Canada's New Minister of State (Science and Technology) Is a Chiropractor

 
It's true. Checkout the Stephen Harper website, which incidentally, is supposed to be the Prime Minister's website.

The Honourable Gary Goodyear
Minister of State (Science and Technology)

Cambridge (Ontario)

Gary Goodyear was first elected to the House of Commons in 2004 and re-elected in 2006 and 2008.

Prior to entering federal politics, Dr. Goodyear practised chiropractic medicine and worked as an advisor to investment firms in the biomedical industry.

Dr. Goodyear was a co-designer of a three-year post-graduate sports fellowship program. He also co-authored “Practice Guidelines” and was Public Relations Director and Past President for the College of Chiropractic Sports Sciences in Toronto. Dr. Goodyear has taught at the Canadian Memorial Chiropractic College and the University of Waterloo. He has worked with many athletes, both amateur and professional, including serving as medical services chair for the Ontario Special Olympics.

Dr. Goodyear is a graduate of the University of Waterloo and the Canadian Memorial Chiropractic College.

It's bad enough that we have a chiropractor advising the government about science but this particular one seem especially unqualified. He also practiced acupuncture when he was actively seeing patients. Dr. (sic) Goodyear is strongly supported by evangelical christians (e.g. Christian Conservatives). That may not have anything to do with his ability to understand modern science. Gary Goodyear was endorsed by Vote Marriage Canada, a group that opposes gay marriage.

The website of the Canadian Memorial Chiropractic College has a lengthy article praising the 4 MPs who are chiropractors (3 Conservatives, 1 Liberal) [Chiros on the Hill].

“The single biggest criticism of politicians,” explains Dr. Colin Carrie, Class of ’89 and Member of Parliament for the electoral district of Oshawa, Ontario, “is that they don’t listen.” Chiropractors, he says, are educated to be exceptional listeners. “Regardless of our political stripes, we want to do what’s right for our patients and our constituents.”
It’s people skills, agrees his colleague and fellow Conservative Dr. Gary Goodyear (MP for Cambridge, Ontario). “Every chiropractor has to be a people person, that’s what we were taught at CMCC.”

Goodyear, Class of ’83, and Chair of the Committee of Procedure and House Affairs, adds with a laugh that his advisors have had occasion to remind him not to be quite so hands-on when dealing with his constituents. “My election team has actually told me to stop touching people so much, but I can’t help it. It’s just natural to me. As a chiropractor, you automatically love people. Chiropractic is a touchy-feely profession—that transfers.”

Interestingly, all four chiropractic MPs tell similar stories about how—for each in his or her own way—they have come to view their constituents in much the same light as chiropractors perceive their patients: “You can’t be a successful chiropractor without good interpersonal skills,” explains Dr. James Lunney, (Class of ’83, Nanaimo-Alberni, BC). “Our job as chiropractors is taking complicated issues, and finding ways of explaining them—interpreting X-rays, for example—you have to be able to communicate to your patient what needs to be communicated.” The job requirements are strikingly similar, he says, on Parliament Hill. “Any chiropractor who deals with patient issues successfully has the skills to make the transition into politics. If you can manage a practice, you have an aptitude for politics.”

I'm beginning to see the parallels between being a politician and a chiropractor. This is not complimentary to politicians.

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Good IDEA?

 
The Discovery Institute is promoting the IDEA Center.

As part of our efforts to support academic freedom on evolution, we are teaming up with the IDEA Center (Intelligent Design and Evolution Awareness) to help students in starting an IDEA chapter on their campus. Such campus clubs are a fun and educational way for students to examine all sides of the debate over evolution.

IDEA Clubs are student-initiated clubs that foster academic freedom as students learn about scientific evidence that supports intelligent design and also learn about modern evolutionary theory. IDEA Clubs are a growing network of student-led clubs on university and high school campuses around the United States with thirty new chapters formed to date. (my emphasis)

Here's a challenge for everybody no matter which side you are on. Finding anti-evolution articles on the IDEA Center website is trivial. All the standard lies are there, sometimes in multiple articles. But can anyone find a single bit of evidence that supports Intelligent Design Creationism?

What about modern evolutionary theory? Is there anything on the website that comes remotely close to explaining modern evolutionary theory?

I didn't think so? How many campus have clubs of IDiots like this?

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Riding in the Car to Get Cherries

 
Riding in the Car to Get Cherries is a painting by Kanzi who also gave it the title. The painting is part of Apes Helping Apes.

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Were Neanderthals stoned to death by modern humans?

 
Were Neanderthals stoned to death by modern humans? is the provocative title of a press release reported in New Scientist. The author of the study is interviewed,

Human aerial bombardments might have pushed Neanderthals to extinction, suggests new research. Changes in bone shape left by a life of overhand throwing hint that Stone Age humans regularly threw heavy objects, such as stones or spears, while Neanderthals did not.

"The anatomically modern humans would have this more effective and efficient form of hunting," says Jill Rhodes, a biological anthropologist at Bryn Mawr College in Pennsylvania, who led the new study. A warmer Europe would have opened up forests, enabling longer range hunting, she says.

Rhodes and a colleague studied changes to the arm bone that connects the shoulder to the elbow – the humerus – to determine when humans may have begun using projectile weapons.

"If we're trying to understand whether anatomically modern humans had projectiles, then why not read the signature that it can imprint in the skeleton," Rhodes says.

The paper by Jill Rhodes of the Department of Anthropology, Bryn Mawr College and Steven E. Churchill of the Department of Evolutionary Anthropology, Duke University appears in The Journal of Human Evolution under Article in Press.

Rhodesa, J.A. and Churchill, S.A. (2008) Throwing in the Middle and Upper Paleolithic: inferences from an analysis of humeral retroversion. [doi:10.1016/j.jhevol.2008.08.022M]

Here's the complete text of the conclusiosn from that paper.

Clinical evidence from professional and college-level throwing athletes reveal differences in the humeral retroversion angle both between athletes and comparative (non-throwing) samples and between the dominant (throwing) and non-dominant limbs in the athletes. Comparative analysis of humeral architecture, specifically the humeral retroversion angle, in Pleistocene fossil humans has the ability to contribute new insights into the origins of projectile weaponry by examining the individuals who would have wielded those weapons. While the data is equivocal (in part because of confounding variables that affect humeral retroversion and in part because of small fossil sample sizes), we can reach two conclusions. First, while Neandertals tend to have high amounts of humeral retroversion, the overall pattern between limbs and between sexes strongly suggests that it is not due to habitual throwing behavior. The humeral retroversion data is largely consistent with other lines of evidence pertaining to projectile weaponry; the preponderance of evidence, ranging from fossil spears and Mousterian lithics to the articular and diaphyseal morphology of upper limb bones, suggests that Neandertals did not habitually employ long-range projectile weapons ([Churchill et al., 1996], [Schmitt et al., 2003], [Shea, 2003a], Shea, 2006 J.J. Shea, The origins of lithic projectile point technology: evidence from Africa, the Levant, and Europe, J. Archaeol. Sci. 33 (2006), pp. 823–846. Article | PDF (774 K) | View Record in Scopus | Cited By in Scopus (15)[Shea, 2006] and [Churchill and Rhodes, in press]). It is worth noting that earlier hominins also lack humeral torsion, further demonstrating that the increased retroversion found in Neandertals is unlikely to be linked to throwing. Second, we cannot reject the suggestion of projectile weapon use in the European Upper Paleolithic. The patterns seen in bilateral asymmetry in humeral retroversion angle suggest a variable use of throwing in the middle Upper Paleolithic (and thus great inter-individual variation in asymmetry), perhaps related to regional differences in hunting practices or the importance of projectile-based hunting. The levels of asymmetry seen in late Upper Paleolithic males are consistent with the regular use of projectile technology by this time.

Is it just me, or does there seem to be a disconnect between what's in the paper and what's in the press release? Why would the author allow the press release to say something that cannot be found anywhere in the paper?

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Creationists Fight Dirty, Scientists Don't

 
Martin at The Atheist Experience has been posting about the Texas State Board of Education hearings on science standards. Several members of the board want to "teach the controversy," which means teaching the creationist lies about evolution in an attempt to discredit it. His latest posting (Crippled dogs and one-trick ponies) is quite interesting.

Martin points out that when creationist board members use the standard lies and misconceptions to make their point about flaws in evolution, the pro-science witnesses should be prepared to hit back just as hard. They lose credibility if they waffle.

This is not a scientific dispute. Creationists don't care about science.

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This Is Ridiculous

 
The New York Times has an article by Nicholas Wade on Regenerating a Mammoth for $10 Million. It outlines a possible method for re-creating extinct organisms from a knowledge of their DNA sequence. The idea is to produce a mammoth.

I suppose there's nothing wrong with this kind of speculation. After all, we all did it back when Jurassic Park first came out. But there's a time to be serious as well. Why in the world would we want to spend $10 million of valuable research money to bring back the mammoth? I can see the importance of resurrecting the dodo or the sabre tooth tiger, but mammoths? Who need them? Do they even taste good?

Wait a minute ... there's even more exciting news in the New York Times article. George Church, a "genome tecchnologist" at Harvard Medical School was interviewed. He describes out a way to resurrect Neanderthals.

The full genome of the Neanderthal, an ancient human species probably driven to extinction by the first modern humans that entered Europe some 45,000 years ago, is expected to be recovered shortly. If the mammoth can be resurrected, the same would be technically possible for Neanderthals.

But the process of genetically engineering a human genome into the Neanderthal version would probably raise many objections, as would several other aspects of such a project. “Catholic teaching opposes all human cloning, and all production of human beings in the laboratory, so I do not see how any of this could be ethically acceptable in humans,” said Richard Doerflinger, an official with the United States Conference of Catholic Bishops.

Dr. Church said there might be an alternative approach that would “alarm a minimal number of people.” The workaround would be to modify not a human genome but that of the chimpanzee, which is some 98 percent similar to that of people. The chimp’s genome would be progressively modified until close enough to that of Neanderthals, and the embryo brought to term in a chimpanzee.

“The big issue would be whether enough people felt that a chimp-Neanderthal hybrid would be acceptable, and that would be broadly discussed before anyone started to work on it,” Dr. Church said.

What a clever way to get around all the ethical issues (not)! However, aren't we missing the point here? Why would we want to clone a Neanderthal in the first place? (BTW, you need two of them.)

What if the Neanderthals turn out to be smarter than us—a distinct possibility? Wouldn't they take over all the good jobs, like university professors? And what if they turn out to be stupider than the average human? Don't we already have enough creationists?

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[Hat Tip: john hawks weblog: Clone your own Neanderchimp baby?]

Closed for the Winter

 
We've just had our first significant snowfall in Toronto and the campus maintenance people have sprung into action. The main ramp leading into my building from the subway station has been closed for the winter. You may recall that this is the entrance where the expensive stone walkway is useless [If you build it, will they follow?].

Toronto is in Canada. In Canada we have real winters, with snow and ice. You may be asking yourself why anyone would build an entrance that has to be shut down for five months of the year. That's a very good question.

This entrance was constructed a few years ago when the Terrence Donnelly Centre for Cellular and Biomolecular Research (CCBR) was built. The ramp consists of wood slats with about one centimeter spaces between them. I'm told that a special kind of wood was used and it's very expensive.

Here's the problem as it was explained to me. First, it is difficult to clean ice and snow from a wooden walkway without damaging it. Second, when this kind of wood gets wet it becomes very slippery. That means you can't use salt to get rid of the ice without creating dangerous conditions in the winter.

I'm told that the university and the architects have been unable to reach agreement on who should fix this problem.

CCBR was designed by the architectural firms of Alliance & Behnisch Architekten. The architects won the Royal Institute of British Architects Awards (RIBA) in 2006 for this building [RIBA 2006]. They also won the Governor General's Medal in Architecture for 2008 for this building.

Here's part of the press release from the University of Toronto.

The Governor General's Medals in Architecture recognize outstanding achievement in recently built projects by Canadian architects. These awards are administered jointly with the Canada Council for the Arts, which is responsible for the adjudication process and contributes to the publication highlighting the medal winners. The recipients of the 2008 Governor General's Medals in Architecture were selected by a jury of distinguished architects.

Elizabeth Sisam, assistant vice-president (campus and facilities planning), said buildings like the Donnelly CCBR are very complex and boast many notable features.

"The CCBR is a very clever design that knits the Medical Science Building to the CCBR while being respectful of the heritage buildings and at the same time maintains and enhances pedestrian routes and entrances through to the campus," Sisam said. "Below grade, there are research laboratories that extend all the way to the sidewalk. The inside of the building in the area of the laboratories is a flexible design allowing the research teams to expand and contract. The exterior has a very unique treatment, a 'double façade' which is an excellent example of sustainable design."

The original design did not "knit the Medical Science Building to the CCBR." That was only added after many of us complained about the original design and the Dean of Medicine (David Naylor) intervened to provide extra funding to build the proper connection. In the original plan the buildings would have been quite separate.

The end product does not "maintain and enhance pedestrian routes and entrances through to the campus." The entrance off College St. requires that you climb up an annoying two flights of steps inside the building before gaining access to the lobby where the cafeteria is located. The direct entrance to this lobby from the other side (see photo above) could only be considered an "enhancement" by someone with a wicked sense of humour.

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Science 2.0

 
You may have heard of Science 2.0. It's the latest "revolution" in science. You can read a nice summary from the Howard Hughes Medical Institute [Science 2.0 You Say You Want a Revolution?].


Personally, I think blogging is going the become part of the culture in the same way that newsgroups did in the past except that more people are going to read the blogs. I don't think it's going to be a revolution. I don't think the majority of scientists and students are going to become regular readers of blogs. The blogosphere culture is not for everyone. Many of my colleagues are completely turned off. Blogging is going to be just one more way of communicating science and sharing ideas.

I'm skeptical of OpenWetWare (OWW) and other software that allows you to put all your notes and protocols on the web. Right now, most labs don't make shared electronic versions of protocols and notes even though we've been able to do that for 25 years. I don't see why that's going to change. My notebooks have lots of comments that I've scribbled in the margins (F**k - forgot to add magnesium!). I don't know why I'd want to share that with everyone on the planet.

I've done lots of "secret" experiments in my lifetime just to check out some crazy idea. So have the graduate students and post-docs in my lab. Does this sort of thing never go on in the labs that have adopted open access lab books? That doesn't sound like any kind of lab that I'd like to be in. Too much control for my liking. (According to the article it's "where the cool people are." I don't think so.)

Open-Access Journals are here to stay and will only increase in popularity.

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[Hat Tip: A Blog Around the Clock]

Reprogenetics and Genetic Variants

 
Reprogenetics is a company that offers the following service.

Preimplantation Genetic Diagnosis consists of the biopsy of a single cell per embryo, followed by its genetic diagnosis through different techniques (FISH, PCR, or CGH), and the subsequent replacement to the patient of those embryos classified by genetic diagnosis as normal.

Reprogenetics provides PGD analysis to IVF centers, including diagnosis of aneuploidy for advanced maternal age (such as Down's syndrome), repeated IVF failure, recurrent spontaneous abortions, chromosome translocations and inversions, as well as for gene defects such as Cystic fibrosis, fragile X, Myotonic Dystrophy, Thalasaemia, Tay Sachs, and others. We can also provide an experienced embryologist to perform embryo biopsy and cell processing.

Other tests may be offered soon including predisposition for diabetes and other genetic diseases.

The research director of Reprogenetics was interviewed for an article that appeared today on the Nature website [Gene testing of embryos needs guiding]

Last week, at a meeting of the American Society for Reproductive Medicine in San Francisco, California, researchers cautioned that they do not yet advocate this use of genetic tests. But as the technology advances, consumer demand is likely to overwhelm societal ethical qualms. "If people think they can make their babies healthier at year one, year two, or in utero, they will do it," says Jacques Cohen, research director at Reprogenetics, a genetic-testing company in West Orange, New Jersey.

...

Cohen says that as the understanding of disease genetics progresses, use of tests that seem controversial now may become more acceptable in the future: "If you had the chance to decrease your child's risk of a disease like diabetes and you didn't, society would blame you."

I assume this is a profit-making company. I wonder why Nature chooses to rely on the opinion of someone who has a vested interest in the technology? Especially someone who has an opinion like that?

What can he be thinking? Does he think that the average American in the future will be forced to undergo in vitro fertilization to avoid being sued by their children?

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[Hat Tip: The Sciphu Weblog: This pisses me off a little]

Nobel Laureate: Sinclair Lewis

 


The Nobel Prize in Literature 1930.

"for his vigorous and graphic art of description and his ability to create, with wit and humour, new types of characters"

Sinclair Lewis (1885 - 1951) won the Noble Prize in Literature for his novels about average Americans doing non-average things. The prize committee specifically mentions Main Street, Babbitt, Arrowsmith, Elmer Gantry, and Dodsworth.

Sinclair Lewis was the first American to win a Nobel Prize in Literature.

Arrowsmith is a novel about a scientist. It is one of the first works of the 20th century to describe the realities of being a scientist and really should be required reading for all science students. Lewis relied heavily on his scientific adviser, the microbiologist Paul de Kruif, and the novel is based loosely on Félix d'Herelle. Here's how the novel is described in the presentation speech on the Nobel Prize website.

THEME:
Nobel Laureates

Arrowsmith (1925) is a work of a more serious nature. Lewis has there attempted to represent the medical profession and science in all its manifestations. As is well known, American research in the natural sciences, physics, chemistry, and medicine ranks with the best of our age, and it has several times been recognized as such from this very platform. Tremendous resources have been placed at its command. Richly endowed institutions work unceasingly on its development.

That even here some speculative persons want to take advantage of their opportunities may be regarded as inevitable. Private industries are on the alert for scientific discoveries and want to profit from them before they have been tested and finally established. The bacteriologist, for instance, searches with infinite care for vaccines to cure widespread diseases, and the manufacturing chemist wants to snatch them prematurely from his hand for mass production.

Under the guidance of a gifted and conscientious teacher, Martin Arrowsmith develops into one of the idealists of science. The tragedy of his life as research worker is that, after making an important discovery, he delays its announcement for constantly renewed tests until he is anticipated by a Frenchman in the Pasteur Institute.

The book contains a rich gallery of different medical types. We have the hum of the medical schools with their quarrelling and intriguing professors. Then there is the unpretentious country doctor, recalled from Main Street, who regards it as an honour to merge with his clientele and become their support and solace. Then we have the shrewd organizer of public health and general welfare, who works himself into popular favour and political power. Next we have the large institutes with their apparently royally independent investigators, under a management which to a certain extent must take into consideration the commercial interests of the donors and drive the staff to forced work for the honour of the institutes.

Above these types rises Arrowsmith's teacher, the exiled German Jew, Gottlieb, who is drawn with a warmth and admiration that seem to suggest a living model. He is an incorruptibly honest servant of science, but at the same time a resentful anarchist and a stand-offish misanthrope, who doubts whether the humanity whose benefactor he is amounts to as much as the animals he kills with his experiments. Further we meet the Swedish doctor, Gustaf Sondelius, a radiant Titan, who with singing and courage pursues pests in their lairs throughout the world, exterminates poisonous rats and burns infected villages, drinks and preaches his gospel that hygiene is destined to kill the medical art.

Alongside all of this runs the personal history of Martin Arrowsmith. Lewis is much too clever to make his characters without blemish, and Martin suffers from faults which at times seem obstructive to his development, both as a man and as a scientist. As a restless and irresolute young man he gets his best help from a little woman he encountered at a hospital where she was an insignificant nurse. When he begins to drift about the country as an unsuccessful medical student, he looks her up in a little village in the Far West, and there she becomes his wife. She is a devoted and simple soul, who demands nothing and who patiently waits in her solitude when, bewitched by the siren of science, her husband loses himself in the labyrinths of his work.

Later she accompanies him and Sondelius to the plague-infected island where Arrowsmith wants to test his serum. Her death in the abandoned hut, while her husband listens distractedly to another and more earthy siren than that of science, seems like a poetically crowning final act to a life of primitive self-sacrificing femininity.

The book is full of admirable learning, certified by experts as being accurate. Though a master of light-winged words, Lewis is never superficial when it comes to the foundations of his art. His study of details is always as careful and thorough as that of such a scientist as Arrowsmith or Gottlieb. In this work he has built a monument to the profession of his own father, that of the physician, which certainly is not represented by a charlatan or a faker.

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Gene Genie #40

 
The 40th edition of Gene Genie has been posted at Human Genetics Disorders [Gene Genie Edition 40].

NSGC Conference exibit and MBA thesis poster presentation videos from the October 24-28 2008 AEC Conference by Chavonne Jones

The beautiful logo was created by Ricardo at My Biotech Life.

The purpose of this carnival is to highlight the genetics of one particular species, Homo sapiens.

Here are all the previous editions .....

1. Scienceroll
2. Sciencesque
3. Genetics and Health
4. Sandwalk
5. Neurophilosophy
6. Scienceroll
7. Gene Sherpa
8. Eye on DNA
9. DNA Direct Talk
10. Genomicron
11. Med Journal Watch
12. My Biotech Life
13. The Genetic Genealogist
14. MicrobiologyBytes
15. Cancer Genetics
16. Neurophilosophy
17. The Gene Sherpa
18. Eye on DNA
19. Scienceroll
20. Bitesize Bio
21. BabyLab
22. Sandwalk
23. Scienceroll
24. biomarker-driven mental health 2.0
25. The Gene Sherpa
26. Sciencebase
27. DNA Direct Talk
28. Greg Laden’s Blog
29. My Biotech Life
30. Gene Expression
31. Adaptive Complexity
32. Highlight Health
33. Neurophilosophy
34. ScienceRoll
35. Microbiology Bytes
36. Human Genetic Disordrs
37. The Genetic Genealogist
38. ScienceRoll
39. Genetics & Health
40. Human Genetics Disorders

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My Desk

 
Eva re-starts another meme.

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I Hate Ironing

 
But these guys seem to like it. What am I missing?

I've been following this sport for several years and I still don't get how they do it. Maybe I need a new iron?

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[Hat Tip: Canadian Cynic, of course.

They're Coming to Your Town!

 
The American Family Association sells Christmas crosses that remind you of something evil [Hide it under a bushel? NO!]. But the website has lots more stuff as pointed out by one reader who commented on my earlier posting.

You really need to see They're Coming to Your Town DVD.

Residents of the small Arkansas town of Eureka Springs noticed the homosexual community was growing. But they felt no threat. They went about their business as usual. Then, one day, they woke up to discover that their beloved Eureka Springs, a community which was known far and wide as a center for Christian entertainment--had changed. The City Council had been taken over by a small group of homosexual activists.

The Eureka Springs they knew is gone. It is now a national hub for homosexuals. Eureka Springs is becoming the San Francisco of Arkansas. The story of how this happened is told in the new AFA DVD “They’re Coming To Your Town.”

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Arwen

 
This is Arwen. Ms. Sandwalk tells me there's a connection between her and Monday's Molecule #97. I didn't know that.¹ Did you?

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1. This is really just an excuse to post the photo.

Monday's Molecule #97

 
Today we're taking a bit of a break from boring old biochemical molecules and fruit flies to look at some specific individuals of the species Homo sapiens. Your task for today is to identify these men. I need all of their names and the name that collectively identifies them.

The answer is indirectly related to this week's Nobel Laureate. See if you can make the connection.

The first one to correctly identify the individuals and name the Nobel Laureate(s), wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are only three ineligible candidates for this week's reward: Bill Chaney of the University of Nebraska, Dima Klenchin of the University of Wisconsin and Dale Hoyt from Athens, Georgia. Dale has agreed to donate the free lunch to a deserving undergraduate so the first undergraduate to win and collect a free lunch can also invite a friend.

THEME:

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

Correct responses will be posted tomorrow. I reserve the right to select multiple winners if several people get it right.

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

The band is Aerosmith and this should remind you of the book "Arrowsmith" by Sinclair Lewis who won the Nobel Prize for Literature in 1930. Arrowsmith is a book about scientists.

Three people knew who the band was—one of them was Ms. Sandwalk! Only one person saw the connection between Aerosmith and a Nobel Laureate but that person (Dima) is ineligible. I decided to award the free lunch to Ms. Sandwalk, making her ineligible for any more lunches for one month!!!

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Hide it under a bushel? NO!

 

This is the latest in Christmas decorations from the American Family Association.

Let Your "Light" Shine For Christ This Christmas Season!

Looking for an effective way to express your Christian faith this Christmas season to honor our Lord Jesus? Now you can.... with the "Original Christmas Cross" yard decoration.

Light up your front yard, porch, patio, driveway, business, organization or church this holiday season with a stunning Christmas cross.

Can't you just picture these five and-a-half foot crosses in the middle of front yards all across America?

What in the world are they thinking?

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[Hat Tip: LuLu at Canadian Cynic]

Be Afraid

 
There have been some changes on Uncommon Descent. Bill Dembski won't be posting as often (Boo!) and the chief web person will be Barry Arrington [What’s New At UD].

Here's a warning from the new chief IDiot.

We live in exciting times. The Darwinist/materialist hegemony over our culture has definitely peaked, and we are privileged to watch the initial tremors that are shaking the Darwinist house of cards. These are only the beginning of woes for St. Charles’ disciples, and I look forward to one day watching the entire rotten edifice come crashing down. I am persuaded that just as when the Soviet Union went seemingly overnight from “menacing colossus astride the globe” to “non-existent,” the final crash of the House of Darwin will happen with astonishing suddenness. You can be sure that we at UD will be there not only reporting on events, but also lending our intellectual pry bars to the effort.

Hmmm ... "intellectual pry bars" ... that's an image that's going to be hard to shake.

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Why do we blog and other important questions

 
OK, so I'm not a Nature Network blogger, but I thought I'd answer the questions anyway.

1. What is your blog about?
   It's about science, religion, universities, politics, and almost everything else I'm interested in. Mostly science and science education.


2. What will you never write about?
   Aha! A trick question! You almost got me!


3. Have you ever considered leaving science?
   No.


4. What would you do instead?
   I dunno, what do other people do? (Eva has a much funnier reply to this question)


5. What do you think will science blogging be like in 5 years?
   Pretty much the same as it is now. Which is pretty much the same as it's been for the past five years. Which isn't a lot different than the newsgroups were for the previous 20 years before that.


6. What is the most extraordinary thing that happened to you because of blogging?
   I've made dozens of new friends. (For me, that's extraordinary.)


7. Did you write a blog post or comment you later regretted?
   Yes.


8. When did you first learn about science blogging?
   I don't recall exactly. It was probably sometime around 2002 when I first learned that people were actually reading them.


9. What do your colleagues at work say about your blogging?
   Most of them don't understand the blogging culture. They think it's bizarre. They think I'm bizarre—but they thought that even before I started Sandwalk

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Be the First in Your School

 
Be the first in your school, or church, to have one of these T-shirts—or others like it. (It also comes in red and black.) Go to Evo-Ts.

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Making Sense in Biology

When I teach students how to read the scientific literature, I caution them not to believe everything they read. Science is, by it's very nature, tentative and exploratory. Much of what is published doesn't get confirmed and is quietly ignored. Many of the ideas and speculations that are published never amount to anything. Some experiments are flawed. Many skim over hidden assumptions so that the conclusions aren't valid.

How do you tell the difference between the wheat and the chaff? Well, for one thing, you ask yourself whether the results "make sense" in light of what you already know. Are there any basic principles of biology that conflict with the conclusions? You always have to be on the lookout for papers that just don't fit in with your current model of how things work.

There are two potential problems with this approach. First, your model may not be correct. Maybe you don't know enough to make a judgment. Second, it prevents you from recognizing truly novel results that may change your idea of what makes sense.

The first problem is curable. The second is more serious. Science is basically conservative in its acceptance of new ideas. This may seem like a bad thing but, in fact, it's the only way to do good science. You simply can't afford to believe in several paradigm shifts every day before breakfast because most of them will turn out to be wrong. Today, when scientists want to convince their colleagues of something new that may not "make sense", they are obliged to present solid evidence that will convince the skeptics. It's an uphill fight. And it should be.

One of my colleagues has been following the discussion about alternative splicing and he directed my attention to a paper he just published in Nature Genetics. He pointed out that far from being an overestimate of alternative splicing, the EST data actually underestimates the extent of alternative splicing.

The paper by Pan et al. (2008) makes two extraordinary claims.

1. Their data indicates that about 95% of all multiexon human genes undergo alternative splicing.
2. They estimate that there are, on average, seven (7) alternative splicing events per multiexon human gene.

Neither of these claims make sense. It's not reasonable to assume that most conserved housekeeping genes produce variants by alternative splicing yet that's exactly what would have to happen if 95% of all genes undergo alternative splicing. It means that most most genes for things like metabolic enzymes, RNA polymerase, ribosomal proteins and transport proteins will have variants due to alternative splicing. This doesn't make sense from an understanding of biochemistry and it doesn't make sense in light of evolution.

That's good reason to be skeptical.

But surely the data must be convincing? Surely the proponents of these extraordinary claims have extraordinary data to back their cease?

Frankly, I don't know. I can't evaluate the Pan et al. (2008) paper because I have no idea how they actually do their experiments and whether those experiments are reliable. Part of the problem is that the authors don't tell me enough and part of it is that this is unfamiliar technology (to me).

All I know is that it doesn't make sense. I've asked the author to give me some specific examples of alternative splicing predictions for common genes, like those in the citric acid cycle. By looking at specific, rather than global, data it might be possible to see whether the results make sense.

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Pan, Q., Shai, O., Lee, L.J., Frey, B.J. and Blencowe, B.J. (2008) Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nature Genetics, published online Nov. 2, 2008. [DOI:10.1038/ng.259]

Students and a Sense of Entitlement

 
A recent study by Greenberger et al. (2008) looked at student's sense of entitlement in order to see where it comes from. Here's the abstract ...

Abstract Anecdotal evidence suggests an increase in entitled attitudes and behaviors of youth in school and college settings. Using a newly developed scale to assess ‘‘academic entitlement’’ (AE), a construct that includesexpectations of high grades for modest effort and demanding attitudes towards teachers, this research is the first to investigate the phenomenon systematically. In two separate samples of ethnically diverse college students comprised largely of East and Southeast Asian American, followed by Caucasians, Latinos, and other groups (total N = 839, age range 18–25 years), we examined the personality, parenting, and motivational correlates of AE. AE was most strongly related to exploitive attitudes towards others and moderately related to an overall sense of entitlement and to narcissism. Students who reported more academically entitled attitudes perceived their parents as exerting achievement pressure marked by social comparison with other youth and materially rewarding good grades, scored higher than their peers in achievement anxiety and extrinsic motivation, and engaged in more academic dishonesty. AE was not significantly associated with GPA.

I don't put a lot of credence in these studies but I thought it was interesting that the problem was at least being investigated. The survey results, below, are interesting.

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[Hat Tip: Musings of the Mad Biologist]

Greenberger, E., Lessard, J., Chen, C. and Farruggia, S.P. (2008) Self-Entitled College Students: Contributions of Personality, Parenting, and Motivational Factors. Journal of Youth and Adolescence 37:1193-1204 [Springerlink]

Tangled Bank #118

 
The latest issue of Tangled Bank has been published on Submitted to a Candid World [Tangled Bank #118: Yes We Did Edition].

It’s my pleasure to bring you this edition of Tangled Bank, a biweekly collection of posts on important issues of biology and science. How I managed to secure the first post-election Tangled Bank for this little politics blog is beyond me: far be it for me to complain, but it really makes you wonder about PZ Myers’ processes for vetting new hosts… I’ll try my best not to play Sarah Palin to his John McCain.

Common readers of this site will know from experience that I, like all the co-writers of this blog, pushed hard for Obama’s election, and new visitors will guess as much from the site’s browser icon (surprise!). Now that the man’s elected, though, there’s a lot of work to be done - especially because, over the past eight years, scientific integrity somehow became a Democrats-only issue. America’s science community has a lot of ground to recover and, until Obama decides to restore the office to its pre-Bush grandeur, we, the concerned netroots, are the closest thing he has to White House science advisers. Thus, I present to you President-Elect Barack Obama’s first science briefing -

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Send an email message to host@tangledbank.net if you want to submit an article to Tangled Bank. Be sure to include the words "Tangled Bank" in the subject line. Remember that this carnival only accepts one submission per week from each blogger.

Nobel Laureate: Edward Lewis

 

The Nobel Prize in Physiology or Medicine 1995.

"for their discoveries concerning the genetic control of early embryonic development"

Edward B. Lewis (1918 - 2004) won the Noble Prize for his studies on the genetics of Drosophila melanogaster, especially the homeotic mutants in the bithorax complex. These are the mutations that cause transformation of the 3nd thoracic segment into the 2nd, giving rise to a fly with four wings instead of two.

The significance of this work can't be underestimated. It led to our modern understanding of development and evolution. Thanks to Lewis, we now know that small changes in the regulation of gene expression can have large effects on phenotype. It means that the number of mutations required to make the difference between mice and humans, for example, may be far less that what people imagined 50 years ago.

Edward Lewis shared the prize with Christiane Nüsslein-Volhard and Eric Wieschaus. Here's what the press release said about Lewis.

THEME:
Nobel Laureates

The fly with the extra pair of wings

Already at the beginning of this century geneticists had noted occasional malformations in Drosophila. In one type of mutation the organ that controls balance (the halteres), was transformed into an extra pair of wings (Fig. 2). In this type of bizarre disturbance of the body plan, cells in one region behave as though they were located in another. The Greek word homeosis was used to describe this type of malformations and the mutations were referred to as homeotic mutations.
Figure 2.

Fig. 2. Comparison of a normal and a four-winged fruit fly. The third thoractic segment has developed as a duplicate of the second due to a defectic homeotic gene. In the normal fly only the second segment develops wings.

The fly with the extra pair of wings interested Edward B. Lewis at the California Institute of Technology in Los Angeles. He had, since the beginning of the forties, been trying to analyze the genetic basis for homeotic transformations. Lewis found that the extra pair of wings was due to a duplication of an entire body segment. The mutated genes responsible for this phenomenon were found to be members of a gene family ( bithorax-complex) that controls segmentation along the anterior-posterior body axis (Fig. 3). Genes at the beginning of the complex controlled anterior body segments while genes further down the genetic map controlled more posterior body segments (the colinearity principle). Furthermore, he found that the regions controlled by the individual genes overlapped, and that several genes interacted in a complex manner to specify the development of individual body segments. The fly with the four wings was due to inactivity of the first gene of the bithorax complex in a segment that normally would have produced the halteres, the balancing organ of the fly (Fig 3). This caused other homeotic genes to respecify this particular segment into one that forms wings.

Edward Lewis worked on these problems for decades and was far ahead of his time. In 1978 he summarized his results in a review article and formulated theories about how homeotic genes interact, how the gene order corresponded to the segment order along the body axis, and how the individual genes were expressed. His pioneering work on homeotic genes induced other scientists to examine families of analogous genes in higher organisms. In mammalians, the gene clusters first found in Drosophila have been duplicated into four complexes known as the HOX genes. Human genes in these complexes are sufficiently similar to their Drosophila analogues they can restore some of the normal functions of mutant Drosophila genes.

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[The book is a tribute to Edward Lewis, edited by my colleague Howard D. Lipshitz.]

[Image Credit: California Institute of Technology]

Two Examples of "Alternative Splicing"

THEME:
Transcription
Last week I bumped into a colleague who teaches in our third year molecular biology course. I was lamenting about the sad state of science these days and we got to talking about alternative splicing. I repeated my complaint that much of the predicted alternative splice variants are artifacts. It makes no sense that conserved genes would be producing alternative protein variants that are species specific. I am convinced that the EST databases are full of artifacts and that most predicted splice variants do not exist.

My colleague was shocked. He is firmly convinced that most human genes express a number of different protein products that are produced as the result of alternatively spliced mRNA precursors. I asked him if he had ever looked at his favorite genes to see if the predicted variants make any sense. The ones that I've looked at certainly don't. (Join in the fun: see the challenge below.)

My colleague is very knowledgeable about the genes for the major subunits of eukaryotic RNA polymerase since it was his lab that cloned the first one. I suggested that he look at the predicted alternative splice variants of the two human genes and let me know if he is still convinced that these variants make biological sense. I'm not sure he will do it so let's take a look ourselves.

Eukaryotic RNA polymerase is a complex protein machine consisting of ten different subunits. Two of the subunits, Rpb1 and Rbp2, are more commonly known as A and B. In the human genome they are encoded by the genes POLR2A and POLR2B respectively [RNA Polymerase Genes in the Human Genome].

If you click on the Entrez Gene URLs you will end up at a page that summarizes what is known about the gene. Down the right-hand side of the page there are links to several other webpages, including a link to AceView, a database of alternative splice variants. Before following this link to the POLR1A variants, let's note that on the annotated Entrez Gene website there are no alternative splice variants listed. Apparently someone has decided that the predicted variants are probably artifacts.

Go to the AceView page for AceView POLR2A. The first thing you see is a short explanation.

RefSeq annotates one representative transcript (NM included in AceView variant.a), but Homo sapiens cDNA sequences in GenBank, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 11 spliced variants.

AceView summary
Note that this locus is complex: it appears to produce several proteins with no sequence overlap.
Expression: According to AceView, this gene is expressed at very high level, 4.8 times the average gene in this release. The sequence of this gene is defined by 537 GenBank accessions from 518 cDNA clones, some from breast (seen 40 times), marrow (29), head neck (19), brain (18), eye (18), leukopheresis (18), lung tumor (18) and 132 other tissues. We annotate structural defects or features in 13 cDNA clones.
Alternative mRNA variants and regulation: The gene contains 29 different introns (28 gt-ag, 1 gc-ag). Transcription produces 13 different mRNAs, 11 alternatively spliced variants and 2 unspliced forms. There are 7 probable alternative promotors and 5 non overlapping alternative last exons (see the diagram). The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, overlapping exons with different boundaries, alternative splicing or retention of 4 introns. 337 bp of this gene are antisense to spliced gene pluvu, raising the possibility of regulated alternate expression.
Protein coding potential: 10 spliced and the unspliced mRNAs putatively encode good proteins, altogether 11 different isoforms (3 complete, 4 COOH complete, 4 partial), some containing domains RNA polymerase Rpb1, domain 1, RNA polymerase, alpha subunit, RNA polymerase Rpb1, domain 3, RNA polymerase Rpb1, domain 4, RNA polymerase Rpb1, domain 5, RNA polymerase Rpb1, domain 6, RNA polymerase Rpb1, domain 7, Eukaryotic RNA polymerase II heptapeptide repeat [Pfam]. The remaining 2 mRNA variants (1 spliced, 1 unspliced) appear not to encode good proteins.

Here's the figure showing the various predicted alternatively spliced transcripts and the various different proteins.


It's really difficult to imagine that any of these are biologically relevant. How could a small bit of the large RNA polymerase subunit ever be part of the RNA polymerase protein complex? It's not a surprise that the Entrez Gene annotators have ignored these predictions.

If, as I believe, most of the small ESTs on which these predictions are based are artifacts, then the overall pattern makes sense. What you see are examples of splicing errors where an intron has not been correctly removed. These extremely rare splicing errors are copied into cDNA during construction of EST libraries and specifically selected by screening out all the correctly spliced mRNAs. (That's how you make most EST libraries.)

Here's what AceView says about the gene for the other large subbunit [AceView: POLR2B].

RefSeq annotates one representative transcript (NM included in AceView variant.a), but Homo sapiens cDNA sequences in GenBank, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 9 spliced variants.

One again, AceView notes that the annotated human genome has ignored the predicted alternative plice variants but maintains that there are at least nine of them.

Here's the figure, decide for yourself whether this is credible.


There are several well-known examples of human genes producing different protein variants due to alternative splicing. The ones I can think of off the top of my head are the genes for class I antigens, α-tropomyosin, and calcitonin. I'm sure there are half a dozen others.

Here's the challenge. See if you can find a human gene for a well-studied protein where the structure of the protein is known and there are multiple protein variants derived by alternative splicing. I bet that readers of Sandwalk can't find very many where the predicted variants many any sense and are likely to be biologically significant.

What does this mean? Whenever you look at your favorite well-studied gene you see that the predictions of alternative splicing are silly. So why should we believe the genome wide analyses? Is it just a coincidence that the more we learn about a given gene the most we become willing to reject the ESTs as artifacts? Or is it possible that alternative splicing is mostly confined to those genes that have not been well studied?

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Genes and Straw Men

Just in case there's someone who doesn't understand the concept of "straw man," here's a good description from Wikipedia: Straw Man.

A straw man argument is an informal fallacy based on misrepresentation of an opponent's position.[1] To "set up a straw man," one describes a position that superficially resembles an opponent's actual view, yet is easier to refute. Then, one attributes that position to the opponent. For example, someone might deliberately overstate the opponent's position.[1] While a straw man argument may work as a rhetorical technique—and succeed in persuading people—it carries little or no real evidential weight, since the opponent's actual argument has not been refuted.[2]

The term is derived from the practice in ages past of using human-shaped straw dummies in combat training. In such training, a scarecrow is made in the image of the enemy, sometimes dressed in an enemy uniform or decorated in some way to vaguely resemble them. A trainee then attacks the dummy with a weapon such as a sword, club, bow or musket. Such a target is, naturally, immobile and does not fight back, and is therefore not a realistic test of skill compared to a live and armed opponent. It is occasionally called a straw dog fallacy, scarecrow argument, or wooden dummy argument.[citation needed] In the UK, it is sometimes called Aunt Sally, with reference to a traditional fairground game.

You'd be surprised how often this fallacy comes up—and it's not just IDiots who use it.

The other day I attended a seminar by Jacek Majewski of McGill University (Montreal, Quebec, Canada). The subject was alternative splicing.

As most of you already know, this is a controversial field. Many people believe that alternative splicing is very common and that 50-70% of all human genes produce multiple versions of proteins due to alternative splicing. Majewski is one of those people.

Others, I am one, believe that much of the data is based on artifacts—especially expressed sequence tag (EST) artifacts. We believe that there are some very well established, and well-studied examples of alternative splicing but these represent only a small percentage of the total genes in the human genome.¹ We'll call these two groups the "splicing is common" advocates and the "splicing is rare" advocates.

The "common" group likes to think of themselves as the leading edge of a paradigm shift. They believe that alternative splicing is so common that it requires a new way of looking at biology. Unfortunately, in their haste to promote the new paradigm, they often misrepresent the other side. As a matter of fact, the very existence of a legitimate scientific controversy is often deliberately overlooked because they set up a straw man that is easily refuted.

Here's an example. In Majewski's seminar he started by describing the current "dogma" of one gene-one enzyme. According to him, most biologists are wedded to the idea that each gene makes a single protein. They believe, according to Majewski, that the intermediate step of mRNA synthesis is unimportant. He even showed a slide illustrating the dogma. It represents the old paradigm.

At the end of the seminar I pointed out that we have been teaching a different version of information flow for over thirty years. I mentioned that all the leading textbooks talk about splicing and alternative splicing and, furthermore, this material has been in the textbooks for 25 years (e.g. Genes II by Benjamin Lewin published in 1983). I asked him if he actually knew any scientists who believed in the dogma that he described. His response was confusing but he didn't back down.

Why is this important? Because most of the "common" advocates focus on convincing us that alternative splicing is real rather than focusing on whether it is common. By refuting the straw man they hope to bolster their case for the prevalence of alternative splicing. But they do no such thing. Most scientists are well aware of alternative splicing and have been for decades. The dispute is not over whether it occurs but whether it is common. The straw man version of the opposition does not exist.

I was prompted to write about this form of rhetorical device by reading an article in Monday's New York Times. The article (Now: The Rest of the Genome) was written by Carl Zimmer. Most of you know what I think of Carl Zimmer. He is one of the best science writers on the planet [Carl Zimmer at Chautauqua] but this time he slipped up.

Zimmer writes about Sonja Prohaska, a bioinformatician at the University of Leipzig in Germany.

... new large-scale studies of DNA are causing her and many of her colleagues to rethink the very nature of genes. They no longer conceive of a typical gene as a single chunk of DNA encoding a single protein. “It cannot work that way,” Dr. Prohaska said. There are simply too many exceptions to the conventional rules for genes.

It turns out, for example, that several different proteins may be produced from a single stretch of DNA. Most of the molecules produced from DNA may not even be proteins, but another chemical known as RNA. The familiar double helix of DNA no longer has a monopoly on heredity. Other molecules clinging to DNA can produce striking differences between two organisms with the same genes. And those molecules can be inherited along with DNA.

The gene, in other words, is in an identity crisis.

I don't think there are any significant number of biochemists or molecular biologists who literally believe that every gene encodes a single protein. Everyone I know understands that there are ribosomal RNA genes, tRNA genes, and genes for all kinds of small RNAs. Everyone I know understands alternative splicing. (On the other hand, nobody I know thinks that epigenetics is any threat to our definition of a gene.)

If the gene has an identity crisis, which it does, it's not because of ignorance of these phenomena, it's because we can't all agree on a good definition. My own preference is to define as a gene as, "A gene is a DNA sequence that is transcribed to produce a functional product" [What Is a Gene?] and I've been using that definition in my own textbooks since 1989.

It's sad to hear that up until recently Sonja Prohaska and her colleagues believed in a long-discredited definition of a gene. It suggests that throughout her undergraduate and graduate education she never heard of ribosomal RNA genes or alternative spicing. (She got her Ph.D. in 2005.) Either that or she's deliberately setting up a straw man.

Carl Zimmer goes on to describe recent work on the analysis of the human genome, especially the work done by the ENCODE project.

Encode’s results reveal the genome to be full of genes that are deeply weird, at least by the traditional standard of what a gene is supposed to be. “These are not oddities — these are the rule,” said Thomas R. Gingeras of Cold Spring Harbor Laboratory and one of the leaders of Encode.

A single so-called gene, for example, can make more than one protein. In a process known as alternative splicing, a cell can select different combinations of exons to make different transcripts. Scientists identified the first cases of alternative splicing almost 30 years ago, but they were not sure how common it was. Several studies now show that almost all genes are being spliced. The Encode team estimates that the average protein-coding region produces 5.7 different transcripts. Different kinds of cells appear to produce different transcripts from the same gene.

With all due respect to Carl, these sentences contradict what he implied earlier on. Yes, it's true that scientists have known about alternative splicing for 30 years. In other words, they have known for at least that long that the old idea about one gene-one protein is incorrect. So what was the point of letting readers think that Sonja Prohaska's personal misunderstanding of a gene has any relevance?

As I mentioned above, the scientific controversy over alternative splicing is about how common it is and not about whether modern scientists recognize its existence. And it has nothing to do with the modern understanding of a gene since for the past 20 years everyone has incorporated alternative splicing into their understanding of a gene.

Thomas Gingras is clearly on the "common" side of the issue and not on the "rare" side. Unfortunately Zimmer doesn't do a good job of balance here. A better way to describe the results would be ...

Taken a face value, some of the published results from the ENCODE project suggest that, far from being a rare event, alternative splicing may be very common. In fact, some scientist think that most of our genes produce several different proteins due to alternative splicing. They even suggest that an average gene may produce five or six different alternatively spliced transcripts.

Other scientists dispute these results, pointing out that the predicted alternatively spliced transcripts make no sense for those genes that have been well-studied. These predictions are being quietly removed from the annotated human genome database. As more and more genes are being looked at, the number of proven protein variants gets smaller and smaller.

The original predictions rely heavily on the sequences of small bits of RNA called "ESTs" and it is becoming increasingly clear that many, perhaps most, ESTs are artifacts. It is quite possible that talk of changing paradigms is premature and the number of genes exhibiting alternative splicing may be closer to what scientists thought twenty years ago.

These are interesting times in genome research and, like all new fields, the preliminary results are exciting and provocative. Who knows whether the preliminary results will lead to new ways of looking at biology? Time will tell.

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1. I'm using the human genome as an example. The same arguments apply to other genomes.

[Image Credit The Information Paradox: A Favorite Theist Logical Fallacy: The Straw Man]

November 11, 2008

 
This is what the front campus of the University of Toronto looks like today, Remembrance Day 2008. This is the 90th anniversary of the end of World War I.

Each cross bears the name of one of 628 alumni, students, or faculty members who died in World War I. It reminds us of what happens when we fail to resolve our differences peacefully. War is the failure of peace.

The crosses remind us that war is evil and horrible. All of these lives were wasted in a war that never should have happened. War is not glorious. War is not something we should be proud of even though we may honor those individuals who answered the call, and sacrificed their lives, when the politicians and diplomats failed to do their duty.

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Enzyme Efficiency: The Best Enzyme

One of the first things you learn about enzymes is that they catalyze, or speed up, reactions that would normally take place at a much slower rate. This is a difficult concept for students to understand because they're used to thinking of biochemical reactions in terms of reactions that would never happen without an enzyme.

The trick in understanding the role of enzymes is to appreciate the difference in rates between the enzyme-catalyzed reaction and the spontaneous reaction. While it's true that all enzyme-catalyzed reactions would eventually proceed even in the absence of enzyme, the rate of the spontaneous reaction might be way too slow. We often emphasize that the spontaneity of a reaction can be determined from the thermodynamics (i.e. if ΔG <0 the reaction is spontaneous) but we sometimes forget to show real data on how fast such a reaction can occur under physiological conditions. Typical rates for enzyme-catalyzed reactions are described by a constant called k_cat.¹ These values are usually in the range of 100-1000 reactions per second but there are some enzymes than have rates of over 1,000,000 reactions per second.

Spontaneous reactions can often approach these rates but, as you might imagine, the ones that require enzymes are very much slower. Proteins, for example, will eventually break down into amino acids but the rate of the reaction is so slow that spontaneous protein degradation is not a problem in living cells. In order to degrade proteins for food, we need to make enzymes such as chymotrypsin, trypsin, pepsin, and elastin to do the job at a faster rate.

Most of the important metabolic reactions take years in the absence of enzyme. The spontaneous degradation of a protein, for example, takes about 100 years (rate constant ~ 4 × 10^-9). Since chymotrypsin catalzyes this reaction at a rate of about 1000 molecules per second, this means that the enzyme speeds up the reaction by a factor of more than 10¹¹ (100 billion times)!

This value (10¹¹) is sometimes called the catalytic proficiency of an enzyme although for technical reasons we won't go into here, the real measure of catalytic proficiency is higher by several orders of magnitude.¹ The catalytic proficiency of chymotrypsin is 2 × 10¹⁶.

Naturally, this invites a comparison with those enzymes showing the greatest rate enhancements. But there's a problem. You can measure spontaneous rates that are on the order of a few years because you don't have to wait until the reaction goes to completion. But if the spontaneous reaction takes hundreds of years it can be difficult to measure—even the most dedicated graduate student won't wait that long!

Fortunately there are a few tricks that will make the job easier. You can observe the spontaneous reaction at high temperatures, for example, and calculate what the rate would be at physiological temperatures. That's what Radzicka and Wolfenden did in 1995 when they reported that the spontaneous decarboxylation of ornithine 5′-phosphate (OMP) had a rate constant of 3 × 10^-16 s^-1. This is a half-life of 78 million years.

The enzyme that catalyzes this reaction is ornithine 5′-phosphate decaboxlyase and up until last week it was the record holder with a catalytic proficiency of 2 × 10²³. (OMP decarboxylase catalyzes an essential step in the synthesis of pyrimidine nucleotides that are required to make RNA and DNA.)

That record has now been broken. Lewis and Wolfenden (2008) studied a reaction catalyzed by uroporphyrinogen decarboxylase, an enzyme involved in the synthesis of porphyrins such as heme, the cofactor in hemoglobin, and the chlorophylls. There were able to model the reaction and determine that the rate of spontaneous decarboxylation is 9.5 × 10^-18 s^-1, which corresponds to a half-life of 2.3 billion years! Lewis and Wolfenden published a chart showing typical half-lives of spontaneous reactions.

The catalytic proficiency of uroporphyrinogen decarboxylase is 2.5 × 10²⁴, a new record.

Into the textbook it goes.

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1. A better description of an enzyme's real rate constant is k_cat/K_m.

Radzicka, A. and Wolfenden, R. (1995) A proficient enzyme. Science 267:90-93.

Lewis,C.A. Jr. and Wolfenden, R. (2008) Uroporphyrinogen decarboxylation as a benchmark for the catalytic proficiency of enzymes. Proc. Natl. Acad. Sci. (USA) published online November 6, 2008 [Abstract] [doi:10.1073/pnas.0809838105]

Saturday Night Live: Joan Baez

 
On Saturday night we went to see Joan Baez. She older than she used to be but still wonderful. I remember her from the 60s in spite of what they say.¹

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If you remember the 60s, you weren't there.