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Wednesday, November 20, 2013

Fred Sanger (1918-2013)

BBC News is reporting that Fred Sanger
has died [Frederick Sanger: Double Nobel Prize winner dies at 95]. Sanger is one of the few people to win two Nobel Prizes. His first was for sequencing insulin and his second was for developing a technique for sequencing DNA (Sanger sequencing).

Most people, even most scientists, have no idea how much he influenced molecular biology. Sanger worked at Cambridge (UK). When Francis Crick first arrived at Cambridge in 1947 he soon met a number of important scientists. Here's how Horace Freeland Judson describes Sanger in The Eight Day of Creation (pp. 88-89).
One of these in particular, the biochemist Frederick Sanger, came to have great intellectual importance in Crick's thinking and then to molecular biologists generally as the field developed. Sanger is temperamentally and in scientific style Crick's opposite. Where many scientists, Crick among them, flower at conferences and do a great deal of their science by talking, Singer is a quiet man—reticent, even shy, a man who worked with his hands, at the bench. He almost never talked to the press, never despite the editor's importuning wrote the big article for Scientific American. One might spot him bicycling to work on a spring morning, in a drab brown coat, in the rain. Once I stopped to talk with him in the corridor of the laboratory building, where he was waiting in the queue for his turn at the ultraviolet-light box, in order to illuminate the spots on a sheet of chromatography paper he was holding. Sanger is a Quaker by upbringing, and stayed at Cambridge through the second world war; holding only a junior fellowship in the biochemistry department, and even when the war dried up the usual sources of research funds, with family money he was able to keep going. In the course of nearly a decade, beginning in the mid-forties, Sanger settled upon the new techniques of chromatography to determine the amino-acid sequences of the two chains of the bovine insulin molecule. He proved that the sequences are unique and always the same, meaning that every molecule of insulin in every cow is exactly like every other. Yet the sequences show no general periodicities: they are not predictable from ordinary chemical rules.

Sanger published very rarely. His papers came to be red with heart in mouth by other scientists, for they are technically brilliant. Even as he worked, though, the news slowly spread and the implications sank in. For one thing, his department held a biochemistry tea club where perhaps once a month research that was relatively finished, though not yet submitted for publication, was presented. Brigitte Askonas, later an important figure in immunology in England, came to Sanger's lab as a doctoral student late in 1948, staying on into 1952. "Even then, Fred had only a minor fellowship—and some had wanted to kick him out," she told me once. "When one would ask him how his work was going, he would say very little. 'Oh, I've got another peptide.'" Then at a lab meeting he would bring a stack of cards showing overlapping short sequences, and slowly, diffidently, build up his latest segment of the molecule. "Crick always came to the tea club," Askonas said. "And he always asked awkward questions. Enfant terrible questions. And then he would explain, somewhat disingenuously, 'You see, I'm just learning.'" Sanger's general conclusion was forceful by 1949, when he went to the annual symposium on quantitative biology at Cold Spring Harbor (his only such visit). In a paper published on the first of June of that year—the earliest of his magisterial series of papers on insulin appearing every odd-numbered year until 1955—he was already able to say that "there appears to be no principle that defines the nature of the [amino-acid] residue" occupying any particular position in a protein. The conclusion was definitive by 1951. For this work and the methods of sequencing he invented to do it, Sanger was awarded the Nobel Prize in chemistry in 1958. (He later turned to the more difficult problem of sequencing nucleic acids, which earned him a share of another Nobel Prize, in 1980. Crick, from his first arrival in Cambridge, new of Sanger's work step by step, months and even years before new steps were published.


Tuesday, November 19, 2013

The Green Party (of Canada) vs Science

The Green Party of Canada is led by Elizabeth May who has a seat in parliament. The Green Party (of Canada) advocates many positions that are anti-science [Do Not Vote for the Anti-Science Green Party].

The National Post is a major Canadian newspaper that leans to the right so it has never been a friend on the Green Party. In spite of this bias, they got something right when they wrote, Elizabeth May’s Party of Science seems to support a lot of unscientific public policies.

The article was written by Tristin Hopper. Here's what he says in the opening paragraphs.
Two months ago in Halifax, Green Party leader Elizabeth May appeared at a Stand Up For Science rally; one of many demonstrations held across the country to protest, among other things, a Canada-wide “muzzling” of government scientists.

“You may not like the opinions you get from science, but you have to listen to science,” Ms. May told Halifax radio.

Only a week before, however, Ms. May had been at a town hall meeting in her Saanich, B.C. riding telling her constituents not to trust federal science — albeit from a different agency than the ones being defended on the streets of Halifax.

“Agriculture Canada is increasingly a corporate model for profits, for Monsanto and Cargill, and certainly not to help farmers and certainly not to ensure safe food for Canadians,” said Ms. May.
The point needs emphasis. There's really no serious scientific debate over the safety of GM food. It is safe to eat. That does not mean that every single scientific paper that has ever been published proves that GM food is safe. You can always find some paper somewhere that backs up your preferred view of a scientific issue. Most Sandwalk readers know that real science is determined by the consensus views of the experts in the field and not by the rogue scientists who disagree. If you've been reading my blog, you will also know that in any debate that involves science both sides have to appear to have science on their side because, if you don't have science on your side in the 21st century, you've lost the debate.

Here's how Michael Kruse puts it. (He is quoted in the National Post article.)
“I really think the Green Party is just doing the same things everybody else does, which is to make up an idea that matches with your ideology, and then go looking for evidence to support it,” said Michael Kruse, chair of Bad Science Watch, a non-profit devoted to rooting out false science in public policy.
Michael has it right. The Green Party is doing exactly what a long list of groups do when their favorite beliefs aren't supported by the scientific consensus. They cherry-pick. Then they make up conspiracy theories to explain why climatologists, evolutionary biologists, nutritional scientists etc. are misleading the general public about the real science in their field.
In a July essay, Aaron Larsen, a Canadian-born Harvard post-doctoral fellow publicly called out the Green Party—his preferred choice at the ballot box—for its platform declaring that genetically-engineered crops are a “potentially serious threat to human health and the health of natural ecosystems.”

“Just to be clear, there has never been a single reputable, peer-reviewed study that has found any link between the consumption of genetically modified foods and adverse health effects,” he wrote.
That's why the Green Party is anti-science. There are many other examples of Green Party policies that are anti-science. You should not vote for the Green Party if you value science. I hate to think what might happen to science if it ever became the governing party of Canada.


[Hat Tip: Canadain Atheist]

Monday, November 18, 2013

Another Example of IDiot Reasoning

My philosopher friend, Chris DiCarlo, and I are trying to teach our students how to think critically. We use the evolution/creation debate as an example of how to make valid arguments (and how not to make them). Two of the important points we emphasize are that you should try to avoid the strawman fallacy and you should try very hard not to misrepresent your opponent's point of view. (These are related.)

I tell my students that it's important to understand what your opponents are arguing—you must try and walk in their shoes, so to speak. This is crucial. You may decide that their arguments are completely wrong and ridiculous but you must make sure you interpret them correctly or you are guilty of several sins.

You might recall that I recently posted a comment about David Evans, Executive Director of the National Science Teachers Association (NSTA) [David Evans Says, "Teach What the Vast Majority of Scientists Affirm as Settled Science"]. I liked the idea that we should teach what the "vast majority of scientists affirm as settled science." When it comes to teaching, you have to make a decision about what is good science and what is bad science and it seems reasonable to NSTA (and to me) that the consensus among the experts is a good criterion to use. If you read the comments in that post you'll see that it's not always easy to decided what that consensus is, but that's not the main point.

Monday's Molecule #223

Last week's molecule was a Holliday junction, one of the key intermediates in recombination. It's named after Robin Holliday who has since retired from science to concentrate on being a sculptor. He has produced several "biological" sculptures including "DNA Structure" (top) and "Cross Over" (bottom). The winner is Caroline Josefsson from British Columbia. The undergraduate winner is Andrew Wallace but since he lives in Australia, I suspect he won't be coming to lunch [Monday's Molecule #222].

Today's molecule (below) is not one of my favorite molecules for many reasons. However, it's pretty important in some species. Name the molecule, being as specific as you can without resorting to IUPAC rules. I need the most common name as well as a more detailed name.

Email your answer to me at: Monday's Molecule #223. I'll hold off posting your answers for at least 24 hours. The first one with the correct answer wins. I will only post the names of people with mostly correct answers to avoid embarrassment. The winner will be treated to a free lunch.

There could be two winners. If the first correct answer isn't from an undergraduate student then I'll select a second winner from those undergraduates who post the correct answer. You will need to identify yourself as an undergraduate in order to win. (Put "undergraduate" at the bottom of your email message.)

Thursday, November 14, 2013

Toronto Mayor Rob Ford Likes Tim Hortons Coffee!

The mayor of Toronto is an alcoholic, a drug user (cocaine), and many other things that make him unsuitable to hold any political office. The city of Toronto is trying really hard to get him to resign or take a leave of absence but there's not much they can do if he refuses to act in an honorable and responsible manner.

It's really hard to find anything likeable about the man but I did notice that he likes Tim Hortons coffee. Look at what's in his hand as he walks down Danforth Street in drunken stupor! He can't be all bad, can he?



Wednesday, November 13, 2013

Baldness Is not a Disease. It Does not Need to Be "Cured"

A recent article in New Scientist made me annoyed. The title in the print edition is Cure for Baldness Finally Cuts It. It starts off with ...
We may be a hair's breadth away from a cure for baldness.
Baldness is not a disease so it doesn't need to be cured.1 Gray hair is also not a disease and neither are the wrinkles that appear on your face as you get older.

You may choose to disguise baldness with hair transplants or paint your white hairs to make it look like you don't have them. You can even inject botox to hide wrinkles. If you do this, the only disease you have is vanity. And stupidity, for letting the cosmetic industry trick you into feeling guilty about a perfectly natural phenomenon.

I'm never going to let my tax money pay for your vanity "cure." Don't even ask if it should be covered by our public health insurance.


1. Don't quibble. You know that what I'm talking about is the normal kind of baldness in men that develops as you get older.

Tuesday, November 12, 2013

David Evans Says, "Teach What the Vast Majority of Scientists Affirm as Settled Science"

The National Science Teachers Association (NSTA) is responsible for The Adaptation Assessment Probe that I criticized last week. It's a remarkably poor question on adaptation—expecially considering that it was designed by teachers.

David Evans1 is the Executive Director of NSTA and he has written about the recent attempts to insert creationism into textbooks in Texas [In Texas, Standing Up for Science]. He says one very good thing in these two paragraphs.
There are many ways that humans come to know, experience, understand and appreciate the world in which we live. Consider, for example, the different realms of religion, science and art. We can all appreciate the beauty of a sunset without understanding that its beauty comes from the energy of a thermonuclear reaction and the refraction of its light in the atmosphere. Likewise, understanding the scientific processes of the sunset does not prevent one from capturing its beauty on canvas or making a spiritual connection.

There are countless differing opinions about how best to educate our children, but presenting non-scientific or religious ideas in science class or in science textbooks is simply wrong and blurs the line about what is and what is not science. This will only confuse and mislead students and does nothing to improve the quality of science education and everything to weaken it. Decisions about what counts as science should not be a popularity contest. No matter how many people object, public schools must teach what the vast majority of scientists affirm as settled science.
I like the way he expresses the idea that we "must teach what the vast majority of scientists affirm as settled science." This avoids getting into definitions about what counts as science. It avoids the "methodological naturalism" trap. Well done!

The next paragraph isn't quite as good. It could have been a lot better. All he had to do was leave out the little phrase that I underline and enclose in brackets. It would not change the meaning but it would properly reflect "what the vast majority of scientists accept as settled science."
Texas students deserve the best science education possible, as do students everywhere. This means teaching them sound science, including evolution [by natural selection] as a major unifying concept in science. It is firmly established as one of the most important and robust principles in science, and is the best and most complete scientific explanation we have for how life on Earth has changed and continues to change. Furthermore, the very foundation of science is grounded in, and based upon, evidence. Classrooms will use the textbooks Texas adopts for years (the last science textbook adoption was a decade ago). Compromising the integrity of science for a whole generation of students to satisfy a few vocal ideologues is simply not acceptable.


1. From the website: "Evans holds a Ph.D. in oceanography from the University of Rhode Island and a bachelor’s degree in mathematics from the University of Pennsylvania. He studied for his teaching certification at Villanova University."

Monday, November 11, 2013

Monday's Molecule #222

Last week's molecule was D-serine. (Not L-serine.) The winner is undergraduate Zhimeng Yu [Monday's Molecule #221].

I was reminded of this week's molecule by a discussion we are having in an evolution forum and by a comment from a student who took a MOOC on genetics. Does it depict something that should be taught in every introductory genetics course? Is it something that should be discussed in an evolution course? You need to name the structure formed by the blue, gray, and black strands. It has a specific name.

Email your answer to me at: Monday's Molecule #222. I'll hold off posting your answers for at least 24 hours. The first one with the correct answer wins. I will only post the names of people with mostly correct answers to avoid embarrassment. The winner will be treated to a free lunch.

There could be two winners. If the first correct answer isn't from an undergraduate student then I'll select a second winner from those undergraduates who post the correct answer. You will need to identify yourself as an undergraduate in order to win. (Put "undergraduate" at the bottom of your email message.)

Mechanisms of Evolution – Philipp Dettmer (2013)

This is a video that's specifically designed to teach the mechanisms (plural) of evolution. It's produced by Philipp Dettmer who, as near as I can tell, is an expert on video presentations but not on evolution. A perfect example of style trumping substance.

How many errors can you spot?




They're Firing Cannons Across the Street!

Today is November 11th and the cannons started blasting at 11am in Queen's Park just across the street from the building where my office is located. It's a day when we should remember the horrors of war and the waste of lives, both civilian and military. It's a day when we should resolve never to let army generals run the world. It's a day to reflect on the many times that we failed to keep the peace and the terrible cost of those mistakes.

So how do we celebrate peace and remember the evils of armies, guns, and bombs? In Toronto we do it by a public display of soldiers dressed in their finest uniforms bedecked with medals. And the army brings its cannons. It's all very glorious.

I long for the day when we don't even have an army and all the cannons are rusting in some junk heap. That will be the day when we have truly learned about the evils of war and the purpose of November 11th.

I agree with PZ Myers when he asks Who deserves honor?


Sunday, November 10, 2013

I'm Related to a Philosopher! Edwin Proctor Robins (1872-1899)

I'm been filing and organizing my mother's genealogical data and I came across a list of people buried in various Prince Edward Island (Canada) cemeteries. One of the tombstones in the Lower Bedeque United Church Cemetery says, "In Memory Of / Edwin Proctor Robins, / Born At / Central Bedeque / July 2, 1872. / Died at / Cornell University, Ithaca, N. Y. / April 19 1899. / Mors Janua Vitae [Death is the gate of [everlasting] life]" [Edwin Proctor Robins].

This was intriguing. I know I am related to all the Robins (Robbins) descendents from Prince Edward Island but I'd never heard of Edwin Proctor Robins. His great-grandfather, Robert Robbins, is a United Empire Loyalist who came to PEI from New Jersey when the American Revolution ended. Edwin Proctor Robins and I are fourth cousins, three times removed. Why did he die at Cornell University?

I still don't know how he died and why he was so young (26 years old) but I did find a book he published on Some Problems of Lotze's Theory of Knowledge. I think the book was first published in 1900—a year after he died. Sounds like Edwin Proctor Robins might have been an epistemologist. Does anyone know anything about my relative or about Lotz's Theory of Knowledge?


Friday, November 08, 2013

Evolution: A Course for Educators: Week One

I'm taking a MOOC! It's called Evolution: A Course for Educators. The principle instructors are Joel Cracraft and David Randle of the American Museum of Natural History in New York (USA).
Welcome to Evolution: A Course for Educators! We’re excited to have almost 13,000 students enrolled in the course and look forward to spending the next four weeks together as we learn about the Tree of Life, natural selection, the history of life, and human evolution, as well as how to incorporate an exploration of these issues into your classrooms.
You can earn a "Verified Certificate" by paying $29.00.

Science Journal Blows It Again

This week's issue of Science contains three separate papers analyzing transcription factor binding sites and chromatin modification sites in the genomes of different individuals. If most of these sites are spurious sites that just happen to contain a consensus sequence, then you would expect a lot of variability since the sites are mostly in junk DNA where the sequences make no difference. That's what all three papers found but, of course, they interpret this to mean that the regulatory sites must be responsible for the variation between individuals.

The papers were summarized in the form of a "press release" called a "Perspective." The complete citation is ...
Furey, T.S. and Sethupathy, P. (2013) Genetics Driving Epigenetics. Science 342:705-706. [doi: 10.1126/science.1246755]
These authors are affiliated with several departments at the University of North Carolina in Chapel Hill but, most significantly, they are part of the Carolina Center for Genome Sciences. This strongly suggests that they know something about genomes.

Thursday, November 07, 2013

Why Humanists Should Be Vegans

I am not a humanist and I'm not a vegan. Sarah Moglia explains why I don't subscribe to either of those two beliefs. I first saw this on Skepchick: Why Vegan Values are Humanist Values.



Alfred Russel Wallace (8 January 1823 – 7 November 1913)

Alfred Russel Wallace died1 on this day in 1913. That's exactly one hundred years ago.

Jerry Coyne has posted a guest article by Andrew Berry that should be required reading for everyone who admires Wallace but wonders why he didn't get much credit for natural selection [A guest post for Wallace Day].

The IDiots over on Evolution News & Views (sic) have, of course, an entirely different version of the truth [Counter the History Deniers: Get Out the Word on Alfred Russel Wallace; We've Got the Resources You Need]. Here's what David Klinghoffer has to say about historical truth.
Today is the 100th anniversary of the death of Alfred Russel Wallace (1823-1913), co-discoverer with Charles Darwin of the theory of evolution by natural selection.

If you follow us at all at ENV you'll already know that the scientific and scholarly communities have done a terrible disservice to Wallace's legacy by airbrushing out the fact that he broke with Darwin over what University of Alabama science historian Michael Flannery calls "intelligent evolution." That is, Wallace's steadily more certain and detailed view that an "overruling intelligence" guided the evolutionary process. He anticipated major elements of the modern theory of intelligent design. Oh, the irony! It burns! It burns!

Well, the massive effort by scientists, journalists, bloggers and others to defend Darwinian theory often proceeds by such airbrushing. You can fight back and counter the censors by passing along the historical truth to friends, students, and teachers, online and in person.

...

It's time everyone agreed to be honest about Wallace -- about the important historical truth that one of the two men to first spell out the modern theory of evolution came to reject that theory as an adequate explanation of life's development, in favor of proto-intelligent design. Toward that end, please join us in refuting the history deniers.
You just can't make this stuff up. Every time you think that the IDiots can't get any worse, along comes one of them to show you that you were being far too optimistic.


1. I refuse to use the stupid phrase "passed away."

Wednesday, November 06, 2013

The Adaptation Assessment Probe

I'm taking a MOOC on evolution that's designed for educators [Evolution: A Course for Educators]. One of the things that was covered in the first lecture was a test on "adpatation" taken from a book called "Uncovering Student Ideas in Science, Volume 4: 25 New Formative Assessment Probes. The book is published by the National Science Teachers Association (NSTA).

Let's take the test ...
Adaptation

Three friends were arguing about what would happen if a population of rabbits from a warm, southern climate were moved to a cold, northern climate.1 This is what they said:

Bernie: "I think all of the rabbits will try to adapt to the change."

Leo: "I think most of the rabbits will try to adapt to the change."

Phoebe: "I think few or none of the rabbits will try to adapt to the change."

Which person do you most agree with and why? Explain your ideas about adaptation.
I agree with Bernie. I think all the rabbits will try to adapt to the colder weather by finding warmer, more cozy, burrows and by cutting down on their activity during the cold nights. I think they will adapt by eating more. If hair growth is related to temperature, as it is in some mammals, then the rabbits will adapt by growing thicker coats.

Let's see how I did.

Oops! That's not the "right" answer. The correct answer is what Phoebe said. Here's what they say on the website ...
The best answer is Phoebe's: "I think few or none of the rabbits will try to adapt to the change." The key word here is try. Biological adaptation involves genetic variation that allows some individuals to survive a particular change, such as a change in the environment, better than others.
I didn't read the question carefully. I didn't notice that what they were asking about was not just "adaptation" but "adaptation by natural selection." Silly me.

We turned our clocks back one hour last weekend and I'm still adapting adjusting to the change.

If this is the kind of nonsense that the National Science Teachers Association thinks is important then it's no wonder that evolution education is in trouble.


1. Not a good test for Australian students! :-)

Tuesday, November 05, 2013

Test Your Scientific Skepticism

I once posted a series of articles on Roundup® (glyphosate) explaining how it works and how one makes Roundup®-Ready genetically modified plants.

A reader has alerted me to a paper published last Spring that purports to show the dangers of glyphosate. This paper has gone viral—as you might have guessed. It led to an interview with the lead author, Anthony Samsel, on Moms Across America [Part 1 Samsel on Glyphosate and Autism, Asthma, COPD, Diabetes and more]. Here's part of what blogger Zen Honeycutt has to say about this paper ...

Stop Using the Term "Noncoding DNA:" It Doesn't Mean What You Think It Means

Axel Visel is a member of the ENCODE Consortium. He is a Staff Scientist at the Lawrence Berkeley National Laboratory in Berkeley, California (USA). Axel Visel is responsible, in part, for the publicity fiasco of September 2012 where the entire ENCODE Consortium gave the impression that most of our genome is functional.

He is also the senior author on a paper I blogged about last week—the one where some journalists made a big deal about junk DNA when there was nothing in the paper about junk DNA [How to Turn a Simple Paper into a Scientific Breakthrough: Mention Junk DNA].

Dan Graur contacted him by email to see if he had any comment about this misrepresentation of his published work and he defended the journalist. Here's the email response from Axel Visel to Dan Gaur.

Sunday, November 03, 2013

The Carnival of Evolution #65: Horror Host Edition

The latest issue of Carnival of Evolution is hosted by PZ Myers, a developmental biologist with an interest in evolution (among other things). He's a professor at the University of Minnesota in Morris. PZ blogs at Pharyngula. Perhaps you've heard of it?

Read: The Carnival of Evolution #65: Horror Host Edition.
I prepared for the Carnival of Evolution late at night over the last several days, bracketing the Halloween holiday, and coupled them with my traditional custom of watching horror movies. It wasn’t a good match. The evolutionary stories were far more frightening!
There are several dozen contributions and some of them are very scary.

If you want to host a Carnival of Evolution please contact Bjørn Østman. Bjørn is always looking for someone to host the Carnival of Evolution. He would prefer someone who has not hosted before but repeat hosts are more than welcome right now! Bjørn is threatening to name YOU as host even if you don't volunteer! Contact him at the Carnival of Evolution blog. You can send articles directly to him or you can submit your articles at Carnival of Evolution although you now have to register to post a submission. Please alert Bjørn or the upcoming host if you see an article that should be included in next month's. You don't have to be the author to nominate a post.

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How Many Different Cell Types in an Adult Human?

We're having a little discussion about complexity in the comments from my post of last Friday [Vertebrate Complexity Is Explained by the Evolution of Long-Range Interactions that Regulate Transcription?]. I pointed out that many scientists just can't come to grips with the idea that humans aren't much more complicated than other animals. We are not special. I call this The Deflated Ego Problem.

One of the minor arguments in favor of human exceptionalism is the idea that we (mammals?) have more cell types that other species. Therefore, we are more complex. The number that's often bandied about is 210 cell types. PZ Myers debunks this myth (once again) in Methinks it is like a fox terrier". I love it when people like PZ make oblique references to Stephen Jay Gould as he does in the title. If you don't know what this has to do with fox terriers then you're in for a double treat.


Friday, November 01, 2013

Vertebrate Complexity Is Explained by the Evolution of Long-Range Interactions that Regulate Transcription?

The Deflated Ego Problem is a very serious problem in molecular biology. It refers to the fact that many molecular biologists were puzzled and upset to learn that humans have about the same number of genes as all other multicellular eukaryotes. The "problem" is often introduced by stating that the experts working on the human genome project expected at least 100,000 genes but were "shocked' when the first draft of the human genome showed only 30,000 genes (now down to about 25,000). This story is a myth as I document in: Facts and Myths Concerning the Historical Estimates of the Number of Genes in the Human Genome. Truth is, most knowledgeable experts expected that humans would have about the same number of genes as other animals. They realized that the differences between fruit flies and humans, for example, didn't depend on a host of new human genes but on the timing and expression of a mostly common set of genes.

This isn't good enough for many human chauvinists. They are still looking for something special that sets human apart from all other animals. I listed seven possibilities in my post on the deflated ego problem:

A "Perfect Painting" Proves that Beneficial Mutations Are Impossible and Neutral Mutations Are Impossible

There are times when the stupidity of creationists just makes you gasp. This is one of those times. The creationist is Denyse O'Leary, who holds some kind of record for stupidity.

In this case she can be partially excused since she seems to be quoting someone named Laszlo Bencze. You can read the whole thing at: Is there no such thing as a neutral mutation? Art explains why there probably isn’t.

Denyse quotes Laszlo Bencze (I think) talking about a painting by French artist Jean-Auguste-Dominique Ingres (1780-1867).
Here is a famous and gorgeous painting by Ingres which I just saw in person at the Frick Museum in New York.

Let’s imagine we can improve it by adding a dot of paint 1mm in diameter to it. In evolutionary terms we will give it a “point mutation,” the smallest possible change. If we add this dot randomly, the odds are pretty high it will damage the painting by creating an obvious, intrusive speck. So let’s give evolution every advantage. Let’s make the process far more likely to succeed by having the great contemporary painter, David Hockney, add the speck wherever he thinks it will “do the most good.”

Now I happen to know that Hockney is a great admirer of Ingres and would be shocked and dismayed at any such request. But if a cruel tyrant under pain of death forced him to do it, Hockney would understand that there is no place he could possibly place a dot of paint that would improve the painting. Like a living thing, the painting is so well crafted that anything he might add to it could only be neutral at best. So Hockney would strive to place the most neutral dot he could by choosing a pigment that matched some dark portion of the painting and hope to hide his speck there.

But would such a speck be truly neutral? No matter how well it matched the color, wouldn’t it be visible as a raised dot under the right lighting conditions? And wouldn’t that actually damage the painting even if ever so slightly? And this is precisely Sanford’s point. In the world of biology it is impossible to create a neutral mutation. The change may be extremely slight, even invisible, yet always a degradation no matter how small.
When you think about it, it's really very sad this this is the best the Intelligent Design Creationists can offer. They are so ignorant that you can almost feel sorry for them.


Wednesday, October 30, 2013

Time to Re-Write the Textbooks! Nature Publishes a New Version of the Citric Acid Cycle

I was looking through my copy of Nature the other day trying to take seriously all the special reviews on "Transcription and Epigenetics." One article caught my eye ...

Gut, P. and Verdin, E. (2013) The nexus of chromatin regulation and intermediary metabolism. Nature 502:489-498. [doi: 10.1038/nature12752]
Living organisms and individual cells continuously adapt to changes in their environment. Those changes are particularly sensitive to fluctuations in the availability of energy substrates. The cellular transcriptional machinery and its chromatin-associated proteins integrate environmental inputs to mediate homeostatic responses through gene regulation. Numerous connections between products of intermediary metabolism and chromatin proteins have recently been identified. Chromatin modifications that occur in response to metabolic signals are dynamic or stable and might even be inherited transgenerationally. These emerging concepts have biological relevance to tissue homeostasis, disease and ageing.
The authors argue that, among other things, methylation of histones is regulated by changes in the concentrations of some citric acid cycle metabolites. I find it difficult to imagine that the concentrations of the citric acid cycle intermediates could change significantly enough to act as allosteric effectors but that's not what grabbed my attention.

It's the figure showing the citric acid cycle (TCA cycle) that shocked me.


Textbooks show that the products of the citric acid cycle are ...
That's three NADH, one QH2, and one GTP (or ATP) for a total of ten ATP equivalents. The new version, published last week in the most prestigious science journal in the world, shows that there are six NADH produced per cycle for a total of 15 ATP equivalents. It must be correct because this is a paper about intermediary metabolism and it was reviewed by experts in the field. Unfortunately, the authors don't give a reference to this new information. I assume that it's common knowledge among the top metabolism researchers so they didn't bother citing the papers.

Can anyone out there direct me to the revolutionary papers that I missed?

P.S. I'm not even going to mention that FADH2 is NOT a product of enzyme-catalyzed β-oxidation.


I Just Signed Up for an Evolution MOOC!

I'm not a big fan of MOOCs but I just couldn't resist a course called "Evolution: A Course for Educators". The instructors are two Ph.D. employees from the American Museum of Natural History in New York (USA). As you probably know, the American Museum of Natural History is very proud of its tradition in education. Here's what they say on their website.
The American Museum of Natural History is one of the world’s preeminent scientific, educational and cultural institutions. Since its founding in 1869, the Museum has advanced its global mission to discover, interpret, and disseminate information about human cultures, the natural world, and the universe through a wide-ranging program of scientific research, education, and exhibition.
This is a course for educators and that's right up my alley. You may want to sign up as well. Here's the description and the video.
How are all of the species living on Earth today related? How does understanding evolutionary science contribute to our well-being? In this course, participants will learn about evolutionary relationships, population genetics, and natural and artificial selection. Participants will explore evolutionary science and learn how to integrate it into their classrooms.

....

The AMNH course Evolution: A Course for Educators provides an overview of biological evolution for educators. Informed by the recently released Next Generation Science Standards, the course explores the history of evolutionary theory and the evidence that supports it. We will learn about patterns of human evolution and societal implications of modern evolutionary biology, and how scientists determine relatedness among living and extinct organisms. Course participants will bring their understanding of course themes - along with content resources, discussion questions, and assignments - into their own teaching.
It's a bit disturbing that the Next Generation Science Standards don't mention random genetic drift, Neutral Theory, speciation, or population genetics [Natural Selection and Evolution] but the course promises to cover population genetics and I assume that it will also cover all mechanisms of evolution since it's being taught by an evolutionary biologist (Joel Cracraft).

The purpose of the course is to train the next generation of high school (and university) teachers. One of the instructors, David Randle, is an expect on education. We all know that teachers need to be updated on modern evolutionary theory.

It starts next Monday. I'll let you know how I'm doing when I write the first test.



Tuesday, October 29, 2013

The Khan Academy and AAMC Teach Evolution in Preparation for the MCAT

Ross Firestone is a 2nd year MD/PhD student at the Albert Einstein College of Medicine. He is one of the winners of the MCAT Video Competition. Apparently the Khan Academy and the Association of American Medical Colleges were impressed with his presentations on evolution. You can see all six videos at Evolution and population dynamics.

I'm posting the first one on Evolution and Natural Selection. It's all about natural selection but it's a very strange kind of natural selection. The organisms are parthenogenic and each individual is genetically programed to have a certain probability of reproducing. One type has a 50% probability of reproducing and another type has only a 25% probability of reproducing. These probabilities seem to be independent of any competition between them. Each successful individual produces four offspring. After some time the number of one type remains constant (25% probability) but the number of the other type (50% probability) doubles with each generation. This is natural selection according to Ross Firestone.

"Naturally," I was disappointed that natural selection was the only mechanism mentioned. There's nothing about random genetic drift in this video and nothing about the stochastic nature of natural selection. But my face lit up when I saw that there was another video on "Alternative Selection: Learn about driving forces of evolution other than natural selection." This could almost make up for screwing up the description of natural selection.

Alas, the second video is even worse. The "alternatives" are group selection and artificial selection. It gets even more worse. The example of group selection is the grandmother hypothesis. According to Ross Firestone, the fact that grandmothers help their grandchildren survive is group selection.

The video on "Bottlenecks and the environment" is also quite interesting. I didn't know that that the peppered moth story is an example of a bottleneck. Did you?


I think these videos are horrible—so horrible, in fact, that the Khan Academy should take them down. What do you think?

Are you wondering why a 2nd year med student feels so confident that he knows enough about evolution to teach it to pre-med students? Me too.


The Khan Academy and AAMC Teach the Central Dogma of Molecular Biology in Preparation for the MCAT

Here's a presentation by Tracy Kovach, a 3rd year medical student at the University of Virginia School of Medicine. Sandwalk readers will be familiar with my view of Basic Concepts: The Central Dogma of Molecular Biology and the widespread misunderstanding of Crick's original idea. It won't be a surprise to learn that a 3rd year medical student is repeating the old DNA to RNA to protein mantra.

I suppose that's excusable, especially since that's what is likely to be tested on the MCAT. I wonder if students who take my course, or similar courses that correctly teach the Central Dogma, will be at a disadvantage on the MCAT?

The video is posted on the Khan Academy website at: Central dogma of molecular biology. What I found so astonishing about the video presentation is that Tracy Kovach spends so much time explaining how to remember "transcription" and "translation" and get them in the right order. Recall that this video is for students who are about to graduate from university and apply to medical school. I expect high school students to have mastered the terms "transcription" and "translation." I'm pretty sure that students in my undergraduate class would be insulted if I showed them this video. They would be able to describe the biochemistry of transcription and translation in considerable detail.


There are people who think that the Central Dogma is misunderstood to an even greater extent than I claim. They say that the Central Dogma is widely interpreted to mean that the only role of DNA information is to make RNA which makes protein. In other words, they fear that belief in that version of the Central Dogma rules out any other role for DNA. This is the view of John Mattick. He says that the Central Dogma has been overthrown by the discovery of genes that make functional RNA but not protein.

I wonder if students actually think that this is what the Central Dogma means? Watch the first few minutes of the video and give me your opinion. Is this what she is saying?


The Khan Academy and the Association of American Medical Colleges (AAMC) Team Up to Teach Evolution and Biochemistry for the New MCAT

Theme

Better Biochemistry
Students have to write an exam called the MCAT in order to get into American Medical Schools (Canadians students also write the MCAT). The exam is created and marked by the Association of American Medical Colleges (AAMC). The format of the exam is changing in 2015 to include more biochemistry and molecular biology. This means that "pre-med" students will likely be taking more biochemistry and molecular biology courses.

Most American schools teach to the MCAT in their biochemistry and molecular biology courses because there are large numbers of wannna-be doctors in their class. The biochemistry lecturers feel that it's their duty to prep the pre-med students to pass the MCAT. This has a devastating effect on American biochemistry courses [Better Biochemistry: Teaching to the MCAT?] [Better Biochemistry: Teaching ATP Hydrolysis for the MCAT]. It is inconsistent with the American Society for Biochemistry and Molecular Biology (ASBM) goals of developing concept-driven courses that focus on fundamental principles [Fundamental Concepts in Biochemistry and Molecular Biology ].

The Khan Academy is taking advantage of the new MCAT in 2015 by posting a series of videos on basic biochemistry and evolution. The content is approved by the AAMC in order to make sure it is suitable for MCAT preparation. Here's what they say on their website [Khan Academy MCAT].
This collection is being developed for the revised MCAT® exam that will first be administered in spring 2015. Videos will be added to the collection through fall 2014. All content in this collection has been created under the direction of the Khan Academy and has been reviewed under the direction of the Association of American Medical Colleges (AAMC). All materials are categorized according to the pre-health competencies tested by the MCAT²⁰¹⁵ exam; however, the content in this collection is not intended to prescribe a program of study for the MCAT²⁰¹⁵ exam. The content is also included in the Pre-health Collection within MedEdPORTAL’s iCollaborative sponsored by the AAMC: www.mededportal.org/pre-health *MCAT® is a program of the AAMC and related trademarks owned by the Association include Medical College Admission Test, MCAT, and MCAT²⁰¹⁵. For more information about the MCAT exam visit : www.aamc.org/mcat2015.
So, how did the Khan Academy prepare the videos? They set up an MCAT Video Competition and picked the best ones. You can read about the winners at MCAT Video Competition Winners. It's an eclectic mix of people but 11 out of 15 winners are medical school students or graduate students. Keep in mind that teaching introductory subjects like evolution and biochemistry is hard and Teachers Have to Know Their Subject.

I'm going to look at the videos on evolution prepared by a second year MD/PhD student at Albert Einstein College of Medicine and videos on biochemistry prepared by a second year MD student at Harvard Medical School and a third year med student at the University of Virginia School of Medicine. Medical students are very bright and very confident of their abilities. We'll see if these students learned enough in their undergraduate courses to be able to create accurate videos that will help university graduates pass the MCAT.

Before looking at some specific examples, let me make a general comment on Khan Academy videos. I've looked at quite a few of them over the years and every single one I've seen is a "kindergarten-level" video. What I mean by that is that the level of the presentation is barely suitable for students beginning high school and in some cases they really are pitched at the level my three-year old granddaughter could understand in a year or two. They certainly aren't up to the level of any university course that I've ever taught.

These MCAT videos are no exception. But they are intended for students who are about to graduate from university. Most of these students will be getting a science degree. The mini courses are intended for students who are about to write the MCAT exam and this should represent the level of knowledge expected of medical students. As a general rule, the students who are preparing for the MCAT have achieved high grades in their biology and chemistry courses and in their biochemistry and molecular biology courses. They wouldn't be considering medical school if they weren't in the top 25% of their class.

Why are the videos pitched at such a low level of education? Is this truly representative of the quality of university education in American universities? Check them out for yourself at: Biomolecules.


Teachers Have to Know Their Subject

I've said it before and I'll say it again. The top three criteria for good teaching are: (1) accuracy, (2) accuracy, and (3) accuracy. Everything else is in fourth place or lower and that includes style. If what you're teaching is not accurate then nothing else matters.

It is hard to teach an introductory science course. You have to go back to basics and make sure that what you cover all the fundamental principles and concepts and that ain't easy. That's why the best teachers in introductory courses are often senior professors and lecturers with plenty of experience behind them. They have learned what's important and what's not and they can tell the difference between wheat and chaff.

PZ Myers puts it very well in a blog post defending teachers [Teaching is so easy, anyone can do it!].
One of the first things you learn when you start teaching is that you have to know the content inside and out — it’s simply not enough to know the bare minimum that you expect the students to master, because as a teacher, you need to push just a bit farther to get them up there. You need to be able to lead them to knowledge, and you need to be able to point off in the distance to all the cool stuff they can learn if they continue. How can you inspire if you’re not drinking deeply from the Pierian Spring yourself?
Keep this in mind next time we discuss teaching evolution and biochemistry. Teachers have to be experts and it takes a lot of work to make sure you know your content. If what you're teaching is not correct then you are not a good teacher no matter what the student evaluations say. And it's not only a question of accuracy—as PZ points out, you need to be more than a few steps ahead of your students in order to inspire them to do better.


Submitting to Carnival of Evolution

PZ Myers is hosting the next Carnival of Evolution [Guess who’s hosting the Carnival of Evolution?]. I tried submitting an article but I was unable to read the stupid fuzzy words that you need to type before submitting. Now I can't submit unless I log in. When I do that, my time seems to expire before I can enter the necessary information. Very frustrating.

So, I figured I would just add a comment on PZ's blog. Easier said than done. You have to log in to his blog and none of my usual names and passwords work. I'm beginning to understand why submissions to the Carnival of Evolution are way down.


Monday, October 28, 2013

Michael Egnor Keeps Digging

When you find yourself in a hole, stop digging.
Will Rogers
I favor teaching biochemistry from an evolutionary perspective and I was pleased to see that ASBMB considers evolution to be one of the fundamental concepts in biochemistry and molecular biology [ASBMB Core Concepts in Biochemistry and Molecular Biology: Evolution]. (ASBMB screws up their description of evolution but at least their heart's in the right place.)

Unless they understand evolution, students can't really understand why some parts of a protein are the same in all species and other parts are quite variable. They certainly can't understand why you can construct a phylogenetic tree from sequences and why this tree closely resembles those trees made from comparing anatomy/embryology. They won't know why those molecular trees are consistent with a fossil record unless they understand evolution.

Monday's Molecule #221

Last week's molecule was 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU). It is an intermediate in the degradation pathway from uric acid (or urate) to carbon dioxide and ammonia. Uric acid is the main breakdown product in purine catabolism. Humans have lost activity of all of the enzymes of this pathway so they excrete urate. Most other species excrete ammonia, although in other animals some of the terminal enzymes have been lost.

Some textbooks do not show the uric acid degradation pathway since it doesn't occur in humans and those textbooks aren't interested in an evolutionary approach to biochemistry (e.g. Berg, Tymoczko, and Stryer). The other majors textbooks (Voet & Voet, Garrett & Grisham, Nelson & Cox [Lehinger]) all show uric acid converted directly to allantoin via urate oxidase. This reaction was shown to be incorrect about 15 years ago. The actual pathway from uric acid to allantoin involves two intermediates; 5-hydroxyisourate and OHCU.
Image Credit: Moran, L.A., Horton, H.R., Scrimgeour, K.G., and Perry, M.D. (2012) Principles of Biochemistry 5th ed., Pearson Education Inc. page 568 [Pearson: Principles of Biochemistry 5/E] © 2012 Pearson Education Inc.
The winner, for the second week in a row, is Jean-Marc Neuhaus. [Monday's Molecule #220]. Jean-Marc lives in Switzerland so I've made arrangements to fly over there to visit him and treat him to two fondues at the Pinte de Pierre-à-Bot in Neuchatel. Jean-Marc was kind enough to send me a menu [PDF]. There are about 30 different fondues to choose from. If you would like to join us you can leave a comment on last week's post.

This week's molecule is related to a discussion we are having on the How Do the IDiots Explain the Origin of Life? post. Can you identify this molecule? You have to be very specific.

Email your answer to me at: Monday's Molecule #221. I'll hold off posting your answers for at least 24 hours. The first one with the correct answer wins. I will only post the names of people with mostly correct answers to avoid embarrassment. The winner will be treated to a free lunch.

There could be two winners. If the first correct answer isn't from an undergraduate student then I'll select a second winner from those undergraduates who post the correct answer. You will need to identify yourself as an undergraduate in order to win. (Put "undergraduate" at the bottom of your email message.)

Sunday, October 27, 2013

Trace Dominguez of Discovery News Says 98% of Your Genome Is Junk

Theme Genomes & Junk DNAI happened to stumble on this video where Trace Dominguez (@trace501) promotes the idea of junk DNA based on the C-value Paradox—a version of the Onion Test. It's good that he tells the general public about junk DNA but it's bad that he equates "noncoding DNA" with "junk DNA." It's really silly to tell people that the only important part of your genome is the 2% that codes for proteins.

Just so you know, some of the important known functions of "noncoding DNA" are [What's in Your Genome?] ....
  1. Genes for functional RNAs like ribosomal RNA, tRNA, and a host of others.
  2. Regulatory sequences that control expression of all genes.
  3. Part of intron sequences.
  4. Origins of replication;specific sites where DNA replication begins.
  5. Telomeres.
  6. Centromeres.
  7. SARS or scaffold attachment regions; sites required to organize chromatin.
  8. Functional transposons or "selfish DNA."
  9. Functional DNA and RNA viruses.
Scientists believe that about 2% of our genome encodes proteins and about 8% has other functions. It is not true that all noncoding DNA is junk. No knowledgeable scientist ever said that.

I realize that the kind of presentation shown in this video doesn't lend itself to a detailed description of noncoding DNA functions but surely we can do better than this? Why not say that scientists have determined that genes make up about 2% of our genome and about 8% contains information necessary for the proper functioning of genes and chromosomes? The rest, about 90%, is thought to be junk?

98% of your DNA is junk


Saturday, October 26, 2013

How to Turn a Simple Paper into a Scientific Breakthrough: Mention Junk DNA

Attanasio et al. (2013) published a paper in Science where they identified several thousand possible enhancers that were active in the facial area of developing mouse embryos. About 200 of them appear to be controlling genes that determine the size and shape of the face. (Recall that there are about 20,000 protein-encoding genes in mammals.)

Lynn Yarris of Lawrence Berkeley National Laboratory in California (USA) wrote up the press release [What is it About Your Face?]. It's a really good press release that fairly represents the published work and explains some of the significance. There's no mention of junk DNA in the press release or the published paper.

This is what it looks like when science correspondent Alok Jha published it in The Guardian.
Faces are sculpted by 'junk DNA'

Though everybody's face is unique, the actual differences are relatively subtle. What distinguishes us is the exact size and position of things like the nose, forehead or lips. Scientists know that our DNA contains instructions on how to build our faces, but until now they have not known exactly how it accomplishes this.

Visel's team was particularly interested in the portion of the genome that does not encode for proteins – until recently nicknamed "junk" DNA – but which comprises around 98% of our genomes. In experiments using embryonic tissue from mice, where the structures that make up the face are in active development, Visel's team identified more than 4,300 regions of the genome that regulate the behaviour of the specific genes that code for facial features.
It's pretty clear that science correspondent Alok Jha doesn't understand what he's writing and it's about time we started publicizing the names of those science writers who mislead the public about science. The consensus among knowledgeable scientists is that at least 80-90% of our genome is junk. It's time for science writers to admit that the science favors junk.

Scientists have known for decades that a lot of noncoding DNA is functional. The idea that all noncoding DNA (98%) is junk is false. No knowledgeable scientist ever made such a claim. It is a myth perpetuated, in part, by ignorant science writers; albeit, aided and abetted by ignorant scientists. Scientists have known for fifty (50!!) years that gene expression is controlled by regulatory sequences in noncoding DNA. Scientists have known for at least that length of time that during embryogenesis different genes are turned on and off and that this is due, in part, to binding of transcription factors to those regulatory sequences (enhancers). Scientists have known for one hundred years that the morphological features of mammals, including humans, are controlled by genes.

Move along folks. There's nothing to see here.


Attanasio, C. et al. (2013) Fine Tuning of Craniofacial Morphology by Distant-Acting Enhancers. Science 342: Oct. 25, 2013 [doi: 10.1126/science.1241006]

Friday, October 25, 2013

Thursday, October 24, 2013

ASBMB Core Concepts in Biochemistry and Molecular Biology: Matter and Energy Transformation

Theme

Better Biochemistry
Tansey et al. (2013) have described the five core concepts in biochemistry and molecular biology. These are the fundamental concepts that all biochemistry instructors must teach and all biochemistry students must understand.

The five core concept categories are:
  1. evolution [ASBMB Core Concepts in Biochemistry and Molecular Biology: Evolution ]
  2. matter and energy transformation [ASBMB Core Concepts in Biochemistry and Molecular Biology: Matter and Energy Transformation]
  3. homeostasis [ASBMB Core Concepts in Biochemistry and Molecular Biology: Homeostasis]
  4. biological information [ASBMB Core Concepts in Biochemistry and Molecular Biology: Biological Information]
  5. macromolecular structure and function [ASBMB Core Concepts in Biochemistry and Molecular Biology: Molecular Structure and Function]
I like the idea of teaching biochemistry from a concept-driven perspective and I like the five categories. However, I was not too pleased with the description of the core concept of evolution [ASBMB Core Concepts in Biochemistry and Molecular Biology: Evolution]. It's one thing to identify the main categories but you also have to get the concepts right if you are going to advocate teaching them!

Let's see how they do with the second core concept.
Matter and Energy Transformation

The Many Forms of Energy Involved in Biological Processes

The energetics of a biological system or process—be it an ecosystem, an organism, a cell, a biochemical reaction—conforms to and is understood in terms of the fundamental laws of thermodynamics. Biological systems capture and process energy from the environment in many forms including that emanating directly from the sun (photons through photosynthesis), heat from the environment (kinetic energy), and energy rich compounds produced by geothermal processes (e.g. sulfur compounds) or other organisms (e.g. carbohydrates). Energy from all sources is chemically converted into useful chemical and physical work in a controlled and regulated fashion. The potential
energy stored in chemical bonds can used to generate motion, light, heat, and electrochemical gradients; likewise, electrochemical gradients can be used to generate motion and new chemical bonds. The input of energy from the environment allows living systems to exist in a state of nonequilibrium with their environment. The discussion of energy and matter conversions in biological systems makes use of the physical concept of changes in Gibbs free energy, or ΔG.
I think we can all agree that a basic understanding of thermodynamics is an important core concept. However, I would have worded this paragraph somewhat differently.

First, I would have mentioned that organisms can capture energy from simple inorganic compounds such as H2 or those containing Fe2+. These are energy sources for many chemoautrophic bacteria. If you are teaching biochemistry from an evolutionary perspective, it's important that students understand how these organisms capture energy. That's the process that is most like the mechanism found in the earliest living cells.1

Second, I would have put more emphasis on using captured energy in biosynthesis pathways. The paragraph mentions that energy can be used to generate new chemical bonds but that doesn't convey the importance of the process. Think about bacterial cells growing and dividing in the ocean or plants growing from a single seed. Most of the energy goes into making proteins, nucleic acids, lipids, and carbohydrates.

Third, I would drop the reference to cells being in "a state of nonequilibrium with their environment." That conceptt is covered under "homeostasis."
Catalysis

Biologically relevant energy and matter interconversions do not occur rapidly enough (often by many orders of magnitude) to support life. In living systems, biological catalysts called enzymes facilitate these reactions. Enzymes are macromolecules, usually proteins or RNA molecules with a catalytic function. Enzymes do not alter reaction equilibria; instead, they lower the activation barrier of a particular reaction so that reactions proceed much more rapidly. The presence of powerful enzymatic catalysts is one of the key conditions for life itself.

Description of the rates of enzymatic reactions represents the subdiscipline enzyme kinetics. Key concepts of kinetics, including the definitions of the terms vo, Vmax, Km, and kcat, constitute a common language for biochemists and molecular biologists in discussing the properties of enzymes.

Students should be able to apply their knowledge of basic chemical thermodynamics to biologically catalyzed systems, quantitatively model how these reactions occur, and calculate kinetic parameters from experimental data.
This is pretty good. I would only add that there are some fundamental concepts of enzyme mechanisms that need to be covered. The idea of a transition state is important. I put a lot of emphasis on oxidation-reduction reactions as a core concept in biochemistry.
Coupling Exergonic and Endergonic Processes

Biochemical systems couple energetically unfavorable reactions with energetically favorable reactions to allow for a wider variety of reactions to proceed.

Students should be able to discuss the concept of Gibbs free energy, and how to apply it to chemical transformations, be able to identify which steps of metabolic pathways are exergonic and which are endergonic and relate the energetics of the reactions to each other.
I have a problem with this section. I don't think that the concepts of "exergonic" and "endergonic" processes are very important in biochemistry and I don't use them in my textbook. They're not found in many other textbooks, either. Also, the idea of "coupled" reactions is very poorly taught in biochemistry courses. It's almost never true that enzymes simply link up two independent reactions, one of which is "favorable" and the other "unfavorable." What usually happens is that a completely new reaction is catalyzed. For example, ATP is not hydrolyzed but, instead, a group transfer reaction is created. This important concept is covered in the next section but the authors do not appear to have grasped its significance.

Not only that, what does it mean to say that a reaction is "energetically unfavorable"? Usually this refers to the standard Gibbs free energy (ΔG°′) but one of the most important concepts in biochemistry is the difference between the standard Gibbs free energy change and the actual Gibbs free energy change (ΔG) inside the cell. In most cases ΔG = 0.

It's true that there are potential "endergonic" reactions occurring inside cells. Think about ATP hydrolysis, for example. The concentration of ATP is maintained at a high level relative to ADP and Pi so the Gibbs free energy change in the direction of hydrolysis is actually more negative that even the standard Gibbs free energy change. What this means is the the reverse reaction is extremely "endergonic."

However, it is simply not true that there are steps in metabolic pathways that are "endergonic" as the authors state. That statement reflects a profound misunderstanding of a fundamental concept in biochemistry. There will not be any flux in the "forward" direction of a metabolic pathway as long as even one reaction is "endergonic." All reactions have to be near-equilibrium reactions or reactions with a negative ΔG that's maintained because the enzyme activity is regulated to prevent the reaction from reaching equilibrium.

The important concept is "flux" or flow of metabolites in one direction along a metabolic pathway. There are many pathways where flux can occur in either direction as in the central part of the gluconeogenesis/glycolysis pathway or the citric acid cycle. Students need to understand what controls flux in one direction or another. They should know that, like water, metabolic flux cannot flow uphill.
The Nature of Biological Energy

In biological systems, chemical energy is stored in molecules with high group transfer potential or strongly negative free energy of hydrolysis or decomposition. These molecules, particularly ATP, provide the free energy to drive otherwise unfavorable biochemical reactions or processes in tightly coupled and highly controlled fashion. Most frequently, the free energy needed for a process or metabolic pathway is provided by group transfer rather than by hydrolysis. In this way, efficient energy transfer is optimized, while inefficient energy transfer to the environment (in the form of heat for example) is minimized.

Students should be able to show how reactions that proceed with large negative changes in free energy can be used to render other biochemical processes more favorable.
The essence of these statements is correct but it is not explained very well. The important concept is not that you "couple" a "favorable" reaction like ATP hydrolysis to an "unfavorable" reaction like synthesis of glutamine from glutamate and ammonia (ΔG°′ = +14 kJ mol-1).
The point is that the enzyme (glutamine synthetase) catalzyes a completely different reaction—a phosphoryl group transfer reaction—with a negative standard Gibbs free energy change of ΔG°′ = −18 kJ mol-1.

[see Moran et al. (2011): Introduction to Metabolism]
If there were an enzyme that catalyzed the first reaction involving only glutamate and ammonia then this reaction could easily occur inside the cell in spite of the positive ΔG°′. It would be a near-equilibrium reaction with steady-state equilibrium concentrations of glutamate that were very much higher than the concentration of glutamine.

It's likely that the concentration of glutamine would then be too low to support all the reactions that require it. That's why the reaction involving ATP is more useful. It means that the steady-state concentration of glutamine can be maintained a much higher concentration. This requires regulation of glutamine synthetase in order to prevent the reaction from reaching equilibrium.

It seems to me that the authors (Tansey et al.) have not thought about the fundamental core concepts. They are promoting widespread misconceptions about thermodynamics and metabolism and they are missing some important concepts. I've already mentioned flux. The other missing concept is oxidation-reduction reactions (electron transfer) and the importance of reduction potentials. NADH, NADPH, and QH2 are important energy currencies inside the cell—just as important as ATP.

There's something seriously wrong with biochemistry teaching if ASBMB educators can't even correctly explain foundational concepts like "evolution" and "matter and energy transformation."


1. I believe that all introductory biochemistry students should be able to explain where chemoautrophs get their energy. If they can't do it, they haven't been taught the fundamental concepts.

Tansey, J.T., Baird, T., Cox, M.M., Fox, K.M., Knight, J., Sears, D. and Bell, E. (2013) Foundational concepts and underlying theories for majors in “biochemistry and molecular biology”. Biochem. Mol. Biol. Educ., 41:289–296. [doi: 10.1002/bmb.20727]

Wednesday, October 23, 2013

How Do the IDiots Explain the Origin of Life?

We don't know how life on Earth originated. We're not completely ignorant because we have a good idea of basic biochemistry and we know which enzymes and pathways had to be present in the earliest cells. We're pretty sure that the first life forms captured energy by oxidizing inorganic molecules. We're pretty sure that the first cells formed in the ocean.

We also know from the fossil record that the first organisms were single-celled organisms that resemble modern bacteria in size and shape. We know that they appear more than 3 billion years ago and there were no complex organisms for another billion years. We know that the idea of a primordial soup is nonsense and that speculations about an RNA world are not helpful.

Other than that, all we have is informed speculation. The correct answer to the question of how did life begin is "I don't know."

Denyse O'Leary asks: Origin of life: How are we doing?. She is shocked to learn that scientists have not figured out all the details of how life began. She acts like she knows the answer. She acts like she has an explanation that accounts for all of the data and for the subsequent history of life.

Why isn't she sharing that information? How do the IDiots explain the origin of the first primitive cells more than 3 billion years ago?