Where Was I Yesterday? (1)

 

Nobel Laureate: Christiaan Eijkman

 
 

The Nobel Prize in Physiology or Medicine 1929.



Christiaan Eijkman (1858-1930): "for his discovery of the antineuritic vitamin"



Christiaan Eijkman won the Nobel Prize in 1929 for his observations leading to the discovery of thiamine or vitamin B₁. Deficiencies of thiamine cause beriberi, a disease that was widespread in Asia before the cause was discovered by Eijkman.

The story of Christiann Eijkman is well-known to most biochemistry students. Here's the story as recounted in the Nobel Prize presentation speech.

That the fruits of civilization are not solely beneficial is shown by, inter alia, the history of the art of medicine. Not a few illnesses and diseases follow close on the heels of, and are more or less directly caused by, civilization. This is the case with the widespread disease beriberi, first described more than 1,300 years ago from that ancient seat of civilization, China. In modern times, however, it was not until towards the end of the 17th and the beginning of the 18th century that the disease attracted more general attention. Subsequently it has, on different occasions and with varying degrees of violence, made its appearance in all five continents, but more particularly its haunts have been in Eastern and South-Eastern Asia. At times the disease has been a serious scourge there. Thus in 1871 and 1879, Tokio was visited by widespread epidemics, and during the Russo-Japanese War it is said that not less than one-sixth of the Japanese army was struck down.

Beriberi shows itself in paralysis accompanied by disturbances in the sensibility and atrophy of the muscles, besides symptoms from the heart and blood vessels, inter alia, tiredness and oedema. Decided lesions have been shown in the peripheral nerves which seem to explain the manifestations of the disease. Mortality has varied considerably, from one or two per cent to 80 per cent in certain epidemics.

A number of circumstances indicated a connection between food and beriberi: for example, it was suggested that the cause might be traced to bad rice or insufficiency in the food of proteins or fat.

The severe ravages of beriberi in the Dutch Indies led the Dutch Government to appoint a special commission to study the disease on the spot. At the time, bacteriology was in its hey-day, and it was then but natural that bacteria should be sought as the cause of the disease, and indeed it was thought that success had been attained. The researches were continued in Java by one of the commission's coadjutors, the Dutch doctor Christiaan Eijkman. As has so often been the case during the development of science, a chance observation proved to be of decisive importance. Eijkman observed a peculiar sickness among the hens belonging to the laboratory. They were attacked by an upward-moving paralysis, they began to walk unsteadily, found difficulty in perching, and later lay down on their sides. The issue of the disease was fatal unless they were specially treated. It has been said that the secret of success is to be prepared for one's opportunity when it presents itself, and indubitably Eijkman was prepared in an eminent degree. With his attention focussed on beriberi, he immediately found a striking similarity between that disease and the sickness that had attacked the hens. He also observed changes in numerous nerves similar to those met with in the case of beriberi. In common with beriberi, this ailment of the hens was to be described as a polyneuritis. In vain, however, did Eijkman try to establish micro-organisms as the cause of the disease.

On the other hand, he succeeded in establishing the fact that the condition of the hens was connected with a change in their food, in that for some time before they were attacked they had been given boiled polished rice instead of the usual raw husked rice. Direct experiments proved incontestably that the polyneuritis of the hens was caused by the consumption of rice that by so-called «polishing» had been deprived of the outer husk. Eijkman found that the same disease presented itself when the hens were fed exclusively on a number of other starch-rich products, such as sago and tapioca. He also proved that the disease could be checked by the addition to the food of rice bran, that is to say, the parts of the rice that had been removed by polishing, and he found that the protective constituent of the bran was soluble in water and alcohol.

Eijkman's work led Vorderman to carry out investigations on prisoners in the Dutch Indies (where the prisoner's food was prepared in different ways according to the varying customs of the inhabitants), with a view to discovering whether beriberi in man was connected with the nature of the rice food they consumed. It proved that in the prisons where the inmates were fed on polished rice, beriberi was about 300 times as prevalent as in the prisons where unpolished rice was used.

When making investigations to explain the results reached, Eijkman considered that protein or salt hunger could not be the cause of the disease. But he indicated that the protective property of the rice bran might possibly be connected with the introduction of some particular protein or some special salt. At the time it might have been readily imagined that the polyneuritis in the hens and beriberi were due to some poison, and Eijkman set this up as a working hypothesis, though his attempts to establish the poison were in vain. In his view, however, such a poison was formed, but it was rendered innocuous by the protective substance in the bran. It was only Eijkman's successor in Java, Grijns, who made it clear that the substance in question was used directly in the body, and that our usual food, in addition to the previously known constituents, must contain certain other substances, if health is to be preserved. Funk introduced the designation vitamins for these substances, and since then the particular substance that serves as a protection against polyneuritis has been called the «antineuritic» vitamin.

It might have been expected that Eijkman's discovery would lead to an immediate and decided decline in beriberi - perhaps to the disappearance of the disease. But this was by no means the case, and not even in the Dutch Indies, where Eijkman and Grijns had worked, were the results particularly brilliant. The reasons for this were several: the reluctance of the inhabitants to substitute the less appetizing unpolished for polished rice, the opinion that polyneuritis in birds was not a similar condition to beriberi in man, and an inadequate appreciation of Eijkman's work. As a result of numerous experiments by different investigators on animals and human beings, who offered themselves for experimental work, it has gradually become clear that beriberi is a disease for the appearance of which lack of the vitamin found in rice bran - but also other circumstances - is of decisive importance. These experiences, in addition to successful experiments made in various places on the basis of Eijkman's observations, especially in British India, have gradually led to a general adoption of Eijkman's views. The successful attempts to combat beriberi which are now proceeding are the fruits of Eijkman's labours.

It was the analysis of the nature of the food used in cases of polyneuritis in hens that led Eijkman to his discovery. As a rule, analysis and synthesis complete each other, and indeed the employment of both these avenues of approach has been of decisive importance also for the development of the science of vitamins.

Bacteriophage Lambda

 
Bacteriophage λ is one of the most important model organisms but it's often omitted from the list, especially if the list has been written by anyone under 40.

Hop on over to The Evolutionary Biologist and read up on What has phage lambda ever done for us?. I mentioned in the comments that it's possible to create an entire course on the principles of molecular biology based on bacteriophage λ. That may be a bit of an exaggeration ... but not by much.

I believe strongly that you can't teach a course on developmental biology, for example, without describing the genetic switch in λ.

Today's students know nothing about the valuable contributions made by the phage group. That's a shame because it illustrates science in one of its purist moments. You shouldn't be allowed to graduate if you don't know the real reason why Max Delbrück and Salvador Luria got Nobel Prizes.

My Six Months Are Up!

 
I started Sandwalk six months ago. The goal was to give it six months to see how things worked out. I was told that you have to reach 1000 visits a day to be "successful" as a blogger and, as you can see, I didn't make it. But it's close—the average number of visits per day is a bit over 900.

It will take me a few days to evaluate the experiment.

The worst thing about Washington is ....

 
There's no Tim Horton's.

Everybody drinks Starbucks coffee. I don't like Starbucks and even if I did I have no idea how to order one. They seem to speak a different language. Whatever happened to "small," "medium,"and "large?"

Incidentally, the price of coffee is like the price of hotel rooms. It's outrageous but that doesn't seem to stop anyone from buying.

Everybody Should Have One of These

 
One of the most popular exhibits was the Leica booth. They set up a number of their most popular microscopes including the one shown in the photo. People gathered around drooling.

I wondered whether I could buy one so I asked the price, "three-fifty" was the answer. That's not bad. For only $350 dollars (US funds?) I'm thinking of getting one to put in my basement. Since I'm driving I don't have to worry about carrying it on a plane.

Herbert Tabor/Journal of Biological Chemistry Lectureship

 
One of the big events for ASBMB is the Herbert Tabor JBC lecture. It was held Saturday night in one of the large ballrooms. There were about one thousand people attending.

The first lecture was by Tony Hunter from The Salk Institute in California (USA). He spoke about mammalian kinases and phosphorylases with an emphasis on tyrosine kinases, which he discovered back in 1979. Tyrosine kinases are enzymes that attach phosphate groups to tyrosine residues in proteins. They are important because the phosphorylation and dephosphorylation of enzymes regulates their activity. Many of the genes that cause cancer (oncogenes) encode tyrosine kinases.

Hunter is trying to find out how many different proteins kinases there are in humans. The latest count suggests about 900 different enzymes. This is a remarkable number when you think about it. It means that 3-4% of all genes in our genome are kinases.

The second award winner was Tony Pawson from the Samuel Lunenfeld Research Institute and the University of Toronto (Ontario, Canada). I've heard Tony speak many times so I wasn't quite as attentive during his lecture. Tony discovered a number of proteins domains, notably the SH2 domain, that interact with tyrosine kinases and their target proteins. The work of the two Tony's is complementary and that's why they received this joint award.

UPDATE: I forgot to mention that there was a reception after the talks. Lots of delicious munchies and an open bar. I had a beer (or two). Most biochemists drink wine or fruit juice. It was not a wild bunch.

Monday's Molecule #24

 
Name this molecule. We need the exact name, preferably the correct one.

As usual, there's a connection between Monday's molecule and this Wednesday's Nobel Laureate. This one is dead easy. The prize (free lunch) goes to the person who correctly identifies both the molecule and the Nobel Laureate. (Previous free lunch winners are ineligible for one month from the time they first won.)

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

Experimental Biology: Posters & Exhibits

 
Poster sessions and exhibits are a big part of any scientific meeting but at big meetings such as this one the number of posters and the number of exhibitors is so huge that they can only be accommodated in a very large convention center. The photos show the main exhibit hall in the process of being set up for posters and exhibits and what it looks like when people start viewing the posters and visiting the exhibits.

Happy Birthday Jane!

 


My daughter was born on this day in Geneva Switzerland some significant number of years ago. It was one of the best days of my life.

Happy Birthday Jane.

I think I'll Skip This One!

 
There's so much going on at the Experimental Biology meeting you just can't hope to see everything. You have to be ruthless in making decisions about what to attend and what to skip. Sometimes there are important talks going on at the same time and you just can't decide.

In addition to the formal talks there are lots of the things on the notice boards that look exciting. On the other hand, there are lots of things that don't.

Today I have to set aside time for the poster sessions because that's where I get a lot of ideas for my textbook (and for blogging). I also want to visit the displays in Publishers' Row and in the scientific equipment/supplies areas. I won't have time for church or fellowship meetings.

Washington Convention Center

 
The Washington Convention Center is a wonderful facility. It covers four city blocks in downtown Washington just north of Massachusetts Ave. between 7th and 9th. It's about a fifteen minute walk due north of the Capitol where the Congress is housed. The neighborhoods on the South, North, East, and West sides of the building are good examples of the diversity of a typical American city.

The inside of the building is huge and the facilities are as good as, or better than any I've seen in other cities.

I love Washington. Whenever I'm here I think it's the best city in the United States. If only they could fix the parking problem ....

Noncoding DNA and Junk DNA

Scientific American has published another short note on junk DNA [Jumping 'Junk' DNA May Fuel Mammalian Evolution]. RPM noticed that there was no reference to the actual study being quoted in the article so it wasn't possible to verify the accuracy of the reporting [Junk DNA in Scientific American]. I couldn't find it either when I looked last week but it has now appeared on the PNAS website [Thousands of human mobile element fragments undergo strong purifying selection near developmental genes]. RPM also complained about the over-use of the term "junk DNA" in the Scientific American Article. That's what I want to discuss.

The author of the Scientific American article, JR Minkle, has responded on the Scientific American website [The DNA Formerly Known as Junk]. Minkle is a science writer who has covered a lot of stories in many different fields. As far as I know Minkle has not written very much about biology before summarizing the work in the PNAS paper. There was a time when all the science in that journal was written by scientists who were experts in the field [The Demise of Scientific American]. Anyway, that's not the main point here. JR Minkle has listened to the critics and made a decision to avoid the term "junk DNA" from now on.

That's a bad decision. RPM never asked anyone to avoid the word "junk." He merely called for appropriate use. Ryan Gregory has serious doubts about the usefulness of the term as he explains in his excellent article A word about "junk DNA".. If you want to keep up with the discussion about junk DNA you need to read that article—but you don't need to agree with everything in it. :-)

Gregory has also commented on the Scientific American article by proposing a new term, Junctional DNA, to describe DNA that probably has a function but that function isn't known. According to him, this avoids the confusion between using "junk" DNA to describe DNA that we really know to be junk (pseudogenes) and DNA for which no function has been discovered so we assume it has none.

I think we don't need to go there. It's sufficient to remind people that lots of DNA outside of genes has a function and these functions have been known for decades. Thus, it is highly inappropriate to assume that all non-genic DNA is junk and no scientist should ever do this. Note that I'm avoiding the term "noncoding" DNA here. This is because to me the term "coding DNA" only refers to the coding region of a gene that encodes a protein. Thus, in my mind, there are many genes for RNAs that are not properly called coding regions so they would fall into the noncoding DNA category. Also, introns in eukaryotic genomes would be "noncoding DNA" as far as I'm concerned. I think that Ryan Gregory and others use the term "noncoding DNA" to refer to all DNA that's not part of a gene instead of all DNA that's not part of the coding region of a protein encoding gene. I'm not certain of this.

The importance of the term "junk DNA" is to highlight the fact that it has not evolved by natural selection. This is a point I made in one of my first blog postings way back in November [Bill Dembski Needs Help, Again] and again a few days later [The IDiots Don't Understand Junk DNA] [Two Kooks in a Pod].

This isn't original. Everyone knows that junk DNA poses a major threat to both Intelligent Design Creationism and adaptationism [Junk DNA Disproves Intelligent Design Creationism] [Evolution by Accident]. Read Gregory's article for the short concise version of this dispute. What it means is that junk DNA threatens the worldviews of both Dembski and Dawkins!

Science writers often get trapped into thinking like an adaptationist when it comes to junk DNA. Remember that according to the adaptationist worldview the existence of huge amounts of truly nonfunctional DNA in a genome must be a problem. It can't be explained if natural selection is a powerful driving force behind most of evolution. You can't propose that all minor changes in behavioral genes, for example, have been selected and then turn around and admit that 95% of the human genome is junk!

Adaptationists celebrate every discovery that some little bit of DNA has found a function. That's because in their heart of hearts they think that almost all of the junk DNA will eventually be found to have a function. This is one of the reasons why papers like the PNAS paper mentioned above get so much attention.

I want to keep the term "junk DNA" to refer to all functionless DNA. That includes DNA for which we have direct and indirect evidence of no function (pseudogenes, most of intron DNA, corrupted transposons etc.) and it also includes the rest of the DNA for which no function has currently been discovered and we think it's junk because it's not conserved (among other reasons). Junk DNA is not noncoding DNA and anyone who claims otherwise just doesn't know what they're talking about.

The term "junk DNA" forces people to think about the underlying causes of evolution. It makes them stop to appreciate the fact that modern organisms could have evolved with useless DNA in their genomes and the only way this could have happened is if there's a lot more to evolution than just natural selection and adaptation. It's a good term. It's an accurate term. It's a useful term. And it makes people think.

Undergraduate Research

 
My society has a long history of sponsoring undergraduate research and inviting undergraduates to present their work in a poster session at this meeting. I look forward to seeing these posters and meeting some of the undergraduates who did the work.

This is a contest. There's a prize for the best poster, I think it's several thousand dollars. Judges interview all the students who are dutifully standing by their posters. It's a lot of fun.

I took a photo of the poster session from a small balcony overlooking the giant exhibit area. This was the only session for today—all the rest start tommorrow. The reason for having the undergraduate posters first is so the prize can be awarded at a special presentation tomorrow at noon. As you can see in the photo, the poster session was well attended. By the time I got downstairs there were two or three people in front of every poster.

This was an impressive group of students. I had serious science discussions with about a dozen presenters. I don't think I could identify the winner because some of the topics were way outside my areas of knowledge but here are two posters that I liked very much.

Amit Gautam is an undergraduate at Johns Hopkins. He works with bacterial release factors. These are proteins that terminate protein synthesis and stimulate the release of the completed polypeptide chain from the translation complex (ribocsome). His particular release factor comes in two different conformations. You can see them just over his left shoulder. The compact version is what was seen when purified protein was crystallized. The elongated form was the conformation observed when the release factor was bound to the ribosome.

The extended form is almost certainly the active form since it spans the distance between the termination codon and the site where the completed polypeptide is bound to tRNA in the P site. The protein has to do this to function, that's why the compact form was a surprise when it was first discovered.

Amit reasoned that the release factor had to shift from the compact form in solution to the extended form when it attached to ribosomes. He also reasoned that if he could block that shift the release factor would not work.

Amit introduced two cysteine residues into the release factor at positions that were in close contact in the compact form but far apart in the extended form. He predicted that a disulfide bond would form when the release factor was folded into the compact form and this covalent bond would lock it into the compact form preventing, it from adopting the extended form when it bound to ribosomes. As predicted, the modified release factor formed a disulfide bridge and was unable to catalyze release.

Under reducing conditions the disulfide bridge is disrupted and the release factor regains full activity. This is a nice example of a prediction and an experiment that tests the prediction. It's a nice piece of work.

Beccy Joscwitz used the split ubiquitin yeast two hybrid system to look for proteins that interacted with a membrane protein in yeast [see Technology reveals 'lock and key' proteins behind diseases]. She's a very impressive student and seems to be right on top of the work. She knew most of the problems and she also knew when to ask questions. I think the judges were very impressed.

Beccy, like Amit, wants to be scientist. Any graduate school would be lucky to have them.

What Do Scientists Eat?

 
There are six societies at this meeting: American Association of Anatomists; The American Physiological Society, American Society for Biochemistry and Molecular Biology,American Society for Investigative Pathology; American Society for Nutrition; and American Society fpr Pharmacology and Experimental Therapeutics. The slogan for the conference is "Today's Research: Tomorrow's Health."

So, you might be wondering what this group would eat for lunch? I was, especially since I was practically starving by the time noon hour rolled around.

There's an excellent food court in the lower level of the Washington Convention Center. I love food courts. This one had seven stations.

1. Center Plate (sandwiches,salads, yogurt)
   
2. Cluck Universal Chicken (fried chicken)
   
3. Foggy Bottom (burgers, fries, hot dogs)
   
4. Hannam's Caribbean Cuisine (spicy Caribbean dishes)
   
5. Philadelphia (cheese steaks)
   
6. Tam's Asian Cuisine (chinese food)
   
7. Wolfgang Puck (pizza, salads)
   

What would 12,000 scientists working in health-related fields choose for lunch. The winner was obvious. There were three times as many people lined up at one of the stations. The most popular food was ....

Tam's Asian cuisine. There was nobody at the Center Plate—the station with the "healthiest" choices. Everyone was buying General Tso's Chicken .... mmmmmmm, good. Lots of calories. Lots of fat.

I don't know what they'll be buying tomorrow. Stay tuned.