Friday, December 21, 2007

Not so Studly?

In an interesting article available in Biology Letters; Alastair J. Wilson and Andrew Rambaut apply evilutionary biology to the question of whether race horse studs are worth the money. Racehorses from prized bloodlines can command stud fees upwards of hundreds of thousands of dollars, but according to Wilson and Rambaut, stud fee is a poor predictor of offspring performance.

Using techniques developed in evilutionary biology to answer questions regarding sexual selection and quantitative genetics, Wilson and Rambaut, "test whether there is genetic variation for success on the racecourse by analysing data on lifetime prize money earnings [and] ask whether stud fees are a useful indicator of a stallion’s genetic quality and hence its offspring’s prize-winning potential."

Unfortunately for breeders, parentage only accounts for 10% of the variation in lifetime earnings.

Dr. Wilson says, "The offspring of expensive stallions might tend to win more money, but not necessarily because they have inherited the best genes.

"It is likely that those breeders best able to pay high stud fees are also those who are able to spend more on care of the horse, how it is trained, and who rides it -- all of which will contribute more to how much it will win.''

Of course, given the competitiveness of horse racing, this probably will not deter studs from commanding high fees because people with money will spend it for any advantage no matter how small.

Photo: Secretariat winning the Preakness.

Monday, December 17, 2007

This Week's Citation Classic

I am a little late with the post, but there's been a perfect storm of conflicting obligations. Without further ado, here is this week's citation classic:

Lenski, R. E., M. R. Rose, S. C. Simpson, and S. C. Tadler. 1991. Long-term experimental evolution in Escherichia coli. I. Adaptation and divergence during 2,000 generations. American Naturalist138:1315-1341.

The field of experimental evolution is a surging one; many scientists have seen that they can observe the process of evolution in real time using microbes and other model organisms. Jacques Monod's aphorism, "anything that is true of E. coli must be true of elephants, except more so", can be extended to say that evolutionary processes are the same for E. coli as they are for elephants.

Lenski et al. recognised this and initiated one of the longest experiments in evolutionary biology history. At the time of publication, 12 populations initiated from a single E. coli ancestral strain had undergone 2,000 generations of evolution and adaptation. ~20 years later, the group is up to 40,000+ generations. The initial environment was a poor one, a restricted diet of glucose, but the beasties have responded to this challenge vigorously, and because Lenski and team have saved individuals from various times during the experiment, the process of adaptive evolution can be traced via this "frozen fossil record".

Lenski et al.'s experiments have proved to be enormously informative, have generated 40+ publications and have launched the careers of numberous graduate students and postdocs. Indeed an entire Gordon Conference is devoted to the subspecialty, Microbial Population Biology, and a substantial number of attendees are Lenski's intellectual descendants.

On a personal note, when I was in graduate school, my mentor suggested that I model my career after a successful scientist. "Who?", I asked. "How about Rich Lenski?" I then downloaded all of Lenski's papers and read, for the first time, about the fascinating series of experiments that began with the present classic. Inspired, I soon dropped my researches into the population biology of mosquitoes (well I was looking for justification to do so anyway ;) and dived into the field of experimental evolution. When it came time to seek out postdoctoral mentors, I queried Dr. Lenski, but unfortunately his lab lacked funding for a postdoc. He did, however, suggest his former grad student, Dr. Paul Turner, whom I began working for in 2003. And the rest is history...

Carl Zimmer wrote about the experiments for the Science Times here. Another interesting article is available from Science. A website dedicated the the long-term evolution experiment is available here. And Rich Lenski's lab page is here.

Photo of Rich Lenski courtesy of Bruce Fox, MSU.

Monday, December 10, 2007

Nobel Week

Nobel Week is coming to a close. This year's highlight was Al Gore's Nobel Lecture on the dangers of global climate change. Gore says, "We are what is wrong, and we must make it right."

Gore states unequivocally that CO2 is pollution, and the consequences of its accumulation are devastating.

"Last September 21, as the Northern Hemisphere tilted away from the sun, scientists reported with unprecedented distress that the North Polar ice cap is "falling off a cliff." One study estimated that it could be completely gone during summer in less than 22 years. Another new study, to be presented by U.S. Navy researchers later this week, warns it could happen in as little as 7 years.

Seven years from now.

In the last few months, it has been harder and harder to misinterpret the signs that our world is spinning out of kilter. Major cities in North and South America, Asia and Australia are nearly out of water due to massive droughts and melting glaciers. Desperate farmers are losing their livelihoods. Peoples in the frozen Arctic and on low-lying Pacific islands are planning evacuations of places they have long called home. Unprecedented wildfires have forced a half million people from their homes in one country and caused a national emergency that almost brought down the government in another. Climate refugees have migrated into areas already inhabited by people with different cultures, religions, and traditions, increasing the potential for conflict. Stronger storms in the Pacific and Atlantic have threatened whole cities. Millions have been displaced by massive flooding in South Asia, Mexico, and 18 countries in Africa. As temperature extremes have increased, tens of thousands have lost their lives. We are recklessly burning and clearing our forests and driving more and more species into extinction. The very web of life on which we depend is being ripped and frayed."

He singles out, USA and China for action: "But the outcome will be decisively influenced by two nations that are now failing to do enough: the United States and China. [I]t should be absolutely clear that it is the two largest CO2 emitters – most of all, my own country – that will need to make the boldest moves, or stand accountable before history for their failure to act."

Quoting Henrik Isben, Gore says, ""One of these days, the younger generation will come knocking at my door."

They will ask either, ""What were you thinking; why didn't you act? "Or they will ask instead: "How did you find the moral courage to rise and successfully resolve a crisis that so many said was impossible to solve?"

When the next generation knocks on your door, what are you going to say?

The full text is available here.

Photo: Scanpix/Tom Hevezi

Venter Interview in SD Union Tribune

There's an interesting interview with Craig Venter in the San Diego Union Tribune. In the interview, the sequencing maven reflects on being a scientist. There's a lot of things about Venter that I didn't know, such as his having served as a medic in Vietnam.

Venter writes, "I was feeling lucky, that I had escaped with my life. I had seen so much death, 19-and 20-year-old boys maimed and killed, that I felt I had been given a second chance to do something with my life."

Perhaps this is why he has little patience for roadblocks and is often described as a "maverick".

Venter is, of course, one of two humans to have their entire genome sequenced (Jim Watson is the other). Celera Genomic's race with the National Human Genome Research Institute is the stuff of legend. Venter's company sequenced the genome for far less money than the government, and accomplished it in approximately the same amount of time.

However, Venter seems disappointed with the progress made since the human genome was published.

"I think it's because we're dealing with humans, and that paralyzes things. The government, which has the deepest resources, is increasingly unwilling to fund research if it involves human genetics. Government research is becoming irrelevant. Instead, the work is being left to private groups who have less money and maybe conflicting agendas."

Venter also expressed disappointment with the state of science in America when questioned about the anti-evolution stances of some presidential candidates (Brownback, Huckabee, Tancredo) and reports of another (Kucinich) to have seen a UFO.

"I saw those debates. It's a disturbing phenomenon. People simply aren't making decisions based on evidence. I don't object to people believing in God, but our thinking has to adjust to new facts and discoveries about the universe. We're past the age of Galileo. As a modern society, we are now 100 percent dependent upon science. It's not optional."

It's a sobering interview. Venter sees that "We're at a critical juncture in human existence. I just hope we haven't screwed things up so much that there's no real chance for the future."

I agree. The evidence is out there. Do we have the courage to take off the blinders and see the world as it really is?

Hat tip to Moselio Schaechter.

Friday, December 7, 2007

This Week's Citation Classic

Brenner S. 1974. The genetics of Caenorhabditis elegans. Genetics 77: 71-94.

Sidney Brenner is one of the founding fathers of molecular biology, having identified mRNA and the nature of the triplet code. Brenner, like other far-sighted scientists, felt that mo-bio was pretty played out by the late '60s and early '70s. Benzer switched to fruit fly behavior. Crick decided to study consciousness. Brenner decided to focus on behavior and development. In his Nobel speech, Brenner stated, "choosing the right organism for one’s research is as important as finding the right problems to work on."

Brenner certainly benefited from bacteriophage, the organism of choice for many molecular biologists, but he was drawn in that direction by Delbruck and the Phage Group. This time, now a mature scientist in his own right, Brenner had a chance to select an organism of his own. He chose wisely: Caenorhbabditis elegans. C. elegans is an ~1mm long bacteriophagous soil nematode. Large populations can be maintained in the laboratory on bacteria cultured on agar, and they have the added advantage of being almost entirely transparent (a huge benefit for neuronal studies).

Brenner's classic 1974 paper asked “How genes might specify the complex structures found in higher organisms?", a major problem in biology today as well as then. Brenner's approach was to link genetics with detailed studies at the cellular level, and introduced C. elegans as the worm of choice for this work.

As Brenner wrote, “Behaviour is the result of a complex ill-understood set of computations performed by nervous systems and it seems essential to decompose the question into two: one concerned with the question of the genetic specification of nervous systems and the other with the way nervous systems work to produce behaviour.”

Thus Brenner launched a two-pronged effort to map the genetics and complete structure of the worm. This effort succeeded marvelously. Today we have unprecedented knowledge of this humble beastie. The developmental fate of each of the worm's 959 cells has been determined. The patterns of connectivity for each of its 302 neurons has been completely mapped. Its entire genome has been sequenced (the first multicellular eukaryote to be sequenced).

Brenner's choice of study organism was enormously influential. I don't think there are many full-fledged biology departments around the country that don't have at least one "worm person". Brenner has produced an amazing legacy.

Some last thoughts...
I am still, at the age of 76, excited by scientific research and the prospect of what can be done in biology. Science is something one is tied to for life and one should never retire from anything until one has secured one's next job. The endless quest for knowledge will continue as long as humans exist.

Brenner won the Nobel Prize in 2002 for his contributions; his speech was wonderful and can be accessed here (video and text). Brenner wrote an autobiography here. Visit the Brenner lab here. The Worm Nation maintains a web presence here.

Image: C. elegans neurons expressing green fluorescent protein.

Wednesday, December 5, 2007

Book Review: The Body Has a Mind of Its Own

Body maps are areas of the brain that represent all areas of your body inside and out. Most of us recall the goofy pictures of homunculi, the distorted figures that represent the relative space our body parts occupy in the somatosensory cortex. Because sensory schemata of the hands and face occupy relatively large areas of our cortex, they are overrepresented in the physical map.

In The Body Has a Mind of Its Own mother-son science writing team Sandra and Matthew Blakeslee write about these and other body maps as revealed by cutting edge neuroscience. My first impression on reading was that neuroscience and, by extension, the authors were overselling body maps and their implications. But after reading a few chapters, I was impressed.
While the authors freely admit, "certain details and caveats that a specialist would consider vital have been condensed, glossed over, or shoehorned into metaphors", their ability to summarize the complex and confusing field of neuroscience is admirable. Granted much of the information is highly speculative, but as an introduction to the field of body maps, I found the book highly informative and entertaining. The take home message is that body maps and the brain are far more plastic than most of us are aware of.

Some of the best topics include:

Can sports players improve their "games" by mental means alone?
How do body maps figure into eating disorders?
What causes phantom limbs?
Can you fool your body into regaining body areas lost to strokes?
What are the "yips"?
Why do video game players move their bodies to the action on the screen?
What happens when you have an "out of body" experience?
Can inanimate objects become part of your "body"?

The book contains many interesting anecdotes, such as:

“Carter” was a master chef at a well-known New York restaurant when, in late 1994, a blood clot in his brain almost cost him his livelihood. Rushed to the hospital in time to receive state-of-the-art clot dissolving care, Carter was left with a potentially devastating problem: He could no longer recognize fruits and vegetables. He couldn’t tell a banana from a leek, though he could still tell a bread knife from a butcher knife and a hawk from a handsaw. He could use English fluently, and his senses were all intact. He had no discernible problems naming or thinking about any other categories of object—just fruits and veggies.

It sounds like a career killer for a chef, but Carter managed to get by. You see, his brain's network body maps still knew what to do with each item. There was nothing wrong with the body maps containing his visual-motor templates for how to manipulate objects. And there was nothing wrong with the body maps that storehoused his library of well-practiced motor sequences involved in food prep. He could still peel a carrot, slice a tomato, or dice an onion—but first he had to be told what each thing was. He would simply query the kitchen staff: “Hey, Jane, is this a cucumber?

"Yeah? Thanks.” Chop chop chop.

On the whole, this book is an excellent introduction to a complex and important topic of science. The prose is lively and easy to read, and once I got going, I was able to finish it in a matter of days. The book is intended for a wide audience, and other than the occasional jargony neuroanatomy term, it is accessible to anyone with a high school education. The only notable failure of this book is to make clearer distinctions on the science that is well-established and the science that is pure speculation. I'm no specialist, yet I would have liked to have seen more pointers to primary sources; an appendix containing citations and/or pointers for further reading would have been highly appropriate and useful.

Clay model on display at the Natural History Museum in London.

Saturday, December 1, 2007

This Week's Citation Classic

This week's citation classic honors Seymour Benzer who passed away yesterday.

Benzer S. 1955. Fine structure of a genetic region in bacteriophage. PNAS 41(6):344-54.

Benzer began his career as a physicist, but was inspired to switch to molecular biology by Schrodinger's book What is Life and by Max Delbruck. He took a leave of absence from his position at Purdue to pursue research on the structure of the gene, and he never looked back. Biology, bacteriophages in particular, captivated him.

In his classic 1955 PNAS paper, Benzer used the bacteriophage T4 to map the r gene.

Benzer describes his experiments:

I plated some of these r mutants on two different strains of E. coli bacteria. And I had two different strains of K-12 phage, one that was lysogenic and had Lwoff’s lambda phage in it, and one that didn’t. What happened first was that when I plated these r mutants on the plain K-12 strain, instead of making the big plaques they made the little plaques. So they were showing lysis inhibition on that strain. Then, when I plated them on the strain that had the lambda, I got zero plaques. And having been alerted by reading Pontecorvo’s article, I immediately, really instantly, realized…. Well, at first I thought I made a mistake. I thought I had forgot to put the phage on there. Dummkopf, do it again! I did it again and saw the same phenomenon.

Benzer's key insight was that he had stumbled upon a system where he could do genetic mapping by using recombination between r mutants to map the r gene much in the way that Alfred Sturtevant used recombination to map Drosophila. The trouble with using recombination to map genes is that the closer two genes are together, the less likely they will recombine. Thus mapping a single gene was thought to be impossible.

But not so for phage. So many offspring (~100 million) are produced that the odds are that recombination can occur even among two adjacent nucleotides.

Benzer describes the moment:

So I immediately realized—a eureka moment, and they’re all too rare—that this was a system in which I could do very fine genetic mapping. I could take two r mutants, cross them with each other, and take the progeny and put them on this K-12 lambda strain. The r mutants themselves would produce no plaque, but if in any of the progeny there was a crossing-over between these two different mutations, such as to produce a wild-type recombinant that had neither mutation, that would produce a plaque. And that you could put 100 million plaques on one plate. So a quick calculation told me that that was enough, knowing the number of nucleotides in the DNA of the bacteriophage. This was about 1954 or ’55—after the Watson-Crick discovery. So, based on the number of nucleotides in the DNA and the phage, I would have enough resolving power to separate the rII mutations, even if they were just one nucleotide apart.

When r mutants are plated on lysogenic K-12 E. coli, only those that have undergone recombination within the r gene to form wild-type phage will form plaques. The number of plaques on the bacterial lawn indicates how far apart the two nucleotide mutations were on the gene. Thus, Benzer had the tool of exceptionally high resolution; he could to map the r gene down to the nucleotide.

Benzer's results showed conclusively that genes were not indivisible as commonly thought.

Benzer later went on to dissect the nervous system of Drosophila in a third highly productive career.

Even at 86 years of age, Benzer still ran a laboratory at CalTech. A very entertaining oral history interview series with Benzer is available here. Benzer's CV should give us all pause; he was a tremendously accomplished man.

Updates: Larry Moran points out this paper: Adventures in the rII Region and other tributes to Benzer in the blogosphere.

Thursday, November 29, 2007

Way Cool Post

Frequent readers may know that a prominent sub-theme of this blog is the relationship between science and art, a subject of considerable interest to myself. Scientist/Artist Jessica Palmer at Bioephemera has an excellent post on the subject.

Although the article is mostly about whether art can inform science, I found it jarring at some points because my view of art and science is so conflated, namely that science IS art (note this doesn't make the reverse also true). I don't know if Jessica would agree with me on that point, I was struck by this sentence from her post:

"Even in the simplest botanical print, or inventory of a wonder cabinet, the artist always “frames” the science - it can’t be helped! Choice of medium, choice of angle, choice of context - all of these are choices. The line between representation and story-telling is very fuzzy indeed...."

Now substitute scientist for artist. Science, then, is a way of constructing a world-view from our experiences. This does not imply that science is making stuff up and passing it off as "truth". In fact quite the opposite; fiction is abhorrent in science as, I would argue, it is in art. Look at the following depiction of three molecules. Which one looks "real" to you?
My gut reaction on looking at the picture (before reading the text) was that there was something wrong with the one on the right. The one on the left was better, but there was still something weird about it. The middle one looked "right". As it turns out, "#3, the DNA cube, is a fictitious structure - but a real (though synthetic) molecule; #1, a nanotube synthase, is the one that’s entirely made up. #2, the rotary motor, is the real structure." Now I am totally not a structural biologist and I spend very little time looking at molecular structures. Why then did the middle one just "feel" right to me? I have no clue.

But I suspect that it's because science is art and beauty is our guide. "Beauty is truth, truth beauty", right?

Queen of Decay
watercolor on paper
Jessica Palmer 2005

Wednesday, November 28, 2007

Bug Art

This week's issue of Nature has an interesting review of an exhibition, The Art of Arthopods. California entomologist Steven Kutcher uses insects as living paintbrushes to generate his "paintings". Read more about it here.

Kutcher's bug art is on display at the Entomological Society of America meeting in San Diego (9–12 December) and at the Lancaster Museum (15 December–13 January 2008), in California.

Incidentally I used to have a couple of Madagascan hissing cockroaches (above), but I failed to think of using them to create art work.

Tuesday, November 27, 2007

Quorum Sensing or Diffusion Sensing?

I'd like to call attention to an interesting couple of posts at one of my favorite science blogs, RRResearch. I find them interesting because they highlight two opposing views of the function of small signaling molecules (autoinducers). One view (Quorum Sensing) suggests that microbes secrete these molecules in order to estimate population density and predict the utility of investing in secreting molecules that can be used by the whole population. In this view, secreting shared molecules is an inherently cooperative behavior, and as such is exploitable by cheating.

Rosie Redfield has suggested an alternative explanation: diffusion sensing. Her paper in Trends in Microbiology hypothesized that "bacteria instead secrete and detect autoinducers as a method of determining whether the benefits of secreting more expensive effector molecules will limited by diffusion and mixing." This is an inherently selfish behavior because "it would be a waste of resources to secrete degradative enzymes such as proteases if they are going to immediately wash away."

The whole issue hearkens back to George Williams classic, Adaptation and Natural Selection. If that book is to be summarized in one sentence, it might be "Thou Shalt Not Invoke Group Level Adaptations When Individual Level Adaptations Will Suffice!" That is, don't claim an adaptation benefits a group of organisms when plausible explanations invoking benefits to individuals are available. By this rule, quorum sensing might be a valid explanation for autoinducer secretion, but only after diffusion sensing explanations are ruled out.

I share Rosies' frustrations. Every time someone tells me about this wonderful new experiment showing that bacteria cooperate (which, in some cases, they no doubt do), I always groan and ask if they read Rosie's paper. Invariably they haven't.

The series of posts is interesting in another light. It shows the process of science in action, which is usually an opaque process to most people. Here we have two opposing "schools of thought" arguing about the proper way to interpret ambiguous data. In the long run, it will be the hypothesis that best explains the data that "wins". In this case, the debate plays out in the blogosphere and not behind the august pages of Nature (available by subscription only).

Update: I missed this earlier, but Ford Denison of This Week in Evolution wrote a nice post about the original Diggle et al. Nature paper here.

Photo: Vibrio fischeri growth on Petri dishes after incubation in nano CuO suspension. V. fischeri is a putative case of quorum sensing. Photo from KBFI.

Thursday, November 22, 2007

This Week's Citation Classic

Olsen MW & Mardsen SJ. 1954. Natural parthenogenesis in turkey eggs. SCIENCE 120 (3118): 545-546.

Almost all vertebrates reproduce sexually, i.e. the sperm and egg join to form an embryo. Vertebrates that reproduce asexually are exceptionally rare, however turkeys are one such species that can do so. Many explanations are given as to why turkeys reproduce asexually on occasion (as high as 40% of offspring are products of parthenogenesis): low sperm count, male unavailability etc. I'll offer one of my own. Female turkeys see males (photo above) and think, "No way in hell am I having sex with that!"

Here is a quote from the Ohio State University 4H site:

Dr. M. W. Olsen working for the United States Department of Agriculture extensively studied the development of parthenogenesis in turkeys. He worked with a small variety of turkeys called Beltsville Small Whites. He found that the onset of parthenogenetic development in turkeys takes place three or four hours prior to ovulation or soon after ovulation of the ovarian follicle from the ovary. In Dr. Olsen’s early studies, the parthenogenetic development in eggs from nonmated hens would only proceed though the development of membranes and early blood formation by the embryo. He bred a strain of Beltsville Small Whites for a higher incidence of parthenogenesis in unfertilized eggs. As selection continued, the incidence of the condition increased and parthenogenic development proceeded to more advanced stages until an embryo that developed parthenogenetically from an unfertilized egg. The first poult that hatched by this method was moved, for safe keeping, from the research farm to Dr. Olsen’s basement. Unfortunately, his dog killed the turkey.

Whoops!

Happy Thanksgiving!!!

Saturday, November 17, 2007

Rivers and Tides

I just finished watching Rivers and Tides, a film about Andy Goldsworthy, one of my favorite artists. Goldsworthy creates ephemeral art sculptures from materials found in nature. The film is amazing. Here is a clip.

More images are available from the Andy Goldsworthy Digital Catalog, the Met, Morning Earth and WebShots.

Time interviewed Goldsworthy earlier this year.

This Week's Citation Classic

Volkin E & Astrachan L. 1956. Phosphorus incorporation in Escherichia coli ribonucleic acid after infection with bacteriophage T2. Virology 2 (2): 149-161.

After the discovery of DNA structure by Watson and Crick, the way seemed paved to a quick resolution of how proteins were made. Unfortunately, both theory and experiment quickly stalled at an impasse. Data from several labs was extremely difficult to interpret, namely findings that 1) for several bacterial species, DNA bases varied widely, but the cytoplasmic RNA did not (Belozersky & Spirin 1958) and 2) the cytoplasmic RNA was exceptionally stable (Davern & Meselson 1960). These findings seemed to suggest it was impossible for RNA to be a template for protein synthesis.

The problem was that this cytoplasmic RNA was not what later came to be known as messenger RNA (mRNA), but rather a relatively "inert" form of RNA associated with ribosomes (i.e. rRNA)(Note: rRNA is now thought to carry out key reactions during translation).

On Good Friday 1960, Sidney Brenner, Francis Crick and Francois Jacob were hanging out at Brenner's rooms at King's College when they put together some anomalous data and created a theory to explain protein synthesis. These data were 1) Hershey et al.'s (1953) discovery of a small fraction of RNA that was synthesized rapidly just after phage infection, 2) Pardee et al.'s observation of extremely rapid enzyme synthesis following mating between two bacterial types and 3) a report from two relative unknowns, Eliot Volkin and Lazarus Astrachan, from Oak Ridge National Laboratory.

Volkin and Astrachan infected E. coli with phage, then exposed the culture to radioactive 32P for a few minutes. What they found was a "DNA-like RNA" that did not resemble the previously found RNAs (i.e. rRNA and tRNA) and turned over very rapidly. The main difference was that it had similar bases to the DNA of phage.


f DNA labelled f RNA E. coli DNA E. coli RNA
A 32 33 25 26
U or T 32 29 25 19
C 18 20 25 25
G 17 18 25 19

What Volkin and Astrachan did not realize is that they discovered the key to solving the protein synthesis mystery.

Crick describes the Good Friday Meeting in What Mad Pursuit, "What the PaJaMo [i.e. Pardee et al. 1959] type of experiment showed was that the ribosomal RNA could not be the message.... Where, then, is the message? At this point Sydney Brenner let out a loud yelp -- he had seen the answer. (So had I, for that matter, though nobody else had). One of the peripheral problems of this confused subject had been a minor species of RNA [found by Volkin and Astrachan] that occurred in E. coli ... [Volkin and Astrachan's] result had hung in midair, surprising but unexplained.... What Sydney had seen was that the Volkin-Astrachan RNA was the messenger RNA for the phage-infected cell... It is difficult to convey two things. One is the sudden flash of enlightenment when the idea was first glimpsed. It was so memorable that I can recall just where Sydney, Fran├žois, and I were sitting in the room when it happened. The other is the way it cleared away so many of our difficulties. Just a single wrong assumption (that the ribosomal RNA was the messenger RNA) had competely messed up our thinking, so that it appeared as if we were wandering in a dense fog."

Paul Berg, winner of the 1980 Nobel Prize in Chemistry, calls Volkin and Astrachan's research an "unsung but momentous discovery of a fundamental mechanism in genetic chemistry" and a "seminal discovery [that] has never received its proper due."

What happened? Everybody knew of Volkin and Astrachan's findings at the time. In an interview at his Oak Ridge home in late 2003, Volkin recalled his conversation with Sydney Brenner at Cold Spring Harbor Laboratory in New York, where Volkin conducted research on the hot topic of bacterial viruses during the summers in the late 1950s. "I can well remember sitting on the lawn at Cold Spring Harbor and telling Sydney Brenner about our experiments," Volkin says. "I gave a presentation on our RNA research to the group there." In a 1977 issue of Nature, renowned biophysicist T. H. Jukes wrote that in 1956, "I had squeezed my way into a doorway of a packed room to hear a paper by Volkin and Astrachan on DNA-like RNA." (ORNL).

The problem was that Volkin and Astrachan's data was self-admittedly "sloppy", Volkin and Astrachan weren't well known, ORNL wasn't highly regarded and the data simply did not fit with the dominant paradigm at the time. Brenner, Crick and Jacob ended up getting recognized with "discovering" mRNA, while Volkin and Astrachan were never properly credited. Many scientists felt Volkin and Astrachan deserved Nobel recognition.

Belozersky AN & Spirin AS. 1958. A correlation between the compositions of the deoxyribonucleic and ribonucleic acids. Nature 182: 11–112.

Hershey AD, Dixon J & Chase M. 1953.Nucleic acid economy in bacteria infected with bacteriophage T2 .1. Purine and pyrimidine composition. Journal of General Physiology 36 (6): 777-789.

Davern CI & Meselson M. 1960. Molecular conservation of ribonucleic acid during bacterial growth. Journal of Molecular Biology 2: 153.

Pardee AB, Jacob F & Monod J. 1959. Genetic control and cytoplasmic expression of inducibility in the synthesis of Beta-galactosidase by E. coli. Journal of Molecular Biology 1 (2): 165-178.

Photo: One of the early RNA electron micrographs scanned with the vidicon/RTPP system (Jacob Maizel, Bruce Shapiro, and Lewis Lipkin). The sample was adenovirus type 2 messenger RNA. Bruce developed boundary segmenters and boundary shape descriptors that could map electron micrograph data to the secondary structure.

Friday, November 16, 2007

Welcome Gastrolith

Christopher Boynton was recently accepted at Columbia AND started a cool new blog, Gastrolith.

Congrats and Welcome, Chris!

Thursday, November 15, 2007

First Direct Evidence of Flying Spaghetti Monster!

A recent report found first fossilized evidence of the Flying Spaghetti Monster.

The resemblance is uncanny!
Ha! Just kidding, this is a report of exceptionally well preserved jellyfish from the Middle Cambrian i.e. ~505 mya. This finding sets the origins of jellyfish back ~200 mya. Previously fossilized jellyfish were found in Pennsylvanian shale ~320 mya. This is an exceptional find because the fossils are so pretty and jellyfish are, of course, soft bodied, thus difficult to find preserved.

Tuesday, November 13, 2007

Star-nosed Moles

I mentioned Star-nosed moles in a previous post. The illustration doesn't really do it justice. I suppose the illustrator toned down the drawing because, in RL, its just too freaky. Nobody would believe him.

Here's a nice post on Star-nosed moles.

Addenum: Ed Yong pointed out this post. Holy crap! That's awesome! Moles rock!

Sunday, November 11, 2007

Evilution sucks...


Heh.. this gave me a chuckle.

Comic by Rosemary Mosco of Bird and Moon.

Saturday, November 10, 2007

This Week's Citation Classic

Haig D. 1993. Genetic Conflicts in Human Pregnancy. The Quarterly Review of Biology, 68 (4): 495-532.

I suppose most people think the bond between a mother and her child is the strongest among all human relations. In a Darwinian sense, this is generally true; mothers and their offspring share ~50% of their genes. Moreover, unlike father-offspring relationships, mothers can be absolutely certain of the relatedness between themselves and their children by virtue of giving birth.

Perhaps this is why the internecine warfare that occurs between the mother and the fetus during pregnancy is so shocking.

The existence of parent-offspring conflicts was first popularized by Robert Trivers in the early 1970s. However the examples proffered of parent-offspring conflicts were animals such as caribou, baboons and macaques. The connection to humans was rarely made explicit.

David Haig changed this. He pointed out that the interests of the fetus differed from that of the mother. The offspring can best increase its evolutionary fitness by taking all it can get from the mother because it values itself (100% relatedness) over that of potential future sibs (50% relatedness). The mother on the other hand can best increase her fitness by spreading her reproductive resources over several offspring.

Some medical implications of the mother offspring conflict include:

Gestational diabetes--the mother loses control of her blood sugar levels to the offspring. As wiki notes, this can lead to a "large baby" or macrosomia.

Pre-eclampsia--the fetus induces high blood pressure in the mother in order to access more resources.

Beckwith-Wiedemann syndrome--fetus overgrowth syndrome

I previously wrote about Mother-Offspring Conflict here.

Carl Zimmer has a great article here.

"Mother & Child" by Gustav Klimt (1862-1918).

Friday, November 9, 2007

Blog Readability Test

Uh, I guess regular readers should be proud... but maybe I should make an effort to broaden my audience.

Level of education required to understand this blog: Genius

Find out what your blog's readability level is here.

I'd be interested in finding out what level of education readers have!

Hat tip: Larry and Bora

Wednesday, November 7, 2007

Get Ready for Judgement Day!

PBS is airing at two hour special on 2005's Kitzmiller v. Dover Area School District trial, otherwise known as Scopes II. Science won a deserved victory when, on December 20, 2005, Judge Jones issued his 139-page findings of fact and decision, ruling that the Dover mandate was unconstitutional, and barring intelligent design from being taught in Pennsylvania's Middle District public school science classrooms.

I, for one, will be TiVo-ing this one.

In defense of Matt Kaplan

Recently I responded negatively to an article in the Economist about research in my former lab. My complaints were, 1. sensationalistic title, 2. oversimplification, 3. sexing up the subject matter, and 4. failure to credit first author. Several respondents convinced me I was being too harsh, so I've retracted the post and apologized to Matt. The problem is that the Economist's Editors, not authors, choose titles, and Editors also have a significant influence on the tone and content of the article. The issues are not really Matt's fault.

The issues I raise are actually part of a dilemma for many science writers: what is an acceptable level of detail in an article? Naturally not all readers can be expected to understand science writing at the level of Science and Nature, but does science writing in the Economist need to be dumbed-down? The editors apparently think so. The sad thing is that they are probably right. Many people have a difficult time understanding even rudimentary science. Take for example the recent experience of the British National Lottery. In their game, Cool Cash, players scratch away a window to reveal a temperature. If that temperature is lower than temperature on the card, the player wins. The problem is that many players could not determine which number was smaller: -7 or -8.

Matt wonders, "if sacrificing some detail [is] acceptable to reach a wider audience? Is it right that editors have total control of titles to popularise complex science? Do they really know better than the journalist?"

My opinion is that there is that, beyond a certain level, sacrificing detail is counter-productive because the science itself is mis-represented, giving the reader a false understanding of science and the state of scientific knowledge. Easy to say, of course, but what is that level. I don't think there are any easy answers. Publishers know that if their readers cannot understand the material, they probably won't buy the work. Ultimately the consumer is responsible for the content because they exercise choice in the marketplace.

I, and Matt, would be very interested in what others have to say.

Photo from the Onion.

Tuesday, November 6, 2007

What would you improve?

Mark Hoofnagle at Denialism has a neat article on what would you improve if you could redesign the human body. I'm fine with an appendix, I'm not female so I don't really care about childbirth, and I'm still fairly young so I am not really concerned with my prostate. However, I would like to upgrade my senses. I'd like eyes like a hawk, ears like an owl, touch like a star-nosed mole, and a nose like bloodhound.

Birds have acute vision, but also can see ultraviolet light. Their world must be especially colorful. How cool is that?

Besides having rather keen hearing, Owls have asymmetrical ear openings permitting it to precisely locate things even in the absence of visual cues. My hearing isn't so great so this would be nice for me.

Star-nosed moles have rather exquisite senses of touch since they are functionally blind.

Bloodhounds have exceptionally sensitive noses. Imagine being able to figure out where your partner is in the grocery store by following their scent? I guess the drawback is that garbage will smell pretty bad...

Presumably it is possible for humans to evolve all these traits given enough time and the proper selective forces. In fact, it is likely that many of our senses have degenerated via relaxed selection over the millennia.

I'd also like to be able to jump higher than four inches, but let's leave that for another time...

Drawing from WikiCommons.

Monday, November 5, 2007

Author Order

EMBO Reports Science and Society section has an interesting note about author position in publications. Wren et al. 2007 note that a prominent publication trend is "author inflation", where the number of authors per paper is growing. This is probably linked to the increase in complexity of biological research and the trend towards greater collaboration across disciplinary boundaries. Naturally everyone wants the coveted first or last author spots, but those are in short supply, so more researchers are listed in the middle author spots. Given that there are, on average, more authors, what happens to those in the middle? Wren et al. report that the perception is that the more authors there are, the less each middle author contributed.

Wren et al. provide some valuable advice for untenured faculty and grad students: if possible, become corresponding author.

"Respondents reduced last-author credit when the corresponding author was the middle author. This suggests that candidates for promotion or tenure would be well advised to highlight publications on which they acted as corresponding author, especially if they were not the last author."

I found this surprising since I thought that nobody paid attention to who was corresponding author. At any rate, I am in favor of clearly delineating contributions in the paper itself, preferably on the first page, but not many journals require this.

Sunday, November 4, 2007

Night on the Town

Friday night a couple of friends and I received an after-hours tour of one of my favorite places in the world, the American Museum of Natural History. It's really nice to tour the museum when there are no screaming kids running around. One of the highlights was a trip to the roof where we had a view much like the one above (I was kicking myself for not bringing my camera). The other highlight was viewing the hominan phylogeny now including the purported newest member, Homo floresiensis in the Hall of Human Origins. Since the first reports of the little man; some have suggested that it is a clear cut case of microcephaly and over-eager anthropologists. There has been a lot of back and forth on this hypothesis, but if in fact the skull is that of a new human species, it doesn't look anything like that of the more recent hominids. Actually you have to go back to Australopithecus before you really see something that looks similar to H. floresiensis. Now wouldn't that be stunning; a new genus of hominids contemporaneous with Homo ~20k years ago!

John Hawks has a superb series of posts on H. floresiensis.

Top photo by ezola.

Thursday, November 1, 2007

This Week's Citation Classic

Readers of this blog may notice that my choices for classic papers come mainly from the evolution, ecology and molecular biology literature. This is not to imply that findings in other fields are less important, but rather that my command of the literature in other fields such as phylogenetics, developmental biology and cellular biology is less apt. However, even a caveman such as myself is familiar with the Homeobox discovery.

McGinnis W, Levine MS, Hafen E, Kuroiwa A, Gehring WJ. 1984. A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes. Nature 308: 428-33.

Homeotic genes determine when, where and how animal body segments develop. In other words, they tell cells in the developing embryo what kind of structures to make, i.e. legs, head, arms etc. Mutations in homeotic genes can result in dramatic changes in animal body plans, such as the antennapedia in the fruit fly that causes legs to develop instead of antennae (see photo). These genes, as the Nobelist Edward B. Lewis discovered, usually are co-linear in space and time with their segments of activity.
Many homeotic genes contain a common motif, a region termed the homeobox. This 180bp sequence encodes a 60 amino acid transcription factor, a protein that switches on and off other genes by binding to the relevant regions of DNA. The awesome thing about the Homeobox is that they are evolutionarily highly conserved, as McGinnis et al. discovered. The homeobox of the fruit fly is nearly identical to that of a wide variety of animals including the mouse and even humans! This is extraordinarily strong proof of common descent. Next time you see a fly, think about how you and she share a very similar stretch of DNA, the Rosetta Stone of life.

The master himself, PZ Meyers, covers Homeobox
here.

Top photo from NIH. Fruit fly head showing the effects of the Antennapedia gene. This fly has legs where its antennae should be. Embryo cartoon from NobelPrize.org.

Sunday, October 28, 2007

Biology and Art

I love reading bioephemera; Jessica always has interesting things to say about biology and art (and her artwork is amazing). I was impressed at the insight in her latest post. It taught me a thing or two about detachment and human nature. Don't take my word for it, get over there and read it.

Jessica Palmer
Bee and Echinacea
watercolor on Strathmore paper
2007

Friday, October 26, 2007

This Week's Citation Classic


Fraenkel-Conrat H. and Williams R.C. (1955). Reconstitution of active tobacco mosaic virus from its inactive protein and nucleic acid components. PNAS USA 41: 690-698.


This week's citation classic is probably the coolest experiment you've never heard of. Fraenkel-Conrat and Williams literally took a virus apart, separated its components, then put it back together again. Granted TMV is a relatively simple virus, consisting of 2130 molecules of coat protein and one molecule of genomic RNA 6390 bases long. Nonetheless, this experiment caused quite a buzz in the scientific world.

Gunther Stent wrote to Sidney Brenner, "Frankel-Conrat seems to have done the biggest thing with TMV since Stanley crystalized it. He can add soluble TMV protein to soluble TMV RNA, aggregate the whole mess into rods of which 0.1% are infective!!! Naturally, you don't believe it--nor did I or anyone else, but unless he has made up the whole thing it seems that it must be true. You can't beat that for laughs, can you buddy?"

It was true.

First Fraenkel-Conrat and Williams treated TMV with a mild acid. This treatment eliminated the charges that held the virus together. Then they separated and purified the protein. In parallel, they treated TMV with a detergent to strip away the protein, and recovered the RNA. After these steps, the viruses were no longer infective. Then they mixed the whole mess together again, and lo and behold! Reconstituted viruses!

The following year, Fraenkel-Conrat hybridized the viruses by mixing protein from one strain with RNA from another. Not only did he get viable viruses, he also was able to show that progeny viruses always had the same type of protein coats as the parent strain that donated the RNA. Thus proof that RNA was the genetic material for these viruses.

Photo of Tobacco Mosaic Virus from NIH.

Wednesday, October 24, 2007

I'm #1 on Google!

From David Ng: I'd like to suggest a meme, where the premise is that you will attempt to find 5 statements, which if you were to type into google (preferably google.com, but we'll take the other country specific ones if need be), you'll find that you are returned with your blog as the number one hit.

Looks like I've cornered the market in all things Evilutionary.
Was I the first to ask "What has phage done for you?"
How is it that I'm not the number one John Dennehy?
Admittedly bacteriophage art is kind of an exotic interest.
Is there anything bacteriophages cannot do? I dunno. You tell me.

Hat tip Larry Moran


Virus Traps

Hmm my virus traps work seems to be generating quite a bit of interest. I originally thought it was kind of a neat idea, but just a special case of a broader research program I've been involved in: bacteriophage growth in environments containing multiple host types.

However the virus trap idea seems to have captured the popular imagination. First, Carl Zimmer wrote about virus traps for the NY Science Times. Then the we the German public broadcaster ARD contacted my former PI about including a segment about virus traps in a series of documentary films about viruses. (No word yet whether they will go thru with it; as the director mentions, it might be difficult to "find a 'visual' way to explain your work"). Finally, Janet Ginsburg wrote about virus traps for New Scientist. (Unfortunately it is not open access so go buy a copy at your newsstand or get 4 issues for $4.95 if you purchase online). Janet promises to write about it for her excellent blog as well. I, for one, am eagerly waiting the article.

In the meantime, I've copied a quote from the article.

"Tackling the issue from a different perspective is ecologist Paul Turner of Yale University. To him, a virus trap is an example of an 'ecological trap' - a habitat that looks fertile but is actually a blind alley. The classic example is mayflies mistaking asphalt for water and laying their eggs on it. In nature, ecological traps can cause local populations to decline, or even die out if they outnumber fertile habitats. Turner wanted to know under what conditions artificial virus traps could do the same, so he created a mini-ecosystem made up of the bacterium Pseudomonas syringae and a virus called phi 6, which preys on it (Ecology Letters, vol 10, p 230).

He chose this system because it is easy to introduce a trap. To attack Pseudomonas, phi 6 first latches onto telescopic appendages called pili, which the bacterium uses to invade plants. When the pili are retracted, the virus is pulled inside. However, there is a mutant 'superpiliated' strain of Pseudomonas which has more pili than normal but cannot retract them, meaning phi 6 can bind to but cannot enter and infect the bacterium. This is the strain used to trap would-be invaders.

To test its effectiveness, Turner prepared test tubes of the bacterium with varying levels of trap, then introduced the virus. 'We set up a game playing by the simplest rules possible,' he explains. He judged success or failure by viral survival and growth rates. If the trap works, virus levels should decline - which is exactly what happened. A 50:50 mix of traps and normal bacteria vanquished phi 6 completely.

Turner's team is now looking to turn experiment into therapy, removing red blood cells and adding decoy attachment sites for viruses. Their focus right now is HIV. 'All of our drugs against HIV are effective because they keep immune cell counts up,' says Turner. 'That's a very expensive venture that a lot of people can't afford. If you could find a way to protect those cells through a sheer onslaught of traps, that might be another way to achieve the same thing.'"

Photo of HIV budding from a CD4 cell from NIH.

Monday, October 22, 2007

Aging in Bacteria

Previously I posted on aging in bacteria. One question I posed was "is, given an initial population that supposedly contains both old and young cells, are the differences in growth rate between cells sufficient to produce large differences in microcolony sizes when microcolonies are initiated on agar?" If true, this finding would have considerable bearing on the biology of an organism I am interested, the bacteriophage. Eric Stewart, author of the original manuscript I wrote about, responded to my question. Turns out there is not much reason to expect large differences in microcolony size due to cell age. However, other factors, such as whether the cell recently divided or not, could affect microcolony size. Here is what Dr. Stewart had to say:

I did not record the size variation of the microcolonies, but even a two-fold difference is completely expected, based on the fact that some cells should arrive on the agar just after division, and some just before (a two-fold difference in starting biomass). Elio noted little variance in his colony sizes, and you wondered if old and new cells were different enough in growth rate to cause visible size differences in microcolonies. In fact, the very mechanism of how cells age (and rejuvenate) makes this almost impossible. Even a very old cell, as long as it can divide once, will produce one young cell in addition to its even older self. That young cell will have a nearly maximal growth rate, and should divide again relatively quickly, producing one more young cell, in addition to its now slightly older self. This means that as long as one division occurs, the colony is once again quickly populated with young cells, and eventually, at large enough population sizes, the entire 'standard' distribution of ages is recapitulated in every colony.

While the explanation above reduces the microcolony size difference due to
the age of the starting cell, there are other factors at play as well. First, the difference in growth rates is something like 2% per old pole cell division, so if the cells are not extremely different in age, it will be very hard to detect, given the already two-fold variation in microcolony size due to the cell cycle timing of the first cell. Second, old cells are exponentially decreasing in frequency, by the very nature of the division that produces them. Young (first division) cells make up half of any E. coli population, due to the fact that one is produced in every division. The exact same process means that one half of the population is at least one division old, one quarter is at least two divisions old, 1/8th is at least three divisions old, etc. This means that in order to find one arbitrarily old cell, you must examine 2^X cells, where X is the division age you are seeking. As this doubles with each additional division, you can see that truly huge numbers must be examined to find really old cells. For example, examining about one thousand colonies will, on average, reveal one that arose from a ten division old cell; this would then need to be detected in the distribution of nine, eight, seven, etc. division old cells, taking into account the fact that the very first division produces a young cell, as noted above. Finally, there is a large amount of noise; that 2% difference is an average of very many cells. The distribution is quite
large.

For those reasons, it is quite difficult to detect senescence in bacteria.
We accomplished it by examining very large numbers of cells, and measuring their actual individual growth rates (exponential fit to the increase in length over time). It was the automation that allowed us to achieve this; others had come very close in the past, but were limited by the need to measure and record all of the data by hand e.g. Powell EO and Errington FP. 1963. Generation times of individual bacteria: Some corroborative measurements. J Gen Microbiol 31: 315–327.

Dr. Stewart also responded to questions regarding the number of cells dying during the course of the experiments.

Elio Schaechter wrote that he spread Salmonella cells on nutrient agar on a slide, and counted how many didn't form colonies. This type of experiment was also performed by others (e.g. Gallant, J., and Palmer, L. (1979) Error propagation in viable cells. Mech. Ageing Dev. 10: 27-38), as well as repeated by myself before the timelapse experiments in the paper. Counting 17,000 microcolonies, I found a 'failure to grow' rate of about 1 in 400 for E. coli, which agreed with the Gallant and Palmer results as well. I suspect that there may be a 'plating shock' that results in such relatively high levels of non-growth, compared with the different measurement of non-growth during timelapse, which came out at about 1 in 2000. Therefore, this rate probably doesn't indicate much about senescence, but some other cause of 'death' (non-growth).

So there you have it. Cells age. But you have to check quite a few cells before you notice much of an effect.

Photo of Bacillius subtilis by Dr. Leendert Hamoen, Institute for Cell and Molecular Biosciences, University of Newcastle upon Tyne.