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Monday, July 16, 2007

The Calvin Cycle

Are You an Intelligent Designer?

The Rubisco reaction results in fixation of carbon dioxide and the production of two molecules of glyceraldehyde 3-phosphate each of which contains three caron atoms [Fixing Carbon: the Rubisco Reaction]. The starting substrate is ribulose 1,5- bisphosphate, a 5-carbon sugar derivative [Monday's Molecule #34]. Here's a schematic diagram of the reaction showing the carbon skeletons with the newly incorporated carbon atom in blue.
In order for this to become a cycle you have to regenerate the original substrate—a five-carbon compound. And in order for it to be a biosynthesis pathway you have to have net synthesis of one of the products. It was the working out of this stoichiometry that got Melvin Calvin the Nobel Prize in 1961 [Nobel Laureate: Melvin Calvin]. Do you think you can figure out the strategy for regenerating the five-carbon substrate? Here are the rules.
  1. You start with three cycles of the Rubisco reaction, using up three 5C molecules and producing six 3C molecules. One of the 3C molecules enters the normal metabolic pathways and the other five are used to regenerate three 5C molecules (5 x 3C = 3 x 5C).
  2. You can fuse molecules to create larger ones (e.g., 3C + 3C = 6C).
  3. You can cleave large molecules to create smaller ones (e.g. 6C = 3C + 3C) as long as there are no intermediates with only one carbon (1C) or two carbons (2C).
  4. You can swap 2C units between molecules provided that no products are 1C or 2C (e.g, 7C + 3C = 5C + 5C is allowed).
  5. You can swap 3C units between molecules provided that no products are 1C or 2C (e.g, 7C + 3C = 4C + 6C is allowed).
Here's an outline of the Calvin Cycle. Your task, should you choose to accept it, is to design the regeneration pathway beginning with five molecules of glyceraldehyde 3-phosphate (5 x 3C) and ending with three molecules of ribulose 1,5- bisphosphate (3 x 5C). You just need to account for the carbon shuffling reactions.

Monday's Molecule #35

 
This is a very common chemical found in most biochemistry labs. There's a very familiar form of this molecule and most of you will know it by the name of the salt. You need to supply the correct IUPAC name in order to win the prize.

There's an extremely obvious, but indirect, connection between this Monday's Molecule and Wednesday's Nobel Laureate(s).

The reward (free lunch) goes to the person who correctly identifies the molecule and the Nobel Laureate(s). Previous free lunch winners are ineligible for one month from the time they first collected the prize. There are no ineligible candidates for this Wednesday's reward since many recent winners haven't collected their prize. The prize is a free lunch at the Faculty Club.

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

Casy Luskin Gets it Wrong (Again)

 
This is getting to be really annoying. What is it about the concepts of junk DNA and Darwinism that confuse the IDiots? It's not rocket science.

In today's posting on the Discovery Institute anti-science website, Casey Luskin leads off an anti-evolution posting with,
It’s beyond dispute that the false “junk”-DNA mindset was born, bred, and sustained long beyond its reasonable lifetime by the neo-Darwinian paradigm.
Let me try and make this simple for the IDiots.
  1. Junk DNA is here to stay. It's a lie to claim that the concept has been abandoned by scientists. True, there are some stupid scientists who don't understand what's going on but they do not represent the consensus.

  2. The concept of junk DNA is anti-Darwinian. There's no possible way that a true Darwinist could accept junk DNA. It is incredibly ignorant to claim that the idea of junk DNA was "born, bred, and sustained" by the neo-Darwinian paradigm. On the contrary, it has helped overturn that paradigm, replacing it with a more pluralistic approach to evolution.
It goes without saying that Intelligent Design Creationists think they have a better "paradigm" than real scientists. Luskin is amazed by recent discoveries that some heritable diseases are caused by mutations in regulatory sequences, which he, in his ignorance, thinks are equivalent to junk DNA.
How much earlier might these non-coding “junk” DNA causes of disease have been recognized had scientists operated under an intelligent design paradigm rather than a Neo-Darwinian one?
Me, me, me (pumping his hand in the air). I know the answer ...

Poufs of Art

 
Leslie (Mrs. Sandwalk) has a friend, Carmi, who lives in a small town north of Toronto.* She makes these wonderful things called poufs of art. Here's the description from her Etsy site [Carmi's Art].
Cushion is "pouf" in French.

These are tiny "poufs of art" that I create to celebrate my love of vintage imagery, fabric, beads, embellishments, sewing and quotes. Together, I use all these items to create one-of-a-kind keepsakes. They are handmade by me and no two will ever be alike.

I think these are perfect gifts to commemorate a special birthday, achievement or life event. No doubt, you will think of someone in particular when you read the quotes. They can be displayed on a picture stand, hung from a hook or light fixture or simply displayed in a box.

They are each approximately 2½ X 2 ½ inches wide. I will ship them in very pretty wrapping in a bubble wrap envelope.
Leslie has just ordered a bunch of them. Here's my favorite, I hope she bought it for me ...


Carmi also has a couple of blogs. Carmi's Art/Life World is about her life as an artist [see poufs to go] and My Napoleon Obsession is about Napoleon Bonaparte [Big Head's Crib].

* Kleinburg, for those of you who know the area.

Sunday, July 15, 2007

A Strange Molecule

 
Last Wednesday an image of strange base pair was published on Discovering Biology in a Digital World [Puzzle]. We were asked to figure out what was so strange about his base pair (see below). I got part of the answer but not the complete answer.



The answer has already been posted but I won't link to it just yet in order to give you a chance to figure it out. Please don't comment if you've already seen the answer.

Here's another view that promises to be a lot more helpful.

Gene Genie #11

 
The 11th edition of Gene Genie has been published at Med Journal Watch [Gene Genie #11].

Get on over there to find out where this photograph comes from.

Saturday, July 14, 2007

Friday, July 13, 2007

Personality Quiz

 
I wonder what the common personalities look like? Has anyone posted one of those?
Your Personality is Very Rare (INTP)

Your personality type is goofy, imaginative, relaxed, and brilliant.

Only about 4% of all people have your personality, including 2% of all women and 6% of all men
You are Introverted, Intuitive, Thinking, and Perceiving.


[Hat Tip: GrrlScientist]

Friday the 13th in Port Dover

 
More than 100,000 people and 10,000 motorcycles are expected to descend on Port Dover, Ontario today [Port Dover hogs Friday 13th fame]. It happens every Friday the 13th but the crowd is much larger when the date falls in the summer months. Todays entertainment will include Steppenwolf and the Jeff Healey Band [PD13 News]. I'm told that beer is sometimes served at these events. Go figure.

Sandwalk Resists

 

Afer considerable debate, and much agonizing, I've decided not to join ScienceBorg ScienceBlogs at this time.

When I first started Sandwalk, I was anxious to be part of that group but now, seven months later, there doesn't seem to be a good reason to give up this site for one in the SEED consortium. There are very few advantages to joining ScienceBlogs. They do not come close to outweighing the one major disadvantage—you have to give up a great deal of independence in order to become part of the SEED site.

At one time it seemed as though ScienceBlogs was cornering the market on good science blogging so it was desirable to be associated with a group that had a reputation for quality blogging. That time has past. Now there are lots of good science blogs that have resisted assimilation so it's not so bad to remain on the outside.

[The image is from Borg trioM copyright Paramount Pictures and CBS Television. Its use is consistent with fair use laws in many jurisdictions throughout the world.]

Can You Recognize Propaganda When You See it?

 
Michael Yon is a (very) freelance reporter in Iraq. He has a blog where he solicits support for his mission in Iraq. The mission is to bring the "truth" to the American public. Why does he do it?
I do it because we need to see this clearly: what happens in and to Iraq is a defining moment for our nation, and the world. This enemy is smart and they are deadly, but they are also losing. Iraq can become a strong and free nation. But it will take the constant application of pressure over time to stem the flow of blood. If we back off too soon, they will rebound. If we cut our losses and run, they will follow us home. Peace can prevail here, if we can use our strength to maintain our progress.
It's sort of refreshing to see a "journalist" who lays his cards on the table. At least he doesn't pretend to be objective, like many other journalists.

But, having declared his intentions, it falls upon his readers to interpret his writings with a great deal of skepticism. That doesn't seem to have happened recently when his story about "baked Iraqi boys" attracted the attention of the right-wing warmongers in the USA and elsewhere. It spread like wildfire.

Here's what Michael Yon wrote on July 5, 2007 [Baqubah Update: 05 July 2007].
At a meeting today in Baqubah one Iraqi official I spoke with framed the al Qaeda infiltration and influence in the province. Although he spoke freely before a group of Iraqi and American commanders, including Staff Major General Abdul Kareem al Robai who commands Iraqi forces in Diyala, and LTC Fred Johnson, the deputy commander of 3-2 Stryker Brigade Combat Team, the Iraqi official asked that I withhold his identity from publication. His opinion, shared by others present, is that al Qaeda came to Baqubah and united many of the otherwise independent criminal gangs.

Speaking through an American interpreter, Lieutenant David Wallach who is a native Arabic speaker, the Iraqi official related how al Qaeda united these gangs who then became absorbed into “al Qaeda.” They recruited boys born during the years 1991, 92 and 93 who were each given weapons, including pistols, a bicycle and a phone (with phone cards paid) and a salary of $100 per month, all courtesy of al Qaeda. These boys were used for kidnapping, torturing and murdering people.

At first, he said, they would only target Shia, but over time the new al Qaeda directed attacks against Sunni, and then anyone who thought differently. The official reported that on a couple of occasions in Baqubah, al Qaeda invited to lunch families they wanted to convert to their way of thinking. In each instance, the family had a boy, he said, who was about 11 years old. As LT David Wallach interpreted the man’s words, I saw Wallach go blank and silent. He stopped interpreting for a moment. I asked Wallach, “What did he say?” Wallach said that at these luncheons, the families were sat down to eat. And then their boy was brought in with his mouth stuffed. The boy had been baked. Al Qaeda served the boy to his family.
We're used to thinking of propaganda as something that's just made up by a disinformation committee whose job it is to discredit and demonize the enemy. But that's not how effective propaganda works. The best kinds of stories are those that can be attributed to an apparently reliable but unnamed source such as an "Iraqi official." That way you can repeat it ad nauseum without invoking any of the normal skepticism that a journalist should use. This is how we learned about rape rooms [Rape Rooms: A Chronology] and weapons of mass destruction. In some cases the source is identified but later exposed a liar (e.g. the Kuwait incubator story [ The Lie]). It doesn't seem to matter if a story turns out to be untrue once it has served its purpose.

Remember that the point of propaganda is to make your enemy look as evil as possible. That's how you justify killing them and sacrificing the lives of your troops. Both sides do it. In the case of the insurgents, the propaganda consists of endless stories about the brutality of the occupying forces and this includes stories that are just as horrible as the one quoted above.

The key for rational people is to recognize that the "good guys" aren't all that "good" and the "bad" guys aren't all bad. War is hell.

[Hat Tip: Canadian Cynic]

Francis Crick Isn't Always Right

 
A few days ago I posted pictures of the telegram notifying Francis Crick that he had won the Nobel Prize [Wellcome Trust Images]. The photos were from the Wellcome Images website.

Since then, a number of bloggers have commented on a brief note that Crick wrote on the back of a letter in 1989. I deliberately skipped that image last week because I thought it was embarrassing. I still do, in spite of the fact that the famous PZ Myers has declared it a nice quote [That's a nice quote].

What's so nice about it? It looks pretty stupid to me. What is there about DNA that gives support to evolution by natural selection—or even just "evolution" for that matter? Are my fellow bloggers just mesmorized by the juxtaposition of Francis Crick's name with the words "evolution" and "natural selection"?

Remember that 1989 corresponds to Crick's dotty period in La Jolla.

[Some people will argue that the sequences of various DNA's from different species lend support to evolution. Of course that's true but it's not what Crick wrote and I doubt very much it's what he meant. He was probably thinking about the beauty of the DNA molecule and it's appearance of "design" by natural selection.]

Thursday, July 12, 2007

Calling All Adaptationists

 
If you need some practice making up just-so stories then get on over to Pharyngula and join the party. The commenters are having a gay old time making up adaptationist explanations for homosexuality [Gay roundup]. If you don't want to make up your own stories then you can vote for your favorite on seyd [Evolution and Homosexuality]. All the tired old standards are there including ...
Likewise, removing a portion of the population from breeding relieves the breeders of some of these costs either directly by assisting with child rearing, or indirectly by taking over other costly activities (like food collection) so that t he parents can spend more resources on their progeny.
Naturally, PZ is not joining in. He doesn't believe that an adaptationist explanation is required. I agree. In fact, I'm not even sure that an evolutionary explanation is needed since the evidence for a heterosexual gene is practically nonexistent. (Note that if there's a gay and/or lesbian allele then there has to be a heterosexual one as well.)

Fixing Carbon: Building a Better Rubisco

On Not Getting with the Adaptationist Program

As its complete name indicates, ribulose 1,5- bisphosphate carboxylase– oxygenase (Rubisco) catalyzes not only the carboxylation but also the oxygenation of ribulose 1,5-bisphosphate [Fixing Carbon: the Rubisco Reaction]. The two reactions are competitive—CO2 and O2 compete for the same active sites on the Rubisco molecule [Fixing Carbon: the Structure of Rubisco]. The oxygenation reaction produces one molecule of 3-phosphoglycerate and one molecule of 2-phosphoglycolate.

Oxygenation consumes significant amounts of ribulose 1,5- bisphosphate in vivo. Under normal growth conditions, the rate of carboxylation is only about three to four times the rate of the oxygenation reaction. The oxidative pathway consumes NADH and ATP because the products have to be converted back into ribulose 1,5- bisphosphate in order to continue carbon fixation. The light-dependent uptake of O2 catalyzed by Rubisco, followed by the release of CO2 during the subsequent metabolism of 2-phosphoglycolate, is called photorespiration.

The appreciable release of fixed CO2 and the consumption of energy—with no apparent benefit to the plants—arise because of the lack of absolute substrate specificity of Rubisco. This side reaction can greatly limit crop yields. It looks very much as though Rubisco is just an inefficient enzyme that's incapable of distinguishing between two very similar substrates, CO2 and O2. It appears to be an example of a badly "designed" enzyme*, not unlike many others that have significant error rates.

The inefficiency of Rubisco, both in terms or its low reaction rate and its propensity for errors, is why massive amounts of the enzyme are needed in plants. The result is that Rubisco is probably the most abundant enzyme on Earth.

But if nature has done such a bad job of design, can scientists do better? That's the goal of many research labs since improving the efficiency of Rubisco can greatly enhance crop yields, and, incidentally, makes lots of money for the inventors of the genetically modified crops.

Several labs are attempting to genetically modify plants to enhance the carboxylation reaction and suppress the oxygenation reaction. The “perfect” enzyme would have very low oxygenase activity and very efficient carboxylase activity. The kinetic parameters of the carboxylase activity of Rubisco enzymes from several species are listed in the table below (Andrews and Whitney, 2003).


The low catalytic proficiency of the enzyme is indicated by the kcat/KM values. These values should be compared to those of typical enzymes that have values from ten to one thousand times greater. It seems likely that the carboxylase efficiency can be improved 1000-fold by modifying the amino acid side chains in the active site.

The difficult part of the genetic modification is choosing the appropriate amino acid changes. The choice is made easier by a detailed knowledge of the structures of several Rubisco enzymes from different species and by examination of the contacts between amino acid side chains and substrate molecules. Models of the presumed transition states are also important. Additional key residues can be identified by comparing the conservation of amino acid sequences in enzymes from a wide variety of species.

The underlying strategy assumes that evolution has not yet selected for the most well–designed enzyme. This assumption seems reasonable since there are many examples of ongoing evolution in biochemistry. Nevertheless, progress has been slow in spite of the enormous financial rewards.

In addition to intelligently-directed genetic engineering to improve on nature, some groups have relied on a form of artificial evolution to do the job. Here's the abstract of a recent paper (Parikh et al. 2006).
The Calvin Cycle is the primary conduit for the fixation of carbon dioxide into the biosphere; ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) catalyzes the rate-limiting fixation step. Our goal is to direct the evolution of RuBisCO variants with improved kinetic and biophysical properties. The Calvin Cycle was partially reconstructed in Escherichia coli; the engineered strain requires the Synechococcus PCC6301 RuBisCO for growth in minimal media supplemented with a pentose. We randomly mutated the gene encoding the large subunit of RuBisCO (rbcL), co-expressed the resulting library with the small subunit (rbcS) and the Synechococcus PCC7492 phosphoribulokinase (prkA), and selected hypermorphic variants. The RuBisCO variants that evolved during three rounds of random mutagenesis and selection were over-expressed, and exhibited 5-fold improvement in specific activity relative to the wild-type enzyme. These results demonstrate a new strategy for the artificial selection of RuBisCO and other non-native metabolic enzymes.
©Laurence A. Moran and Pearson Prentice Hall 2007

*As you might imagine from our discussion of the adaptationist program, there are many biochemists who are very uncomfortable with the notion of a function that has no adaptive explanation. Textbooks are full of adaptive just-so stories that try to justify the oxygenation reaction. None of them hold up to close scrutiny. The Voet and Voet textbook (Biochemisty) avoids the worst just-so stories by saying, "Although photorespiration has no known metabolic function, the RuBisCOs from a great variety of photosynthetic organisms so far tested all exhibit oxygenase activity. Yet, over the eons, the forces of evolution must have optimized the function of this important enzyme." They then go on to describe two unlikely adaptive explanations of the oxygenation reaction. Note that Don and Judy Voet assume that the very existence of the oxygenation reaction demands an optimization assumption and, consequently, an adaptationist explanation. Accident is not a possibility in their minds.


Andrews, J. T. and Whitney, S. M. (2003) Manipulating ribulose bisphosphate carboxylase/oxygenase in the chloroplasts of higher plants. Arch. Biochem. Biophys. 414:159–169.

Parikh, M.R., Greene, D.N., Woods, K.K., Matsumura, I. (2006) Directed evolution of RuBisCO hypermorphs through genetic selection in engineered E.coli. Protein Eng Des Sel. 19(3):113-9.

Is There a Correct Way to Do Science?

 
I think there are incorrect ways of doing science and I think that much of today's scientific literature is an example of bad science. This isn't news. Back in 1963 Peter Medawar felt the same way and he expressed this viewpoint on a BBC radio show. The transcript, Is the scientific paper a fraud, is published in Medawar's collection of essays called "The Strange Case of the Spotted Mice" (Medawar, 1996). (The title of the book refers to a scientific fraud in immunology that Medawar uncovered in the early 1970's.)

Medawar says,
... the scientific paper may be a fraud because it misrepresents the processes of thought that accompanied or gave rise to the work that is described in the paper.
Janet Stemwedel discuses this paper on her blog Adventures in Ethics and Science [Why does Medawar hate the scientific paper?]. Janet uses the paper as a way of introducing some key concepts in epistemology—loosely defined as "the investigation of the origin, nature, methods, and limits of knowldege." (Burr and Goldinger, 1980). Read Janet's blog and the comments in order to see this perspective.

I want to take the discussion in another direction. Medawar's complaint is that the scientific paper distorts the real process of science by misrepresenting the steps that are actually followed in a scientific investigation. In particular, the typical paper suggests that induction is the main mechanism of scientific discovery. Here's how Medawar describes the naive scientific method,
What induction implies in its cruder form is roughly speaking this: scientific discovery, or the formulation of scientific theory, starts with the unvarnished and unembroidered evidence of the senses. It starts with simple observation—simple, unbiased, unprejudiced, naïve, or innocent observation—and out of this sensory evidence, embroidered in the form of simple propositions or declarations of fact, generalizations will grow up and take shape, almost as if some process of crystallization or condensation were taking place. Out of a disorderly array of facts, an orderly theory, an orderly general statement, will somehow emerge.
Now, nobody has ever accused Peter Medawar of being stupid so before you start to quibble about this sort of generalization, be aware that Medawar does not apply it to all of science and every scientific paper. He's talking about common, but not exclusive, practice.

One of the reasons why pure inductive reasoning is misleading is because we never start an investigation with a clean slate.
... the starting point of induction, naïve observation, innocent observation, is a mere philosophic fiction. There is no such thing as unprejudiced observation. Every act of observation we make is biased. What we see or otherwise sense is a function of what we have seen or sensed n the past.
This seems like something that's so obvious that it hardly deserves mentioning. But it does deserve mentioning. Medawar was right to have brought it out into the open and it's something we always need to keep in mind.

Now we get to a famous quotation from Medawar's talk. Janet Stemwedel discusses it in the context of Popper and falsification—conveniently ignoring Kuhn, who is far more relevant—but I want to use it to talk about adaptationism.
We wish to question a deeply engrained habit of thinking among students of evolution. We call it the adaptationist programme,
or the Panglossian paradigm.

Gould and Lewontin (1979)
What is wrong with the traditional form of the scientific paper is simply this: that all scientific work of an experimental or exploratory character starts with some expectation about the outcome of the inquiry. This expectation one starts with, this hypothesis one formulates, provides the initiative and incentive for the inquiry and governs its actual form. It is in the light of this expectation that some observations are held relevant and others not; that some methods are chosen, others discarded; that some experiments are done rather than others. It is only in the light of this prior expectation that the activities the scientist reports in his scientific papers really have any meaning at all.
The debate between the adaptationists and the pluralists is often dismissed—usually by the adaptationists—as mere quibbling about scientific data. After all, they argue, all we need to do is collect data on each characteristic under discussion in order to resolve the question; is it an adaptation or an accident?

They are wrong. This is not a debate about facts at all. It's a debate about the the prior expectations that one has before any data is collected. Criticism of the adaptationist program focuses on the state of mind that researchers posses when they are designing experiments and formulating hypotheses to test. In other words, it's what Medawar refers to when he says that scientists start with "some expectation of the outcome of the enquiry." It's their bias or prejudice that's being questioned and not just whether the horns of an Indian rhinoceros are adaptations or not [Visible Mutations and Evolution by Natural Selection].

One of the main arguments of the Intelligent Design Creationists is that modern scientists adopt a naturalist assumption whenever they do science. This rules out creationism by definition. Some scientists attempt to deny that scientists have any pre-conceived notions at all. They promote the myth of pure inductive reasoning driven only by facts and evidence. It would be wise to drop this form of argument since it is obviously false. Scientists do have prejudices and biases. We need to recognize them and try to deal with them. The essence of skepticism is to always question your assumptions and discard them if they cease to become useful. That's what distinguishes the scientist from the preacher.


Burr, John, R. and Goldinger, Milton (1980) Philosophy and Contemporary Issues Macmillan Publishing Co., New York

Gould, S.J. and Lewontin, R.C. (1979) The Spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist programme. Proc. R. Soc. Lond. B 205:581-598.

P. B. Medawar (1996) "Is the Scientific Paper Fradulent?" in THE STRANGE CASE OF THE SPOTTED MICE, Oxford University Press, Oxford.