Perfume for the gods

Almost two years ago, I relished giving a departmental seminar on a novel theory of smell by Luca Turin, which proposed that we smell molecules not by their shape, but by their vibrations. The seminar was largely inspired by this book, which then encouraged me to explore the fascinating literature on smell. Turin's theory was then largely discounted, although it predicted that dimethyl sulfide and dimethyl sulfide-d6 would smell different because of different vibrations of the C-H and C-D bonds. I tested this hypothesis myself and indeed could detect a slight difference in their smell. All ten of of my test subjects also could.

A critical editorial in Nature Neuroscience, based on an experiment conducted in Rockefeller University, dismissed the theory with what I thought was a little too much chutzpah. But now, in an article published in the Physical Review Letters, Turin's theory seems to receive support. I still have to read the details; not that the equations of quantum physics are exactly at the tip of my tongue, but still.

Turin has also come out with a book about smell and the science behind it. I just got a copy from Amazon and have started on it. One thing that you have to appreciate about the man is his fine perception of smell, as both science and art, as well as his wide-ranging knowledge. His descriptions of smell are sometimes poetry exemplified, and his ability to nail down a smell in the weirdest description is uncanny ("...smells like the breath of a newborn infant mixed with its mother's hair spray").

On the other hand, the science in the earlier book was sometimes pretty sketchy, and Turin's words about why the holy Angstrom is an appealingly natural unit are not entirely scientifically appealing. He says that the Angstrom seems very natural, because a C-C bond length is about 1 A. Well, a C-C bond length is 1.54 A, very different from 1 A as chemists will realise, and saying that a C-C bond length is 'about' 1 A is alarming. On a similar note, the difference between a C-C and a C=C is 'only' 0.12 A, and yet it makes a world of difference in the chemistry. As they say, chemistry (and biology) are worlds encapsulated within 0.5 A and 2kcal/mol.

Frankly, I have always thought that there's definitely much more to smell than shape. And as far as the difference in smell of deuterated compunds was concerned, I thought the vibration theory bore good weight. The problem is that smell is not quantifiable the way the effect of a drug is, through quantitative dose-response curves. I have to admit that SAR for smell looks even more bizarre than SAR for drugs, which is bizarre enough sometimes. The Nobel prize awarded to smell two years ago was really about the biology, and not about the molecular recognition part. So we definitely have a long way to go in deciphering smell. Smell is fascinating by any standards, no doubt about that.

pKa bamboozle

In a recent publication by a famous chemist, I came across this illustration in which they have calculated the pKa values of guanine and xanthine, among other bases.



Not only does the NH in the five membered ring in xanthine have a lower pKa than the NH next to the carbonyl in the six membered ring, but the pKa of the NH next to the carbonyl in the six membered ring does not change at all when you go from guanine to xanthine.

Maybe I have just had a long day, but this does not make sense to me at all. For the love of god, explain.

Look ma, pet dinosaur

An enormously fun debate is going on in the pages of Nature (subscriber link), initiated after the magazine published the 'Creationism in Europe' article which prompted me to write this post a couple of days ago. After that article was published, a Polish gentleman named Maciej Giertych of the Institute of Dendrology of the Polish Academy of Sciences sent a letter to Nature, in which he questioned the validity of evolution, apparently without citing a single reference, although he did cite his seemingly impressive credentials from the universities of Oxford and Toronto. Giertych said:

"I believe that, as a result of media bias, there seems to be total ignorance of new scientific evidence against the theory of evolution. Such evidence includes race formation (microevolution), which is not a small step in macroevolution because it is a step towards a reduction of genetic information and not towards its increase. It also includes formation of geological strata sideways rather than vertically, archaeological and palaeontological evidence that dinosaurs coexisted with humans, a major worldwide catastrophe in historical times, and so on."

What on earth (pun intended)?! First of all, assuming that what he means by "microevolution" is evolution on the scale of genes and biomolecules, such microevolution has been demonstrated thousands of times, in fact thus enormously supporting and widening the purview of evolution. Secondly, he actually has the audacity to suggest that humans and dinosaurs may have walked together on the earth!

Quite appropriately, this rash letter invoked a series of no less than eight rebuttals in the latest correspondence section of Nature. There are those who have also criticised Nature for publishing such a hack letter, but most have directly condemned Giertych's views. There is the correspondent from the Institute of Dendrology who is prompt to dissociate his institute's views from Giertych's views, and then there are those who lambast him directly for his opinions and deplore his lack of reference citing. But there are also two correspondents who say

"The very fact that his letter was published shows that Nature has no bias against critics of evolution."

This is an interesting point. Should scientific journals publish letters and so-called articles from people like Giertych? At one end, we may think that this is necessary to prove that scientific journals have no bias in publication. Thus, creationists cannot accuse them of actively suppressing evidence. On the other hand, it is not the responsibility of scientific journals to refute every hack creationist unscientific assertion.

I don't know whether Nature published Giertych's letter to allow dissent (no matter how misguided and unsubstantiated) or to actually publish a serious opposing point of view. It surely cannot be the latter, and I am convinced it is the former reason. But as a matter of principle, I completely agree that scientific journals have absolutely no obligation to publish any pseudoscientific cricticism of sound scientific facts, let alone dissenting correpondence. If pseudoscientists cry foul, it's quite clear they are really crying sour grapes. It's one thing to be a valid scientific critic of evolution, but it's quite another to be a pseudoscientific opponent of evolution who cites not one scientific reference. Since it's really the creationists who assert that the earth was created six thousand years ago, the onus of proof has always been on them to prove their assertions, and no journal needs to pander to their dissenting views that don't have an iota of scientific basis to support them.

The other point is related to Dawkins's stance that we can never disprove the existence of god and creation. Naturally, the creationists tout that as proof of their contentions. Scientific journals also don't have any duty whatsoever to publish assertions that are not disproved. Because in science and the reality seeking world, innocent until proven guilty is a non-existent principle.

On a different note, Poland is a staunchly Catholic country, and I won't be surprised if they start teaching creationism in schools as an "alternative theory". The only condition should be that they should teach all "theories" of creation, including that of the Flying Spaghetti Monster and the Dozing Fatty Spinster.

Strontium ralenate

Came across this nifty site that features many old and new drugs and a brief and accessible description of their basic properties and licensing and patent information.
That's how I got to know about strontium ralenate, never heard of before.

Clerical Chemistry

I want to lay claim to a new field; clerical chemistry. Unfortunately, I can't because millions before me seem to have already exploited it and sucked it dry. In one sentence, clerical chemistry is the art and science of lists. Lists which may not indicate anything. Lists which may aspire to but never reach a Voila! conclusion. And lists that are included for no reason except to clutter up powerpoint presentations.

Case in point. A med chem colleague who gave a presentation today about her efforts to develop a new molecule for some receptor (what else). Admirable that she synthesized 175 molecules without having any idea of what they were doing, but does she have to list all her 170 failed molecules on every slide? Not only does it make the head spin, but it deprives one of any inkling of rational drug design. No offense here, but sure, you may have even synthesized 1075 molecules separately, but please give us the bottom line. We admire your heroic efforts sincerely even without you listing all of them till our eyes water. Plus, we waited for the SAR for about 30 minutes, and in the end, the SAR was something which any one of us may have guessed.

Med chem presentations like this one really put me off. I dread it when someone has SAR in the title. Of course, SAR is the heart of med chem, but what we want is a tidy little package that gives us the details. You may have really synthesized every molecule out there with all possible permutations and combinations including one with Uglium, but we already know that, and we really don't care about every single possibility that did not work.

And did I mention that this was a practice talk for a job interview in pharma? Best of luck to her.