Monday, April 30, 2007

What has phage lambda ever done for us?

Murray and Gann published an essay in this month's Current Biology titled "What has phage lambda ever done for us?" Since my current study organism is phage lambda, naturally I was interested. The essay is informative and interesting and, for those who have institutional access, I urge you take a gander at it for your own edification.

Bacteriophage lambda was first discovered in 1951 by Esther Lederberg (wife of Nobelist Joshua Lederberg and probably deserving of a Nobel in her own right, but that's another story). Lambda was immediately interesting to the burgeoning molecular biology community because it propagates by two alternative pathways: lytic and lysogenic. In the lytic cycle, the phage's DNA enters an E. coli cell, induces the cell to produce phage progeny, then subsequently causes the cell to lyse (break open) releasing the contents into the surrounding media. By contrast, the lysogenic cycle is largely harmless, possibly even beneficial, to the cell. Here the phage's DNA enters the cell whereupon it is integrated into the cell's own DNA. As the cell replicates, the phage replicates as well. How cool is that?

Murray and Gann highlight where phage lambda was used as a model organism in many major biological discoveries. Here is a ^not so^ brief listing:

* gene regulation (Lwoff, Jacob and Monod 1961; Roberts 1969; Guarneros and Galindo 1979)

* DNA recognition and cooperative binding (Ptashne 1967)

* genetic fine structure (Benzer 1957)

* messenger RNA (Volkin and Astrachan 1956, 1957)

* acquisition and loss of genes from genomes (Campbell 1959, 1962)

* triplet nature of DNA code (Crick, Barnett, Brenner and Watts-Tobin 1961)

* restriction and modification (Dussoix and Arber 1962)

* DNA and protein are colinear (Sarabhai, Stretton, Brenner and Bolle 1964)

* DNA ligase (Gellert 1967)

* epigenetic gene regulation (Ptashne 2004)

* chaperones and protein folding (Georgeopoulos, Hendrix, Casjens and Kaiser 1973)

* repression and activation (i.e. turning genes on and off, Ptashne 2004)

* molecular basis of DNA recombination (Meselson and Weigle 1959, 1961)

That's quite a list. And it is nowhere near being exhaustive. Phage lambda has proven uniquely malleable in the laboratory and has illuminated large facets of previously hidden knowledge to biologists. Today lambda is still being used in many laboratories, which is testament to its enduring legacy.

The photo depicts Ur-Lambda (the father of all laboratory lambda phages); it's a lambda with LEGS! *ahem* tail fibers. The Electron Microscopy image was taken by Bob Duda at the Pittsburgh Bacteriophage Institute.

Sunday, April 29, 2007

Applied Phage Biology

I study bacteriophages, i.e. viruses that infect and destroy bacteria. Although no one has said it to my face, I figure some folks out there probably think that phages are somewhat of an odd choice of study organism. Weird even. But hey, I think they are cool. When I first saw a picture of them, I thought, this can't possibly be real. Check out the photo above (false color, FYI). Does it not look like a spasm from the over-active imagination of a science fiction author?

Anyway, lest it be believed that phages are solely biological curiosities of little interest for humans, I'd like to highlight the work of a biotechnology company in Maryland, Intralytix ,which recently gained FDA approval to market a novel defense against the food-borne bacteria, Listeria monocytogenes. Listeria causes listeriosis, which is responsible for ~500 deaths and 2,500 illnesses in Americans each year. Adhering to the dictum, "the enemy of my enemy is my friend", Intralytix's anti-Listeria treatment is a cocktail of six bacteriophages that can be sprayed on ready to eat foods such as hot dogs and deli meats. The phages are completely harmless to humans, but are deadly to the bacteria. In addition, the phages are highly specific to Listeria and should have no effect on our natural biofauna. These advantages are not shared by current antibiotic treatments, which are susceptible to being subverted by antibiotic resistance evolution, and moreover, are highly nonspecific and can kill many good bacteria as well.

Intralytix has treatments for E. coli and Salmonella in the pipeline as well. The E. coli O157:H7 treatment can be sprayed on raw hamburger and fresh vegetables, such as spinach, which was the source of a major outbreak causing 205 confirmed illnesses and three deaths last year. The Intralytix website also details applications in veterinary medicine, environmental sanitation, and human therapeutics.

Thursday, April 26, 2007

This Week's Citation Classic

Beadle, G.W. & Tatum, E.L. 1941. The genetic control of biochemical reactions in Neurospora. Proceedings of the National Academy of Science, 27:499-506.

Behind every major scientific effort is a story. Beadle and Tatum's story is one of persistence. They began with a hypothesis: each gene causes the production of a single enzyme, and that enzyme catalyzes a biochemical reaction within an organism. The seeds of this hypothesis were spawned by Sir Archibald Garrod, who reported in 1909 that alkaptonuria - an inherited condition in which the urine is colored dark red by the chemical alkapton - results from a single recessive gene, which causes a deficiency in the enzyme that normally breaks down alkapton.

After graduating from Cornell in 1931, George Beadle arrived at T.H. Morgan's CalTech lab determined to follow up on Garrod's work. Morgan's lab, at that time, was perhaps the premier genetics lab in the world. There Beadle teamed up with Boris Ephrussi to examine eye pigment development in the fruit fly, Drosophila. Together, they proposed that eye color changes in mutant strains of Drosophila could be caused by inactivation of specific proteins, acting in a single biosynthetic pathway.

However, Beadle soon realized that Drosophila were entirely inappropriate for the work he had in mind.

"Isolating the eye-pigment precursors of Drosophila was a slow and discouraging job. Tatum and I realized this was likely to be so in most cases of attempting to identify the chemical disturbances underlying inherited abnormalities; it would be no more than good fortune if any particular example chosen for investigation should prove to be simple chemically."1

The other major epiphany Beadle had was that finding mutants in Drosophila was complicated by the lack of biochemical knowledge of the fruit fly's developmental pathways. He and Tatum decided to reverse the procedure and look for mutations that influence known chemical reactions, but for what organism?

Beadle recalled from grad school a seminar given by B.O. Dodge on inheritance in the bread mold Neurospora. The team soon discovered that Neurospora could be grown on a simple mixture of salt, sugar and biotin, a vitamin.

The procedure was then simple: "Induce mutations by radiation or other mutagenic agents. Allow meiosis to take place so as to produce spores that are genetically homogeneous. Grow these on a medium supplemented with an array of vitamins and amino acids. Test them by vegetative transfer to a medium with no supplement. Those that have lost the ability to grow on the minimal medium will have lost the ability to synthesize one or more of the substances present in the supplemented medium. The growth requirements of the deficient strain would then be readily ascertained by a systematic series of tests on partially supplemented media."1

Their only worry was that the frequency of mutation would be so low that they would give up before finding one.

"We believed so thoroughly that the gene-enzyme reaction relation was a general one that there was no doubt in our minds that we would find the mutants we wanted.... [but we] were so concerned about the possible discouragement of a long series of negative results that we prepared more than thousand single-spore cultures on supplemented medium before we tested them. The 299th spore isolated gave a mutant strain requiring vitamin B6 and the 1,085th one required B1. We made a vow to keep going until we had 10 mutants. We soon had dozens."1

Thus through years of persistence and experimental drudgery, Beadle and Tatum finally procured the data for their famous 1941 PNAS paper. They had experimentally demonstrated that a single gene specifies the production of a single enzyme.2 Many authors point to this study as the cornerstone of molecular biology and the beginning of the field of biochemical genetics. Beadle and Tatum shared (with Joshua Lederberg) the 1958 Nobel Prize in Medicine for their work.

Photo credit:
"Identification of multiple distinct Snf2 subfamilies with conserved structural motifs" Flaus A, Martin DMA, Barton GJ and Owen-Hughes T Nucleic Acids Research v34 pp2887-2905 (2006) (published as open access, so full text is freely available).

1. Beadle, G. W. 1958. Nobel lecture: Genes and chemical reactions in Neurospora.

2. Today we now know that each gene specifies the production of a single polypeptide—that is, a protein or protein component. Thus, two or more genes may contribute to the synthesis of a particular enzyme. Also, depending on transcription regulation, multiple proteins can be transcribed from essentially the same gene. In addition, some products of genes are not enzymes per se, but structural proteins. But the general accuracy of Beadle and Tatum's statement stands.

Beadle, G.W. & Tatum, E.L. (1941). The genetic control of biochemical reactions in Neurospora. Proceedings of the National Academy of Science, 27, 499-506 DOI: 16588492

Peer Review

In the movie Jaws, Hooper, Quint and Brody try to one-up each other comparing battle scars. Scientists engage in analogous grandstanding; we try to outdo each other with horror stories of peer review. For many of us, this is one of the most frustrating parts of science. One works hard designing experiments, collecting data and writing a manuscript. Then one submits it to a journal for peer review, and it disappears, sometimes for periods longer than it took to complete the work in the first place. In the meantime, your work on the subject often languishes in limbo, your CV remains unaccredited or contains a line with the explanation (submitted), and your personal gratification remains unsatisfied. I find myself selecting journals for publication based mainly on their "turn-around time".

What is most surprising to me is that many scientists shirk peer review when asked to perform it. I recall one colleague who suggested the following strategy: after acquiescing to a request for peer review, ignore it until after the deadline, until the editor writes asking where it is. Only then should you perform the task and submit your comments. The colleague reasoned, perhaps then the editors would leave you alone and not request future reviews from you. The strategy, in addition to being appalling and uncollegial, is particularly shortsighted. If the strategy spread, it eventually would be applied to your own submissions as well.

In a letter to PLoS Biology, Marc Hauser and Ernst Fehr propose to incentivise the peer review process by punishing transgressors. Here editors would keep databases on when papers were sent to reviewers and when the reviews were returned. The late reviews would be punished accordingly: "For every day since receipt of the manuscript for review plus the number of days past the deadline, the reviewer's next personal submission to the journal will be held in editorial limbo for twice as long before it is sent for review."

Naturally the system is not without bugs. Who is punished when multi-authored papers are submitted? What happens if one of the authors is a timely reviewer and another is a slacker? Hauser and Fehr suggest penalizing only the primary corresponding author, but I think that might easily be gamed by making the least penalized author the correspondent. Also slackers could avoid penalties by refusing requests for reviews. Hauser and Fehr suggest penalizing them by adding a one-week delay their own next submission. However, this also penalizes those who turn down reviews because of time constraints and or because they feel unqualified to do the service.

Hauser and Fehr's suggestion is interesting. Something surely must be done about the broken review process. I would object to monetizing the review process, as some commenters have suggested, but penalizing slackers with embargoes seems like a workable solution. I also like the open peer review system where submitted papers are posted for comments from scientists at large. The internet provides many new avenues to fix the peer review system and I hope journal editors consider them seriously.

Wednesday, April 25, 2007

Everybody is interested in pigeons...

The Times of London reports that a 150-year-old correspondence between the publisher, John Murray, and a clergyman, the Rev. Whitwell Elwin, has been unearthed. In the letter (an early example of peer review), Elwin responds to Murray's request for an opinion on a recently submitted manuscript, "On the Origin of Species" by a Charles Darwin. Elwin apparently did not think highly of the work, thinking the theories contained therein were so far-fetched and ridiculous that no one could possibly believe them. “At every page I was tantalised by the absence of the proofs,” Elwin wrote. Moreover, he found the writing style excessively dry and difficult. Elwin suggested that Darwin write about pigeons because “everybody is interested in pigeons”.

Tuesday, April 17, 2007

Science 2.0

In addition to giving my blog a nod, Carl Zimmer at The Loom wrote about how scientific discourse is changing in the internet era. It used to be that most scientific debate took place over the course of months (years?) on the pages of august journals or in the hallways at scientific conferences. Criticism, whether positive or nasty, tended to be visible to a select few specialists in the field, and rarely spilled over into the popular press.

Today that is changing. The internet permits a wider exchange of ideas, and is open to anyone who cares to log on and direct their browser thither. Scientists are increasingly looking to blogs as additional outlets for their ideas and comments. Consequently, the pace of scientific debate is speeding up tremendously, with positive and negative repercussions.

Case in point. Yesterday a paper by Liu and Ochman was published online by PNAS. I wrote about it later that evening, highlighting it as additional evidence against the concept of Irreducible Complexity proposed by creationists. Later Nick Matzke of the National Center for Science Education blogged about it at the Panda's Thumb and TR Gregory wrote about it for Genomicron (where Larry Moran of the Sandwalk added his two cents in the comments). All this (and Zimmer's comments) happened within 24 hrs of the paper being released.

I find this discourse thrilling and am happy to be part of the burgeoning movement of scientists to the blogosphere. Moreover, it is fantastic that the general public has an opportunity to observe scientific debate. Facts in textbooks aren't simply placed there by fiat, but are the result of plenty of give and take on the part of working scientists. However, it is important to remember that this new debate is open to all, not just a few close colleagues, and hence, it is especially important to maintain a civil tone. I think Matzke could have chosen his words better in titling his piece, but I commend him on making his comments known. Nothing illustrates the validity of the scientific process like the free exchange of ideas.

The ideal model for this type of discourse is, as Zimmer pointed out, PLoS ONE. I, for one, love the idea of an open-access, freely annotatable journal, and I hope to see it drive pay-journals to a much deserved extinction. True, it is a bit quiet over there now, but I suspect, once scientists get used to the idea, it will be buzzing with activity soon enough.

Notes: The photo was obtained from Joe Felsenstein's website. It depicts the speakers at the International Union of Biological Sciences Symposium on Genetics of Population Structure in Pavia, Italy, in 1953. Their identities are as follows.

Back row: Mather, da Cunha, Haldane, Dobzhansky, Waddington, Epling, Carson, Robertson, Falconer

Middle row (crouching): Ford, Wallace, ?, (large gap) Lerner, Cordeiro(?)

Bottom row (sitting on ground): Mayr, Levine, Buzzati-Traverso, Fisher, Clausen, Pavan

The unidentified one may be Renzo Scossiroli. I have a complete list somewhere and will post it when I find it.

Monday, April 16, 2007

Irreducible complexity, indeed...

Irreducible complexity is the hallmark of many anti-evolutionist arguments as it stipulates that many biological structures are too complex to have evolved from simpler, less-complex precursors. A common straw man is the mousetrap, whereby it is claimed that removing any part of the mousetrap makes it useless. (Biologist John McDonald elegantly dismembers this argument by describing a reducibly complex mousetrap). Anyway, such irreducible complexity is supposed to be proof of an intelligent designer (i.e., an immortal creator). Flagella, whip-like projections from some cells that are used for locomotion (see photo), are often claimed to be irreducibly complex biological structures. This view has been thoroughly discredited, even in a court of law (see Kitzmiller v. Dover).

A paper by Liu and Ochman in PNAS compiles further evidence against the hypothesis of irreducible complexity. They took advantage of full genome sequence for 41 bacterial species to trace the phylogenetic occurrence of flagellum proteins. The results show, amazingly, that the "core components of the bacterial flagellum originated through the successive duplication and modification of a few, or perhaps even a single, precursor gene." Flagella don't sound so irreducibly complex, then, do they? The take-home message is that evolutionary theory is sufficient to explain even the origin of complex organs and organelles and we needn't postulate intelligent designers. My compliments to Renyi Liu and Howard Ochman for a fine piece of work.

Sunday, April 15, 2007

Step It Up!

Yesterday I participated in a rally in Great Barrington, MA for action on global climate change organized by Step It Up. As Stockbridge Indian representative Steve Comer led a prayer at the Stockbridge Indian Burial Site, my mind wandered to the difficulty of communicating the gravity of the global warming crisis to non-scientists. One problem may be that people have trouble connecting warming temperatures to negative consequences for themselves. Indeed one of the most frequent comments I hear about global warming is "Why are our winters still so long and cold?!"

This is why I had mixed emotions about the recent articles in the popular press about global warming and polar bears. On the one hand, it does provide a great hook, a concrete way to appeal to people with a strong affinity for large, furry mammals. Unfortunately the true significance of global climate change might be lost. While the extinction of polar bears would be an unmitigated tragedy, the fact of the matter is their loss would have little effect on human economics. As Wilmers et al. points out in this month's American Naturalist, it is the highly fecund species most at risk. These are the bugs, worms and creepy-crawlies that do the heavy lifting in providing the ecosystem services our civilization is utterly dependent on. I think this argument bypasses the controversy over whether climate change is "natural" or human-induced, whereas the "Save the Polar Bears" argument might be rebutted by the "Well It's Just Part of the Natural Process" argument. One would not argue that one should not shelter from a hurricane because it is a "natural" phenomenon. I'm afraid, unless we make obvious in no uncertain terms that global warming is going to hit us squarely in the pocketbook, progress in mitigation efforts will be long in coming. Let us not forget that those that can most affect carbon dioxide emissions respond most strenuously to threats to their bottom lines.

Friday, April 13, 2007

Fierce Chickens...

So it turns out that our docile barnyard friends, the chickens, have quite a fearsome ancestor: T-rex. Asara et al. used mass spec to determine the amino acid sequence of collagen extracted from 68-year-old Tyrannosaurus rex bone. The determined sequence closely resembled that obtained from chickens. Of course most popular current hypothesis for the origin of birds is that they are the descendants of dinosaurs, but most of the evidence comes from anatomical structure. This is the first evidence to come from actual molecular data. Actually the most surprising thing about this study is that collagen survived 68 million years.

It doesn't quite mean the onset of Jurassic Park quite yet, but as my friend Thad said, "Barbecued or fried T-Rex sounds good!!"

Thursday, April 12, 2007

This week's citation classic

Hutchinson, G. E. 1959. Homage to Santa Rosalia or why are there so many kinds of animals? American Naturalist, 93: 145-159.

One of the things I enjoyed most about my time at Yale was the history of the place. I was pleasantly surprised to discover the famous scientists that worked there, including Lederberg, Tatum, Altman, Palade, Gilman etc. It gave me a sense of being part of a long tradition, part of something important. But most interesting, to me, was that George Evelyn Hutchinson spent his career there. Hutchinson is best known as the founder of Limnology, but truly he was a renaissance man, cognizant of many fields of arts and sciences. He served as mentor to many future ecologists, including Robert MacArthur, Lawrence Slobodkin and Fred Smith.

The paper, "Homage to Santa Rosalia" is my favorite of Hutchinson's. Here he observes two species of waterbugs living in the same pond in a cave at the Shrine of Saint Rosalia on Monte Pellegrino, Sicily, and asks, "Why are there so many kinds of animals?" The whole story is just so fantastic to me, that a person would travel halfway across the world to visit a shrine in Palermo, Sicily, and would be most interested in the waterbugs. Not only that, but goes on to write one of the most beautiful and lyrical papers in science. Simply stunning!

Check out Hutchinson's wonderful prose:

"A few months later I happened to be in Sicily. An early interest in zoogeography and in aquatic insects led me to attempt to collect near Palermo, certain species of water-bugs, of the genus Corixa, described a century ago by Fieber and supposed to occur in the region, but never fully reinvestigated. It is hard to find suitable localities in so highly cultivated a landscape as the Concha d'Oro. Fortunately, I was driven up Monte Pellegrino, the hill that rises to the west of the city, to admire the view. A little below the summit, a church with a simple baroque facade stands in front of a cave in the limestone of the hill. Here in the 16th century a stalactite encrusted skeleton associated with a cross and twelve beads was discovered. Of this skeleton nothing is certainly known save that it is that of Santa Rosalia, a saint of whom little is reliably reported save that she seems to have lived in the 12th century, that her skeleton was found in this cave, and that she has been the chief patroness of Palermo ever since. Other limestone caverns on Monte Pellegrino had yielded bones of extinct Pleistocene Equus, and on the walls of one of the rock shelters at the bottom of the hill there are beautiful Gravettian engravings. Moreover, a small relic of the saint that I saw in the treasury of the Cathedral of Monreale has a venerable and petrified appearance, as might be expected. Nothing in her history being known to the contrary, perhaps for the moment we may take Santa Rosalia as the patroness of evolutionary studies, for just below the sanctuary, fed no doubt by the water that percolates through the limestone cracks of the mountain, and which formed the sacred cave, lies a small artificial pond, and when I could get to the pond a few weeks later, I got from it a hint of what I was looking for. Vast numbers of Corixidae were living in the water."

The scientific significance of the paper is undeniable. Hutchinson extends the conception of niche that he first presented at a Cold Spring Harbor symposium in the subtly named paper titled, "Concluding Remarks". Hutchinson's conception of niche came to be known as Hutchinsonian (or realized) niche as opposed to the Eltonian (or fundamental) niche. Arguably Santa Rosalia is the origins of the study of biodiversity. In fact, Santa Rosalia has become shorthand for the basic question of species numbers; I found 52 papers that contained Santa Rosalia in the title or keywords and 1,326 papers that cited the work. Although many of the concepts Hutchinson wrote about did not begin with him, he might be credited with bringing order to the discipline by shifting focus to the central role of energy in food chains, available habitat, community stability and environmental grain, and how all this relates to the maintenance of biodiversity.

Even ~50 years later, ecologists can read Homage to Santa Rosalia, not simply for entertainment, but for valuable insight into their own research.

Hutchinson, G. (1959). Homage to Santa Rosalia or Why Are There So Many Kinds of Animals? The American Naturalist, 93 (870) DOI: 10.1086/282070

We are sorry to see them go...

Two of my personal heroes passed away recently.

Knut Schmidt-Nielsen wrote one of my favorite books ever. It is not often one reads textbooks for pleasure.
September 24, 1915-January 25, 2007

Kurt Vonnegut
November 11, 1922 –
April 11, 2007
So it goes...

Wednesday, April 11, 2007

Blue leaves...

Who hasn't wondered if there is life elsewhere in the universe? What would it look like? How would it function? Through biology, especially evolutionary biology, we can make educated guesses as to the form and function of the flora and fauna of other worlds. Kiang et al. go a step further, into a realm seldom imagined. They calculated the photosynthetically relevant radiation on earth-like planets orbiting other stars. The results are surprising. Different stars have different optimal photo spectra. Therefore, plant colors on other worlds might be different from plants on earth to capitalize on these differences. This would no doubt have cascading effects to all other species on those planets. Imagine blue lizards adapted to hide among blue leaves, and the birds adapted to find them.

Photo by Vincent Lillis.

Tuesday, April 10, 2007

Big dogs, little dogs...

Dogs, interestingly enough, show greater size variation than any other terrestrial mammal. Last week in Science, Sutter et al. reported finding the locus controlling size variation among dogs. A single allele (with a single nucleotide difference from large dogs) at the IGF1 locus is found in all small dogs (but probably not Sarah, at right). IGF1 produces an insulin-like growth factor and is linked to size mice and humans. Presumably, if you knock out IGF1 function, you will get a dog no bigger than a large rodent. Although Sutter et al. didn't speculate as such, I will boldly predict that this locus is pleiotropic (i.e. one gene, many functions). My guess is that IGF1 also functions as a Yap repressor. In the absence of IGF1, the Yap pathway is active and much yapping ensues. For want of a Yap repressor, those very small friends of ours have an unfortunate tendency to yap incessantly.

Monday, April 9, 2007

Is your emotional state a consensus?

Photo by Laura Rosa Brunet

It is estimated that bacterial cells out-number your cells ten to one. Sears (Anaerobe, 2005) claims that about 5,000 to 10,000 different species make themselves at home on the vast continent that is your body. So what effect do these "guests" have on you? Traditionally they have been credited with aiding digestion and competitively excluding pathogens, but a recent report suggests that at least one species of bacteria may improve your mood.


Following up on anecdotal reports that cancer patients treated with Mycobacterium vaccae claimed improvements to their moods, Dr. Chris Lowry and team treated mice with M. vaccae, and found that the bacterial treatment led to increases in systemic serotonin. Lowry et al. speculated that immune activation by the bacteria led to the increased activity of serotonergic neurons in the interfascicular part of the dorsal raphe nucleus. Since increasing serotonin levels is the mechanism of action for most antidepressants, the team suggested that M. vaccae may have effects in humans similar to that of antidepressants.

Given that behavioral changes concomitant with microbial infection are not unprecedented (viz. Toxoplasmosis gondii, see also The Loom), it does seem plausible that M. vaccae could alter human serotonin levels and reduce depression, but further experimentation is required to test this hypothesis. It even seems plausible that this enhances M. vaccae's fitness. Perhaps your emotional state is the consensus of imputs from various sources, environmental, nutritional, microbial etc. I think there is a whole new field of science waiting to emerge with regards to human community ecology.

Friday, April 6, 2007

This Week's Citation Classic

Luria SE, Delbruck M, & Anderson TF. 1943. Electron microscope studies of bacterial viruses. Journal of Bacteriology 46 (1): 57-77.

It didn't exactly happen this way, but nevertheless, I like to think it did.

In 1942, a German national (Max Delbruck) and an Italian national (Salvador Luria) approached the National Research Council Committee on Biological Applications of the Electron Microscope and asked whether they could use it to take pictures of, erm, bacterial viruses.

Of course at this time, the US was at war with Germany and Italy, and
"powerful elite committees in American science and industry were ubiquitous during wartime," regulating access to expensive, sensitive machinery. It's amusing to imagine Luria and Delbruck before the committee asking for the keys to an immensely powerful and highly mysterious microscope. One might have expected the committee to throw them out on their backsides and dial the FBI to report a couple of spies.

But they didn't. Luria, Delbruck and Anderson (a postdoc at RCA) shot some of the first photos of viruses, and lovely photos they are. I particularly like the photo of the bursting E. coli cell. The truth is that today's photos are more detailed and crisper, but not by much. Considering how difficult it is to take EM photos, Luria et al.'s photos are magnificent.

Much of my current work involves making movies of lambda phage lysing E. coli and determining mean and variation of lysis timing among different genotypes, so I feel a certain kinship to Luria and Delbruck, who were working on similar problems with similar organisms over 60 years ago. In the intervening time, stunning advances have taken place in biology, but some of the most fundamental questions remain unresolved.

Luria and Delbruck, both former physicists, later won the Nobel Prize in Medicine in 1969 (along with Al Hershey). Another interesting connection is that Luria's first graduate student was the 18 yr old James D. Watson. Indeed Luria and Delbruck can be, as much as anyone, credited with sparking the molecular biology revolution.

Nicolas Rasmussen. Picture Control: The Electron Microscope and the Transformation of Biology in America, 1940-1960. Writing Science. Stanford, Calif.: Stanford University Press, 1997. xv + 338 pp. Ill.

S. E. Luria, M. Delbrück, and T. F. Anderson (1943). Electron Microscope Studies of Bacterial Viruses Journal of Bacteriology, 46, 57-77

Thursday, April 5, 2007


Photo by John Wertz

I'm an evolutionary biologist. I study the evolutionary ecology of bacteriophages (viruses that infect bacteria, see inset). No, we aren't really evil as the title of this blog suggests. We just think that biological phenomena is best explained by evolutionary theory, and if evolutionary theory contradicts long cherished beliefs formulated in ancient societies, so be it. Personally I think there is much wisdom in the ancient beliefs, but we can't expect all these beliefs to be correct, or even relevant, today. The only constant is change, and we, as a species, must continually adapt. Science is the only belief system that truly adapts to changing circumstances.

I'm going to post thoughts about things that excite me. These may naturally be as random and idiosyncratic as my interests at present, but generally speaking, I'm interested in evolutionary biology, molecular biology, genetics, ecology and parasites, particularly bacteriophages. Once a week I will post on a Citation Classic i.e. science papers that, for me, best epitomize the aesthetics of science. Contrary to common belief, science is an art, and some art is more beautiful than others. These papers mainly will fall among my major interests.