 324, December 4, 1986, p. 418)

The discussion was initiated by a letter from John Paul, a scientist in Australia who contended that the specific heat capacity of water is lowest at 36 degrees, and therefore heat loss would be minimal at that temperature

But he neglected a fundamental principle of physical chemistry; the rate of heat loss is proportional to the difference between the temperature of the body and that of the surroundings and is independent of the specific heat capacity (remember high school and Newton's Law of Cooling?). More importantly, the specific heat capacity of a body can be thought of as a measure of how well the body offers "resistance" to fluctuations in temperature. The reason why water works so well as an essential life fluid for example is because its specific heat is so high; there is minimal fluctuation in the temperature of water when heat is injected or taken away from it.

Thus, an optimal substance for maintaining a given temperature would be one whose specific heat capacity is as high as possible under the given circumstances, not one whose specific heat capacity is minimum at the given temperature.

These facts were pointed out by William Calder from the University of Arizona and by Steven Benner and Jack Dunitz at the ETH, Zurich. Dunitz as is known is an extremely versatile scientist, a veteran researcher and one of the greatest structural chemists and technical writers of the last century.

Dunitz and Benner make their objections to Paul's explanation clear and offer an alternative partial explanation; that 36 degrees is the optimum compromise between viscosity and hydrophobicity. It's high enough for the viscosity to not become so low as to impede diffusion-limited processes, and low enough that hydrophobic molecules do not "dissolve" too easily.

Natural selection must have taken a remarkable number of factors into account in optimizing this property.