Land Snails and Slugs

 
Most of us don't know very much about slugs and land snails but Christopher Taylor at Catalogue of Organisms is doing his best to educate us (and himself): Wild Slug Chases (Taxon of the Week: Gastrodontoidea).

I need to warn you that his posting isn't suitable for all audiences. Some of these animals are capable of having sex with themselves and that's not something you want your children to know. Also, some of these animals aren't as pretty as warm fuzzy animals like cats. I find it helps to think of snails and slugs as dinner rather than pets.¹

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1. For some people, this works for cats too.

Monday's Molecule #132

 
This is a very famous molecular complex. You need to identify this complex by naming all the major components. You will not win if you skip this part. (Don't forget the red bit.)

There is a Nobel Prize associated with the discover of this complex although the work was done long before the structure was solved. The first person to identify the molecules and the Nobel Laureate(s), wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are only five ineligible candidates for this week's reward: Dima Klenchin of the University of Wisconsin at Madison, Dara Gilbert of the University of Waterloo, Anne Johnson of Ryerson University, Cody Cobb, soon to be a graduate student at Rutgers University in New Jersey, and Alex Ling of the University of Toronto.

I have an extra free lunch for a deserving undergraduate so I'm going to continue to award an additional prize to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule(s) and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow.

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

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The figure is from Reinherz et al. (1999).

Reinherz, E.L., Tan, K., Tang, L., Kern, P., Liu, J., Xiong, Y., Hussey, R.E., Smolyar, A., Hare, B., Zhang, R., Joachimiak, A., Chang, H.C., Wagner, G., and Wang, J. (1999) Science 286:1913-1921. [PubMed] [doi: 10.1126/science.286.5446.1913]

Breakthrough!! The Third Replicator Is Discovered

 
The editors at New Scientist have become completely incapable of distinguishing between science and things that pretend to be science. The latest evidence of this failing is an article by Susan Blackmore titled: Evolution's third replicator: Genes, memes, and now what?.

WE HUMANS have let loose something extraordinary on our planet - a third replicator - the consequences of which are unpredictable and possibly dangerous.

What do I mean by "third replicator"? The first replicator was the gene - the basis of biological evolution. The second was memes - the basis of cultural evolution. I believe that what we are now seeing, in a vast technological explosion, is the birth of a third evolutionary process. We are Earth's Pandoran species, yet we are blissfully oblivious to what we have let out of the box.

This might sound apocalyptic, but it is how the world looks when we realise that Darwin's principle of evolution by natural selection need not apply just to biology. Given some kind of copying machinery that makes lots of slightly different copies of the same information, and given that only a few of those copies survive to be copied again, an evolutionary process must occur and design will appear out of destruction.

But all is not lost. One of the benefits arising out of the self-destruction of New Scientist is that it gives us all a chance to watch a train wreck in action.

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[Photo Credit: Train Wreck at Gare Montparnasse, Paris, France, 1895 from Answers.com]

Happy Simcoe Day!!

 

Today is Simcoe Day in Toronto, a holiday named after John Graves Simcoe, the first Lieutenant Governor of Upper Canada (1791-1796).

According to Wikipedia ...

He founded York (now Toronto) and was instrumental in introducing institutions such as the courts, trial by jury, English common law, freehold land tenure, and for abolishing slavery in Upper Canada long before it was abolished in the British Empire as a whole (it had disappeared from Upper Canada by 1810, but was not abolished throughout the Empire until 1834).

The holiday is known by many other names in other parts of Canada including the term "Civic Holiday," a name that brings tears to your eyes.

I think the entire country should name this holiday "Simcoe Day" in honor of John Graves Simcoe, the founder of Toronto, which is, after all, the greatest city in Canada. If Canada were to officially recognize the superiority of Toronto (and Torontonians) it would go a long way toward unifying the country.

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Free Health Care Clinic in a Country that Needs It

 
Remote Area Medical (RAM) is a group of doctors, optometrists, dentists, nurses etc. who donate their time to setting up free temporary clinics in primitive places where the natives don't have access to affordable heath care.

Here's a video of this year's annual clinic in Wise County, Virginia. Isn't it strange that such an event is held in a country with the best health care in the entire world?



I got this from Jennifer Smith at Runesmith's Canadian Content: This was Wendell Potter's Epiphany. Read her blog.

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An Educational Lunch

 
Last week, before leaving for Halifax, I had lunch with David Schuller (a Monday's Molecule winner) and Deb Breiter. They were in town for a meeting of crystallographers.

We talked about biochemistry education (among other things) and it was fun to hear the perspective of someone who teaches introductory biochemistry at a smaller college in the mid-west. (Deb is head of the Department of Chemistry and Biochemistry at Rockford College in Illinois.)

The issues she faces are very different than those at a big school like the University of Toronto. Naturally we talked about textbooks and, after scolding her for not using my book, we debated the merits of various introductory biochemistry textbooks. (She has used several different ones and is very knowledgeable on the topic.)

Part of the debate revolves around differing approaches to teaching introductory biochemistry. There are many variations but I like to think of two main ones that I refer to as the "Evolutionary Approach" and the "Fuel Metabolism" approach.¹ Keep in mind that these are just broad categories used to illustrate some points about how to teach biochemistry.

The Evolutionary Approach to biochemistry emphasizes universal concepts that apply to most organisms. It concentrates on comparative aspects of biochemistry and on explanations of where things come from. This approach will almost always include lectures on photosynthesis and will almost always try to explain how metabolic pathways evolve.

In the Evolutionary Approach, the fundamental pathways of lipids, carbohydrates, amino acids etc. are the biosynthetic ones and not the degradation pathways. Some concepts, like the idea of essential amino acids, are relegated to footnotes. Human biochemistry is treated as a specialized version of the big picture and the fundamental concepts are taught first using simple prokaryotic examples.

The Fuel Metabolism Approach is quite different. Here the emphasis is on human biochemistry and almost everything is treated as a potential fuel before its biosynthesis is discussed. Photosynthesis isn't covered in such a course and the biochemistry of bacteria is usually not mentioned. This is the kind of course that's geared for students who are interested in their own metabolism and (it is thought) for pre-medical students.

In the Fuel Metabolism approach, students will learn that gluconeogenesis isn't very important and that there's a big difference between essential and nonessential amino acids. They will learn that the carbons in fatty acids can rarely be converted to carbohydrates. They will study transcription, translation, and DNA replication as they occur in mammals and they usually won't be exposed to the prokaryotic versions of information flow.

I think that the Evolutionary Approach to biochemistry is superior to the older Fuel Metabolism approach. In part, this is because the Evolutionary Approach encourages a "big picture" view of biochemistry where the ideas are more important than the facts. In contrast, the Fuel Metabolism approach encourages the learning of specific pathways since, by and large, it is confined to discussing mammals.

On the other hand, the Fuel Metabolism Approach may be more appealing to students because they are more concerned about themselves than about other species. Furthermore, it lends itself to discussions about diet and nutrition and these are hot topics that attract students.

I learned a lot from Deb Breiter. One of the most important things was that teachers like her get together from time to time to discuss how to teach chemistry/biochemistry. The meetings I attend are dominated by people who write textbooks and run BAMBED (Biochemistry and Molecular Biology Education) and we don't have much contact with many of those on the front line. (Don't get me wrong, most of us at those meetings are also teachers, it's just that we tend to forget that the vast majority of biochemistry teachers aren't even aware of some issues.)

Deb belongs to a group called the "Midwestern Association of Chemistry Teachers in Liberal Arts Colleges" (MACTLAC). The MACTLAC 2009 Annual Meeting is at Hope College in Michigan on Oct. 16-17. It would be fun to attend—I wonder if they allow interlopers?

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1. Many textbook authors refer to the Fuel Metabolism Approach as "rat liver" biochemistry but I won't mention that here because it sounds like I'm taking sides.

Perspectives on the Tree of Life: Day Two

The second day began bright and early with a talk by Jeffrey Lawrence, professor of biology at the University of Pittsburgh, Pittsburgh (PA, USA).

The title of his talk, Fragmented speciation in bacteria: The failure of the coalescent model doesn't really reflect its significance. Jeff showed us his careful analysis of speciation in bacteria focusing on a small clade of bacteria including Escherichia coli, and its closest relatives, Citrobacter kosteri, Salmonella enterica, Enterobacter sp., Klebsiella pneumonia etc.

When "speciation" occurs in bacteria there is considerable lateral gene exchange that obscures the actual relationship. What this means is that there really is no single common ancestor of most pairs of species and, given that it is almost impossible to define a species in the first place, a single phylogenetic tree of organisms is not a correct depiction of the tree of life.

Imagine a situation where our human ancestor was hanging out with the ancestors of gorillas and chimpanzees and a lot of gorilla ancestral genes made it into our genome. We wouldn't be able to depict the true representation of our evolution by just showing a simple bifurcating tree where we are closest to chimpanzees and more distant from gorillas. This treelike representation would ignore the transfer of genes between our ancestor and that of gorillas. You need a net or a web to show the actual path of descent. That's the situation in bacteria, as we saw clearly in the presentation.

But the failure of genomes to coalesce to a single ancestor doesn't make the whole exercise useless. It's still possible to say that Escherichia coli, Citrobacter kosteri and Salmonella enterica are more closely related to each other that any of them are to Klebsiella pneumoniae. Jeff gave us some estimates of the frequency of lateral gene transfer but I didn't write them down. The general consensus at the meeting is that DNA from another species is incorporated at the rate of once every few million years. This is enough to seriously compromise a treelike phylogeny.

Greg Morgan is a philosopher who is currently at a college in New Jersey. He gave the second talk. His title was Defining biodiversity in a world with horizontal gene transfer. He was mainly critiquing a book by the philosophers Maclaurin and Sterelney on biodiversity. Their concept of a species doesn't take lateral gene transfer into account and it doesn't really pay attention to the microbial world and the definition of species. Greg emphasized that there are many ways to define biodiversity and it makes a difference if you are interested in preserving biodiversity.

Laura Franklin-Hall is a philosopher at New York University in New York (NY, USA).Her presentation was an attempt to root for the underdog by defending trees: Scientific models and the history of life: Deep disagreement or mere misunderstanding?

I wish I had time to explain her description of scientific models and how they work but I didn't take enough notes and, besides, I'm still digesting the information. The idea is that no model is perfect—they all suffer from various weaknesses—and we shouldn't necessarily opt for the model that incorporates the most detail. In other words, while a web or a net may be a more accurate description of descent with modification, there's still a lot to be said for a tree if it represents some underlying, but partial, truth.

Maureen O'Malley is a philosopher at the University of Exeter and a former colleague of Ford Doolittle's. She is one of the behind-the-scenes organizers of the meeting. Her talk was on The philosophy of evolution, Ernst Mayr and the tree of life. She gave a really interesting summary of Mayr's views on evolution—a view which obviously didn't consider microbes and didn't concentrate on genes ("beanbag genetics").

I think its fair to say that most evolutionary biologists in the room found it interesting to review the history of Mayr's thoughts, but that's all it was; history. The philosophers, on the other hand, were much more attentive. Apparently Mayr is thought of as one of the founding fathers of the philosophy of biology and an "attack" on Mayr is close to blasphemy. That's shocking to me and it suggests that philosophers of biology are very much out of touch with modern evolutionary biology. This observation is consistent with some of the things that went on at this meeting although I hasten to add that most of the philosophers here seem to have a much more modern perspective. They weren't the least bit unhappy to see Mayr dethroned.

(I gather that photographs of Maureen are unusual. That's why the group photo at the top of the page is so important. She's right there in the second row.)

Eric Bapteste is a philosopher at IHPST in Paris (France). He told us how important it is to incorporate Lateral thinking about trees into our view of evolution. By "lateral thinking" he means the idea that genes can be inherited horizontally and not just vertically.

Lisa Gannet is a philosopher at St. Mary's University here in Halifax (NS, Canada). Her talk was on the difficulties in reconstructing the history of human populations and the various ways of representing it. Much of her talk was peppered with references to racism and it became apparent that she is very concerned about whether a tree of humans populations might support racism. After her talk I asked her about this and it turns out she is one of those people who don't think that human races exist.

The next talk was by James Mallet, a biologist at the Galton Laboratory, University College London, London (UK). The title of his talk certainly got everyone's attention: Was Darwin wrong about the nature of species and speciation?. Jim began by quoting Ernst Mayr, who in several papers, made the point that Darwin was wrong about speciation. Mayr quoted directly from Darwin's works to support the idea that he (Darwin) had an incorrect view of speciation.

Jim demolished that idea by showing that Mayr was as guilty of quote-mining as our typical creationist friends. It turns out that Darwin's ideas on species and speciation were far more accurate than Mayr was willing to admit and it's time we acknowledged that. Jim went on to illustrate real examples of speciation by looking at various races and varieties of butterflies in Venezuela. Just as Darwin imagined, there's a smooth continuum from varieties, races, and subspecies to real speciation events and it's often difficult to distinguish between races and species. Many species interbreed to form hybrids, as he showed using his data, but the hybrids might be quite rare indicating that gene flow between the species is almost nonexistent.

The last talk was by Richard (Dick) Burian, a philosopher at Virgina Tech in Blacksburg (VA, USA). He spoke about "Some conceptual issues deriving from the challenges to tree thinking. The emphasis was on identifying the "process" that can explain the "pattern" of evolution. This becomes difficult in the face of chimeras and symbiosis. Dick tried to establish the criteria that these processes had to fulfill in order to be legitimate contenders in the explanation of evolution. One of the criteria was selection so I asked him whether random genetic drift was a process that could be used to explain the pattern of evolution. The answer was "no." After the talk we had a discussion about this and we both agreed to think about it.

We all went off to dinner at The Cellar restaurant. Much alcohol was consumed and this contributed greatly to the discussions. As usual. we went home satisfied that we have solved most of the problems and woke up forgetting the solutions. We'll try again tonight. I'm more convinced than ever that this is the best meeting I've ever attended. I'm learning things at such a furious rate that my brain is beginning to feel the pain.

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Perspectives on the Tree of Life: Day One

The meeting began with a brief introduction by John Dupré. The first speaker was Ford Doolittleof the Dept. of Biochemistry and Molecular Biology at Dalhousie University here in Halifax. His title was The Tree of Life, from three sides now.

Ford introduced the topic from three perspectives: science, philosophy, and politics. The science is straightforward. You can construct perfectly respectable gene trees for bacteria using all kinds of different genes. Problem is, the trees aren't congruent. They don't agree with each other. This is well-established scientific fact and you need to accept it if you're ever going to understand the issue.

The trees aren't wildly different in most cases and it's possible to make sense of them by postulating the transfer of genes from one species to a different species. This is horizontal gene transfer (HGT), as opposed to the normal vertical gene transfer from generation to generation. It's more common to use the term lateral gene transfer (LGT). There are three very well studied modes of transfer: conjugation, transduction, and transformation.

The scientific evidence shows clearly that early phylogenetic relationships among bacteria cannot be accurately represented by a single tree. The proper relationship is a net, network, or a web. Again, this is not controversial among those scientists who are aware of the data. The facts and the conclusion have been around for over a decade. There is no "tree of life" representing the early evolution of life on Earth.



The philosophical questions have to do with the usefulness of metaphors in science (e.g. tree) and the implications for understanding the history of biology. Do we need to abandon all talk of trees? Is "Darwinism" committed to tree-like interpretations of evolution? Ford spent more time than I would have liked discussing Darwin's thoughts about trees and, unfortunately, the famous New Scientist cover was prominently on display.

Later on, Ford made the point that we need to move beyond Darwinism to postDarwinism and I agree with this point. That's why we need to stop talking about what Charles Darwin did, or did not, believe. He was wrong about a lot of things, but he died over 125 years ago.

The politics part of the talk refers to the fact that questioning the tree of life cases problems for those who are fighting creationists. By challenging a fundamental concept in evolutionary biology we are lending support to the creationists. Ford said that he understands why Genie Scott and the people at NCSE might be upset about this and he understands why there might be some value in focusing on the validity of animal trees instead of drawing attention to the problems with bacterial trees.

Most people at the meeting felt that NSCE and everyone else involved in fighting creationists just have to suck it up and deal with the scientific facts.

The next talk was by Jan SappProfessor of Biology at York University in Toronto (ON, Canada). Sandwalk readers will recall that I devoted several postings to discussing his book on the Three Domain Hypothesis some years ago.

The title of Jan's talk was Thinking laterally on the tree of life. He emphasized history of trees in biology and the history of lateral gene transfer, including hybridization and symbiosis. As it turns out, scientists have been thinking about non-treelike inheritance for more than 100 years.

Jan has a new book coming out that will discuss this history and its implications for a new view of evolution.

The third speaker was Ian Hacking, Professor of Philosophy at the University of Toronto (ON, Canada). He talked about The Fatal Attraction of Trees. The idea is that we all have a preference for organizing information in a treelike manner and this bias gets in the way of accepting a different view of evolution.

Olivier Rieppel works at the Field Museum in Chicago (IL, USA). His talk was about The series,the network, and the tree: Changing metaphors of order in nature. Olivier spent some time on cladism and cladistics and raised interesting questions about the validity of cladism as an approach to phylogeny.

Here's the problem: even in vertebrates, the gene trees don't always agree with the morphological trees. Olivier works with snakes and lizards and sorting out the "true" evolutionary history is extremely difficult. Is there a lot of LGT in vertebrates? Is it possible that we might have to abandon trees even at the this level?

Rob Beiko works in the Faculty of Computer Science at Dalhousie University in Halifax (NS, Canada). He showed us how LGT can mess up your trees. He developed computer simulations to illustrate the effect of lateral genes transfer under various condition. The good news is that reasonable frequencies of lateral gene transfer don't completely obscure the underlying treelike phylogeny.

Yan Boucher is a postdoc at MIT in Boston (MA, USA). His talk was Evolutionary Units: Breaking down species concepts. The main idea was that we should not consider species as the unit of evolution, instead, the appropriate unit is a piece of DNA. This was by far the most controversial talk. Several participants, including me, were quite confused by the presentation. We weren't aware of the fact that a species was considered a unit of evolution.

The next speaker was Peter Gogarten of the University of Connecticut in Storrs (CT, USA). Peter showed us many examples of lateral gene transfer in bacteria.

Joe Velasco is in the Dept. of Philosophy at Stanford University in Palo Alto (CA, USA). He told us about strategies for Inferring phylogenetic networks from a hypothetical computational approach. The bottom line is that it make be possible to construct networks—as opposed to trees—using computer programs but it's going to take a huge amount of effort.

After the talks we retired to the pub at the University Club and dinner in the dining room (salmon). There's was much conversation. At my table the most interesting debates were about sex and race with Andrew Roger and Ford Doolottle.

And so endeth the first day.

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Nova Scotia Lobster

 
On Tuesday evening I met up with John Dupré. John is Professor of Philosophy at the University of Exeter (UK) and director of the ESRC Centre for Genomics in Society (Egenis). He is one of the organizers of the meeting I'm attending in Halifax (NS, Canada).

After a few beers we decided to look for a good restaurant where we could get a lobster dinner. After a bit of searching we found a place that I had heard of. It was right on the Halifax waterfront by the tugboat berths. The meal was delicious, the wine was great, and the conversation stimulating.

We talked about why there aren't more philosophers of science interested in biology. I advanced my favorite hypothesis that it's because biology is so much harder than physics. John wasn't about to buy into that argument completely, although he was somewhat sympathetic. We agreed that biology is messy.

He thinks the future is encouraging. His group at Exeter, and other groups in the UK, have attracted a number of philosophers of biology and it's a rapidly growing part of the philosophy of science.

We talked about some of the philosophers whose names come up frequently in the blogosphere. We agree that John Wilkins is a smart guy—some of the others, not so much.

In addition to questioning the tree of life, John thinks that epigenetics is challenging traditional evolutionary biology and he's skeptical about junk DNA. I warned him that there's a great danger in lumping all these things together because some of these ideas are more scientific than others. Meetings such as this one are often viewed skeptically to begin with and if the participants are seen as proponents of all so-called "challenges" they will lose credibility.

We had a good debate and I'd like to think I made some points, especially about the validity of junk DNA. Epigenetics? No, not much headway there. I'll keep working on him over the next few days.

The tree of life debate is going to be very interesting. The meeting brings together almost all of the main players.

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[Image Credit: Nova Scotia Lobsters]

Perspectives on the Tree of Life: Ford Doolittle

 
As you read this I'll be in Halifax listening to Ford while he explains his version of the tree of life and why it conflicts with Darwinism. And why that shouldn't matter ...

The Tree of Life, from three sides now

My personal experiences in talking about the meaning of Lateral Gene Transfer (LGT) for the Tree of Life (TOL) teach me that people care about this otherwise seemingly hopelessly academic question for three reasons. It challenges their understandings of the history of our science, their often unexpressed philosophies of evolution and science, and their political stances vis-à-vis the struggle against ID creationism. I will review some of the science which has lead to the currently popular notion that what molecular phylogeny ultimately seeks is The Tree of Cells (TOC), a tracing back from the present of all speciation events, and before sex of all cell divisions, to some single ancestral cell. But because of LGT, this single cell cannot have been what most people want LUCA (the Last Universal Common Ancestor) to be – that is, a single cell (or species) whose genome contained the last common ancestral versions of all extant genes. In fact it need have contained none of these, and to equate the TOC with the TOL is a serious misreading of Darwin. Eric Bapteste and I have argued that the TOL was in fact an hypothesis about the relationship of evolutionary pattern (“natural classification”) to evolutionary process (specifically that it is tree-like), and that this hypothesis is false. Saying this causes problems to the brave defenders of evolution (such as Eugenie Scott and others at the NCSE) in the death-struggle against IDers. I will try to ameliorate the damage by suggesting that we evolutionists need to lighten up, stop defending “Darwinism” and admit that all we need to defend is this: Natural genetic, population genetic, ecological and environmental processes – that we for the most part already understand – operating over long periods of time, are necessary and sufficient to account for the diversity and adaptedness of life as we know it.

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Science Journalism and the Two Cultures

 
At the "Two Cultures" meeting in New York last May there was a panel discussion on "Science Communication." The four panelists, Carl Zimmer, Andrew Revkin, Ira Flatow, and Paula Apsell, were all science journalists. I found this disappointing since it implies that there are no scientists who are knowledgeable enough about science communication to sit on such a panel.

Carl has linked to the video on Science Communications so you can watch it yourselves.You won't be surprised to discover that there are many people who get blamed for the lack of science literary and the failure of science communication in America. But there's one group that comes across as being the experts and the champions of good science communication. It's not scientists.

This makes no sense to me. Science journalists are very proud of their role in communicating science and they lament the fact that the general public isn't getting educated. Doesn't the failure to educate the public conflict with the concept that science journalists are so good at what they do?

Carl Zimmer, to his credit, seemed to be the only one on the panel who was willing to discuss the failings of science journalists. Andrew Revkin, on the other hand, is very negative about scientists and thinks they are the problem, not the journalists. My question is at 47 minutes.

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Nobel Laureate: Roger Tsien

 

The Nobel Prize in Chemistry 2008.

"for the discovery and development of the green fluorescent protein, GFP"




Roger Y. Tsien (1952 - ) won the Nobel Prize in Chemistry for his work on adapting green fluorescent protein to serve as a marker for detecting changes within a cell. He shared the prize with Osamu Shimomura and Martin Chalfie.

Tsien's lab learned what causes the protein to flouresce and how to modify the active site on order to create variants that emitted different colors. You can watch an excellent video of his Nobel Lecture: Constructing and Exploiting the Fluorescent Protein Paintbox.

If that's a little too technical, the work is described in a special document called Information for the Public.
THEME:
Nobel Laureates

This is where the third Nobel Prize laureate Roger Tsien makes his entry. His greatest contribution to the GFP revolution was that he extended the researchers’ palette with many new colours that glowed longer and with higher intensity.

To begin with, Tsien charted how the GFP chromophore is formed chemically in the 238-aminoacid-long GFP protein. Researchers had previously shown that three amino acids in position 65–67 react chemically with each other to form the chromosphore. Tsien showed that this chemical reaction requires oxygen and explained how it can happen without the help of other proteins.

With the aid of DNA technology, Tsien took the next step and exchanged various amino acids in different parts of GFP. This led to the protein both absorbing and emitting light in other parts of the spectrum. By experimenting with the amino acid composition, Tsien was able to develop new variants of GFP that shine more strongly and in quite different colours such as cyan, blue and yellow. That is how researchers today can mark different proteins in different colours to see their interactions.

One colour, however, that Tsien could not produce with GFP was red. Red light penetrates biological tissue more easily and is therefore especially useful for researchers who want to study cells and organs inside the body.

At this point, Mikhail Matz and Sergei Lukyanov, two Russian researchers, became involved in the GFP revolution. They looked for GFP-like proteins in fluorescent corals and found six more proteins, one red, one blue and the rest green.

The desired red protein, DsRED, was unfortunately larger and heavier than GFP. DsRED consisted of four amino acid chains instead of one and was of less use as a fluorescent tag in biological processes. Tsien’s research group solved this problem, redesigning DsRED so that the protein is now stable and fluoresces as a single amino acid chain, which can easily be connected to other proteins.

From this smaller protein, Tsien’s research group also developed proteins with mouth watering names like mPlum, mCherry, mStrawberry, mOrange and mCitrine, according to the colour they glowed. Several other researchers and companies have also contributed new colours to this growing palette. So today, 46 years after Shimomura first wrote about the green fluorescent protein, there is a kaleidoscope of GFP-like proteins which shine with all the colours of the rainbow.

The brainbow

Three of these proteins have been used by researchers in a spectacular experiment. Mice were genetically modified to produce varying amounts of the colours yellow, cyan and red within the nerve cells of their brain. This combination of colours is similar to the one used by computer printers. The result was a mouse brain that glowed in the colours of the rainbow. The researchers could follow nerve fibres from individual cells in the dense network in the brain.

The researchers called this experiment “the brainbow”.

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[Photo Credit: UCSD]

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.

The Tree of Life

I'm off to a meeting on Perspectives on the Tree of Life.¹ (See Perspectives on the Tree of Life: Day One, Day Two, Day Three.)


If you want to follow the real scientific debate on the tree of life then read my earlier posting on The Three Domain Hypothesis especially the one on "The Web of Life."

The basic idea is that there is no strict branching tree of life that accounts for the data during the early stages of life on Earth. The first group of single-cell organisms exchanged genes so frequently that the gene phylogeny looks much more like a jumbled web that a traditional tree.

You should also listen to Ford Doolittle's talk on The Tree of Life. If you have any questions you'd like to ask, post them here and I'll bring them up at the meeting.

This part isn't very controversial. There really are good evolutionary biologists who are questioning the tree of life. It's just part of the gradual undoing of the Three Domain Hypothesis in light of the enormous amount of data refuting it.

What's controversial is the rejection of the very concept of trees in evolutionary biology and that's where the philosophers come in. This meeting has a 50:50 mixture of philosophers and scientists. It's gonna be fun.

Do you remember what was wrong with the New Scientist story last winter? It wasn't that scientists were questioning the tree of life 'cause that part of the story is quite accurate. What upset me was the fact that New Scientist exploited Charles Darwin by tying him to the idea that early bacterial evolution was treelike when, in fact, he knew nothing at all about the subject.

How could he have been wrong when he never wrote a thing about the relationship between various divisions of bacteria and archaebacteria and their affinities with eukaryotes?

The other thing that bugged me was that this story wasn't new but New Scientist played it up as a new discovery.

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1. The original title of the meeting was "Questioning the Tree of Life" but it's been changed to more closely reflect the divergent opinions of the participants.

What is NIH up to?

 
We've been debating the appointment of a new NIH Director (Francis Collins) but ignoring the role that NIH's Office of Science Education plays.

On Wednesday night (tomorrow) they're showing Inherit the Wind and that puts them right smack in the thick of the discussion about science and religion.

I think this is a mistake—NIH should keep their nose out of that debate—but that's not the worst of it. Following the movie they've asked Matt Nisbet to lead a discussion about evolution. Here's how he describes it on his blog.

Following the film, I have been invited to make a few remarks on the evolution debate as it plays out in contemporary culture and the enduring themes from the classic movie. The event and film series is designed to facilitate active audience participation and debate, so I expect there will be some very interesting discussion. For more on the relevant themes related to science and public engagement, see this forthcoming article on "What's Next for Science Communication?"

Matt Nisbet? Were all the real scientists too busy? Why didn't they fly in Jerry Coyne for the evening? Or Richard Lewontin? Or Niles Eldredge? Even better, PZ Myers. These are scientists who know and understand science.

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P.S. I don't think Clarence Darrow was an accommodationist. I wonder how Matt is going to frame that?

Good Food, Bad Food

Most of us are all too familiar with the food police. The food police are a group of self-appointed “experts" on nutrition. Not only do they know what to eat and what to avoid, they also feel duty bound to tell everyone else. You may be a victim ... or you may be one of them.

We've all heard the standard dogmas: whole wheat bread is good, white bread is bad; spinach is good, pork is bad; saturated fats are bad, unsaturated fats are good.. And we’ve been told hundreds of times to load up on various vitamins and supplements. You can't keep them straight. One year it's vitamin E that will make you smarter and the next year its vitamin A. At least the food police are consistent on a few things; for example, they all love omega-3 fatty acids.

Most reasonable people have learned to be skeptical about nutritional claims. We've been through several cycles of wine being good for you, then bad for you, and good for you again. We've listened to so many claims about the wonders of this diet or that one that we've given up trying to make sense of it all. About the only thing we agree on is that the diet kooks are probably wrong in spite of the fact that Larry King and Oprah Winfrey believe in them.

Who is to blame for all this mess? Is nutrition science really a science or is the field really in as much trouble as it seems from the outside? Is the media to blame for misrepresenting the science?

Reynold Specter is a clinical professor of medicine whose areas of expertise include vitamins and the effect of diet on kidney functions. He discusses the problem in the May/June issue of Skeptical Inquirer: Science and Pseudoscience in Adult Nutrition Research and Practice.

Here’s the take-home message ....

Human nutrition research and practice is plagued by pseudoscience and unsupported opinions. A scientific analysis separates reliable nutrition facts from nutritional pseudoscience and false opinion.

According to Specter, most nutrition claims are based on bad science. Many of them are unproven and a surprising number have actually been disproven by well-controlled, double-blind clinical studies.

So, what do we know for certain? We know that the average adult needs vitamins, essential amino acids, essential fatty acids, high quality protein (animal or vegetable), minerals, and a source of fuel calories. The fuel can come from carbohydrates, fat, or protein or some combination of these.

We know that carbohydrates, fats, and proteins can be inter-converted once they have been digested. We know that the levels of most metabolites are maintained at steady state levels (homeostasis) in healthy adults. And finally, we know that nutritional requirements change as you get older.

Just about everything else is either wrong or debatable according to Reynold Specter. The majority of people are neither too fat nor too thin. They have a body mass index (BMI) less than 30—usually in the optimal range of 20 to 25. For normal healthy people we can ask whether food supplements are necessary and whether there are particular supplements that will prevent disease.

The answer, notwithstanding thousands of positive EOS [epidemiology observation studies] and, in some cases, small inadequate clinical trials is there is no rigorous scientific evidence for the utility of dietary supplements, including megavitamins in normal weight (nonpregnant) adults with a stable BMI of 20 to 25 eating a diet containing adequate amounts of nutrients in Table 1.

Specter says that many common claims have been shown to be false by scientific studies. They include claims that fibre will prevent bowel cancer, that megadoses of vitamin D will prevent dementia, and that a low-fat diet will reduce your risk of a heart attack

Why then, have so many papers been published in the medical literature claiming benefits for food supplements and certain diets? Part of the problem is that these preliminary studies are just that—they were never intended to be the last word on the subject. Part of the problem is what's called “healthy person bias." Health conscious people tend to exercise and take supplements. This group is going to have fewer medical problems regardless of whether they take supplements or not but small scale studies don't control for that so it looks like there's a causal relationship between taking supplements and good health.

But most of the problem is due to how the system works. There are too many people who benefit from the status quo in nutritional science and hardly anyone who benefits if the quality of publications were to be improved.

Under the current system, authors find it easy to publish preliminary work; journal editors are happy to make larger profits; commercial enterprises enjoy increases in the sales of food supplementals and fad diets; and the news media have lots to write about. Don't expect this to change in favor of good science.

The bottom line is that the food supplement industry is dominated by poor science at best and outright quackery at worst. One could argue that this situation is harmless. After all, if P.T. Barnum's favorite group¹ of people want to waste their money, then why should the rest of us care? Reynold Specter tells us why our society needs to be concerned.

As I noted earlier, even widely used supplements such as vitamins E, C, and carotene in ‘standard megadoses’ (greater than five times the RDA) may indeed be harmful. The potential for harm for many other types of supplements is not been systematically studied, although there are convincing data that certain supplements may damage the liver, kidney, or heart or alter drug metabolism. For example, the amino acid tryptophan (used to induce sleep) and ephedrine-containing herbs (for asthma) were removed from the over-the-counter market because of severe toxicity, including deaths in some people.

What about diets? There is no scientific evidence to support the claims that certain common foods are better than others. For the average person, saturated fats are no better or worse than unsaturated fats and potatoes or white rice aren't any worse for you than whole-wheat. And there's nothing magical about eating five daily servings of fruit and vegetables. Everything works as long as you don't eat too much.

If you are obese you need to eat more moderately in order to cut back on fuel intake. Everybody knows this. It is not rocket science. But do weight loss diets actually work?

None work well. On average, over the long term, obese humans do not lose much weight on voluntary low-calorie diets of any kind. (There are of course a few obese individuals who have ‘self discipline’ and can lose weight and keep the weight off. Their secret is obscure.)

Many people profit from weight loss diets but unfortunately the patients aren't among them.

Be skeptical of the claims of so-called nutritionists. Don't be fooled into thinking that "nutrition science" is any more scientific than creation science.

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1. I know it was really David Hannum, and not P.T. Barnum, who said "There's a sucker born every minute."