Friday, July 31, 2009

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.



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.


[Image Credit: Nova Scotia Lobsters]

Thursday, July 30, 2009

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.


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.


Wednesday, July 29, 2009

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”.



[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.


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.

Tuesday, July 28, 2009

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.


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.



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

Monday's Molecule #131: Winner

 
The reaction pathway depicts the formation of the chromophore of green fluorescent protein (GFP). The light fluorescence is due to light that is absorbed by this chromophore and re-emitted at a longer wavelength.

Roger Tsein analyzed the pathway and created variants that would increase the efficiently and change the color of the light. For this he shared the 2008 Nobel Prize.

A surprising number of you found this easy and responded quickly with the correct answer. Some of you actually knew what it was without resorting to Google! The winner is Alex Ling of the University of Toronto.





This week we have an entire pathway to help you out. The goal is to identify the final product on the right and explain its significance. There are several possible Nobel Laureates who might be associated with this molecule but I'm looking for the one who worked on the pathway and presents it in the Nobel lecture. The Nobel Prize was awarded, in part, for the creation of mutant with a threonine substitution at position 65.

The first person to identify the molecule and the Nobel Laureate, 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: Ian Clarke of New England Biolabs Canada in Pickering ON, Canada. Dima Klenchin of the University of Wisconsin at Madison, Dara Gilbert of the University of Waterloo, Anne Johnson of Ryerson University, and Cody Cobb, soon to be a graduate student at Rutgers University in New Jersey.

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.


The Dutch are p*ssed as well

 
You just can't make this stuff up, ... oh, wait a minute, it's Fox News. Carry on.




[Hat Tip: Pharyngula

Your polite neighbours to the North are p*ssed off

 
From DAILY KOS ...
Oh yes indeedy.

The Shona Holmes thing? You know, the one whose story changes depending on her audience?

In the commercial she was DYING! In her testimony, not so much.

Most people here are aware of who is funding this Shona dog and pony show, that would be the good ol' Koch industry-John Bircher related Americans for Prosperity. The same astroturf factory that brought you teabagging (Branding FAIL) and Joe teh Plumber.

They are using the name Patients United Now. The only united Patients seem to be those with a huge stake in the Healthcare insurance industry and their other think tank friends. Their language and talking points are directly from Frank Luntz, Cunning Linguist part 2: framing healthcare (My co blogger has an interesting way with words too!)
Some of us have gone beyond being angry at the way Canada is being portrayed. My current thinking is that Americans deserve exactly the kind of health care system they wish for.

Why should Canadians care if Americans are dying or going bankrupt because they can't afford health care? While the rest of the civilized world sees universal health care as a basic human right, the USA is allowed to have a different opinion if they choose. After all, they have different opinions on many other important social issues.


Monday, July 27, 2009

Evolution and (lack of) design

 
The recurrent laryngeal nerve in humans begins in the brain then travels down into the the thorax, loops around the aorta, and travels back up the neck where it innervates the larynx.

This pathway doesn't makes much sense. A better design would be to innervate the larynx directly without looping around the aorta.

This isn't much of a problem in humans but in giraffes the recurrent laryngeal nerve has to travel several extra meters in order to get to its final destination. Those who advocate that evidence of design is evidence of God prefer to ignore examples such as these.

But can it be explained by evolution? Of course it can. This branch of the vagus nerve is present in fish were it is the fourth vagus nerve innervating one of the posterior gills. You can trace its evolution as the modern blood vessels evolved in the mammal lineage. Mark Ridley describes it, with diagrams, in his textbook Evolution.

You can also see what the region looks like during development on the Critical Biomass blog.

The point is that this is another example of something that makes sense in the light of evolution but otherwise seems quite senseless. The other point is that Intelligent Design Creationism fails to provide any explanation of phenomena such as the path of the recurrent laryngeal nerve.

This is a well-known example of something that looks like "bad design" and that's why it is often used to refute the main message of the Intelligent Design Creationists. Jerry Coyne uses several examples like this in his book Why Evolution Is True.

Have you ever wondered how the creationists respond to these examples of evolution? Here's an example from Darwin's God by Cornelius Hunter: Are Evolutionists Delusional (or just in denial)?.
Coyne inverts the message to say that imperfect designs make sense in evolution. Of course, but so what? So do perfect designs, and everything in between. All these make sense in evolution just as my bad day yesterday makes sense in astrology and warp drive makes sense in science fiction movies. When you can make up whatever just-so stories come to mind, then everything "makes sense."

The bottom line is that it is precisely from theology and metaphysics that evolution derives its power. Evolution is proclaimed to be a fact by Dobzhansky, Coyne and the evolutionists not on the basis of speculative science. As Elliott Sober has pointed out, evolution's truth status comes from the assumed unlikeliness of design, and all the theology entailed therein. It is, as Sober put it, Darwin's Principle.

Evolutionists like to make factual claims. One fact that is incontrovertible is that evolution is driven by theological claims--that is a matter of public record. Evolution is a religious theory. What is interesting is that the evolutionist denies any such thing. He may as well be denying the nose on his own face. This is truly a fascinating mythology.

Whether evolutionists are liars, delusional or in denial is difficult to say. What is obvious is that evolutionary thought is bankrupt. Religion drives science, and it matters.
Are you having trouble following the logic of this argument? Let me help you out with the short version ....

Intelligent Design Creationism is a religious theory that fails to explain most of what we observe in biology. But that's OK since evolution is also a religious theory. Nyah, nyah!



[Image Credit: Critical Biomass]

How Many M&M's in a Jar?

 
I just had to copy this from GrrlScientist 'cause my favorite1 daughter loves M&M's and physics.

Here's the Science paper that calculates the packing fraction of M&M's.
Donev, A., Cisse, I., Sachs, D., Variano, E.A., Stillinger, F.H., Connelly, R., Torquato, S., Chaikin, P.M. (2004) Improving the density of jammed disordered packings using ellipsoids. Science 303:990-993. [PubMed] [doi: 10.1126/science.1093010]






1. and only

Sam Harris vs Francis Collins

 
Sam Harris has published an op-ed piece in The New York Times where he questions whether the religious beliefs of Francis Collins are compatible with science [Science Is in the Details].
Dr. Collins has written that “science offers no answers to the most pressing questions of human existence” and that “the claims of atheistic materialism must be steadfastly resisted.”

One can only hope that these convictions will not affect his judgment at the institutes of health. After all, understanding human well-being at the level of the brain might very well offer some “answers to the most pressing questions of human existence” — questions like, Why do we suffer? Or, indeed, is it possible to love one’s neighbor as oneself? And wouldn’t any effort to explain human nature without reference to a soul, and to explain morality without reference to God, necessarily constitute “atheistic materialism”?

Francis Collins is an accomplished scientist and a man who is sincere in his beliefs. And that is precisely what makes me so uncomfortable about his nomination. Must we really entrust the future of biomedical research in the United States to a man who sincerely believes that a scientific understanding of human nature is impossible?
I'm not particularly worried about the possibility that Collins' beliefs will influence his decisions at NIH. I'm worried about the mixing of science and religion that occurs when a well-known Christian apologist is appointed to such a prominent scientific position.

It would have been far better to choose someone who was not publicly engaged in the science vs religion debate. NIH should be strictly neutral on this issue.


Monday's Molecule #131

 

This week we have an entire pathway to help you out. The goal is to identify the final product on the right and explain its significance. There are several possible Nobel Laureates who might be associated with this molecule but I'm looking for the one who worked on the pathway and presents it in the Nobel lecture. The Nobel Prize was awarded, in part, for the creation of mutant with a threonine substitution at position 65.

The first person to identify the molecule and the Nobel Laureate, 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: Ian Clarke of New England Biolabs Canada in Pickering ON, Canada. Dima Klenchin of the University of Wisconsin at Madison, Dara Gilbert of the University of Waterloo, Anne Johnson of Ryerson University, and Cody Cobb, soon to be a graduate student at Rutgers University in New Jersey.

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.



Sunday, July 26, 2009

What Does the Roman Catholic Church Believe about Evolution?

 
As I'm sure you all know by now, the "official" position of the Roman Catholic Church is theistic evolution. Humans evolved over billion of years from primitive single-cell organisms. God intervened near the end of the process to add a soul and some other religious goodies but the important idea is that a literal interpretation of Genesis is not part of Roman Catholic dogma.

Or so I thought until I saw this. Here's a Roman Catholic priest, Father Jonathan Morris, stumped by a question about Adam and Eve and their children. I guess he must have forgotten what he learned in seminary? (We can't blame this one on FOX News.)




[Hat Tip: Friendly Atheist]

Saturday, July 25, 2009

Marriage Commissioner Can't Refuse to Marry Gays because of his Religon

 
Orville Nichols is a marriage commissioner in the Province of Saskatchewan in Canada. Some years ago he refused to marry a gay couple because it was against his religion.

The couple was married by another commissioner but one of the partners (M.J.) filed a complaint with the Saskatchewan Human Rights Commission who ruled that Nichols did not have the right to refuse to marry people on the grounds that it was against his religion. M.J. was awarded $2500.

But that wasn't the end of it. Orville Nichols thought that his rights were being violated. According to CBCNews ...
Nichols appealed that ruling, arguing that his religious beliefs should be protected under the Charter of Rights and Freedoms.

But in a 39-page decision dated July 17, Court of Queen's Bench Justice Janet McMurty dismissed Nichols' argument, concluding that the human rights tribunal was "correct in its finding that the commission had established discrimination and that accommodation of Mr. Nichols' religious beliefs was not required."
This makes perfect sense. It you are an employee of the government then you have to do your job, part of which, in this case, was marrying gay couples. You can't refuse to do your job because it conflicts with your personal prejudices. If that conflict makes it impossible to carry out your duties then you must resign your position.

This is not the first time that Nichols has been warned.
He launched his own human rights complaint in 2005, months before he even met M.J., alleging that his religious freedoms would be violated should he be asked to marry same-sex couples. That complaint was dismissed by the Saskatchewan Human Rights Commission in 2006.
In those countries that currently ban gay marriage there's a fear that legalizing gay marriage will lead to situations just like this among those who perform civil ceremonies. That fear is fully justified. Once gay marriage becomes illegal legal, discrimination against gays becomes illegal.

Religious beliefs can never be used to justify discrimination and religious beliefs do not not qualify as "humans rights" when they are used as excuses to violate the civil rights of others.



Oenothera californica subsp. eurekensis

 

This is a photo of the rare, endangered, Eureka Dunes evening primrose. Read about it on Botany Photo of the Day.



Friday, July 24, 2009

Nobel Laureate: Peyton Rous

 

The Nobel Prize in Physiology or Medicine 1966

"for his discovery of tumour-inducing viruses"


Peyton Rous (1879 - 1970) won the Noble Prize in 1966 for his discovery and characterization of several viruses that cause cancer in birds and mammals. He is best known for his work on Rous Sarcom Virus (RSV), a retrovirus that infects chickens and causes cancer.

The original work was done many years earlier as he describes in his Nobel lecture.
In 1910 I described a malignant chicken sarcoma which could be propagated by transplanting its cells, these multiplying in their new hosts and forming new tumors of the same sort. In other ways the growth showed itself to be a neoplasm of a classical sort, yet, as reported in 1911, its cells yielded a causative virus. Numerous workers had already tried by then to get extraneous causes from transplanted mouse and rat tumors but the transferred cells had held their secret close. Hence the findings with the sarcoma were met with down-right disbelief, though soon several other, morphologically different, "spontaneous" chicken tumors were propagated by transplantation and from each a virus was got causing growths of its kind. Not until after some 15 years of disputation amongst oncologists were the findings with chickens deemed valid, and then they were relegated to a category distinct from that of mammals because from them no viruses could be obtained. Only in 1925, through the efforts of a British worker, W.E. Gye, was much attention given them by scientists.

The virus causing the chicken sarcoma first studied, now generally termed the RSV, has been maintained for more than fifty-five years and is still studied in many countries. Throughout most of this time it would engender growths only in chickens and closely related fowls; but of late several extraneous, non-neoplastic viruses have become associated with it, during its passage in unusual avian hosts; and its scope has thus been so enlarged that now not at few mammals, including monkeys, have been found to develop tumors after inoculation with the enhanced material
For many years the idea that a virus could cause cancer was not part of mainstream oncology. It took a number of other advances to make the idea acceptable. Part of the problem was due to a lack of understanding about the various modes of viral infection. Work on bacterial viruses (bacteriophage) showed clearly that a virus genome could integrate into the normal cellular chromosome and be carried along in all the offspring of those cells.

Fifty years after the initial discovery of a cancer-causing virus, scientists could finally begin to formulate a mechanism based on the results of the phage ground and bacterial geneticists. It's interesting to see the state of knowledge in 1966 as seen in the presentation speech.
THEME:
Nobel Laureates
The situation changed radically in the 1950's. The study of tumour viruses is a central area of modern cancer research. Two developments are responsible for this remarkable change. Recent developments in microbial genetics have lead to reinterpretation of the virus concept itself. It turns out that certain types of virus can introduce parts of their own genetic material into a cell without killing it or inhibiting its multiplication. The virus material thus introduced may become actually integrated with the gene material of the recipient cell and behave as a new hereditary factor. Virus infection can thus lead to a permanent change in some cellular characteristics. This re-evaluation of the virus concept made it possible to understand how a tumour virus might change the regulated behaviour of normal cells to the malignant proliferation characteristic of cancer cells. In the same period many new viruses capable of inducing malignant tumours in mammals were discovered. In 1981 Gross found a virus that induces leukemia in mice. A few years later he and two women scientists, Stewart and Eddy, isolated a remarkable new virus, called polyoma, capable of inducing an array of tumours in many different mammalian species. Since 1960 more than a dozen new tumour virus types have been isolated. It was established, furthermore, that tumour viruses could change normal to cancer cells in the test tube after a very short time of contact. This opened the way for direct studies on cancerous transformation of human cells, an approach previously hidden behind the walls of the living organism. Remarkably enough, it could be shown that Rous' own virus, previously regarded as lacking any importance for mammals, induces cancer under certain conditions in many different mammalian species and may even transform human cells in test tube cultures. Swedish scientists in Lund and Uppsala have made important contributions in this regard. It is not yet clear in which way viruses induce cancer but there is much to indicate that the virus does not behave like a little boy setting fire to a hayrick and running away; part of the viruses' own genetic material seems to be directly responsible for the malignant behaviour of the virus transformed tumour cell.


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.

How to deal with scientists who cheat

 
What do you do when a scientists (PI, post-doc, graduate student) is caught falsifying data? Should they be expelled from the community, fired from their job, or given a slap on the wrist and rehabilitated?

This isn't an easy question as Janet Stemwedel demonstrates in Tempering justice with mercy: the question of youthful offenders in the tribe of science. I hate it when she does that. It would be so easy to conclude that cheating scientists should be drummed out of the profession but then along comes Janet to confuse me.

She's right, of course. There ought to be a range of punishments that fit the wide range of crimes and motives.


Cody Cobb's Visit

 
We had a fun visit with Cody Cobb the other day when he flew up to Toronto for a free lunch [Lunch with a winner].

I mentioned that Cody was a blogger but I didn't link to his blog because I wasn't sure if he wanted to be identified as the author of 90% True. Well, apparently he doesn't care, 'cause he's posted two articles about his visit to Toronto.

In Canadian Lunch he reviews a lot of the things we talked about, including our lunch debates with Alex Palazzo. In Science Blogging he covers the discussion about the value and purpose of science blogging. They're both excellent reads—pay him a visit.


Thursday, July 23, 2009

The Richard Dawkins Award Goes to Bill Maher

 
Atheist Alliance International is an organization that gives out The Richard Dawkins Award each year. The criteria, according to Wikipedia are ...
The Richard Dawkins Award will be given every year to honor an outstanding atheist whose contributions raise public awareness of the nontheist life stance; who through writings, media, the arts, film, and/or the stage advocates increased scientific knowledge; who through work or by example teaches acceptance of the nontheist philosophy; and whose public posture mirrors the uncompromising nontheist life stance of Dr. Richard Dawkins.
This year the award goes to Bill Maher. One assumes that he is the man who best exemplifies the criteria for the award.

Does Bill Maher advocate increased scientific knowledge and does his public posture resemble that of Richard Dawkins?

Not bloody likely. As Orac and others have pointed out, Maher believes in all sorts of kooky ideas including the idea that vaccinations don't work [Bill Maher gets the Richard Dawkins Award? That's like Jenny McCarthy getting an award for public health].

Bill Maher may be a good atheist but he sure ain't a good scientist.

So what does PZ Myers think of this? [Put Maher in the hot seat]
However, let's be clear about the obvious. He is being given this award for making a movie this year that clearly promotes atheism and mocks religion, and that's all that is being endorsed.
Nope, sorry PZ but you seem to be wrong about that. Unless, of course, the criteria for the award as described in the Wikipedia article are wrong.

You need to be much more that a good little religion-bashing atheist to meet the criteria and it's as plain as the nose on your face that Bill Maher doesn't qualify.

BTW, like PZ, I was not a big fan of Religulous. Thus, I don't even agree that Bill Maher was in the same league as Richard Dawkins and his Root of all Evil series.


Dawkins, Tyson, Druyan, Stenger

 
This panel discussion took place recently in November 2007 at the Center of Inquiry in New York. The participants are Richard Dawkins, Neil Degrasse Tyson, Ann Druyan and Victor Stenger. I'm becoming a fan of Victor Strenger and you can see why by watching this video. I'm not a fan of Ann Druyan, and Neil Degrasse Tyson doesn't impress me as much as he impresses everyone else (including himself).

The thing that troubles me most about this discussion is the general agreement that "science" is nothing more than learning about physics, astronomy, chemistry, geology and biology. I think "science" is a way of knowing that includes absolutely everything; english, history, music, sociology and whatever. Real knowledge ("truth") in any of these subjects can only come from applying scientific methodology based on evidence and rationality coupled to a healthy degree of skepticism.

The discussion about whether science should confront religion is particularly interesting. Ann Druyan was the wife of Carl Sagan and she helped produce Cosmos. She claims that science has a wonderful story of its own to tell and there's no need to criticize religion. In fact, it's counter-productive to do so.

Ms. Druyan suggests that Sagan's description of science in Cosmos is the best way to sell science to the general public. She says that the TV series is still being shown frequently on television even though it was made in 1980.

To me that raises an obvious question. Thinking scientifically, I can't help but ask the obvious question. If this was such an effective way to communicate science how come after 29 years it hasn't had much effect on science literacy in the USA? Shouldn't we be basing our claims about science education on evidence and not on wishful thinking?





The Problem with Science Journalism

 
There are many problems with science journalism these days. One of the most important problems is that their sources (scientists) are highly unreliable as we witnessed in the recent Darwinius Affair.

One of the other problems is that science journalists have been very reluctant to criticize each other and maintain certain minimal standards of reporting. They are much more interested in giving each other awards for good writing than they are in evaluating good science.

Carl Zimmer has become an exception to the rule.1 He has taken on the role of defending his profession against those science journalists who would abuse science for the sake of a high profile publication [George Will’s Crack Fact-Checkers Continue Their Nap]. We need more journalists like Carl Zimmer and we need more scientists who will chastise their less-than-scientific colleagues when they step out of line.


1. Chris Mooney is another.

Shona Holmes and Canadian Health Care

 
Shona Holmes is a Canadian citizen. She suffered from a number of symptoms including dizziness and loss of vision. Her family doctor in Canada sent her for an MRI and the results suggested a brain tumor. Homes might have to wait months before seeing a neurologist for further tests. (This hasn't been confirmed, to my knowledge.)

Shona Holmes decided to fly to the the Mayo Clinic in Scottsdale Arizona. There she was eventually diagnosed as having a Rathke's cleft cyst (RCC) in her brain. This is not a tumor and it is not life-threatening. It does, however, threaten her vision, which was already impaired.

Eventually, after more tests and at least one further visit to Scottsdale, the cyst was removed. It's not clear how long it took from making the first appointment at the clinic to the actual surgery but the article on the Mayo Clinic website suggests it was about a month. Incidentally, this article has been removed from the Mayo Clinic website but it is cached here.

The bottom line is that Holmes suffered from a non-life-threatening cyst that affected her vision and could have eventually led to blindness. She choose not to wait for treatment in Canada but to pay for treatment in Arizona.

Shona Holmes is suing the Government of Ontario in order to force it to revise and/or dismantle public health care. The suit [Lindsay McCreith and Shona Holmes/The Attorney General for the Province of Ontario] is being supported by the Canadian Constitution Foundation, a right-wing group that's described here.

To summarize, we have a patient with a non-life-threatening brain cyst who may or may not have had to wait a long time for treatment in Canada but choose to go to an American clinic where she was operated on after about a month. This patient is sufficiently opposed to Canada's health care system that she has collaborated with a right-wing group to sue the Government of Ontario for allegedly violating her rights.

Oh yes, one more little bit of information, this is the same Shona Holmes you see in this video warning Americans about the dangers of universal health care. This Shona Holmes was going to die of a brain tumor if she had stayed in Canada.


It's pretty clear that Holmes is not telling the truth in the TV ad. The only question is whether she "misinformed" the group Patients United Now or whether they pressured her into making untrue statements in the TV add. Canadian Cynic wants to know [Shona Holmes: Useful idiot or puppetmaster?].


Wednesday, July 22, 2009

The Positive Case for Intelligent Design Creationism?

 
In biology, when you encounter something that has the superficial appearance of design there are two possible explanations. Either it evolved by entirely natural processes or God did it.

In the Intelligent Design Creationist literature, 99% of the effort is spent on trying to prove that evolution cannot produce the appearance of design.1 They have to focus on the anti-evolution argument because if they admit that evolution can do the job then there's no reason to invoke the supernatural.

The frequent criticism of this negative anti-science rhetoric is an embarrassment to many Intelligent Design Creationists so they often make up stories about the "positive" argument for design.

Sometimes it's fun to watch them twist and turn. Here's Casey Luskin performing: How James Carville’s New Book, 40 More Years Misrepresents Intelligent Design.


1. The remaining 1% is uninterpretable gibberish.

Who goes in the sack?

 
Dara Ó Briain tells us who he would put in a big sack and what he would do with them ...




[Hat Tip: Pharyngula]

Lunch with a winner

 
Cody Cobb was the winner of Monday's Molecule #129. He lives in New Jersey where he is about to start graduate school at Rutgers.

If you live in New Jersey you look forward to traveling, so Cody decided to fly up to Toronto for the day to collect his lunch. Because this was his first time in Canada, I decided to splurge and take him to a restaurant with white table cloths.

Cody has been blogging for many years—much longer than me. We had a good time talking about blogs and their lack of impact on science. Here we are at lunch with Alex Palazzo, another blogger [The Daily Transcript]. Note that Alex has a beer in front of him. This is proof that I've paid off on the bet we made a year ago.

Of course no first time visit to Canada would be complete without ...





The New Seven Wonders of Nature

 
There are 28 finalists in the running for the New 7 Wonders of Nature. You can see the list here.

Guess who didn't make the cut? Niagara Falls wasn't even on the list of possible wonders because the Americans in New York State didn't want to spend money to promote the Falls as a legitmate contender. (I assume the Canadians didn't want to foot the entire bill themselves.)

If you're Canadian you can vote for the Bay of Fundy and if you're American you can vote for the Grand Canyon. Australians, Germans, Irish, South Africans and Italians can all vote for a 7th wonder form their own country. Even the Swiss have an entry.

If you're from the United Kingdom, you are out of luck. Apparently there's nothing wonderful in the UK.


[Photo Credit: The Eire Hiker]

Tuesday, July 21, 2009

Direction and Purpose in Evolution

 
If you put two people together who believe that natural selection is the only important mechanism of evolution and that humans are the only, and best, end product of evolution, then this is what you get.

Watch Robert Wright and Daniel Dennet discuss direction and purpose in evolution.


Now imagine what the discussion would look like if they really understood the important role of chance and accident in evolution and, instead of humans, they used lobsters, ginkgo trees, shiitake mushrooms, rotifers, and cyanobacteria as examples of modern evolved species with three billion years worth of ancestors.

Even worse, think about the octopus. Is there any sane person who would point to the existence of those eight-legged slimeballs as evidence that evolution must have a direction and a purpose?


[Hat Tip: Robert Wright]

Monday's Molecule #130: Winner?

 
The "molecule" is Rous Sarcoma Virus or RSV. It's a retrovirus, specifically an alpharetrovirus. Other types of retrovirus include Lentivirus (e.g. HIV).

Unless you're an expert, you really can't tell from the diagram whether this is an alpharetrovirus or some other type of retrovirus. That's why I provided some clues linking this virus to last week's molecule and Nobel Laureates.

The Nobel Laureate is Peyton Rous.

Bill Chaney was the only person who got the right answer and he isn't eligible. There is no winner this week. Most of you guessed that it was HIV. One person—who shall not be named—guessed RSV and HIV with a total of five possible Nobel Laureates. That's only worth part marks. I'm expecting this person to be a winner real soon!




I thought last week's molecule would be a challenge but Sandwalk readers came up with the correct answer even in the middle of summer in the Northern hemisphere. Considering how well you did last week, following up with this week's "molecule" should be a gift.

Identify the thing shown here and relate it to a Nobel Laureate.

The first person to identify the "molecule" 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 six ineligible candidates for this week's reward: Bill Chaney of the University of Nebraska, Ian Clarke of New England Biolabs Canada in Pickering ON, Canada. Dima Klenchin of the University of Wisconsin at Madison, Dara Gilbert of the University of Waterloo, Anne Johnson of Ryerson University, and Cody Cobb, soon to be a graduate student at Rutgers University in New Jersey.

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.


The image is from Butan et al. (2008) [doi: 10.1016/j.jmb.2007.12.003]

What Is Accommodationism?

 
Are you uninterested in the debate about accommodationism but secretly want to know what it's all about? Here's a brief summary that will get you up to speed without having to wade through all the rhetoric [What is accommodationism?].

It comes with cartoons.


[Hat Tip: John Wilkins]

Questioning the Tree of Life

 
I'm going to Halifax NS (Canada) next week to attend a very exciting conference with a catchy title: Questioning the Tree of life. This is legitimate scientific debate about the tree of life metaphor and its validity in light of massive horizontal gene transfers (HGT, also known as lateral gene transfers - LGT) during the early evolution of single cell organisms. It brings together scientists and philosophers who share an interest in this problem. Should be a blast!

I'm supposed to report the meeting on my blog but I don't know where I'll find the time. Here are the main speakers.
W. Ford Doolittle
Tree of Life, Tree of Cells, LUCA and other questionable entities

Jan Sapp
Thinking laterally on the tree of life: An historical overview

Olivier Rieppel
The series, the network, and the tree: Changing metaphors of order in nature

Gordon McOuat
The origins and politics of trees and non-hierarchical taxonomic systems

Rob Beiko
The impact of different LGT scenarios on simulated genome evolution

Laura Franklin-Hall
Scientific models and the history of life: Deep disagreement or mere misunderstanding?

Peter Gogarten
The indistinguishability of patterns created through gene transfer between preferred partners and patterns created through shared ancestry

Joel Velasco
Inferring phylogenetic networks

Sina Adl
Specimen choice and the implications of modern technology in tree construction

Jeffrey Lawrence
Fragmented speciation in bacteria: The failure of a coalescent model

Greg Morgan
Defining biodiversity in a world with horizontal gene transfer

Yan Boucher
Evolutionary units: Breaking down species concepts

Dick Burian
Conceptual revisions deriving from the loss of the Tree

Maureen O’Malley
Philosophy of biology, Ernst Mayr, and the Tree of Life

Eric Bapteste
Lateral thinking about trees

Lisa Gannett
Trees, trellises, and the Garden of Eden

Andrew Hamilton
TOL issues in macrobes as they relate to taxonomic practice

James Mallet
Was Darwin wrong about the nature of species and speciation?

James McInerney
LUCA and LECA: Gene genesis in the genome of Eden

Chris. Malaterre
On the roots of the tree of life

Bill Martin
Endosymbiosis and gene transfers from endosymbionts, the most glaring insult to the tree

John Archibald
Genic and genomic threads in the tapestry of photosynthetic life: Implications for ‘tree thinking’

Fréd. Bouchard
Endosymbiosis in light of reflections on symbiosis and the superorganism

Rob Wilson
On arguments over the tree of life

Andrew Roger
Deconstructing deconstructions of the Tree of Life: Why a tree of microbes might be realizable, meaningful and useful

John Dupré
Analysing analyses of Tree of Life arguments: A commentary on Wilson and Roger

Susan Spath
Cultural politics and the Tree of Life



Monday, July 20, 2009

Nobel Laureates: J. Michael Bishop and Harold Varmus

 

The Nobel Prize in Physiology or Medicine 1989

"for their discovery of the cellular origin of retroviral oncogenes"


J. Michael Bishop (1936 - ) and Harold E. Varmus (1939 - ) won the Noble Prize in 1989 for proving that viruses contain a cancer-causing gene derived from the genome of the organism they infect. Specifically, they showed that chicken Rous Sarcoma Virus (RSV) carried an oncogene called v-src and this gene was an intronless version of a normal chicken gene called c-src.

The discovery had tremendous implications in many fields. Not only did it explain the origins of a particular chicken cancer but it also suggested that there where many other oncogenes in other well-known retroviruses. This turned out to be correct and several dozen such oncogenes have been discovered (e.g. abl, fos, jun, and erb among others).

The discovery also ignited a burst of activity in signaling because the c-src gene encodes a tyrosine kinase. This is an enzyme that adds phosphate groups to proteins thereby affecting their activity. Such enzymes belong to pathways triggered by specific signals leading to the regulation of growth and cell division.

The discovery lent support to the idea that small changes in regulatory pathways could have large effects—in this case converting a normal cell to a cancer cell. This idea fit nicely with the work of developmental biologists who were showing that single genes could regulate entire developmental pathways. It meant that large-scale changes in morphology during evolution could be effected by small changes (mutations) in the genome.

Finally, the work of Bishop and Varmus helped change our view of the genome. Not only do retrovirus sequences pop in and out of the genome but they can also capture cellular genes by converting them to retrogenes. The work confirmed the idea that genomes were dynamic—a idea that began with transposons. Not only that, the discovery of the retrogene, v-src, showed us that introns were almost certainly not an essential component of a gene.

In my opinion, this is one of the most significant scientific advances of the 2oth century. There aren't many achievements that really count as breakthroughs because either the work was done in many labs and came out piecemeal, or the result wasn't very significant. This is one achievement that truly was a big step forward in biology.

By 1989, the press releases from the Karolinska Institute were becoming excellent educational tools for the scientifically literate general public. In this case, the press release explains how oncogenes cause cancer. I'm going to include the entire Press Release (below) because it's so good.
THEME:
Nobel Laureates
Summary

The discovery awarded with this year's Nobel Prize in Physiology or Medicine concerns the identification of a large family of genes which control the normal growth and division of cells. Disturbances in one or some of these so-called oncogenes (Gk ónco(s) bulk, mass) can lead to transformation of a normal cell into a tumor cell and result in cancer.

Michael Bishop and Harold Varmus used an oncogenic retrovirus to identify the growth-controlling oncogenes in normal cells. In 1976 they published the remarkable conclusion that the oncogene in the virus did not represent a true viral gene but instead was a normal cellular gene, which the virus had acquired during replication in the host cell and thereafter carried along.

Bishop's and Varmus' discovery of the cellular origin of retroviral oncogenes has had an extensive influence on the development of our knowledge about mechanisms for tumor development. Until now more than 40 different oncogenes have been demonstrated. The discovery has also widened our insight into the complicated signal systems which govern the normal growth of cells.

Cellular Oncogenes Discovered by the Use of Retrovirus

The term oncogene was introduced in the middle of the 1960s to denote special parts of the genetic material of certain viruses. It was believed that this part of the genetic material could direct the transformation of a normal cell into a tumor cell under the influence of other parts of the viral genetic material, alternatively via chemical or physical effects. The favourite theory of the time was that virus-mediated cell-to-cell transmittance of oncogenes was the origin of all forms of cancer. This view was later proven to be incorrect.

The original discovery of an oncogenic virus was made in 1916 by Peyton Rous working at the Rockefeller Institute in New York. Fifty years later Rous received the Nobel Prize in Physiology or Medicine. Rous virus, as the infectious agent later was named, is a member of a large virus family named retroviruses. The genetic material of these viruses is RNA (ribonucleic acid). This RNA can be transcribed into DNA (deoxyribonucleic acid) by a unique enzyme in the virus, reverse transcriptase. The 1975 Nobel Prize in Physiology or Medicine was awarded to David Baltimore, Renato Dulbecco and Howard Temin partly for the discovery of this enzyme.

Reverse transcription of the genetic material of the virus into DNA has the important consequence that it can become integrated into the chromosomal DNA in the cells. It was through investigations of Rous virus that this year's laureates Michael Bishop and Harold Varmus in 1975 could demonstrate the true origin of oncogenes. They used one variant of Rous virus which contained an oncogenic gene (Figure 1) and another variant which lacked this gene. By use of these viruses they managed to construct a nucleic acid probe which selectively identified the oncogene. This probe was used to search for the corresponding genetic material in DNA from different cells. It was then found that oncogene-like material could be detected in different species throughout the animal kingdom, in fact even in simple organisms comprising only a few cells. Furthermore, it was shown that the gene had a fixed position in the chromosomes of a certain species, and that the gene, when it constituted part of the cellular genetic material, was divided into fragments (a mosaic gene) (Figure 1).
Figure 1. The difference between an oncogene in a virus and in a cell. In retroviruses causing tumors there is a separate segment of transforming nucleic acid which has been derived from a cell. The cellular gene is split (a mosaic gene) whereas the oncogene in the virus is continuous.
These findings led to the remarkable conclusion that the oncogene in the virus did not represent a true viral gene but a cellular gene which the virus had picked up far back during its replication in cells and carried along. This cellular gene was found to have a central function in the cells. It controlled their growth and division.

Through these studies of the abnormal, i.e. the diseased state, it was possible to elucidate critical normal cellular functions - a not uncommon situation in biomedical research. The original discovery of a cellular oncogene led to an intensive search for further similar genes. The explosive development of this field of research has led to the identification of more than 40 different oncogenes which direct different events in the complex signal systems that regulate the growth and division of cells. Changes in any one or more of these oncogenes may lead to cancer.

Balanced Cellular Interactions - A Biological Wonder

Symmetrical and asymmetrical, multicellular structures develop from the fertilized ovum by a process of differentiation about which only limited knowledge is available. In the fully developed individual carefully balanced conditions prevail. Damage of an organ elicits sophisticated repair processes which lead to restitution of the original condition of the organ. However, if a single cell escapes the network of growth control the result may be an abnormal local proliferation of cells or in the worst case a cancer implying the dissemination of cells running amok.

The development of a cancer is a complicated process involving several consecutive changes of the genetic material. Studies of cellular genes (proto-oncogenes) corresponding to the viral oncogenes, has started to shed light on the intricate systems which control normal cellular growth and division.

Cellular Oncogene Products Constitute Links in Signal Chains which Regulate Growth and Division of Cells

The regulation of growth and division of cells has turned out to be much more complicated than originally believed. Cellular oncogene products with different properties act in different positions of elaborate signal systems (Figure 2). In order to transmit signals from one cell to the other or from one cell to itself there are growth factors. These factors appear in the fluids surrounding cells. There are examples of oncogene products, viz. proteins produced in the cytoplasm, which can act as growth factors. Thus, it was found that the product of the sis1) gene was closely related to a previously identified growth factor PDGF (Platelet Derived Growth Factor).
Figure 2. Oncogene products are links in signal chains that stretch from the cell surface to the genetic material in the cell nucleus. This chain is composed of (1) growth factors, (2) growth factor receptors, (3) signal transducing proteins in cell membranes, (4) phosphokinases in the cytoplasm and (5) proteins transported from the cytoplasm into the nucleus where they bind to DNA. The localization of different oncogene products (Sis, ErbB, Ras, Src, Myc) is schematically indicated.
In order for a growth factor to be able to interact with a cell there has to be membrane structures, receptors, to which they can bind. There are several oncogene products which represent receptors in the cytoplasmic membrane of the cells, e.g. ErbA, Fms, Kit. These receptors have a unique enzymatic activity. They are so-called kinases with a capacity to phosphorylate (=add a phosphate group) the amino acid tyrosine. There are two more groups of oncogene products with phosphokinase activity; firstly tyrosine/phosphokinase which lack receptor function and is located at the inside of the cytoplasmic membrane, and secondly serine/threonine phosphokinase which is found in the cytoplasm.

Thus, oncogene products function as links in signal chains stretching from the surface of the cell to the genetic material in the nucleus. In the cytoplasm there is one more group of oncogene products. These are called Ras and are related to important cellular signal factors called G-proteins.

Finally, there is a large number of oncogene products which are located in the nucleus of the cell, i.e. Myc, Myb, Fos, ErbA and others. These products direct the transcription of DNA into RNA and therefore play a critical role in the selection of proteins to be synthesized by the cell.

Cancer - A Complex, Biological Sequence of Events

Changes in the genetic material constitute the basis for the development of all cancer. Generally there are several consecutive such changes which influence different steps in the signal chains described above. Therefore, one should à priori not expect to find one single clue to the mechanism of origin of cancer. However, application of the expanding knowledge in the oncogene field allows us to start comprehending the disharmonic orchestration behind abnormal cellular growth.

It is conceptually incorrect to speak about "cancer genes". However, historical circumstances explain why the oncogene terminology was introduced before a designation of the corresponding normal cellular genes was proposed. From the point of view of cancer the important matter is to compare oncogenes in normal cells and in tumor cells.

Oncogenes as a Cause of Cancer

The majority of oncogenes have been discovered in experimental studies using retroviruses. However, in a few cases oncogenes were identified by the use of an alternative technique, i.e. genetic material was isolated from tumor cells of non-viral origin and transferred (transfected) to other cells prapagated in culture. The cells receiving the DNA changed growth pattern, and further characterization of the transfected genetic material revealed the presence of oncogenes.

Two principally different forms of activation of oncogenes can be distinguished. Firstly, the normal cellular oncogene is hyperactive, and secondly the oncogene product is altered so that it can no longer be regulated in a normal way. There are several examples of these types of activation of oncogenes.

The discovery of oncogenes was as mentioned originally made by the use of retroviruses. This infers that genetic control elements in the virus itself can be responsible for the abnormal expression of the oncogene. However, in many cases it was found that alterations of the transferred oncogene contributed to its accentuated expression.

There are retroviruses which lack oncogenes but still can induce cancer. This is due to the fact that the virus has inserted its genetic material (in the form of DNA) very close to a normally occurring oncogene in the genetic material of the cell. This may result in an increased turn-over of the oncogene which may lead to abnormal cellular growth. The corresponding phenomenon can also occur in the absence of retroviruses. In this case there is a reorganization of the genetic material in the cell. Such a reorganization may occur within a single chromosome or by exchange of material between chromosomes. Repeated copying of a normal oncogene can lead to its amplification in the chromosome and consequently to increased amounts of the oncogene product. In certain brain tumors, glioblastomas, an amplified erbB-gene has been found, and a correspondingly increased neu-gene activity was shown in some forms of breast cancer.

The same effect can be seen when there is a reciprocal exchange of segments between chromosomes (translocation). Thus the normal myc-gene on chromosome 8 has been translocated to chromosome 14 in many patients with Burkitt's lymphomas (Figure 3). The insertion of the myc-gene containing chromosome segment is such that it becomes located close to hyperactive genes directing the synthesis of antibody protein. As a consequence the myc-gene becomes activated. Chromosome translocations occur in many different tumors. Chromosome analysis can therefore be of considerable value for localization of genetic changes in the genome critical for tumor development.
Figure 3. Chromosome translocation in Burkitt's lymphoma. Segments have been exchanged between chromosomes 8 and 14 which has activated the oncogene myc.
Oncogenes with point mutations have been observed in many tumors. These mutations may cause alterations in the amino acid composition of the gene product. A well-known example of such a modification is the exchange of amino acid 12 from glycine to valine in the ras gene product which has been observed in human tumor material. The mutation may also be somewhat more extensive leading to the absence of part of the protein (deletion). Different examples of modified oncogenes in human tumor material are given in Table I.
The Importance of Viruses for Cancer in Man

Cancer is not a contagious disease. However, infectious agents like viruses can contribute to the origin of cancer. Thus, it is by use of retroviruses that most oncogenes were identified, the starting materials in such investigations often being highly specialized, experimentally derived tumors. It seems likely that retroviruses play a relatively limited role for the development of cancer under natural conditions. The only known example in man in which a retrovirus infection contributes to the origin of cancer is the HTLV-1 associated lymphomas which occur in Japan.

However, there are other kinds of viruses which can contribute to the development of tumors in man. All these viruses have DNA as their genetic material. As examples can be mentioned papillome (wart) viruses and Epstein-Barr virus, a type of herpes virus. Certain types of papillome viruses play a role for the development of cervical cancer in the genital tract, while Epstein-Barr virus is an important factor for the development of Burkitt's lymphomas in Africa and nasopharyngeal cancer in Asia. However, in all these cases factors in addition to the virus infections are required for the cancer to develop.

References

J.M. Bishop: Oncogenes. Scientific American, 1982, 246, 68-78.

T. Hunter: The Proteins of Oncogenes. Scientific American, 1984, 251, 60-69.

C-H. Heldin & B. Westermark: Tillväxtfaktorer och onkgener. Läkartidningen 1988, 85, 497-499.

E. Norrby: I: Våra virus. Virus och cancer. Allmänna Förlaget, 1987, sid. 66-74.

1) All oncogenes are identified by the use of three letter abbreviations. In addition cellular and viral oncogenes are sometimes distinguished by c- and v- prefixes, respectively, e.g. c-src and v-src.


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