Nobel Laureate: Wilhelm Ostwald

 

The Nobel Prize in Chemistry 1909.

"in recognition of his work on catalysis and for his investigations into the fundamental principles governing chemical equilibria and rates of reaction"



Wilhelm Ostwald (1853-1932) won the Nobel Prize in Chemistry for his work on reaction rates and catalysis. His Nobel Lecture On Catalysis is one of the most fascinating and most bizarre Nobel Lectures that I have read. It's worth a look. My impression on Ostwald is that he had lost his edge and was very much aware of it. (There are references in the speech.) Does anyone know the story behind that lecture and the mysterious references?

The presentation speech provides insight into the ways scientists though about biology in those days. The idea that enzymes were catalysts was just coming into favor and it was hoped that their reactions could be followed in the same way chemical reactions were measured.

Your Majesty, Your Royal Highnesses, Ladies and Gentlemen.

The Royal Academy of Sciences has resolved to award the former professor at Leipzig University and Geheimrat, Wilhelm Ostwald, the Nobel Prize for Chemistry 1909 in recognition of his work on catalysis and associated fundamental studies on chemical equilibria and rates of reaction.

As early as the first half of last century it had in certain cases been observed that chemical reactions could be induced by substances which did not appear to participate in the reaction themselves and which at all events were not altered in any way. This led Berzelius in his famous annual reports on the progress of chemistry for 1835 to make one of his not infrequent brilliant conclusions whereby scattered observations were collated in accordance with a common criterion and new concepts were introduced in science. He termed the phenomenon catalysis. However, the catalysis concept soon came up against opposition from another eminent quarter as allegedly unfruitful and gradually fell utterly into discredit.

Some 50 years later Wilhelm Ostwald carried out a number of studies to determine the relative strength of acids and bases. He sought to solve this extraordinarily important matter for chemistry in a variety of ways which all yielded consistent results. Amongst other things he found that the rate at which different processes take place under the action of acids and bases can be used to determine the relative strengths of the latter. He performed extensive measurements along these lines, and in so doing laid the foundations for the entire procedure for studying rates of reaction, all the more essential typical cases of which he examined. From that time onwards the theory of the rate of reaction has become increasingly important for theoretical chemistry; these tests, however, were also able to throw new light on the nature of catalytic processes.

After Arrhenius had formulated his well-known theory that acids and bases in aqueous solution are separated into ions and that their strength depends on their electrical conductivity, or more accurately, on their degree of dissociation, Ostwald tested the correctness of this view by measuring the conductivity and hence the concentration of the hydrogen and hydroxyl ions with the acids and bases which he had used in his previous experiments. He found Arrhenius' theory corroborated in all of the many cases which he himself investigated. His explanation why he consistently found the same values for the relative strength of the acids and bases whichever method he used was that in all these cases the hydrogen ions of the acids and the hydroxyl ions of the bases acted catalytically and that the relative strength of the acids and bases was determined solely by their ion concentration.

Ostwald was hence led to undertake a more thorough study of catalytic phenomena and he extended its scope to other catalysts, as they were called, as well. After consistent, continuous research he successfully formulated a principle to describe the nature of catalysis which is satisfactory for the present state of knowledge, namely that catalytic action consists in the modification, by the acting substance, the catalyst, of the rate at which a chemical reaction occurs, without that substance itself being part of the end-products formed. The modification can be an increase, but also a decrease of the reaction rate. A reaction which otherwise proceeds at a slow rate, taking perhaps years before equilibrium is attained, can be accelerated by catalysts to such an extent that it is complete in a comparatively short time, in certain cases within one or a few minutes, or even in fractions of a minute, and conversely.

The rate of a reaction is a measurable parameter and hence all parameters affecting it are measurable as well. Catalysis, which formerly appeared to be a hidden secret, has thus become what is known as a kinetic problem and accessible to exact scientific study.

Ostwald's discovery has been profusely exploited. Besides Ostwald himself a large number of eminent workers have recently taken up his field of study and the work is advancing with increasing enthusiasm. The results have been truly admirable.

The significance of this new idea is best revealed by the immensely important role - first pointed out by Ostwald - of catalytic processes in all sectors of chemistry. Catalytic processes are a commonplace occurrence, especially in organic synthesis. Key sections of industry such as e.g. sulphuric acid manufacture, the basis of practically the whole chemical industry, and the manufacture of indigo which has flourished so during the last ten years, are based on the action of catalysts. A factor of perhaps even greater weight, however, is the growing realization that the enzymes, so-called, which are extremely important for the chemical processes within living organisms, act as catalysts and hence the theory of plant and animal metabolism falls essentially in the field of catalyst chemistry. As an illustration, the chemical processes involved in digestion are catalytic and can be simulated step by step using purely inorganic catalysts. Furthermore the ability of various organs to transform nutrients from the blood in such a way that they are suitable for the specific tasks of each organ can indubitably be explained by the occurrence of various kinds of enzymes within the organ capable of catalytic actions adapted to their particular purpose. That apart, it is strange that such substances as hydrocyanic acid, mercuric chloride, hydrogen sulphide and others which act as extremely potent poisons on the organism have also been observed to neutralize or "poison"even pure inorganic catalysts such as e.g. finely dispersed platinum. Even from these brief references it should be clear that a new approach to the difficult problems of physiological processes has been possible with the aid of Ostwald's theory of catalysis. Because they are related to the actions of enzymes in the living organism, the new field of research is of an importance for mankind that cannot as yet be fully gauged.

Although the Nobel Prize for Chemistry is now being awarded to Professor Ostwald in recognition of his work on catalysis, he is a man to whom the chemical world is indebted also in other ways. By the spoken and the written word he, perhaps more than any other, has carried modern theories to a rapid victory and for several decennia he played a leading part in the field of general chemistry. In other ways too he has furthered chemistry by his versatile activity with numerous discoveries and refinements in both the experimental and the theoretical spheres.

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[Photo Credit: The photograph of Ostwald's lab is from Ostwald]

The Inversion of Cane Sugar

 

Monday's Molecule #46 was the chemical reaction shown above. This is an historically important reaction that contributed to our understanding of catalysis.

The reaction shows the hydrolysis of sucrose to glucose and fructose in an acid solution. The reason why this was such an important reaction 100 years ago is because it is accompanied by a change in the direction of rotation of polarized light. Sucrose is an optically active compound, which means that it causes polarized light to rotate when you shine it through a solution of sucrose. The rotation is measured in a polarimeter. In the case of sucrose, light is rotated to the right. We call this dextrorotatory or "d" (lower case) from the latin prefix for "turning to the right". In modern chemical terminology it would be (+)-sucrose.

In the presence of acid, sucrose breaks down into D-glucose D-fructose. Both of the sugars are optically active. The "D" forms (Upper case "D" or small caps) are identified by the orientation of the CH₂OH group (red oval) in the ring structures shown above. In both cases the group is above the plane of the sugar so these are the "D" forms of the molecule. In L-glucose and L-fructose those groups would be below the plane of the sugar ring and all the -OH groups would be flipped as well.

Now here's the tricky part. The original determination of the "D" and "L" structures was related to the optical rotation properties. It was thought that all carbohydrates with the "D" configuration were dextrorotary ("d") and that's why they were named "D". The "L" forms were thought to be laevorotary (Latin: "turning to the left). However, it turns out that this assumption isn't correct and D-glucose and D-fructose are good examples. They both have the "D" configuration but D-glucose rotates the plane of polarized light slightly to the right and D-fructose rotates it strongly to the left. The way to identify this property in modern terms is D(+)-glucose and D(-)-fructose. There's a good description of these properties on the Biochemical Howlers website.

That's all very interesting but why was it important back in 1900? It was important because if you treated a solution of sucrose with acid it "inverted" polarized light from rotating to the right to rotating to the left because D-fructose affected rotation more strongly than D-glucose. This meant that you could follow the reaction in real time by carrying it out in a test tube placed in a polarimeter. This was one of the few reactions of this sort that were amenable to kinetic studies back then.

Many workers discovered that the rate of the reaction was increased by increasing acid concentrations and it led to detailed studies of reaction kinetics with large molecules. (There were plenty of inorganic reactions that could be followed by watching changes in color.) An modern example is shown in the accompanying figure from Shalaev et al. (2000).

As you can see, the kinetics of the reaction are easy to follow and the results lead to simple mathematical interpretations of the rate and extent of the reaction. It was experiments like this that led to a theory of catalysis in the early 1900's and the awarding of a Nobel Prize to Wilhelm Ostwald in 1909.

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Shalaev, E.Y., Lu, Q., Shalaeva, M. and Zografi, G. (2000) Acid-catalyzed inversion of sucrose in the amorphous state at very low levels of residual water. Pharm. Res. 17:366-70.

Tangled Bank #90

 

The latest version of the Tangled Bank has been posted on The Other 95% [Tangled Bank #90].

Democracy at Work: The Assembly's Decision

 
I'm very proud of the Ontario Citizen's Assembly on Electoral Reform. That's the group who examined many electoral systems and selected the mixed member proportional (MMP) system for Ontario. We will vote on it in a referendum tomorrow. It won't win this time around.

I think the Citizen's Assembly should be a model for many decision making processes in a democracy. In fact, I think it could be a model for grappling with complex problems in other situations as well.

Today I went to hear the President of the University brief us on long term strategic planning for the University of Toronto. I pointed out that the process was doomed from the beginning because the five major task forces were filled with appointed members of the Board of Governors and senior administrators (and former administrators). No ordinary faculty members, no students, no ordinary staff members. Nobody is going to listen to a group like that telling us what a university should be like in 20 years.

The response was that we need experienced people on these committees and that means people who have served in administrative positions in the university. I disagree. Watch this video to see another way of doing things.

Toronto Star Trashes MMP, Again

 
What in the world are they afraid of? Last week the editors of the Toronto Star came out against the mixed member proportional (MMP) system that voters will decide on in tomorrow's referendum [Electoral reform a backward step].

The editors were widely criticized for misinformation and fearmongering in that Sept. 30th editorial (e.g. The Toronto Star Endorses First-Pass-the-Post and links therein). They attacked the MMP system for giving more power to party bosses when the experience in other countries indicates that this is not a valid concern in the MMP system. Furthermore, all party leaders in Ontario are committed to a fair an open system for selecting list members. It turns out that the list will almost certainly contain only candidates who have been nominated in individual ridings.^1. Indeed, the parties have little choice but to commit to a fair and democratic process if they hope to attract voters. Read the statements of the party leaders on the Vote for MMP website [Party Leaders Quote].

Today, the editorial in the Toronto Star attacks MMP once again [Electoral reform fraught with risk]. The editors seemed to have heard part of the criticism because in this latest attack they avoid any mention of party lists. However, they return to another of the fears they raised earlier; namely, the fear of unstable government.

While some see this as a "fairer" system that produces a Legislature more closely aligned with the popular vote, it has one major drawback.

Countries that have gone this route, including Israel, Italy, Germany, and Belgium, have become notorious for chaotic, horse-trading minority governments and legislative gridlock.

Now let's think about this logically for a minute. The editors would have us believe that the Ontario Citizen's Assembly of 103 Ontario voters simply overlooked this major "problem" when they did all their research. The editors would have us believe that all 80 countries that use a proportional system have chaotic governments. Does that make sense? Of course not.

Germany, Belguim, Italy and Israel are hardly examples of failed governments in spite of what the fearmongers would have you believe. The MMP campaign refuted most of the points raised by the first Toronto Star editorial including the claim that Germany, Italy, Israel, and Belgium are in chaos because of MMP. (Belgium and Israel don't even use the MMP system.)

So why do the Toronto Star editors repeat the same false claims that were refuted 10 days ago? Why do they say the following even though they've been told that it misrepresents the experience in other countries?

Granted, some minority or coalition governments do manage to deliver solid, progressive government. But they are rarities. More commonly, governments in proportional systems are divisive, unstable, short-lived and paralyzed by conflict. Too often, the leading party is forced to align with small, sometimes radical, special-interest parties. That can badly skew the policy-making process.

Is that the kind of government that Ontario voters really want? Will it be good for Ontario? We don't think so.

Wouldn't you expect the editors to do their homework and look at the stability of comparable governments with proportional systems? Countries such as Finland, Denmark, Sweden, Norway, Switzerland, Spain, South Africa, and Austria. Is is fair to say that all these countries have governments that are "divisive, unstable, short-lived and paralyzed by conflict"? Of course not. It's a stupid thing to say. (Incidentally, all those countries use a full proportional system that's even more likely to produce "chaos" than the MMP system according to the reasoning of the fearmongers.)

In light of their previous attempts at misinformation wouldn't you expect the editors to be embarrassed? After all the Toronto Star like all newspapers prides itself on accuracy. Right?

Wrong! It's almost as though the editors have been completely oblivious to the serious attempts by the Ontario Citizen's Alliance to educate them and correct their misinformation. They repeat the same flawed argument they made ten days ago.

When people spread misinformation and fear for the first time you can put it down to ignorance. When they do it a second time there's something more serious going on. Why do the Toronto Star editors fear MMP so much that they have to publish an editorial the day before the vote? This is really strange given that all the polls show that MMP will be soundly defeated tomorrow.

It's a difficult question. As far as I can tell, the main problem is the fear of minority viewpoints—or "fringe" parties as the editors prefer. The editors are comfortable with the present first-past-the-post (FPTP) system because they know that minorities in our society have no chance of being represented in the legislature under that system.

Take the Green Party for example. Under FPTP their chances of electing a member to parliament are close to zero. Under MMP they will get four seats (out 0f 129) if 3% of the population votes for them. (The Green Party is the only "small, sometimes radical, special-interest" party that has a decent chance of electing members.)

This could lead to chaos if you believe the editors because parties with less than a majority of seats would have to negotiate with the other parties in order to get legislation passed—just like the current federal government under Harper and the previous one under Martin. Is that the "chaos" that the Toronto Star fears?

I don't think the editors and their allies are afraid of minority governments so much as they're afraid of giving minority citizens a voice in parliament. In other words, what they really want is a system that blocks out the views of minority groups. That's exactly the flaw that MMP is designed to overcome. It would be more honest if the opponents of MMP would simply come right out and what they're really afraid of instead of making up stories about unstable governments in countries with proportional voting.

Perhaps we could reach a compromise? We could have a mixed member proportional system but then ban all those parties we don't like? The editors and other concerned citizens could draw up a list of minority groups who would be specifically excluded from parliament, like the environmentalist extremists. The sitting members of Parliament would then pass a law preventing these undesirable parties from running candidates in the next election. That way we could have the best of both worlds, a proportional system that excludes all those undesirable minorities who might cause chaos if we let them have a voice in Parliament. That's how democracy is supposed to work, isn't it?

Do you think the fearmongers would go for this? I doubt it, it makes their motive a little too obvious. It's so much better to hide behind the unfair FPTP system on the grounds that it produces "stable" government. Those of you who laughed at this video should watch it again now that the anti-MMP side has triumphed. It pretty much sums up the logic of their arguments.

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1. The reason why the list will contain candidates who have been nominated in ridings—and who will run in those ridings—is because if a party wins an election they will not have any members chosen from the list. Thus, a party who hopes to win would be foolish to put candidates on the list who they want to be in parliament but who don't seek election in a constituency. Since no party will want to be seen to anticipate losing it will probably be standard practice to put people on the list who are running for election in a riding. Thus, the MMP system will end up being similar to FPTP and fears about party bosses choosing favorites are unfounded.

Vanity License Plates

 

Karl Mogel at The Inoculated mind is looking for science-related vanity license plates [My new license plate].

Here's one; it's from my fellow biochemistry Professor Peter Lewis. Peter is also Vice-Dean, Research and International Relations in the Faculty of Medicine.

This Is a Joke, Right?

 
According to several sources, this add is being shown on television in the USA and it's sponsored by the US government. I hope this is an elaborate leg-pulling. Surely there are no rational adults who think that telling kids not to have sex is going to work? I'm even surprised that there might be adults who think it's a good idea. Haven't they heard? Sex is fun and healthy.

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[Hat Tip: Greg Laden: Wait ’till you’re married to have sex]

Tagged by the Evolution Meme

 
Shalini at Scientia Natura has tagged me with the evolution meme [ I've been tagged!]. The idea is to pick five postings that show the evolution of Sandwalk from the time it first started until now.

This is going to be hard since my blog is less than one year old. Starting in the very first week I published an article on the sea urchin genome [Sea Urchin Genome Sequenced and I've continued to post science articles all along. The biggest change occurred in January when I started combining Monday's Molecule with Wednesday's Nobel Laureates to develop themes for the week. Gradually these themes spread over into following weeks (e.g. Blood Clotting). They began to take over my life!

My postings about atheism and religion haven't changed very much over the past year so there doesn't seem to be any evolution there. Many people will be upset by that since they would very much like to have changed my opinion! My interest in the influence of atheism and the confrontation with the "appeasers" was there from the very first weeks. The thing that's changed is that I now avoid the word "appeasers" and "Neville Chamberlain" whenever possible [The Neville Chamberlain Atheists].

When I started Sandwalk I blogged about Canada and local politics but not very often [I'm Voting for Hurricane Hazel!]. I thought I should avoid being seen as too Canadian because it would scare off readers, especially Americans. Now I'm posting more on Canadian issues because there's a large Canadian audience out there and because non-Canadians don't seem to mind—some even find it interesting [MMP: Debunking the Myths, Chastising the Fearmongers].

The biggest change has been the number of people who comment on Sandwalk. In my opinion, some of the most interesting things on this blog are taking place in the debates and discussions that occur after an initial posting [Plants, not Fungi, Are Most Closely Related to Animals?]. This was one of the things I wanted to happen since I'm coming from a newsgroup background but it didn't happen for the first six months. I realize now that you need a critical mass of readers in order to get a discussion going.

I tag:

easternblot
Primordial Blog
Runesmith's Canadian Content
Genomicron [which has definitely evolved]
Sex, Genes & Evolution [which hasn't?]
Thoughts in a Haystack [which should :-)]

Monday's Molecule #46

Today's molecule is actually three molecules. You have to identify each one precisely by giving the complete IUPAC names.

There's an indirect direct connection between the reaction shown above and Wednesday's Nobel Laureate(s). See if you can guess the Nobel Laureate. This one is not easy.

The reward goes to the person who correctly identifies the molecules and the Nobel Laureate(s). Previous free lunch winners are ineligible for one month from the time they first collected the prize. There are two ineligible candidates for this Wednesday's reward. The prize is a free lunch at the Faculty Club.

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 the Nobel Laureate(s). Correct responses will be posted tomorrow along with the time that the message was received on my server. This way I may select multiple winners if several people get it right.

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

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Note: The reaction shown above may not be entirely accurate. If you can identify a way to improve it you can double your prize to two free lunches anywhere within two blocks of the downtown campus!

The 2007 Nobel Prize in Physiology or Medicine

 
The winners of the 2007 Nobel Prize in Physiology or Medicine were just announced this morning. This year's prize goes to Mario R. Capecchi, Martin J. Evans and Oliver Smithies for their work on "principles for introducing specific gene modifications in mice by the use of embryonic stem cells."

This is a bit of a surprise. These were not names that came up regularly in Nobel Prize Gossip. Many people, including me, thought that there would be a specific award for stem cells before anyone got the prize for exploiting stem cells. This doesn't mean that todays winners aren't worthy. I doubt that anyone will question the award to Oliver Smithies, for example. I don't know as much about Capecchi and Evans.

See Press release for a complete description of the work of Capecchi, Evans, and Smithies. Here's the summary ...

This year's Nobel Laureates have made a series of ground-breaking discoveries concerning embryonic stem cells and DNA recombination in mammals. Their discoveries led to the creation of an immensely powerful technology referred to as gene targeting in mice. It is now being applied to virtually all areas of biomedicine – from basic research to the development of new therapies.

Gene targeting is often used to inactivate single genes. Such gene "knockout" experiments have elucidated the roles of numerous genes in embryonic development, adult physiology, aging and disease. To date, more than ten thousand mouse genes (approximately half of the genes in the mammalian genome) have been knocked out. Ongoing international efforts will make "knockout mice" for all genes available within the near future.

With gene targeting it is now possible to produce almost any type of DNA modification in the mouse genome, allowing scientists to establish the roles of individual genes in health and disease. Gene targeting has already produced more than five hundred different mouse models of human disorders, including cardiovascular and neuro-degenerative diseases, diabetes and cancer.

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[Photo Credit: GETTY, Time magazine]

Junk in your Genome: LINEs

Scientists first began to get a glimpse of the organization of mammalian genomes about 40 years ago when they looked at the overall complexity using hydridization technology. It soon became apparent that most of the genome was made up of short stretches of DNA that were repeated thousands of times. One major component of this repetitive DNA was about 6000 bp in length. These sequences were called Long Interspersed Elements or LINEs. The other component was much shorter, about 300 bp. These were called Short Interspersed Elements or SINEs.

We now know that LINEs are a form of retrotransposon. The major human LINE is called L1 and it has two open reading frames (ORF's) that are similar to the gag and pol genes of typical retrotransposons [Retrotransposons].


The LINE sequence (blue, above) is organized like a typical gene with a 5′ untranslated region (5′ UTR) and a 3′ untranslated region (3′ UTR). There are two open reading frames (ORF) encoding an RNA binding protein, a reverse transcriptase, and an endonuclease similar to the retrovirus integrase. Like most transposons, L1 is flanked by a short repeated section of genomic DNA.

The role of the RNA binding protein has not been fully worked out but the roles of the reverse transcriptase and endonuclease proteins are known. When the L1 sequences is transcribed, it can be copied into double-stranded DNA and this copy can be integrated into the genome at a site cleaved by the endonuclease.

The copy-integration scheme is shown in the figure on the left from Current Genetics: junk DNA - repetitive sequences.

The net effect of this mechanism is to spread a copy of L1 to another part of the genome. Thus, L1 is a typical selfish DNA transposon.

The human genome contains about 500,000 copies of L1 but the vast majority are fragments of various sizes. Most of the fragments are missing the 5′ end and they presumably arose when the copying mechanism failed to completely copy the L1 mRNA from the 3′ end. About 10,000 copies are full length (6000 bp) and of these 80-100 are known to be "active." Active L1s have intact ORFs and they are regularly transcribed.

About 17% of your genome is composed of L1 LINEs and fragments. It is one of the major sources of junk DNA in your genome.

The important point to remember is that the active L1 LINEs are constantly producing reverse transcriptase in human cells. This enzyme can copy any available RNA into double-stranded DNA. It is responsible for most of the pseudogenes that litter our genome contributing to the mass of functionless DNA known as junk.

Atheists Spreading the Word

 
On Friday evening there was a 20 minute segment about atheism on CBC's The National. The National is the main evening news program on CBC. The segment is broken up into three YouTube videos (below).

I think it's a pretty good introduction to atheism and I can't imagine that it would have made the evening news a few years ago. No matter what anyone says, the evidence that Dawkins, Harris, et al. have moved this debate into the public realm seems overwhelming. I just don't understand those who think that the "militant" atheists are hurting the cause.

Look for Justin Trottier of the Centre for Inquiry. He's at the beginning of the third video. If you live in Toronto you should come out to our meetings at the centre [Standing Room Only]. It's just a block south of the campus. If you're a student you should join the University of Toronto Secular Alliance. We have many exciting events planned for this year. Watch for "Café Inquiry" coming this winter.

Tea might pose fluoride risk

 
Here's an example of bad science journalism from the latest edition of New Scientist [Tea might pose fluoride risk].

Tea might pose fluoride risk

Tea drinkers beware. Too much of the wrong kind can add significantly to the amount of fluoride you consume, with the tea in just four cups supplying up to one-third of the maximum safe daily amount.

You have to read further in the article to see that it refers to a study done in Sri Lanka where the drinking water contains high levels of fluoride.

In some parts of Sri Lanka drinking water contains up to five times the maximum fluoride recommended by the World Health Organization, and some 98 per cent of people are affected by fluorosis.

The study shows that local tea grown in Sri Lanka contains fluoride so when you make tea with the water containing excess fluoride you get an increased dose of fluoride. Even if you make the local tea with distilled water you still get excessive doses of fluoride with just four cups of this tea.

All this is explained in the article but the headline and the opening paragraph are very misleading. It's only certain kinds of tea that might cause a problem and it's not at all clear whether people in other countries can even buy this tea. It almost seems as though the person who wrote this article was deliberately trying to to scare people in order to attract readers. That's not acceptable science journalism.

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[Photo Credit: Harvesting tea leaves in Malaysia from Encyclopedia Brintannica]

Psychic Arrested in Calgary

 
A psychic who defrauded someone of $220,000 US ($218,000 CDN) was recently arrested in Calgary. I'm not going to give you the details. You'll have to hop on over to Mike's Weekly Skeptic Rant to find out.

Fortunately, Mike makes it a bit easy to guess the right answer when he proposes this multiple choice question.

So there's this "psychic" who reads palms, gives advice, sees the future; she is on the run from police. The cops are hot on her trail. Does she:

a) use her psychic powers to see where the cops are and how they'll approach?

b) influence the "universe" by putting her desires out there to be realized?

c) go downstairs and sit at the kitchen table with a delicious Hot Pocket and a pistol to await her bullet-ridden showdown with Johnny Lawdog? or

d) realize that her "powers" are non-existent and hide in the closet under some blankets?

Mike also has a useful suggestion for what to do with all the money, assuming it's recovered. Should it all be returned to the "victim"?

Gene Genie #17

 

The 17th edition of Gene Genie has just been published on Gene Sherpas [Gene Genie #17 and 10,000 visitors].

If you don't know about Gene Sherpas then this is your chance to check it out. The blog is run by Steve Murphy, a physician with a very special interest.

I am the founder of a Personalized Medicine practice (likely the first private practice of its kind). In addition I am the Clinical Genetics Fellow at Yale University until 2010. Now not under contract and that's why I am posting and running my practice. I also am developing a modern medical genetics curriculum for residents and other physicians. On this blog I am educating the public and hopefully some physicians about the field of genetics and personalized medicine.

A former student of mine shares these interests. He tells me that physicians don't get much education in genetics while in medical school and as a result they aren't up to speed when it comes to understanding the genetics of various diseases.

Another former student of mine is a genetic counselor. This is a growing field of professionals who can advise patients (and doctors) about human genetics.

Linnaeus 2007

 
This year marks the 300th anniversary of the birth of Carl Linnaeus. There will be celebrations all around the would but Sweden is leading the way [Linnaeus 2007].

Linnaeus' Life and Achievements

Carl Linnaeus is the most well-known Swedish scientist, both internationally and in Sweden. He has left traces in many ways: there are places that bear his name, there are locations on the Moon that have been named after him, he is depicted on Swedish banknotes, and "Linnea" is a popular first name for girls in Sweden. Carl Linnaeus placed his stamp on a complete era of scientific history - the Linnaean era. The Linnaean era is characterised by an ambition to catalogue, organise and give names to the whole natural world.

Mapping Nature

Linnaeus is probably best known as a botanist, and for his sexual system. His scientific achievements, however, also extend into the mineral world and zoology, in addition to botany. He was curious about the complete natural world, and wanted to map the whole of nature. This mapping has given us the naming convention known as the "binary nomenclature", that Linnaeus introduced. Linnaeus published a number of rule-books on which the system was based, and the system, after some initial resistance, has come not only to dominate natural history, but also to influence other scientific fields. Linnaeus clarifies language, he bases his science on a rigid terminology, formulates the concept of species and sets the broad dimensions of natural history. Humans in his system, for example, are known as Homo sapiens and they are primates in the class of mammals, Mammalia, - all of these are names and concepts that Linnaeus coined.

The Linnaean Conceptual Structure

The Linnaean conceptual structure has become popular both within the academic world and among hobbyists. The concept has spread throughout the world, initially by those known as the "Linnaean apostles", a group of disciples who reached farther afield throughout the world than any Swedes had previously reached. Their deaths in far-flung places carry a hint of heroism, they died for the sake of science. The continued influence of Linnaeus has stimulated scientific journeys, cataloguing and strange destinies, but it has also had a more calm interaction with nature at many places across the globe, with its placid nature of collection and systematic thought. Linnaeus creativity and sense of curiosity has left traces not only in science but also in literature and in other fields of culture.

Skagit Valley Provincial Park

 
Today's Botany Photo of the Day is a picture of the forest in Skagit Valley Provincial Park in Southern British Columbia on the USA border.

The little thumbnail on the left doesn't do justice to the photograph. You need to see the whole thing. Isn't it beautiful?

The Spandrels of San Marco and the Panglossian Paradigm

This week's citation classic on The Evilutionary Biologist is "The Spandrels of San Marco and the Panglossian Paradigm: A Critique of the Adaptationist Programme" by S.J. Gould and R.C. Lewontin [This Week's Citation Classic].

This is John Dennehy's best choice by far. It's a classic paper and everyone interested in evolution must read it carefully. Whether you agree with Gould & Lewontin or not, you can't participate in the debate unless you've read and understand this paper. I'm pleased that John appreciates it, although I'm a little upset over some of the things he says about Gould. Clearly, he needs some remedial indoctrination re-education ....

[There's a link to an online version of the paper from John's article so nobody has any excuse not to read it.]

Are You as Smart as a Third Year University Student? Q5

 
Question 1
Question 2
Question 3
Question 4
The standard Gibbs free energy change for the aldolase reaction in the direction of cleavage is +28 kJ mol-1. What does this tell you about the properties of this reaction in yeast cells that are actively producing ATP via glycolysis?

         a)  flux through this particular reaction will be
                in the direction of gluconeogenesis
         b)  the activity of this enzyme must be regulated
         c)  there must be another enzyme in yeast that bypasses this reaction
         d)  this is the rate limiting reaction in glycolysis
         e)  the concentration of FBP will be very much higher than
                the concentration of G3P

Are You as Smart as a Third Year University Student? Q4

 
Question 1
Question 2
Question 3The open-chain form of fructose 1,6-bisphosphate is shown as the substrate for the aldolase reaction. Why?

         a)  the open-chain form is more abundant inside the cell
         b)  cyclic molecules destabilize the transition state
         c)  the product of the previous reaction in glycolysis
               is the open-chain form
         d)  the open-chain form is thermodynamically more stable
               and this contributes to the positive standard Gibbs free
               change for the reaction
         e)  the active site of the enzyme can’t accommodate the
                furanose or pyranose forms

The Aldolase Reaction and the Steady State

 
On banning the word "spontaneous" to describe biochemical reactions.Aldolase is an enzyme that's important in gluconeogenesis and glycolysis. I'm discussing it because RPM is describing his work on aldolase genes in Drosophila melanogaster [Aldolase in Gluconeogenesis & Glycolysis].

Fructose 1,6-bisphosphate aldolase ("aldolase") catalyzes the reaction shown below where two 3-carbon compounds are joined to produce a 6-carbon fructose molecule.


The mechanism of aldolase is described in Pushing Electrons. What I want to discuss here is the fact that this reaction is reversible. It has to operate equally efficiently in either direction.

The direction shown is part of gluconeogenesis: the synthesis of glucose. The standard Gibbs free energy change for this reaction is -28 kJ mol^-1 (ΔG°′ = -28 kJ mol^-1). This may not mean a lot to most of you but it indicates that under standard conditions the reaction gives off a lot of energy. Very negative values are associated with release of energy and energy release is favored over uptake of energy.

In terms of old fashioned biochemistry, we would have said that the reaction was spontaneous in the direction shown. In other words, the enzyme will be more likely to synthesize fructose 1,6-bisphosphate (F1,6P) than to break it down.

This perspective is very misleading since inside the cell the reaction can easily flow in either direction depending only on small changes in the concentrations of substrates and products. In the new way of looking at metabolism we no longer talk about reactions being spontaneous and we no longer use the standard Gibbs free energy changes (ΔG°′) as indicators of direction. This change in teaching was stimulated, in part, by the difficulties in explaining how the aldolase reaction could catalyze breakdown of fructose 1,6-bisphosphate to dihydroxyacetone (DAP) phosphate and glyceraldehyde 3-phosphate (G3P) in the face of a standard Gibbs free energy change that was very positive. (The value for the reverse reaction is +28 kJ mol^-1.) Those kind of reactions weren't supposed to happen in the old textbooks and it suggested that glycolysis is impossible.

Here's how we think about it today. What the standard Gibbs free energy change tells us is that under standard conditions the reaction will proceed to the right until equilibrium is reached. The standard conditions are 1M concentrations of all the substrates and products.

When enough of the substrates are converted to product the reaction will start to flow in the opposite direction until eventually an equilibrium is reached where the rate of synthesis of fructose 1,6-bisphosphate equals the rate of its breakdown. At this point the real (as opposed to standard) Gibbs free energy change will be 0 (zero). There will be no overall tendency for the reaction to flow in one direction or the other. The concentrations of substrates and products at this point will be the equilibrium values. I hope it's clear that at equilibrium the concentration of fructose 1,6-bisphosphate will be much higher than the concentrations of dihydroxyacetone and glyceraldehyde 3-phosphate. We can illustrate this in a cartoon that represents the concentrations as blobs of various sizes.


The standard Gibbs free energy change doesn't tell us whether a reaction will be spontaneous or not. Instead, it simply tells us the final concentrations of substrates and products at equilibrium. (You can calculate this using simple equations that you learn in introductory chemistry courses.) The equilibrium concentrations are the concentrations found inside the cell since almost all reactions operate at Gibbs free energy values close to zero. In other words, most biochemical reactions are near-equilibrium reactions with steady-state concentrations close to the equilibrium values.

The concentrations of the substrates and product of the aldolae reaction look like the blob cartoon shown above. If the cell is making glucose then there will be a steady trickle of substrates flowing into the reaction and this increases the substrate concentration (little blobs) a little bit so that more of it is converted to fructose 1,6-bisphosphate (F1,6P) (big blob) in order to restore the equilibrium.

Conversely, if the cell is breaking down glucose then the concentration of fructose 1,6bisphosphate will increase above the equilibrium, steady-state value and more of it will be broken down to the 3-carbon compounds. This will happen in spite of the fact that there is already a lot more F1,6-P inside the cell than G3P and DAP.

This explains why the central reactions of the gluconeogenesis/glycolysis pathways can catalyze reactions in either direction and can swich quickly from one direction to another. The key is that the steady-state concentrations inside the cell are far from the standard concentrations.

Aldolase in Gluconeogenesis & Glycolysis

RPM at evolgen has started a series of articles on publishing original research on blogs. He's going to tell us about the aldolase genes in Drosophila melangogaster. I'm sure he's going to be explaining some interesting studies about the evolution of the two aldolase genes so I urge you to pay attention. Here are the three postings so far.

Publishing Original Research on Blogs - Part 1
Publishing Original Research on Blogs - Part 2
Publishing Original Research on Blogs - Part 3

I hope he won't mind if I describe some of the biochemistry of the aldolase catalyzed reaction and the pathways where aldolase is involved. I don't think RPM is going to do any more than what he briefly described in Part 2.

The first point I want to make is that aldolase is a type of enzyme that forms and cleaves carbon-carbon bonds. There are many different types of aldolases with different substrates and products. The most common of these enzymes is fructose 1,6-bisphosphate aldolase. Because it's so common it is often just called "aldolase." All of the the other aldolases must be specified in order to avoid confusion.


There are two different kinds of aldolases (i.e., the fructose 1,6-bisphosphate kinds). Class I enzymes (left, above) are only found in plants and animals. Class II enzymes (right, above) are usually found in bacteria, protists, and fungi. Many species of plants and animals have both types of enzyme. The two different types of aldolase are completely unrelated. They have different structures and sequences even though they catalyze the same reaction. I think the two Drosophila aldolase genes that RPM is discussing both encode Class I aldolases.

Aldolase is one of the most important enzymes in the pathway known as gluconeogenesis (glucose biosynthesis). In this pathway two molecules of the 3-carbon compound pyruvate [Pyruvate] are eventually converted to one molecule of the 6-carbon compound glucose. The gluconeogenesis pathway reads from bottom to top in the figure on the left.

One of the key steps in this pathway is the joining of two 3-carbon molecules to make a single 6-carbon molecule. That's the step catalyzed by aldolase. The substrates are glyceraldehyde 3-phosphate and dihydroxyacetone phosphate and the product is fructose 1,6-bisphosphate.

All species can synthesize glucose 6-phosphate using this pathway. It is clearly one of the most ancient pathways in cells. Early on in the history of life—once glucose molecules began to accumulate in the biosphere—there was a need to convert them back to pyruvate and recover the energy that had been used to synthesize glucose in the first place. In most species this pathway was the Entner-Douderoff pathway, a pathway related to the pentose phosphate pathway. It involves another type of aldolase called KDPG aldolase that joins glyceraldehyde 3-phosphate directly to pyruvate.

Somewhat later, new enzymes arose that could get around the difficult steps in gluconeogeneis. These are shown as separated red arrows in the figure. This new pathway is called glycolysis and it represents a more direct "reversal" of gluconeogenesis. All eukaryotes, and most bacteria have the glycolysis pathway. They are capable of converting glucose to pyruvate using a few specialized enzymes and most of the same enzymes used in gluconeogenesis. Notice that the enzymes, substrates and products of the core part of the pathway (from fructose 1,6-bisphosphate to phosphoenolpyruvate) are identical in glycolysis and gluconeogenesis (parallel red and blue arrows). What this means is that flux in this part of the pathway can flow in either direction depending on the state of the cell. This includes the aldolase reaction.

Gluconeogenesis is usually more important than glycolysis. In order to appreciate this, think about plants. They make all of their glucose from carbon dioxide so the only glucose that can be broken down is the glucose that the plants make themselves. It follows that more glucose is synthesized than is broken down by glycolysis. This is true of bacteria, protists and fungi.

The situation in animals is a little different since glucose is an important food source. It's possible that the overall flux in this pathway favors glucose breakdown although even in animals there is considerable glucose synthesis going on.

The bottom line is that aldolase is mainly required for gluconeogenesis and only in animals, and some specialized species (like yeast), is glycolysis more important. In older biochemistry textbooks the emphasis was on glycolysis and not gluconeogenesis. This is because the more classical biochemistry tended to focus on mammalian fuel metabolism (rat liver biochemistry) where glycolysis was important and glucoenogenesis was not. The mammal-centric form of teaching ignored the evolutionary history of metabolism and it's importance in other species.

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[Figure credits: The structure of the class I aldolase is from PDB 2ALD. The class II structure is from PDB 1ZEN]

Norway Is Not a Christian Nation

 
Recent poll results for Norway give this breakdown when it comes to religious beliefs.

• 29 percent believe in a god or deity
• 23 percent believe in a higher power without being certain of what
• 26 percent don't believe in God or higher powers
• 22 percent have doubts

No matter how you slice it, Norway is not a Christian nation.

So, how does this lack of firm religious belief translate into Norwegian society? Are Norwegians immoral, warmongering, and poverty-stricken? Here's a letter to the Montgomery Advertiser that answers that question [Norway flourishes as secular nation].

And what has secularism done to Norway? The Global Peace Index rates Norway the most peaceful country in the world. The Human Development Index, a comparative measure of life expectancy, literacy, education and standard of living, has ranked Norway No. 1 every year for the last five years.

Norway has the second highest GDP per capita in the world, an unemployment rate below 2 percent, and average hourly wages among the world's highest.

Hmmm ... now that can't be right, can it?

How does secular Norway stack up against true Christian nations like the USA and South Africa?

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[Hat Tip: RichardDawkins.net]

Alert! There's a Federal Election Coming in Canada!

 
Garth Turner, the blogging MP, posted this cool pirate flag icon on his website [The Turner Report]. (PZ will be jealous.) It's a reference to a comment by Stephen Harper, Canada's (soon to be ex-)Prime Minister) that the Liberal Party should make up their minds whether to "fish or cut bait" when it comes to supporting his minority government.

It's worth reading what Turner has to say even if it's only to get some idea of what it takes to run a credible election campaign. He estimates that it costs $90,000 in his Halton riding.

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[Hat Tip: Jennifer Smith at Runesmith's Canadian Content (Pirates of Sixteen Mile Creek).]

Posting Comments on PLoS One

 
Okay that's it for me. This isn't worth the trouble.

I tried posting a response on the thread "Is "prokaryotic" an outdated term?" over on PloS One and after getting bumped around to several different webpages I finally ended up with what looked like a response form. I typed in an extremely erudite and well-reasoned response that would have blown everyone out of the water then hit the "Post" button. (There's no "Preview" option on PLoS One. This is highly discriminatory—it works against people like me who need to proofread everything before posting.)

The result of trying to post a comment is the error message shown below. I can close the error window and hit "Post" again but this produces an endless cycle of error messages.


I'm not an complete idiot when it comes to using computers. I'm not going to waste any more time trying to post comments on the PLoS Website.

Is "Prokaryote" a Useful Term?

 
Coturnix (Bora Zivkovic) is the Online Community Manager at PLoS-ONE (Public Library of Science). Part of his job is to get people to post comments on the PLoS websites. [New in Science Publishing, etc.]

So when Bora suggested we get involved in a debate on "Is "prokaryotic" an outdated term?" I hopped on over to the PLoS website and read the comments. I discovered that you have to register on PLoS in order to comment so I went ahead and did that and posted a response to the question.

I don't like registering on websites, it's a painful process, especially in this case 'cause you have to answer a lot of questions. It took me about ten minutes to figure out what to do and to convince the program to let me register even though I didn't want to receive email spam from PLoS. I also had to make up a user ID—Larry_Moran, in this case—because, apparently your name isn't good enough. This is not a very open process.

Theme

The Three Domain Hypothesis
Anyway, the question is important. If you think the Three Domain Hypothesis is well established, then you believe there are two non-eukaryotic domains (Bacteria, Archaea). Furthermore, the eukaryotes cluster with the Archaea according to this hypothesis. Thus, the word "prokaryote" encompasses a paraphyletic group and becomes useless.

But we wouldn't be having this discussion if the Three Domain Hypothesis is incorrect. In that case, the root of the tree might well be a split between eukaryotes and prokaryotes. The point is that the discussion about usefulness of "prokaryote" is really a debate about the validity of the Three Domain Hypothesis and we shouldn't forget that. It's wrong to assume that your side has won that debate and then start to solidify your apparent victory by defining your opponent's point of view out of existence!

Phone this Hotline for Technical Support

 

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[Hat Tip: Canadian Cynic]

You Will Be Assimilated!

 
Canada's ongoing attempt to subvert American culture has been noted by Tegumi Bopsulai, FCD (not his real name). He sends this photograph of a Tim Horton's in Geneva, New York. It's not the one that's farthest south—that distinction goes to the Timmy's in Jamestown NY, as far as I know.

Does anyone have any other evidence of Canada's success? I believe the assimilation is more successful in states like New York than in California. I don't think we're even trying in Texas.

Happy 50th Birthday!

 
50 years ago today we were treated to the continuous "beep-beep" of the first artificial Earth satellite. Sputnik ("traveling companion") was launched by the Soviet Union on October 4, 1957. [Listen to it here.]

It was an exciting time. I remember the thrill of realizing that the space age had truly begun and like many others I tried, unsuccessfully, to find Sputnik in my telescope.

For some, the launch was a traumatic event for another reason. It signaled to the entire world that the Soviet Union was a technologically advanced country. Many interpreted this to mean that science (not technology) education in the Soviet Union was ahead of that in the West. This was not an unreasonable assumption, as it turns out, but not because of Sputnick.

Some improvements in science education were made and, according to popular belief, our students in the West rapidly caught up with those in other countries, only to fall behind again in the 1980's. The truth is certainly more complicated.

Does anyone know of a reliable study of science education in various countries over the past 50 years? What was the real effect of Sputnik in the short term and in the long term?

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[Photo credit: Astronomy Picture of the Day for October 4, 2007.]

[See Bad Astronomy for more information and links about Sputnik I.

The Goal of a University Education

 
At the University or Toronto we're about to go through one of our regular navel-gazing exercises where the administrators ask us how they should plan for the future. In this case, it's a document called "Towards 2030." It's another one of those motherhood-type essays about improving the undergraduate experience and coping with a changing research environment. After 43 years in university, it's all beginning to sound a bit repetitive.

I was wondering whether anyone had any new ideas when I saw this article in the New York Times [Academic Business]. It's written by Andrew Delbanco who is the director of American studies and Levi Professor in the Humanities at Columbia University. There's nothing new there either. It's the same old complaints that we protested about in the 1960's; namely, the transformation of the university into a corporation. Even when we became Professors we didn't succeed in reversing this trend. The latest navel-gazing exercise is a case in point. It's the administrators who act as though this is "their" university and everyone else is an employee or a customer.

But Delbanco does make a few points that I'd like to comment on.

College today is a place in which students from many backgrounds converge, and it is neither feasible nor desirable to prescribe for them some common morality. But college should be a place that fosters open debate of the ethical issues posed by modern life — by genetic screening and engineering; by the blurring of the lines dividing birth, life and death; by the global clash between liberal individualism and fundamentalism.

I just came back from a class where my students discussed evolution and creationism with me and my colleague, who happens to be a Jesuit Priest. It was a lot of fun but you know what? In a university of 72,000 students (59,000 undergraduates) this class represents only a tiny fraction of the student body. The vast majority don't want this kind of education no matter how valuable we think it is. It's simply not true that if you create the classes they will come.

It's not good enough to just mouth the words about the value of a liberal education. We need practical solutions to the problem of getting today's students to buy into the concept. Anybody got any ideas on how to do that?

Delbanco also says,

Some signs suggest that higher education is waking up to its higher obligations. There is more and more interest in teaching great books that provoke students to think about justice and responsibility and how to live a meaningful life. Applications are up at Columbia and the University of Chicago, which have compulsory great-books courses; students at Yale show growing interest in the “Directed Study” program, in which they read the classics; and respected smaller institutions like Ursinus College in Pennsylvania have built their own core curriculums around major works of philosophy and literature.

This is where I part company with the Professor of Humanities. There was a time when I thought that the old books were a wonderful way to build a good program in liberal education. But since then I've come to appreciate that part of the problem is scientific illiteracy and we don't solve that problem by focusing all our attention on dead philosophers and even deader novelists.

Don't get me wrong, I still think that philosophy is the core discipline in an university and every student should become familiar with the basic problems in philosophy. What I'm objecting to is the attitude that being literate in the humanities is all it takes to become educated. You simply can't intelligently discuss the "ethics" of genetic engineering these days if you don't learn science. And you don't learn science by reading the great books, even if one of them is The Origin of Species.

Scientists need to speak out. You can stand around at cocktail parties discussing the meaning of Moby-Dick all you want but you can't call yourself educated if you don't know what DNA is or what causes eclipses and earthquakes.

I don't know how to get students interested in science either, by the way. Does anybody? Is the problem beyond the ability of the university to solve?

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[Photo Credit: The top photograph shows a walkway in one of theolder buildings on the University of Toronto campus from the Macleans website]

[Hat Tip: Michael White at Adaptive Complexity who has some interesting comments that are worth reading(Do Universities care about more than image?)]

This is Your Brain on Spirits

 
Denyse O'Leary—Toronto's version of Bill Dembski—has written a book in collaboration with McGill researcher Mario Beauregard. It's about proving the existence of God through the study of brain waves. Denyse has been telling us about this book for over a year.

This isn't my field so I've given his book a pass although I've got no doubts about its scientific validity (none!). PZ Myers isn't nearly so shy. Read his assault review at [The Spiritual Brain]. Here's the bottom line.

Don't buy this book. Stick your brain in a blender first.

Are those the only two choices?

Nobel Laureate: Barbara McClintock

 

The Nobel Prize in Physiology or Medicine 1983.

"for her discovery of mobile genetic elements"

Barbara McClintock (1902-1992) received the Nobel Prize in Physiology or Medicine for discovering transposons, or mobile genetic elements [Transposons: Part I, Transposons: Part II].

Barbara McClintock began her interest in genetics while she was an undergraduate at Cornell in 1921. That was a time when genetics as a discipline was just being recognized [autobiography]. McClintock went on to earn a Ph.D. from Cornell in 1927 and then stayed on to lecture in genetics undergraduate courses. In 1936 she moved to the University of Missouri where she was a Professor until 1941 when she took a position at the Carnegie Institution of Washington, with a lab at the Cold Spring Harbor Laboratories (New York, USA). She remained there in an official position until 1967 but was still a frequent visitor until well into the 1970's.

Most of her scientific work was in the field of maize cytogenetics where she quickly established a reputation as a good experimenter with a very sharp mind. She received many accolades and awards throughout her career and was elected to the National Academy of Sciences (USA) in 1944. In 1945, she became the first female president of the Genetics Society of America.

Her work on mobile genetic elements in maize began in 1944 and this work soon led to the discovery of two transposons, Dissociator (Ds) and Activator(Ac).

The presentation speech was given by Professor Nils Ringertz of the Karolinska Institute and it explains, in easy-to-understand terms, the significance of McClintock's work.

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,

The Nobel prize in Physiology or Medicine for 1983 recognizes a great discovery about the organization of genes on chromosomes and how these genes, by changing places, can alter their function. This discovery, made while investigating blue, brown, and red spots on maize kernels, resulted in new knowledge of great medical importance - information which provides the key to problems as diverse as hospital infections, African sleeping sickness and chromosome changes in cancer cells. In order to explain this link, we must start at the beginning; namely with Barbara McClintock's investigations of coloured spots on maize kernels.

The maize cobs that we buy at the supermarket usually have yellow kernels. This is not always the case with wild forms of maize. In Central and South America where maize originated, one can still find primitive types of maize where the kernels are blue, brown or red. The colour depends on pigments in the surface layer of the kernel endosperm. The endosperm is the food store for the developing seedling. The synthesis of kernel pigments is controlled by the genes of the maize plant. In some cases one finds differently coloured kernels on the same cob. The explanation for this is that the cob is formed from a group of female flowers. Each of these female flowers may be fertilized independently by a pollen gram from a male flower. Maize cobs with differently coloured kernels arise when the pollen grains do not carry the same genes for endosperm pigments. All these phenomena can be explained on the basis of the laws of the inheritance stated by Gregor Mendel in 1866. What cannot be explained, however, and what puzzled plant breeders in the 1920's, was that maize kernels sometimes have numerous spots or dots, rather than being evenly coloured as would be expected. It was suspected that the dots on the kernels were due to the instability of genes involved in the pigment synthesis. These genes were believed to undergo mutations during the development of the kernel. Should such a mutation be inherited by several generations of daughter cells it would result in a differently coloured spot. This idea received further support when it was found that maize with variegated kernels also had broken chromosomes. The problem of variegation in maize was of slight importance from a practical point of view, but it fascinated Barbara McClintock because it evidently could not be explained on the basis of Mendelian genetics.

McClintock analyzed this phenomenon by studying chromosome changes and the results of crossing experiments in maize with different patterns of variegation. She was able to identify a series of genes on chromosome number 9 that determine pigmentation and other characteristics of the endosperm. She found that variegation occurred when a small piece of chromosome 9 moved from one place on the chromosome to another close to a gene coding for a pigment. The usual effect was to switch off the gene, and furthermore, the chromosome frequently showed a break at the site of integration. McClintock called these types of genetic material "control elements" since they clearly altered the function of neighbouring genes. In a series of very advanced experiments carried out between 1948 and 1951, McClintock mapped several families of control elements. These elements affected not only the pigmentation pattern of the maize kernels but other properties as well. She also pointed out that mobile genetic elements were probably present in insects and higher animals. In spite of this, her observations received very little attention. This was because her findings, when first presented, were overshadowed by the discovery that the DNA molecule stores the genetic information in its structure. It also became evident that mutations involving only one change in one of the building blocks in the DNA molecule could have serious effects. Under these circumstances, it is not surprising that few geneticists were prepared to accept that genes could jump in the irresponsible manner that McClintock proposed for controlling elements. The "state of the art" in molecular genetics at that time made it difficult to accept "jumping genes", and thus McClintock had to await the development of methodological tools powerful enough to verify in biochemical terms her great discovery.

In the mid-sixties, mobile genetic elements were found to play an important role in the spreading of resistance to antibiotics from resistant to sensitive strains of bacteria. This type of transferable drug resistance is a serious problem in hospitals since it causes infections that are very difficult to treat. During the 1970's, more support was found for the medical significance of mobile genetic structures. It was found, for instance, that the transposition of genes is an important step in the formation of antibodies. It has always been a mystery how the body, using a limited number of genes, can form an almost endless number of different antibodies to foreign substances. Nature has solved this problem according to the building block principle. When an individual is born, the chromosomes carry a set of mobile building blocks for antibody genes. By recombining these blocks in various ways in different cells, the body is able to generate millions of genes for antibodies.

During the last few years mobile genetic structures have attracted great interest in cancer research. In certain forms of cancer, growth regulating genes called oncogenes, are transposed from one chromosome to another. Tumour viruses in birds and mice have been found to carry oncogenes which they, in all likelihood, originally picked up from a host cell. If a virus then introduces these genes in the wrong place on the chromosomes of a normal cell, the latter is transformed into a cancer cell.

McClintock's discovery of mobile genetic elements in maize, therefore, has been found to have counterparts also in bacteria, animals and humans.

What led McClintock to devote her research to the variegation of maize kernels was that it did not lit in with Mendelian genetics. With immense perseverance and skill, McClintock, working completely on her own, carried out experiments of great sophistication that demonstrated that hereditary information is not as stable as had previously been thought. This discovery has led to new insights into how genes change during evolution and how mobile genetic structures on chromosomes can change the properties of cells. Her research has helped to elucidate a series of complicated medical problems.

Dr. McClintock,

I have tried to summarize to this audience your work on mobile genetic elements in maize and to show how basic research in plant genetics can lead to new perspectives in medicine. Your work also demonstrates to scientists, politicians and university administrators how important it is that scientists are given the freedom to pursue promising lines of research without having to worry about their immediate practical applications. To young scientists, living at a time of economic recession and university cutbacks, your work is encouraging because it shows that great discoveries can still be made with simple tools.

On behalf of the Nobel Assembly of the Karolinska Institute I wish to convey to you our warmest congratulations and I ask you to receive your Nobel prize in Physiology or Medicine from His Majesty the King.

[Photo Credit (top): The Barbara McClintock Papers]