What Color Green Am I?

 

You Are Emerald Green

Deep and mysterious, it often seems like no one truly gets you. Inside, you are very emotional and moody - though you don't let it show. People usually have a strong reaction to you... profound love or deep hate. But you can even get those who hate you to come around. There's something naturally harmonious about you.

What Color Green Are You?

[Hat Tip: Monado]

A New Transitional Fossil

 
This is a new transitional fossil manmmal called Yanoconodon. It's from the Meozoic era (about 200 million years ago). The fossil tells us a great deal about mammalian evolution, especially the evolution of the jaw and ears. If you are interested in evolution you must read PZ Myers' excellent description of this fossil [Yanoconodon, a transitional fossil].

The creationist and intelligent design websites will soon be out with their own explanation of how this fossil fits with their version of the history of life. I'll link to them as soon as they post. If you spot these interpretations before I do, please let me know. I can't wait to see how they handle this news scientific evidence.

Meanwhile, congratulations PZ for a wonderful article.

Intelligent Design for Dummies

 
Do you understand Intelligent Design? Fear not, UK comedian Robin Ince explains it in a clip from the show "Comedy Cuts" aired March 15th on ITV in the UK. (Why can't there be more documentaries like this on TV in the USA?)



[Hat Tip: PZ Myers.]

Stéphane Dion Does Milton

 
Jennifer Smith has all the details over at Runesmith's Canadian Content [Dion Does Milton].

Sounds like it was a lot of fun. I hope he comes to my riding. It was the one formerly represented by Carolyn Parrish. But she was kicked out of the Liberal party so that's not quite the same as supporting a new Liberal like Garth Turner.

Happy St. Patricks Day!!!

 

Today's the day when the Irish—and people who want to be Irish—celebrate by doing typically Irish things; like drinking green beer, dancing Irish jigs, and going to mass. (?)

My ancestors on my mother's side are (mostly) Irish. My grandfather was a Doherty (O'Doherty). Thats the name at the top of the map in country Donegal. That side of the family came to Canada in 1802 and the Irish blood has been diluted—most notably by American refugees from the Revolutionary War (United Empire Loyalists) (gasp!).

The O'Doherty's are descended from Niall Noigíallach who kidnapped St. Patrick.

My grandmother was a Foster from Fermanagh. That's by the two lakes (Lower Lough Erne and Upper Lough Erne) in the upper central part of the country near the seat of the Maguires. Her family came to Canada in 1865 but both of her parents were Irish so at least 1/4 of my genes are undiluted Irish. I'll drink to that.

We don't talk about the nasty little fact that the Foster's were probably English invaders from the 1600's. As they say, somebody had to civilize the Irish and it might as well have been the English!

One of the reasons why the topic was avoided by my grandparents was because the O'Doherty clan was almost wiped out by the English during the O'Doherty rebellion in 1608 led by Sir Cahir O’Doherty. Some of the survivors had to flee to Skye to avoid being hung. I descend from those refugees.

Roundup® Is Safe

There have been dozens of studies on the possible harmful effects of Roundup®. There are many well-funded organizations and tons of lawyers who would like nothing better than to sue Monsanto into bankruptcy. Given the millions of farmers and suburban gardeners who slop Roundup® on themselves on a regular basis, you'd think it would be easy to come up with some who have died of cancer or, at least, suffered serious health problems.

Hasn't happened. Most of the scientific studies find no harmful effects of Roundup® on humans. Here's a bit from a study done for THE COMMONWEALTH OF MASSACHUSETTS in 2003.

TOXICITY REVIEW
Acute (Mammalian)
Glyphosate has reported oral LD5Os of 4,320 and 5,600 mg/kg in male and female rats (15,4). The oral LD5Os of the two major glyphosate products Rodeo and Roundup are 5,000 and 5,400 mg/kg in the rat (15). A dermal LD5O of 7,940 mg/kg has been determined in rabbits (15,4). There are reports of mild dermal irritation in rabbits (6), moderate eye irritation in rabbits (7), and possible phototoxicity in humans (9). The product involved in the phototoxicity study was Tumbleweed marketed by Murphys Limited UK (9). Maibach (1986) investigated the irritant and the photo irritant responses in individuals exposed to Roundup (41% glyphosate, water, and surfactant); Pinesol liquid, Johnson Baby Shampoo, and Ivory Liquid dishwashing detergent. The conclusion drawn was that glyphosate has less irritant potential than the Pinesol or the Ivory dishwashing liquid (120).
Metabolism
Elimination of glyphosate is rapid and very little of the material is metabolized (6,106).
Subchronic/Chronic Studies (Mammalian)
In subchronic tests, glyphosate was administered in the diet to dogs and rats at 200, 600, and 2,000 ppm for 90 days. A variety of toxicological endpoints were evaluated with no significant abnormalities reported (15,10). In other subchronic tests, rats received 0, 1,000, 5,000, or 20,000 ppm (57, 286, 1143 mg/kg) in the diet for 3 months. The no observable adverse effect level (NOAEL) was 20,000 ppm (1,143 mg/kg) (115). In the one year oral dog study, dogs received 20, 100, and 500 mg/kg/day. The no observable effect level (NOEL) was 500 mg/kg (116).

etc.

You may not like Monsanto and genetically-modified food for ethical reasons or because the company exploits third-world farmers. These are valid, if controversial, reasons for opposing the spread of genetically-modified crops. Personally I don't have a problem with genetically modified foods, but I do have a problem with the power of large international for-profit companies.

Express your opposition, if it's rational and scientifically based, but don't fall into the trap of opposing GM foods because you think Roundup® is dangerous. This kind of opposition (see below) is just plain silly. It is a superstitious, anti-science, way of thinking.

If You Think Monsanto's Roundup is a Safer Pesticide,
Please read the articles and papers on this page! Roundup is a pesticide as defined by the EPA.

If you're still not convinced that Roundup is a highly toxic and persistent pesticide, read on, while at the same time remembering the other contributions that Monsanto has made to society such as:

Saccharin, Astroturf, agent orange, dioxin, sulphuric acid, polychlorinated biphenyls (PCBs), plastics and synthetic fabrics, research on uranium for the Manhattan Project that led to the construction of nuclear bombs, styrene monomer, an endless line of pesticides and herbicides (Roundup), rBGH (recombinant bovine growth hormone that makes cows ill), genetically engineered crops (corn, potatoes, tomatoes, soy beans, cotton), and it's most significant product to date; Lies, Factual Distortions and Omissions.

[from Everything You Never Wanted to Know About Monsanto's Modus Operandi (M.O.)]

Glyphosate-resistant Weeds

Roundup® (glyphosate) has been used to control weeds since 1974 [How Roundup® Works]. In all those years, the number of reported cases of resistant plants has been far below predictions. Only in the past ten years have Roundup®-resistant plants been identified and there are only 11 species of resistant weeds known at last count (Perez-Jones et al. (2007).

We now know from studies of the mechanism of resistance of the C4 EPSP synthase that resistance to glyphosate requires very special circumstances; namely, an enzyme active site that can exclude glyphosate while still allowing phosphoenolpyruvate to bind efficiently [The Molecular Basis of Roundup® Resistance]. Thus, with hindsight, it is perhaps not surprising that so few resistant plants have turned up.

One of the first resistance mechanisms to be discovered was one that evolved in a population of goosegrass from Malaysia (Baerson et al. 2002). The glyphosate-resistant biotype (strain) was from a region that had been continuously sprayed for 10 years.

Baerson et al. (2007), working out of the Monsanto Labs in St. Louis MO (USA), discovered that the resistant strain of goosegrass was resistant to about five times the normal level of glyphosate. All of this resistance was apparently due to a single amino acid change in the active site of EPSP synthase. The substitution of a proline for a serine residue at position 106 decreased glyphosate binding without affecting phophoenolpyruvate binding.

Taken together, these studies suggest that an altered EPSPS provides a significant component of the glyphosate resistance mechanism in goosegrass, and represents the first example for target-based resistance to glyphosate occurring in any plant species.

The authors cannot explain why this P106S substitution confers resistance in the goosegrass enzyme, since similar substitutions in other plant enzymes affect substrate binding and render the enzyme ineffective. They conclude with,

It is possible that goosegrass may be predisposed to this type of mechanism due to species-specific genetic or physiological characteristics that remain obscure at present.

This has important implications for our understanding of evolution. Taken at face value, it suggests that in some species an evolutionary path is simply not available—there may not be a route to the so-called "top of the fitness peak." On the other hand, in other species a path can open up with a single mutation because that species, by chance, has the right kind of background. Evolution by accident.

Glyphosate-resistance has independently evolved in two strains of Italian ryegrass (Lolium multiflorum) from Oregon and Chile. The mechanism of resistance was studied by Perez-Jones et al. (2007). In this case there are two different mechanisms of resistance.

The strain from Chile had the same EPSP synthase mutation as that found in goosegrass (proline for serine at position 106). The Orgeon strain was defective in absorbing glyphosate in the roots suggesting a defect of some sort in absorption and/or transport. This is a new kind of resistance and it's not well understood at this time.

There have been rumors of Roundup® resistant coca plants in Bolivia—the ones whose leaves are used to produce cocaine. The rumors were so persistent that the magic crop was tested to see if it had been genetically engineered in a secret lab sponsored by the drug lords [The Mystery of the Coca Plant That Wouldn't Die]. The article reports that tests for C4 EPSP synthase were negative suggesting that the plants have acquired a natural resistance.

The implication is that the farmers' decentralized system of disseminating coca cuttings has been amazingly effective - more so than genetic engineering could hope to be. When one plant somewhere in the country demonstrated tolerance to glyphosate, cuttings were made and passed on to dealers and farmers, who could sell them quickly to farmers hoping to withstand the spraying. The best of the next generation was once again used for cuttings and distributed.

This technique - applied over four years - is now the most likely explanation for the arrival of Boliviana negra. By spraying so much territory, the US significantly increased the odds of generating beneficial mutations. There are numerous species of coca, further increasing the diversity of possible mutations. And in the Amazonian region, nature is particularly adaptive and resilient.

"I thought [genetic engineering] was unlikely," says Gressel, the plant scientist at the Weizmann Institute. "But farmers aren't dumb. They obviously spotted a lucky mutation and propagated the hell out of it."

The effects of this are far-reaching for American policymakers: A new herbicide would work only for a limited time against such a simple but effective ad hoc network. The coca-growing community is clearly primed to take advantage of any mutations.

From what we know of glyphosate resistance it seem unlikely that these Bolivian plants are actually resistant to Roundup®. It's probably just over-active imagination.

Baerson, S.R., Rodriguez, D.J., Tran, M., Feng, Y., Biest, N.A., Dill, G.M. (2002) Glyphosate-resistant goosegrass. Identification of a mutation in the target enzyme 5-enolpyruvylshikimate-3-phosphate synthase. Plant Physiol. 129:1265-1275. [PubMed]

Perez-Jones, A., Park K.W., Polge, N., Colquhoun, J., and Mallory-Smith, C.A. (2007) Investigating the mechanisms of glyphosate resistance in Lolium multiflorum. Planta. 2007 Feb 24 (electronic publication, ahead of print).

Wanna Speciate? Come to Canada

A recent Science paper by Wei and Schluter (2007) asks whether speciation rates really are faster in the tropics as widely believed. They looked at 309 sister species of mammals and birds in North and South America. Sister species are closely related species that have apparently diverged within the past few million years. The time since divergence was estimated by comparing the sequences of the mitochondrial cytochrome b gene. This gives an estimate of the rate of speciation by cladogenesis for each pair of sister species.

The range of each species was estimated from literature data and the time of speciation results were plotted in relation to the midpoint latitude of the range. The result was quite striking.

Near the equator, the ages of sister-species pairs spanned the past 10 million years, with a mean age of 3.4 million years ago. As the distance from the equator increased, the upper limit and mean ages of sister species declined significantly. At the highest latitudes, all of the sister species diverged less than 1.0 Ma.

It's widely known that there are far more species in the tropics than in temperate or arctic climates. How do we explain this apparent discrepancy?

Weir and Schluter (2007) estimated extinction rates at various latitudes and discovered that the rate of species extinction also increased with distance from the equator but the rate of increase was greater than the rate of increase in speciation. Thus, although there were more speciation events in temperate zones, there were also more extinctions, and the extinctions cancelled out the effect of frequent cladogenesis.

The net effect is more species in the tropics even though speciation rates are higher in temperate zones.

John Wilkins is an expert on species. He points out that there's no universal definition of species. I wonder if this result isn't biased by different ways of recognizing species. Perhaps populations and sub-species are more easily named in temperate zones because there's more room for them to spread out into non-overlapping ranges. Does anyone know whether "species" in temperate zones are more likely to be similar in appearance than in the tropics?

In any case, the result is intriguing. It suggests that things move pretty slowly in hot climates. If you want some fast speciation action you need to move north to a cooler place.

Weir, J.T. and Schluter, S. (2007) The Latitudinal Gradient in Recent Speciation and Extinction Rates of Birds and Mammals. Science 315: 1574-1576.

[Hat Tip: RichardDawkins.net; Cold is hot in evolution -- Researchers debunk belief species evolve faster in tropics]

St. Patrick Banished Snakes from Ireland

 
Friday's Urban Legend: FALSE

Connie Barlow describes A St. Patrick's Day Parable.

Ireland is a land of no snakes. It has no slithering serpents. There are no rat snakes in Ireland; there are no rattlesnakes; there are no garter snakes. There are no snakes at all.

The absence of snakes in Ireland seems to cry out for an explanation — but only if one regards or ventures to the island from outside: from England, say, or from continental Europe. To the indigenous Celts, there would, of course, have been nothing to explain. The Gaelic peoples no more needed to explain an absence of snakes on their island home than they needed to explain an absence of kangaroos. To those who came to Ireland from abroad, however, a dearth of serpents was a striking anomaly in need of an answer.

We humans must have answers. And so arose the legend of St. Patrick and the snakes. The reason Ireland has no snakes, the story goes, is that Patrick charmed all snakes on the island to come down to the seashore, slither into the water, and drown. So Ireland did once have snakes, but it has them no more. Patrick charmed them all into the sea.

She goes on to explain why there are no snakes in Ireland but I prefer to swtich to the website of the Smithsonian National Zoological Park for their explanation of Why Ireland Has No Snakes.

Now snakes are found in deserts, grasslands, forests, mountains, and even oceans virtually everywhere around the world. Everywhere except Ireland, New Zealand, Iceland, Greenland, and Antarctica, that is.

One thing these few snake-less parts of the world have in common is that they are surrounded by water. New Zealand, for instance, split off from Australia and Asia before snakes ever evolved. So far, no serpent has successfully migrated across the open ocean to a new terrestrial home. As the world's oceans have risen and fallen over the millennia, land bridges have come and gone between Ireland, other parts of Great Britain, and the European mainland, allowing animals and early humans to cross. However, any snake that may have slithered it's way to Ireland would have turned into a popsicle when the ice ages hit.

The most recent ice age began about three million years ago and continues into the present. Between warm periods like the current climate, glaciers have advanced and retreated more than 20 times, often completely blanketing Ireland with ice. Snakes, being cold-blooded animals, simply aren't able to survive in areas where the ground is frozen year round. Ireland thawed out for the last time only 15,000 years ago. Since then, 12 miles of icy-cold water in the Northern Channel have separated Ireland from neighboring Scotland, which does harbor a few species of snakes. There are no snakes in Ireland for the simple reason that they can't get there.

[The book cover is from a book by Sheila MacGill Callahan (Author) and Will Hillenbrand (Illustrator). You can buy it on Amazon.com.]

War is Not Healthy for Children and Other Living Things

For the longest time we had a poster on our wall that said "War Is Not Healthy for Children and Other Living things" [War Is Not Healthy: The True Story].

The sentence seems trite if you didn't live though the 60's but it's taking on more and more significance every day. The point is that war is hell. People die. Innocent people. We better not forget that.

But there are people who do want to forget. They want to purge war of all of it's ugliness and remember only the bravery and the glory. In Canada the movement to glorify a deadly First World War battle—the battle of Vimy Ridge—is gaining ground. In this battle there were 30,000 casualties and the front advanced a few miles. There was no strategic gain. This was a war that should not have happened and a battle that wasted thousands of lives. It was not glorious and it should be something to be embarrassed about, not celebrated.

But there's an even more important illustration of our tendency to forget the horrors and the mistakes of war. Tuesday's Globe and Mail has an article about veterans protesting a sign at the Canadian War Museum in Ottawa. The issue concerns strategic bombing in World War II and it's a hot button issue in Canada because of a documentary televised several years ago.

The goal of Bomber Command during World War II was to destroy German cities and reduce Germany's will to continue the war. Nobody was under any illusions about the consequences because London and other British cities had been bombed in 1940. They knew that flower gardens would be wiped out and so would little children [Strategic bombing during World War II]. The image below is of bombed out apartment buildings in Hamburg in 1944. People used to live in those buildings. Thousands and thousands died during the firestorms created by massive bombing raids by British and American forces during 1944 and 1945.

These are facts. The controversy is about whether the bombing raids were effective. There are many who say they weren't; in fact, there seems to be a consensus among historians that strategic bombing of Germany did not have as much negative effect as the High Command believed.

Thousands of Allied airmen died in planes over Germany. Many of them were Canadians. The Canadian War Museum has a display dedicated to those airman. I have seen it. I have shown it to my children. My father was a pilot during World War II.

There are plaques and pictures describing the planes and the crews. One of the plaques is titled An Enduring Controversy. It reads,

The value and morality of the strategic bombing offensive against Germany remains contested. Bomber Command's aim was to crush civilian morale and force Germany to surrender by destroying its cities and industrial installations.

Although Bomber Command and the American attacks left 600,000 Germans dead and more than five million homeless, the raids resulted in only a small reduction in German war production until late in the war.

This is what the controversy is all about. The Royal Canadian Legion objects to this plague because it calls into to question the morality of strategic bombing and the morality of bomber crews who served during World War II.

Last year, the veterans complained that the panel made them look like war criminals. Art Smith, a veteran leading the attack, said, "Ten thousand crewmen didn't make it back. It really distresses me that people want to knock their memory." A former member of Parliament, he lobbied for a private member's bill to force a rewrite of the text.

Guess what? War is hell. War is immoral. You can't pretty it up by ignoring the truth. Bombs killed women and children. Lots of them. Their lives may have been wasted because nothing was gained by their deaths.

We owe it to our sons and daughters to leave that plaque just the way it is. We need to remind them that war isn't healthy for children and other living things. The children of Iraq and Afghanistan know this.

The Web of Life

Regular readers of Sandwalk will recall a series of articles on the death of the Three Domain Hypothesis. One of them covered the ideas of W. Ford Doolittle from Dalhousie University in Nova Scotia [If the Tree of Life Fell, Would We Recognize the Sound?]. He advocates a web of life with numerous exchanges of genes during the early years.

The figure below is taken from Doolittle's Scientific American article "Uprooting the Tree of Life" (February 2000). © Scientific American


Doolittle has a new paper out in PNAS (Doolittle and Bapteste, 2007). In that paper he restates his ideas about the web of life and emphasizes the fact that most of us are making unsubstantiated assumptions about the treelike structure of life. This is not a criticism of evolution—far from it—but as you might expect it has attracted the attention of anti-science writers such as Casey Luskin.

Doolittle and Bapteste (2007) are opposed to the bifurcating tree of life such as the one shown on the Dept. of Energy (USA) Joint Genome Initiative website [JGI Microbial Genomes]. They say,

The meaning, role in biology, and support in evidence of the universal "Tree of Life" (TOL) are currently in dispute. Some evolutionists believe (i) that a single rooted and dichotomously branching representation of the relationships between all life forms is appropriate (at all levels above species), because it best represents their history; (ii) that we can with available data and methods reconstruct this tree quite accurately; and (iii) that we have in fact done so, at least for the major groups of organisms. Other evolutionists question the second and third of these beliefs, holding that data are as yet insufficiently numerous and phylogenetic models as yet insufficiently accurate to allow reconstruction of life's earliest divisions, although they do not doubt that some rooted and dichotomously branching tree can in principle represent the history of all life. Still other evolutionists, ourselves included, question even this most fundamental belief, that there is a single true tree. All sides express confidence in their positions, and the debate often seems to be at an impasse.

The argument is long and complex but the essence is that we need to abandon our assumption that the tree of life can be represented by: (i) a unique hierarchical pattern, (ii) the historical record can be best represented by a branching pattern, and (iii) natural selection is the primary cause of speciation.

We've pretty much abandoned the third point ...

As to this third possibility, modern evolutionists accept the uncoupling of selection from divergence, not only at the molecular level (the neutral theory) but in certain models for speciation, without seeing the Darwinian (or at least the neo-Darwinian) theory as refuted (21, 22). We have come to appreciate the plurality of evolutionary processes of lineage diversification. But most of us hold on to the first two tenets, that there is a real and universal natural hierarchy, and that descent with modification explains it, in much the same way as Darwin did. We may be process pluralists, but we remain pattern monists.

This brings us to the title of their paper Pattern Pluralism and the Tree of Life Hypothesis. Doolittle and Bapsiste want us to not only be pluralists with respect to the mechanism of evolution but also with respect to the pattern of evolution.

Doolittle maintains that lateral gene transfer (LGT) is so common that it's impossible to construct a reliable bifurcating tree to represent the actual history of life. In other words, a Tree of Life is not only technically difficult but impossible in theory as well. This problem extends to all branches of the prokaryotic tree including the major divisions. Even the existence of two prokaryotic domains is questionable. Rooting the tree of life is out of the question.

I'm a big fan of Ford Doolittle—after all, he's an honorary Canadian! I certainly agree with him about the demise of the Three Domain Hypothesis. (Most people seem to have missed the death announcement.) I also agree with him that early evolution is more like a web of life than a tree of life. Nevertheless, I think he goes too far. Lateral gene transfer is an important, and common, phenomenon but I don't think it's quite as prevalent as he makes out. I still think that a bifurcating tree can be used to represent most species evolution after about 2.5 billion years ago.

Doolittle, W.F. and Bapteste, E. (2007) Pattern pluralism and the Tree of Life hypothesis. Proc. Natl. Acad. Sci. (USA) 104:2043-2049. [PubMed]

More on Cellphones in Hospitals and How Doctors Deal with Evidence

 
Last Friday I mentioned a study done at the Mayo Clinic where they looked at the practice of banning cellphone use in hospitals [Cell Phones Can Cause Death in Hospitals]. The study concluded that there is no scientific evidence to support such a ban. Cellphones and BlackBerry's do not interfere with hospital equipment, according to the study.

Tuesday's Globe and Mail had a skeptical front page article on banning cellphones in hospitals [Hole Poked in Hospital Cellphone Shroud].

Cellphone use does not interfere with medical equipment and should be allowed in hospitals, according to a study that turns years of warnings on its head.

The study comes amid a sharp debate within the medical profession, with some institutions beginning to loosen their rules while others stick to the view that the devices can be dangerous to patients.

Among the people interviewed was Chris O'Conner at Mississauga Trillium Health Centre. This large teaching hospital is part of the University of Toronto Medical School. It's my local hospital and I've been there many times, both as a patient and a visitor.

Trillium lifted their ban on cellphones two years ago. Not only that, the staff is encouraged to communicate with each other using BlackBerrys and other devices. According to O'Conner, this has not only improved efficiency but also enhanced patient safety by avoiding communications lapses.

So, why are cellphones banned at other hospitals? Is this a problem? I don't know whether you could say the ban is a serious "problem," but it sure is an inconvenience. For parents sitting in an emergency waiting room for 6 hours it is frustrating to have to rely on a pay phone to keep others informed of what's happening. For those of us who are picking up someone from a hospital, it is annoying to not know when a patient is about to be discharged. (We recently had to pick up a patient from a large downtown teaching hospital. Fortunately they don't ban cellphones so we were able to keep in touch with the patient and find out when he was going to be released.) For patients in a hospital bed it is sad that they can't use their cellphones to talk to friends and relatives.

These concerns are real enough but my main interest is the conflict between rationalism and superstition. The Globe and Mail also interviewed spokeswoman Brandy Delves from a major Vancouver hospital.

A spokeswoman for Vancouver Coastal Health said last night that cellphones and other handheld communication devices continue to be banned near sensitive equipment there, including ventilators and incubators.

While a few hospitals have begun to buck the trend, conventional wisdom supports the VCH's view that these devices could interfere with crucial equipment.

Typical of this concern were warnings from the U.S. Federal Communications Commission that electromagnetic waves from cellphones could shut down electronic devices in hospitals.

These fears were firmly enough entrenched to have made their way into popular legend.

According to an e-mail that made the rounds in 2003, a young girl died during a routine operation because "some idiot" used a cellphone near the operating theatre.

"Be compassionate," this e-mail went on to urge. "Do not use your hand phone at any hospital or places where you are told not to use it. You might not be caught in the act, but you might have killed someone without knowing it."

That message was later debunked by snopes.com (an Internet site about urban legends), and, according to a study released by the Mayo Clinic, the fears it addresses are groundless.

The article goes on to note some of the findings of the Mayo Clinic study then returns to a comment from the Vancouver Hospital.

But the policy-makers at VCH are not convinced. Spokeswoman Brandy Delves said the hospital has had the same policy since 1996, banning cellphones and other hand-held communication devices in key areas. "We have reviewed all the recent literature and have decided to keep our current policy," she said last night.

This is interesting. It's very hard to prove a negative so one can't expect absolute "proof" that cellphones are harmless in a hospital setting. Once the idea of possible danger has been planted it always seems better to be safe than sorry. Nevertheless, all of the so-called evidence of danger has been refuted and there are hospitals that have lifted the ban. Those hospitals do not seem to be losing patients due to unexpected equipment failures. In light of data like this why would "policy-makers," many of whom are doctors, not make a rational decision to lift the ban?

What is it about our psychology that causes some people to reject scientific/rational evidence when it conflicts with their superstitions? Even people who are trained in "evidence-based" medicine seem to be incapable of applying the methodology in real life.

The Molecular Basis of Roundup® Resistance

Recall that glyphosate inhibits the enzyme EPSP synthase, an enzyme that catalyzes the following reaction in the chorsimate biosynthesis pathway [How Roundup® Works].

Funke et al. (2006) explored the molecular basis of this inhibition by looking at the structure of EPSP synthase from the C4 strain of Agrobacterium sp. This is the resistant form of the enzyme that has been genetically engineered into Roundup Ready® plants [Roundup Ready® Transgenic Plants].

Note that the structure of glyphosate resembles one of the substrates of the reaction; namely phosphoenolpyruvate (PEP). It was already known that glyphosate binds tightly to the active site of the enzyme and inhibits the reaction by preventing PEP binding. As it turns out, the site for glyphosate binding is exactly the same as the site for PEP binding and this explains the inhibition.

Funke et al. (2006) looked at the C4 EPSP enzyme with and without one of the other substrates: namely, shikimate-3-phosphate (sometimes called shikimate-5-phosphate). The results reveal the precise location of the active site of the enzyme at the base of a cleft between two domains. This form of the enzyme is called class II EPSP synthase because it is distantly related to the class I enzymes in other bacteria and eukaryotes (30% amino acid sequence identity). This is the first paper to examine the structure of a class II enzyme.

As an aside, notice that the enzyme closes up a little bit when the substrate binds—sort of like a Pacman icon. This mechanism of substrate binding is called induced fit and it's proving to be more common than most people realized.

The glyphosate resistant (Roundup Ready®) mutation in C4 EPSP synthase is a substitution of Alanine (A) for Glycine (G) at amino acid position 100. The glyphosate molecule fits nicely into the wild type G100 form of the enzyme (lower image) and it excludes PEP binding completely. Note that glyphosate (green) is in an extended configuration when it is bound. The dotted lines represent non-covalent interactions between the enzyme and the glyphosate molecule. The blue dots are "frozen" water molecules embedded in the active site.

In the mutant form of the enzyme the extra methyl group on alanine is just big enough to cause glyphosate to distort so it can no longer lie in the optimal extended configuration (top image). This means that glyphosate binds much more weakly and doesn't inhibit enzyme activity.

The important point is that the active site can still accommodate phosphoenolpyruvate because it is smaller than glyphosate. What this means is that the overall activity of the enzyme in the absence of glyphosate is unaffected. There are lots of EPSP synthase mutants that don't bind glyphosate but in almost all cases the rate of the reaction is drastically reduced because PEP binding is also weakened. For example, if you mutate the glycine to alanine at the equivalent position in other bacterial or plant enzymes you abolish PEP binding along with glyphosate binding.

What's special about the class II enzymes in general and the Agrobacterium sp. enzyme in particular, is that the amino acids surrounding the PEP binding pocket are positioned just right so that a slight shift can exclude glyphosate without affecting phosphoenolpyruvate. This is mostly due to the positions of the charged amino acid side chains that form weak interactions with the oxygen atoms and the nitrogen of glyphosate; for example, arginines (R) at 128, 357, and 405; lysine (K) at 28; and glutamate (E) at 354.

The results of this study not only shed light on the mechanism of glyphosate resistance but they also help explain the lack of Roundup® resistant plants. Apparently, the class I enzymes in plants have a binding pocket that is difficult to mutate in a way that excludes glyphosate while still allowing PEP binding. Nevertheless, some examples of Roundup® resistant plants are known. I'll describe them tomorrow.

(Funke et al. had to do a bit of sleuthing and reconstruction in order to solve the structure of the C4 EPSP synthase. The C4 strain of Agrobacterium sp. has, naturally enough, not been given out to scientists outside of Monsanto laboratories. So Funke et al. got the amino acid sequence from US Patent 5633435 and reverse engineered the nucleotide sequence of the gene. They synthesized the nucleotide sequence and amplified the fragments by PCR. They then tacked on a promoter and a transcription termination signal and cloned the articfial gene into an E. coli plasmid. The artificially reconstructed protein was then expressed in E. coli, isolated, purified, and crystallized.)

Funke, T., Han, H., Healy-Fried, M,L., Fischer, M., and Schonbrunn, E. (2006) Molecular basis for the herbicide resistance of Roundup Ready crops. Proc. Natl. Acad. Sci. (USA) 103:13010-13015. [PubMed]

Jim Watson Comments on GM Crops and Recombinant DNA Technology

 
Watch this clip of Jim Watson commenting on recombinant DNA technology and its uses in making genetically modified plants [Dr. James Watso]. The video is produced by Monsanto so those of you with a bias can easily dismiss it without a second thought.

The rest of you should pause to think about what Watson is saying. He's definitely outspoken but is he right? He says ...

Recombinant DNA is the safest technology I’ve ever heard.

Read Nobel Laureate: Paul Berg for information about Asilomar and the recombinant DNA controversy of the 1970's. Read the comments to that article for other points of view and references to Watson. Hsien Hsien Lei has an opinion and so does Jeremy.

The Great Muffin Joke Debate

 
Check out The Great Muffin Joke Debate at Cosmic Variance. I think it's funny. It's not ROTFLMFHO funny, but it does make me smile. John Tierney does not think it's funny. Is there a correlation between whether you think the joke is funny and whether you "get" irony and sarcasm?