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Monday, March 30, 2009

Scientific Breakthroughs for March 30, 2009

 
I was reading the list of press releases on ScienceDaily Headlines and I thought you might be interested to learn about some of the most important discoveries in the past 24 hours. For the most part, these are press releases from universities and research institutes.

None of them are real breakthroughs. Some of them are interesting, incremental advances in our understanding of the natural world. Some of them are trivial results that have been elevated to importance by a press release and a headline. Some of them are silly. Some of them are probably wrong.



Free Speech in Oklahoma

 
The Oklahoma legislature is trying to intimidate the University of Oklahoma for inviting Richard Dawkins to speak last month. The Tulsa World publishes an article today that covers both sides of the controversy. After reading that article, the only logical conclusion is that free speech in Oklahoma is being threatened by elected politicians [Dispute evolves on OU speech by scientist].

This is outrageous. How can you have State Representatives advocating laws that violate the American Constitution and the Bill of Rights? Isn't that treasonous?

Oklahoma is one of those states that still has the death penalty and it still carries out executions. According to US Federal Law, the penalty for treason can be death [Capital punishment in the United States]. That raises an interesting possibility when it comes to dealing with creationists.


[Hat Tip: RichardDawkins.net]

Sunday, March 29, 2009

Don McLeroy, Creationist Dentist

 
This has already been posted on Panda's Thumb and elsewhere but it deserves to be seen by everyone. It's Don McLeroy, the creationist dentist who is chair of the Texas Board of Education. He has somehow gotten the idea that he knows more about evolution than the experts.

That makes him very dangerous.




Friday, March 27, 2009

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There's a prize for this one!!



Media distortion damages both science and journalism

 
New Scientist has just published an article on the dangers of bad science journalism. Irony noted.

Simon Baron-Cohen explains how Media distortion damages both science and journalism .
WHEN media reports state that scientist X of Y university has discovered that A is linked to B, we ought to be able to trust them. Sadly, as many researchers know, we can't.

This has three serious consequences. For starters, every time the media misreports science, it chips away at the credibility of both enterprises. Misreporting can also engender panic, as people start to fear the adverse consequences of the supposed new link between A and B. Lastly, there can be a damaging effect on researchers' behaviour. Funding agencies and science institutions rightly encourage scientists to communicate with the media, to keep the public informed about their research and so foster trust. If their work is misrepresented, they may withdraw into the lab rather than risk having to spend hours setting the record straight.

I work in one of those sensitive areas of research, autism, in which the facts are liable to be misreported or - sometimes worse - misinterpreted.


[Photo Credit: Simon Baron-Cohen: by Brian Harris (GNU Free Documentation License).]

Thursday, March 26, 2009

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Carl Zimmer on Science Journalism

 
Carl Zimmer has written a lengthy blog posting about the troubles with science journalism [Visions of the Crash]. You should read all of it but I want to comment on one small part.
The rise of blogs about science has brought me many pleasures. I’ve particularly liked the astringent criticism of bad science journalism. As soon as a piece is published, scientists who know the lot about the subject can, if necessary, rip a journalist a new one. I personally have been very influenced by Mark Liberman, a linguist at Penn, who has time and again shown how important it is for reporters to pay attention to the statistics in science. What seems at first like stark results–like the difference between the male and female brain–can melt away if you look at the actual data.

But some bloggers go a step further. They claim that these individual cases of journalistic misconduct add up to an indictment of the whole business. Hence, as Moran declares, we can live without science journalists.

It’s odd that many of the people making these pronouncements are scientists themselves–people, in other words, who know that you don’t do science by anecdote. If a blogger sits down in the morning and reads ten stories in a newspaper’s science section and notices that one that makes a howler of a mistake, you know what that blogger will be writing about. Blogs are an outlet for righteous fury. Bloggers are much less likely to write a post that begins, “I read nine articles this morning about science that were fairly accurate and pretty well written.” Ho hum.
I'm not an expert in everything. Most of the science articles I read are explaining things that are way outside my area of expertise. They may be good articles or they may not be. I'm usually skeptical.

However, the majority of articles I read that fall within my areas of expertise—biochemistry, molecular biology, genomes, evolution—do not impress me. It's not just a case of picking out the worst article out of ten to criticize. It's more like every second article has a problem.

When I talk to people in other fields there report the same statistics. It's looks like the average quality of science journalism, even in popular science magazines like SEED, Discovery, New Scientist, and National Georgraphic, leaves a lot to be desired.

I'm not very happy with most scientific papers either.


Darwin's two-for-one deal

 
Three cheers for Ryan Gregory! He has published an article in todays Globe and Mail explaining why evolution is both a fact and a theory: Darwin's two-for-one deal.

Go to his blog [Evolution Commentary] and congratulate him.


How Does Streptomycin Work?

Streptomycin is a powerful antibiotic that inhibits growth of bacteria while having very little effect on eukaryotes. It blocks protein synthesis by binding to the bacterial ribosome.

Let's review the steps of protein synthesis. The three steps are initiation, where the ribosome and factors are assembled at the start codon on the messenger RNA (mRNA); elongation, where the polypeptide chain elongates as the translation machinery moves along the mRNA; and termination, where the assembly falls apart and the completed polypeptide chain is release.

During the elongation phase there are three sites at the interface between the ribosome and the mRNA where transfer RNAs (tRNAs) can bind. The P site holds the peptidyl-tRNA molecule. The growing polypeptide chain is bound to the tRNA molecule that contributed the last amino acid. The A site binds the incoming aminoacylated tRNA molecule. The anticodon of this aa-tRNA is complementary to the mRNA codon located in the A site. Insertion of the correct aa-tRNA is mediated by elongation factor Tu (in bacteria)..

Formation of the peptide bond then occurs in a reaction catalyzed by peptidyl transferase—an enzymatic activity of the ribosomal RNA in the ribosome. When this happens the growing peptide chain (grey balls) is transferred to the tRNA that was in the A site.

The next step is to shift the ribosome relative to the mRNA bringing the peptidyl-tRNA molecule into position in the P site and freeing up the A site for a new amimoacyl tRNA to bind. This step is called translocation and it is mediated by elongation factor G (EF-G). During the translocation the uncharged tRNA is temporarily moved to the exit site (E site) before being released.

Streptomycin inhibits the translocation step by binding to the small subunit ribosomal RNA and blocking the activity of EF-G.

Here's a picture (below) of what the bacterial ribosome looks like. Most of it is RNA (yellow chain) folded into a complex conformation. The three dimensional structure is stabilized by a number of small proteins (orange + blue) bound to the outer surface of the RNA. One of these proteins is S12, located in the grove where mRNA binds to the ribosome. S12 stabilizes the RNA three-dimensional structure to which streptomycin binds.


Bacteria rapidly develop resistance to streptomycin, which explains why it isn't as effective today as it was when it was first introduced in the 1940s. One of the common resistance mutations affects ribosomal protein S12. The mutant protein is able to maintain the proper RNA conformation in the presence of streptomycin and this allow translocation to proceed.


Thesis Defense - 35th Anniversary

 
Today is the 35th anniversary of my Ph.D. oral defense. The event took place in the Department of Biochemical Sciences at Princeton University back in 1974.

It began with a departmental seminar. When the seminar was over I retired with my committee to a small classroom for the oral exam.

I don't remember everyone who was on my committee. My Ph.D. supervisor (Bruce Alberts) was there, as was my second reader, Abe Worcel. I know Uli Laemmli was there and so was Arnie Levine. I'm pretty sure the external member of the committee was Nancy Nossal from NIH in Bethesda, MD (USA). It's a bit of a blur after all these years.

I remember being fairly confident about the exam. After five and a half years I was pretty sure that everyone on my committee wanted to get rid of me and the easiest way to do that was to let me pass. Bruce stood to gain $3000 per year of research money and Uli was going to get back the basement of his house where Ms. Sandwalk and I had been living for the past month.

The toughest questions were from Uli Laemmli, which should not come as a surprise to anyone who knows him. He has this annoying habit of expecting people to understand the basic physics and chemistry behind the biochemical sciences. Fortunately, my inability to answer most of his questions didn't deter him from voting to pass me.

This photograph was taken at a party that evening. I look pretty calm at that point but this may have had a lot to do with the various refreshments that were being served.

The amazing thing about the photograph—as I'm sure you all agree—is how little I've changed since then—apart from a haircut.

Back in those days we didn't spend a lot of time writing a thesis. I started in the middle of January and the entire process of writing and defending took nine weeks. My thesis was bound and delivered to the library about one week after the Ph.D. oral.

The second page of my thesis has only three words on it. It says, "To Leslie Jane." This is Ms. Sandwalk. She really should have her name on the cover 'cause I couldn't have graduated without her. Typing my thesis was only one of her many contributions. There are 257 pages in my thesis and she typed every one. As a matter of fact, she typed them twice, one draft and then the final version.

The figures in my thesis were all hand drawn. I've included one (below) to illustrate what I was doing during those five and a half years.

The Alberts lab was interested in DNA replication during bacteriophage T4 infections of E. coli. We knew that replication was carried out by a complex protein machine that assembled at a replication fork but we didn't know all the players or what they did.

The T4 proteins required for DNA replication were known from genetic studies. The most important genes were genes 30 (ligase), 32 (single-stand DNA binding protein), 41, 43 (DNA polymerase), 44, 45, and 62. The products of the unknown genes were called 41P, 44P, 45P and 62P.

We wanted to purify and characterize those proteins; my target was the product of gene 41, or 41P.

We had a cool assay, developed mostly by a postdoc in the lab named Jack Berry. What we did was to prepare a cell lysate from cells that had been infected by bacteriophage carrying an amber mutation in one of the genes. This lysate could not support DNA synthesis, as measured by incorporation of 32P nucleotides, unless we added back the missing component. This is the basis of an in vitro complementation assay that worked for each of the unknown proteins.

In my case, I used traditional protein purification methods to isolate fractions of proteins and them tested them for activity in the complementation assay. The figure below shows the elution profile of proteins bound to a hydroxylapatite column. The peak centered on fraction 61 is the activity of the complementation assay. It indicates that 41P elutes early as a sharp peak in the elution profile.



The complementation assay doesn't tell us anything about the function of 41-protein, only that it complements an extract that's deficient in 41P. Strictly speaking, it doesn't even tell us that the activity is due to the product of gene 41 since it could be something else that complements in vitro.

Fortunately we had another way of identifying 41P. I started my purification with extracts from 17 liters of infected cells. To this I added extracts from cells that had been labeled with radiaoctive amino acids. One batch was from a wild-type infection where all T4 proteins are labeled with 14C amino acids. The other batch is from an infection with an amber mutation in gene 41. In this case every protein except 41P is labeled with 3H amino acids.

You can adjust the settings on a scintillation counter so they distinguish between 14C and 3H but there's some overlap. The equations for calculating the contribution of each isotope in each window are relatively simple. All you need are good standards to get the distribution. One of the most fun things I did as a graduate student was to write a computer program (in Fortran) that did these calculations automatically and plotted them on a plotter. This was back in the time when computers were housed in large separate buildings and required dozens of people to look after them.

If you look of the elution profile in the figure you'll see there's an excess of 14C over 3H in the same fractions where the complementation activity is located. What this means is that the wild-type extract has a protein at that position that's not found in the am41 extract. It's another way of identifying the product of gene 41.

The double label technique was useful 35 years ago but nobody does it anymore. It was fun while it lasted.

(I never did figure out what 41P did during DNA replication but a few years after I left a postdoc identified 41P as a helicase—an enzyme that unwinds DNA ahead of the replication fork. The enzyme is now called gp41 for "gene product.")


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Wednesday, March 25, 2009

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What's the best way to describe a graduate student?

 
The controversy over the 1952 Nobel Prize reminds me that we haven't had a poll in a long time. Check out the poll in the left-hand sidebar. How would you describe a graduate student?

You must answer by April Fool's Day.


Nobel Laureate: Selman Waksman

 

The Nobel Prize in Physiology or Medicine 1952

"for his discovery of streptomycin, the first antibiotic effective against tuberculosis"

Selman Abraham Waksman (1888 - 1973) won the Noble Prize in 1952. The award was for discovering streptomycin.

Waksman was a soil microbiologist at Rutgers University in New Jersey (USA). In the 1930s, after the success of penicillin, he decided to change the focus of his research and look for more antibiotics. He reasoned that soil microorganisms should be a good source of novel anti-bacterial drugs.

Streptomycin was the most famous of the many antibiotics discovered in Waksman's lab. It was largely due to the dedicated work of a graduate student, Albert Schatz, who first identified streptomycin's potent effect on gram negative bacteria in October 1943. Over the next few years, Waksman became famous for discovering streptomycin and Schatz was all but forgotten.

In 1950, Schatz sued his former supervisor for recognition, and a share of the royalties. The case was settled out of court with Rutgers agreeing that Schatz and Waksman would be identified as co-discoverers of streptomycin. Schatz received a share of the royalties.

In spite of this settlement, the Nobel Prize committee awarded the prize to Wakesman and not to Waksman and Schatz. This was mildly controversial at the time but didn't qualify as a major scandal. It seems more egregious today.

The issue is part of a continuing controversy about how to attribute recognition when graduate students are working under the direction of their supervisors. There's no better way to start a fight than to bring this up with a group of graduate students. Are they apprentices, slaves, or collaborators?

I am indebted to Philip Johnson of York University (Toronto, Canada) for alerting me to the controversy and for sending along this excellent article about Albert Schatz.

Waksman does not specifically mention Schatz's contribution in his Nobel lecture but he is mentioned in the presentation speech (see below) in an obvious attempt to minimize his contribution. Knowing what we know now, should the Nobel Prize website be modified to include a discussion of the controversy? I think it should.

THEME:
Nobel Laureates
In 1940 Dr.Waksman and his collaborator had succeeded in isolating the first antibiotic, which was called «actinomycin» and it was very toxic. In 1942 another antibiotic was detected and studied, called «streptothricin». This had a high degree of activity against many bacteria and also against the tubercle bacillus. Further studies revealed that streptothricin was too toxic. During the streptothricin studies Dr. Waksman and his collaborators developed a series of test-methods, which turned out to be very useful in the isolation of streptomycin in 1943.

Encouraged by the discovery of streptothricin and stimulated by the triumphal development of penicillin treatment, the research team headed by Dr.Waksman continued their untiring search for new antibiotic-producing microbes. Before the discovery of streptomycin no less than 10,000 different soil microbes had been studied for their antibiotic activity. Dr. Waksman directed this work and distributed the various lines of research among his young assistants. One of these was Albert Schatz, who had previously worked with Dr. Waksman for 2 months and in June 1943 returned to the laboratory. Dr. Waksman gave him the task of isolating new species of Actinomyces. After a few months he isolated two strains of Actinomyces which were shown to be identical with Streptomyces griseus, discovered by Dr. Waksman in 1915. In contrast to the previous one the rediscovered microbe was shown to have antibiotic activity. To this antibiotic Dr. Waksman gave the name «streptomycin». He studied the antibiotic effect of streptomycin with Schatz and Bugie and found that it was active against several bacteria including the tubercle bacillus. These preliminary studies were completed in a relatively short time, thanks to the clear principles which had been set out previously by Dr. Waksman for the study of streptothricin.


The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

Making Tracks

 
Look at the photo on the right. Do you know why this is an important discovery? Did you know you could win a case of beer for discoveries like this?

Find the answer on Catalogue of Organisms: More Crunchy Scleritome Goodness. Find out more about the little "problematic" animal in the photo.