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Thursday, December 13, 2007

23andMe - More Hype from Genetic Testing Services

 
The Genetic Genealogist promotes another for-profit testing service called 23andMe [The Latest on 23andMe].

Go to their website [23andMe] where you'll find this teaser ...
Connect to the Famous and the Infamous
Are you more closely related to European royalty or American outlawry? Use 23andMe's Ancestry tools to find out whether your maternal lineage links you more closely to Marie Antoinette or Jesse James. Your 23andMe account also connects you genetically to many other celebrities and historical figures, from Bono to Ben Franklin. Read more about 23andMe's celebrity features.
I still find it curious that there are "science bloggers" who promote these for-profit companies without ever mentioning the scam that they're perpetrating by misleading the general public about what the tests can achieve. The kit from 23andMe costs $999.00 (US).

Some of the bloggers are employed by companies in this field (e.g. Eye on DNA). I don't know about The Genetic Genealogist




Killer Pet Food Revisited

 
Do you remember the scandal from last March were pet cats and dogs were dying, allegedly from pet food manufactured by Menu Foods of Mississauga, Ontario (Canada)? At the time I was skeptical of the claims. It didn't seem to me that there were very many confirmed cases and it didn't seem likely that pet food from a reputable supplier could be so poisonous [Killer Pet Food?].

Well, the scientists have returned a verdict. A recent study has confirmed 348 cases of pet food-induced nephrotoxicity (236 cats and 112 dogs) [300 Pets May Have Died From Contaminated Pet Food Due To Lethal Combination Of Contaminants].

Initial reports suggested that the deaths were due to melamine contamination even though melamine is relatively harmless. It turns out that the pet food also contained unusual levels of cyanuric acid and melamine and cyanuric acid together form a very insoluble salt that blocks kidney function, causing death in some animals.

The pet food was contaminated and more than 300 pets died as a result. The study does not say how the food came to be contaminated but other sources attribute it to wheat gluten supplied by ChemNutra Inc. This company imported the wheat gluten from Xuzhou Anying Biologic Technology Development Co. in Wangdien, China.

Here's the original press release that's posted on the Food ad Drug Administration (USA) website [ChemNutra Announces Nationwide Wheat Gluten Recall].

ChemNutra Inc., of Las Vegas, Nevada, yesterday recalled all wheat gluten it had imported from one of its three Chinese wheat gluten suppliers – Xuzhou Anying Biologic Technology Development Co. Ltd.

The wheat gluten ChemNutra recalled was all shipped from China in 25 kg. paper bags, and distributed to customers in the same unopened bags. The bags were all labeled "Wheat Gluten Batch No.: _______ Net Weight: 25 kg Gross Weight: 25.1 kg Made in China". The batch numbers included in the recall are 20061006, 20061027, 20061101, 20061108, 20061122, 20061126, 20061201, 20061202, 20061203, 20061204, 20061205, 20061206, 20061208, 20061221, 20070106, 20070111, 20070116, and 20070126. Each ChemNutra shipment had the certificate of analysis information from the supplier, including batch number and the supplier's content analysis and test results. ChemNutra shipped from its Kansas City warehouse to three pet food manufacturers and one distributor who supplies wheat gluten only to the pet food industry. ChemNutra's shipments commenced November 9, 2006 and ended March 8, 2007. ChemNutra did not ship to facilities that manufacture food for human consumption, and the distributor ChemNutra shipped to supplies wheat gluten only to pet food manufacturers. The total quantity of Xuzhou Anying wheat gluten shipped was 792 metric tons.

ChemNutra learned on March 8 from one pet food manufacturer that the wheat gluten it had sold them – all from the Xuzhou Anying - was among ingredients suspected as a potential cause of pet food problems. ChemNutra immediately quarantined its entire wheat gluten inventory and assisted this customer's investigation.

After that manufacturer issued a pet food recall, the FDA immediately commenced a thorough investigation of ChemNutra's wheat gluten, including documentation analysis, inspection, and laboratory testing. ChemNutra cooperated fully with the FDA and immediately notified its other three wheat gluten customers about the FDA's investigation. Those customers had all purchased smaller amounts of the Xuzhou Anying wheat gluten commencing in January, 2007.

On Friday, March 30, the FDA announced they had found melamine in samples of the wheat gluten ChemNutra had imported from Xuzhou Anying. The FDA did not inform ChemNutra of any other impurities in the Xuzhou Anying wheat gluten, nor of any impurities in the wheat gluten from ChemNutra's other two Chinese suppliers.

The toxicity of melamine is not clear. However, since melamine is not approved by the FDA for pet food, it should absolutely not have been in wheat gluten. ChemNutra is extremely concerned about the purity of all of its products. The company is particularly troubled that the certificates of analysis provided by the above-named supplier did not report the presence of melamine.
The Mississauga company, Menu Foods is selling off assets in order to cover the court costs and the liability settlements. They recently sold a manufacturing plant in South Dakota to Mars, Incorporated.


Wednesday, December 12, 2007

Is Evolution Linked to Environmental Change?

 
As a general rule, adaptationists are mostly interested in the results of natural selection and not very interested in evolution by random genetic drift. They tend to use the word "evolution" when what they really mean is "natural selection" or adaptation.

Most adaptationists see evolution as positive natural selection. They focus mostly on changes where the population is becoming more fit with respect to the environment. Some of them think that this eventually results in populations that stop evolving because they have become optimized to a particular niche. In such cases, "evolution" (i.e., positive natural selection) will only start up again if the environment changes.

Whenever I mention this I'm usually confronted with a storm of denials. Apparently none of the adaptationists who comment on Sandwalk are guilty of such fuzzy thinking.

I'm so happy for them. The idea that species have exhausted all possible adaptations and reached the very tip top of their adaptive peak seems incredibly naive. The idea that "evolution" will have halted—as opposed to adaptation—seems even more naive.

Now that I've got that off my chest, let's turn to the Hawks et al. (2007) paper that's getting so much press [Accelerated Human Evolution]. Remember, this is a paper about human evolution.

I've read the paper and I can't really comment because there's no data in the paper. What I mean is that there are no examples of the 11,439 "selective events" that they found. It would have been nice to see a few examples of their data just to get some feel for it's quality.

The paper is complicated because it consists mostly of a discussion of the data, which we can't see. The first author, John Hawks, has made an attempt to simplify the work by posting an explanation on his blog john hawks weblog.

Here's an excerpt from the article titled Why human evolution accelerated [my emphasis-LAM]. The article explains why he expected to see an big increase in evolution adaptation following the development of agriculture about 10-40,000 years ago.
Still, a very small fraction of the mutations in any given population will be advantageous. And the longer a population has existed, the more likely it will be close to its adaptive optimum -- the point at which positively selected mutations don't happen because there is no possible improvement. This is the most likely explanation for why very large species in nature don't always evolve rapidly.

Instead, it is when a new environment is imposed that natural populations respond. And when the environment changes, larger populations have an intrinsic advantage, as Fisher showed, because they have a faster potential response by new mutations.

From that standpoint, the ecological changes documented in human history and the archaeological record create an exceptional situation. Humans faced new selective pressures during the last 40,000 years, related to disease, agricultural diets, sedentism, city life, greater lifespan, and many other ecological changes. This created a need for selection.

Larger population sizes allowed the rapid response to selection -- more new adaptive mutations. Together, the the two patterns of historical change have placed humans far from an equilibrium. In that case, we expect that the pace of genetic change due to positive selection should recently have been radically higher than at other times in human evolution.
Now, if I understand this correctly, here's the scenario. About 40,000 years ago humans had pretty much stopped accumulating adaptations because they were becoming optimized to their environment. This is reflected in the data, which shows a slow rate of adaptation at that time.

Then humans started to live in larger communities as they abandoned the hunter-gatherer mode of existence for one based on farming. This created a new environment that was less fit than the previous one. The human population responded to this less fit environment by expanding rapidly in numbers. This created more opportunity for beneficial mutations that were required under the new environmental conditions. The result was a huge increase in the rate of adaptive evolution.


Pushing Electrons

 
Most of you remember your first organic chemistry course with great fondness. You recall the thrill and excitement of learning new reaction mechanisms and getting used to pushing electrons using those neat little curved arrows.

I can imagine your sense of pride and anticipation when you started taking your first biochemistry course and realized that you could make use of all that chemical knowledge. Biochemists also like to draw curved arrows to show you where electrons are going.


Well, you can thank this week's Nobel Laureate, Sir Robert Robinson, for those arrows. He was the first chemist to use them back in the late 1920's. The convention didn't become popular until after World War II and it only became common in chemistry textbooks during the 1950's. The curved arrows spread to biochemistry textbooks in the '60's and '70's to the delight of all biochemistry students.

Believe it or not, there are some people who are not big fans of curved arrows (Laszlo, 2002).
This short note reflects upon the widespread practice, in the classroom, of the paper tool of reaction mechanisms, taught with Lewis structural formulas, using curved arrows to denote motions of electrons. It is concluded that this practice, while assuredly improving upon the rational understanding of chemical reactions and their underlying logic, can easily become a modern counterpart to medieval scholastics. It has many of the features of slang with respect to more thoughtful and dignified speech. And it may breed cynicism and skepticism on the part of the students when they see this paper tool turned into a universal explanatory device.
What a spoilsport ..... Today's students aren't cynical—they love organic chemistry. Else why would so many take it at university?


Laszlo, P. (2002) Describing Reactivity with Structural Formulas, or when Push Comes to Shove. Chem. Educ: Res. Prac. Euro. 3:113-118.

Nobel Laureate: Sir Robert Robinson

 

The Nobel Prize in Chemistry 1947.

"for his investigations on plant products of biological importance, especially the alkaloids"



In 1947, Sir Robert Robinson (1886 - 1975) won the Nobel Prize in Chemistry for working out the structure of a number of plant alkaloids, especially morphine and strychnine [Morphine, Heroin, Codeine].

The presentation speech was given by Professor A. Fredga, member of the Nobel Committee for Chemistry of the Royal Swedish Academy of Sciences.
THEME:

Nobel Laureates
Your Majesty, Royal Highnesses, Ladies and Gentlemen.

One of the principal aims of organic chemistry is to make clear the chemical structure of substances found in living nature. Interest has been directed particularly towards substances with vital functions or otherwise obvious qualities. The structure of simpler compounds was largely elucidated during the nineteenth century, the more complicated ones being reserved for our century. Sir Robert Robinson's exceedingly fruitful work treats many groups of such substances. In comprehensive investigations he has dealt with the anthocyans, a group of red, blue, or violet pigments found almost everywhere within the vegetable kingdom, and which we meet with in the cornflower and the lark-spur of the fields as well as in claret and beetroot. He has done important work on sex hormones and synthetic substances of less complicated structure but with similar properties. He has done pioneering work on synthetic drugs against malaria, he has contributed towards the investigation of penicillin and he has successfully attacked fundamental questions concerning the mechanism of organic-chemical reactions. In presenting him with this year's Nobel Prize in Chemistry, the Royal Academy of Sciences has in mind, however, particularly his work on alkaloids.

By alkaloids we understand a numerous group of nitrogenous basic substances from the vegetable kingdom. They usually have striking, sometimes sensational physiological effects. Among them are quinine, cocaine, and atropine, all of which have important medicinal qualities, further morphine, doubtless well-known, and strychnine known for its medicinal value and - in somewhat larger doses - as an exceedingly active poison. Plants containing alkaloids have generally drawn the attention of primitive peoples, and in the cases where they are met with in countries with ancient culture, the knowledge of their properties often goes back to pre-historic age. They have been used as medicines and means of enjoyment, for ritual and criminal purposes. They can carry our thoughts to poetry and romance - it is not only decadent poets who have sung the praise of opium and poppy juice - but they have also been associated with vice, crime and horror.

During the nineteenth century we began to learn how to isolate the active substances themselves, the alkaloids, and investigation of their chemistry still continues with unabated interest. It was soon found that these alkaloids are usually very complicated in structure; the molecule of morphine contains 40 atoms, that of strychnine 47, each of which has its definite place in relation to the others. To reveal the inner architecture of these complicated systems through different chemical operations is a task as difficult as it is fascinating. It requires great experimental skill, creative power and sharp logic. In this sphere of alkaloid research, Sir Robert stands out as our foremost contemporary. He has solved the riddle of the morphine molecule's structure, in connection with which quite 20 different formulae have been under consideration, he has clarified the essential features of the strychnine formula, even though some details are still uncertain, and he has made decisive contributions towards the investigation of many other alkaloids with strangely sounding names like gnoscopine, harmaline, physostigmine, and rutaecarpine.

It has often been asked how plants build up these singular molecules. Here, Sir Robert has formed a theory which rests upon the amino-acids contained in proteins, and which seems to present a satisfactory answer to the question. The theory is illustrated by Sir Robert's famous synthesis of tropinone, a substance closely related to cocaine. We have here a case where three rather simple molecules spontaneously unite into a complicated system, which earlier we could only build up step by step through a long series of reactions. We may suppose that here Sir Robert has found the key to nature's own way of working. This theory has also gained great importance as a guide when determining intricate structures, and it has rendered it possible to trace hidden connections within the multifarious group of alkaloidal substances.

The tendency in natural science tends more and more to the removal of the traditional boundaries between the different sciences. The sum of total knowledge constantly increases, human intellect, however, is limited and cooperation therefore becomes a matter of necessity. For the individual scientist it becomes a difficult task to broaden and deepen his science on its own particular basis without turning his back upon productive collaboration. Perhaps this is felt particularly in chemistry; it is there that the threads of research into life and matter run together, and thus chemistry has acquired a key position within the natural science of to-day. Sir Robert has solved the problem with great success. He has devoted his life to organic chemistry, but the importance and the consequences of his work extend far into the fields of biological and medicinal research.

Professor Sir Robert Robinson. The intricate problems of organic structure are not of a nature to attract the interest of the general public. Our science is an exclusive one. You have not gained your scientific reputation by startling discoveries, which, like the atomic fission, resound in the columns of the daily press.

By your very important and very numerous investigations, you have gradually changed our ideas on fundamental questions. As a student of molecular architecture you have, with eminent success, pursued the line of work emerging from Kekulé and Couper, and you have thrown light upon the formation of complicated structures within the living plant. Among organic chemists, you are to-day acknowledged as a leader and a teacher, second to none. In recognition of your services to Science, the Royal Academy has decided to bestow upon you the Nobel Prize for Chemistry for your investigations on plant products of biological importancc and especially for your outstanding work on the structure and the biogenesis of complicated alkaloids.

Sir Robert. On behalf of the Academy, I request you to receive your prize from the hands of His Majesty the King.


Tuesday, December 11, 2007

Mendel's Garden #21

 
The 21st version of Mendel's Garden has just been posted on The Inoculated Mind [Mendel’s Garden #21: Old DNA never dies…].
Welcome to the 21st edition of Mendel’s Garden, here at The Inoculated Mind. Genetics-related blog posts were submitted from around the blogosphere during the month of November, and here you will find the best of them for your reading enjoyment this December, 2007. It seemed that although the topics were mixed, as they always are, there was a general theme to this month’s submissions. Old DNA never dies.


Stop the Press - Genes Have Regulatory Sequences!

 
You heard it here first—well, not exactly. The breaking news was first reported over at Biology News Net. Junk DNA isn't junk at all because it's full of regulatory regions controlling gene expression. This is excuse #5 of The Deflated Ego Problem.

Here's the scoop from More 'functional' DNA in genome than previously thought.
Surrounding the small islands of genes within the human genome is a vast sea of mysterious DNA. While most of this non-coding DNA is junk, some of it is used to help genes turn on and off. As reported online this week in Genome Research, Hopkins researchers have now found that this latter portion, which is known as regulatory DNA and contributes to inherited diseases like Parkinson’s or mental disorders, may be more abundant than we realize.


The False Icon of Progressive Evolution

 
Elaine Warburton of Genetics & Health has just posted an article on the Hawks et al. (2007) paper [Humans on evolutionary fast track].

Unfortunately, she choose to illustrate it with the image shown on the right. This is a misleading representation of human evolution because it implies a linear change, or progress, from chimpanzees to humans. The late Stephen Jay Gould railed about this icon on several occasions—most notably in the opening chapter of Wonderful Life. He would be tuning over in his grave if he knew that Elaine had used such an icon.


Are humans evolving faster?

 
The press release from the University of Utah [Are humans evolving faster?] describes the Hawks et al. (2007) paper I blogged about earlier [Accelerated Human Evolution].

One paragraph caught my attention ...
The new study comes from two of the same University of Utah scientists – Harpending and Cochran – who created a stir in 2005 when they published a study arguing that above-average intelligence in Ashkenazi Jews – those of northern European heritage – resulted from natural selection in medieval Europe, where they were pressured into jobs as financiers, traders, managers and tax collectors. Those who were smarter succeeded, grew wealthy and had bigger families to pass on their genes. Yet that intelligence also is linked to genetic diseases such as Tay-Sachs and Gaucher in Jews.
The idea that selection for intelligence among Askenazi Jews could be observable in only a few hundred years seem far-fetched, to say the least [Evolution in the Ashkenazi Jewish Population]. Natural selection just ain't that strong if all it has to work with is a few (male) money lenders.

The fact that these are the same authors as the Hawks et al. (2007) paper is disquieting.

Call me even more skeptical ....

The press release from the University of Wisconsin-Madison, where John Hawks is located, says [Genome study places modern humans in the evolutionary fast lane] ...
In a study published in the Dec. 10 issue of the Proceedings of the National Academy of Sciences (PNAS), a team led by University of Wisconsin-Madison anthropologist John Hawks estimates that positive selection just in the past 5,000 years alone — around the period of the Stone Age — has occurred at a rate roughly 100 times higher than any other period of human evolution. Many of the new genetic adjustments are occurring around changes in the human diet brought on by the advent of agriculture, and resistance to epidemic diseases that became major killers after the growth of human civilizations.

"In evolutionary terms, cultures that grow slowly are at a disadvantage, but the massive growth of human populations has led to far more genetic mutations," says Hawks. "And every mutation that is advantageous to people has a chance of being selected and driven toward fixation. What we are catching is an exceptional time."

The findings may lead to a very broad rethinking of human evolution, Hawks says, especially in the view that modern culture has essentially relaxed the need for physical genetic changes in humans to improve survival. Adds Hawks: "We are more different genetically from people living 5,000 years ago than they were different from Neanderthals."
Wow! We are more different genetically from people living at the time the pyramids were built that they are from the Neanderthals from whom they separated 100,000 years earlier.

This must be a really, really good paper if that's what it proves. I can hardly wait for it to show up on the PNAS website.


[Photo Credit: Al Pacino as Shylock in The Merchant of Venice]

Accelerated Human Evolution

 
We frequently hear claims that humans have stopped evolving. Most of these claims have to do with medical advances that are now allowing people to survive who might have died in earlier times. The idea is that natural selection is no longer working so we have stopped evolving.

This is a flawed argument [Have Humans Stopped Evolving?]. Assuming that medical advances are having a significant impact on the world's population, it follows that the impact is to speed up evolution and not slow it down!

To understand this, you have to keep in mind that evolution is defined as ... [What Is Evolution?].
Evolution is a process that results in heritable changes in a population spread over many generations.
In the past, mutations that were detrimental were rapidly purged from the population (or kept at a very low level) because humans could not save those with genetic diseases such as diabetes. Today, those alleles are not being removed from the population by negative selection.

Thus, the frequency of alleles that used to be detrimental is increasing at a faster rate than in the past. Modern humans are evolving faster than before the advent of medical advances.

In addition to the major flaw in logic, there are many other things wrong with the claim that modern humans have stopped evolving. The claim carries with it a very loaded assumption that is never explicitly stated. The assumption is that humans have pretty much reached their optimal level of fitness for all other characteristics. For example, we are no longer selecting for higher intelligence, or a better immune system, or more efficient energy production, or stronger muscles, or any of a host of other things that might make us better adapted to all environments.

Why is this assumption necessary? Because nobody could possibly suggest that we have stopped evolving without assuming that we have reached optimal fitness for all those things in our present environment.

There's another problem with the claim. It assumes that adaptation is the only form of evolution. Nobody who understand random genetic drift would ever say that humans have stopped evolving because you can't stop drift.

Today I learned of another variation on this claim. Apparently there are people out there who say that biological evolution of humans has slowed (stopped?) because it has been supplanted by cultural evolution. I imagine that this is similar to the argument about medical advances. Presumably humans aren't adapting to different climates, for example, because we can make clothes and air-conditioned houses. Presumably we aren't dying of food shortages because, with the coming of agriculture, everyone has enough food.

The flaws in those arguments are the same; (a) there's more to evolution than natural selection and (b) lots of ongoing adaptations do not depend directly on the physical environment and cannot be replaced by culture.

A new paper about to be published in PNAS claims that human evolution has accelerated, not slowed, in the past 10,000 years (Hawks, et al. 2007). The first author is John Hawks of john hawks weblog. One of the press releases is from Scientific American [Culture Speeds Up Human Evolution]. The authors of the PNAS paper looked at variations within the human population and asked whether any of it showed evidence of selective sweeps. This would indicate that the alleles had moved rapidly toward fixation by natural selection. The results were surprising ...
We found very many human genes undergoing selection," says anthropologist Gregory Cochran of the University of Utah, a member of the team that analyzed the 3.9 million genes showing the most variation. "Most are very recent, so much so that the rate of human evolution over the past few thousand years is far greater than it has been over the past few million years."

"We believe that this can be explained by an increase in the strength of selection as people became agriculturalists—a major ecological change—and a vast increase in the number of favorable mutations as agriculture led to increased population size," he adds.
What they mean, of course, is that they have detected more presumed examples of natural selection in recent times than they deduce must have happened in the past. Whether this is an increase in the overall rate of evolution, as opposed to positive selection, is another thing entirely. I'll have to read the paper to see if they establish a baseline rate that includes all mechanisms of evolution.

The idea here is that with the switch from hunter-gatherer to farmer, humans created a new environment and this stimulated rapid natural selection in order to adapt to this new environement.
Roughly 10,000 years ago, humanity made the transition from living off the land to actively raising crops and domesticated animals. Because this concentrated populations, diseases such as malaria, smallpox and tuberculosis, among others, became more virulent. At the same time, the new agriculturally based diet offered its own challenges—including iron deficiency from lack of meat, cavities and, ultimately, shorter stature due to poor nutrition, says anthropologist John Hawks of the University of Wisconsin–Madison, another team member.

"Their bodies and teeth shrank. Their brains shrank, too," he adds. "But they started to get new alleles [alternative gene forms] that helped them digest the food more efficiently. New protective alleles allowed a fraction of people to survive the dread illnesses better."
The assumption here is that evolution among the hunter-gatherers had slowed down because they had become very well adapted to that environment. That's a big assumption but if that's what their data shows then I guess we'll just have to accept the fact that our ancestors were very fit.

I wonder how evolution proceeded from the time of Homo erectus to all of the groups that must have been present 10,000 years ago (i.e., Asians, native Americans, Africans, Europeans)? I suppose evolution was quite rapid until about 50,000 years ago then it slowed down as all the various groups became well-adapted to a hunter-gatherer form of existence?

Then evolution positive natural selection took off as all these groups switched to farming, which caused a change in the environment so that people were no longer well-adapted to the point where selection had slowed down? It's an easy prediction to test. All the new alleles should be present at high frequency in European, Asian and Middle Eastern groups but not in the existing hunter-gatherer groups who haven't been living in large agricultural communities.

It will be interesting to follow the discussion on John Hawks blog [Human Evolution Has Accelerated]. He promises to explain the work in considerable detail. One of the statements he makes today is quite interesting, he says,
It is a powerful paper because it shows why a rapid acceleration of our evolution is expected in theory, and it matches those expectations to real empirical data. It shows the absolute impossibility of a constant rate of selective change in humans, and that gives reality to our estimate of the amount of acceleration.
I'm anxious to find out why "theory" predicts a rapid acceleration of evolution natural selection. I'm also anxious to find out why it's impossible for there to be a relatively constant rate of adaptive change in the human lineage.

John includes the last paragraph of his paper on today's blog article. Here it is ...
It is sometimes claimed that the pace of human evolution should have slowed as cultural adaptation supplanted genetic adaptation. The high empirical number of recent adaptive variants would seem sufficient to refute this claim. It is important to note that the peak ages of new selected variants in our data do not reflect the highest intensity of selection, but merely our ability to detect selection. Due to the recent acceleration, many more new adaptive mutations should exist than have yet been ascertained, occurring at a faster and faster rate during historic times. Adaptive alleles with frequencies under 22% should then greatly outnumber those at higher frequencies. To the extent that new adaptive alleles continued to reflect demographic growth, the Neolithic and later periods would have experienced a rate of adaptive evolution more than 100 times higher than characterized most of human evolution. Cultural changes have reduced mortality rates, but variance in reproduction has continued to fuel genetic change. In our view, the rapid cultural evolution during the Late Pleistocene created vastly more opportunities for further genetic change, not fewer, as new avenues emerged for communication, social interactions, and creativity.
Call me skeptical ...


[Photo Credit: The photograph of the San tribesman, Klaas Kruiper, with his 4-year-old son is from (Save the San]

Hawks, J., Wang, J.T., Cochran, G., Harpending, H.C. and Moyzis, R.K. (2007) Recent acceleration of human adaptive evolution. PNAS in press

Morphine, Heroin, Codeine

Monday's Molecule #55 was morphine [(5α,6α) -7,8-didehydro-4,5-epoxy- 17-methylmorphinan-3,6-diol]. Morphine is an opiate. It is the main analgesic in opium. Morphine is generally recognized as the strongest pain killer known.

Morphine is derived from the creamy latex found in the seed pods of the opium poppy, Papaver somniferum. It seems likely that the opium poppy is derived from wild poppies that grow in the Mediterranean basin. Selection for plants that produce more and more opium has led to the evolution of a new human-made species.

In addition to morphine, the seed pods contain a number of similar opiates; codeine, noscapine, papaverine and thebaine, that are less potent than morphine. It is not clear why wild poppies contain small amounts of these chemicals. Maybe they help prevent the seed pods from being eaten by some animals?

Although opium was widely used in China, it is almost certain that the opium poppy originated in the Middle East and was only imported into China about 400 AD. Historical records suggest that the ancient Sumerians and Egyptians knew about opium and probably used it as a recreational drug.

In addition to its action as a painkiller, morphine produces a sensation of euphoria and well being. Both effects are due to binding of morphine to specific opiate receptors in the brain. Morphine resembles endorphins, which are released in response to stress, and by binding to some opiate receptors further endorphine released is stimulated.

The analgesic effect is due to binding to other opiate receptors that block pain transmission at nerve synapses.

See Brandon's Blog: Poison, Medicine, and Things that Grow for some more information on morphine and opiates. The article Toxic Talk (Ed. 8.1) explains the difference between opiates and opioids. Toxic Talk (Ed. 8.0) has a nice description of morphine showing a different view of the structure than the one shown above.

Pure morphine can be converted to codeine by a simple chemical reaction that adds a methyl group to one of the hydroxyl groups on morphine. Codeine is much less effective as a painkiller than morphine and even less effective at inducing euphoria. It has the benefit of being much less addictive (and legal).

Heroin was first manufactured by English chemists in the 1870's. Later on it was manufactured and sold by the Bayer pharmaceutical company. Heroin is easily made by boiling morphine solutions (or opium) with acetic anhydride. This produces an acetylated form of morphine that is much more potent than morphine in all its properties . The enhanced effects are probably due to its increased solubility and more efficient transfer to the brain, where heroin is converted back to morphine. Heroin is more addictive than morphine, although susceptibility to opiate addition varies considerably from person to person.



[Image Credti: The rotating three-dimensional image of morphine is from Wikipedia]

Monday, December 10, 2007

SEED and the Central Dogma of Molecular Biology - I Take Back My Praise

On October 1, 2007 I praised SEED magazine for being one of the few science magazines to correctly define the Central Dogma of Molecular Biology. Here's what I said two months ago.


One of my pet peeves is the misuse of the term "Central Dogma of Molecular Biology" [Basic Concepts: The Central Dogma of Molecular Biology]. Most people define it as the flow of information from DNA to RNA to protein. Many then go on to declare that the Central Dogma has been overthrown because of reverse transcriptase, alternative splicing, microRNA, epigenetics, or whatever.

This month's issue of SEED has a tear-out summary (cribsheet) of "Genetics." In one of the boxes titled "The Central Dogma of Molecular Biology" there's a drawing of the major pathways of information flow [Cribsheet #12]. The caption says.
There are nine ways information can theoretically flow between DNA, RNA, and protein. Of these, three are seen throughout nature, DNA to DNA (replication), DNA to RNA (transcription), and RNA to protein (translation). Three more are known to occur in special circumstances like viruses or laboratory experiments (RNA to RNA, RNA to DNA, and DNA to protein). Flows of information from protein have not been observed. The trend is clear: information flow from DNA or RNA into protein is irreversible. This is known as the "central dogma," and forms the foundation of molecular biology.
Yeah! As far as I know this is the only popular magazine to get it right.


I take it all back.

This month's issue has an article by Philip Ball outlining another revolution in molecular biology that overthrows the Central Dogma of Molecular Biology. This time it's microRNAs that have done the dirty deed [Redefining Genes].

Philip Ball is a London (UK) based freelance science writer with a Ph.D. in Physics. He has written 10 books on science and many articles for the news section of Nature. Philip Ball blogs at homunculus.

Here's what he says on page 29 of the current newsstand issue of SEED.
For nearly 50 years, the central dogma of molecular biology has been that genetic information is contained within DNA and is passed by rote transcription through RNA to make proteins. ...

The central dogma is being eroded, and it now appears as if DNA's cousin, the humble intermediary RNA, plays at least an equal role in genetics and the evolution of the species.
Philip Ball then gives two recent examples of work showing the involvement of noncoding RNA in gene expression. Then comes the revolution ...
These and a host of other recent findings are rewriting the textbooks of molecular biology. They are beginning to show not only that RNA is more fundamental to genetics than once believed, but also that it can directly affect evolution and elucidate the differences between species. The result is a story that looks a lot messier, but potentially a lot more interesting, than anyone ever guessed.
This is deeply insulting to all biochemists and molecular biologists. What in the world must people like Ball be thinking of us when he writes such nonsense? Does he really believe that for over half a century we have been slavishly adhering to the dogma that genes only make proteins? I know lots of scientists who think the Central Dogma refers to the general pathway of information flow (DNA → RNA → protein) but I never met a biochemist or a molecular biologist who thought that this pathway ruled out genes whose final product was RNA.

That idea is total nonsense, of course, and Philip Ball would know this if he only bothered to read any of the textbooks of molecular biology. Not only have we been teaching about ribosomal RNA, and transfer RNA for 40 years, we've also covered all of the small RNAs involved in splicing, telomeres, signal recognition particle, RNAse P etc. etc. Does he think we're completely ignorant of the Nobel Prizes awarded to Sidney Altman and Tom Czech in 1989 "for their discovery of catalytic properties of RNA"?

Furthermore, we've been teaching about regulatory RNAs for almost as long. The classic examples are the antisense RNAs in bacteriophage λ, attenuation in the trp operon and small RNAs that control the initiation of DNA replication at plasmid origins.

If you were to believe Philip Ball, molecular biologists have clung to his version of the Central Dogma of Molecular Biology in spite of all these counter-examples. Only now are they waking up to the fact that some genes make RNA as their final product. How stupid is that?

Science writers have a special obligation when writing for a general audience. Not only do they have to explain things in simple language but they have to be accurate as well. Pert of being accurate in science is having enough knowledge of the subject to be able to sort out the hype from reality. Philip Ball does not know anough about molecular biology to make that call. He should have read the cribsheet.


Monday's Molecule #55

 
This is a strange-looking molecule. You have to name it, giving us the common name and the correct systematic IUPAC name.

There's a direct connection between this molecule and Wednesday's Nobel Laureate(s). Your task is to figure out the significance of today's molecule and identify the Nobel Laureate(s) who worked out the structure of the molecule.

The reward goes to the person who correctly identifies the molecule and the Nobel Laureate(s). Previous winners are ineligible for one month from the time they first collected the prize. There is only one ineligible candidates for this week's reward because Sandwalk readers have not been very successful in recent weeks. The prize is a free lunch at the Faculty Club.

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 the Nobel Laureate(s). Correct responses will be posted tomorrow along with the time that the message was received on my server. I may select multiple winners if several people get it right.

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

UPDATE:We have a winner! Alex Ling (again) knew that the molecule was morphine [(5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol] and he guessed the Noble Laureate correctly. Two other readers got morphine and the Nobel Laureate but they did not provide the correct IUPAC name as required.


IDiot Logic on Display at Uncommon Descent

 
GilDodgen is at it again, displaying his unique sense of logic in defense of Intelligent Design Cretionism [A Practical Medical Application of ID Theory (or, Darwinism as a Science-Stopper)].

This time he's responding to someone who challenges the ability of Intelligent Design Creationism to make a contribution to medical science.

Never fear, GilDodgen is always ready to lower himself to the occasion,
Here’s a prediction and a potential medical application from ID theory: Design a chemical or protein which would require a triple CCC to defeat its toxic effects on a bacterium, and it will exhaust the probabilistic resources of blind-watchmaker mechanisms to counteract the toxic effects.

Such a success could and will only come from engineering and reverse-engineering efforts, not from Darwinian theory.
You have to wonder whether some of these IDiots are mentally challenged. This is so not a prediction of Intelligent Design Creationism. Here's the real prediction ...

Scientists have known for some time that evolution is limited by the availability of useful mutations. Some evolutionary biologists have even proposed mutationism to describe the fact that evolution may be much more dependent on mutations than most people realize [Evolution by Accident]. One of the possible ways in which evolution could be limited is if a beneficial allele could only arise when three or four mutations must happen simultaneously. (This is what GilDodgen means by a "triple CCC.") This conclusion comes directly from an understanding of genetics, population genetics, and evolution.

Thus, real scientists would predict that you could design an effective antibiotic if you knew that the only way to develop resistance would be via a highly improbable event. This is a conclusion that's based entirely on an understanding of evolution and how it works. Scientists would love to be able to do this but, unfortunately, they don't know all possible ways that bacteria could develop resistance. Evolution is very unpredictable.

Intelligent Design Creationism, on the other hand predicts the exact opposite of what scientists would predict. According to Michael Behe in The Edge of Evolution the Intelligent Designer will frequently design things that are impossible to evolve. Specifically, according to Behe, we often see things in nature that are so improbable that the required mutations could never have occurred in the lifetime of the planet. The fact that we see these things means that Intelligent Design Creationism is true.

Thus, Intelligent Design Creationists predict that no matter what kind of drug we create, the bacteria will always be able to overcome it because the Intelligent Designer isn't bound by the naturalistic rules of mutation and evolution. God can always step in and create the right series of mutations no matter how improbable they might be by natural causes.

It's a waste of time for humans to try and second guess God by creating very sophisticated drugs because God is omnipotent and he will always defeat us if he chooses. This is the exact opposite of the prediction that GilDodgen seems to be making.

Isn't that strange? And you wonder why we call them IDiots?


Sunday, December 09, 2007

Qualified to Be "Leader of the Free World"? I Don't Think So.

 
It's too bad Wolf didn't ask the question he should have asked. Here it is, Wolf, in case you ever get another chance.
Scientists have demonstrated that life has evolved, that humans and the other apes share a common ancestor and that the Earth is 4.5 billion years old. Do you accept these scientific facts or do you prefer to believe in the truth of your particular religious viewpoint over that of modern science?
Followup question;
It's not acceptable to dismiss scientific evidence on the grounds that you weren't there when evolution was happening. Pleading ignorance is tantamount to rejecting modern science. The question relates to your ability to accept scientific evidence when making decisions that affect America and the free world. Do you, or do you not, believe what scientists discover?




[Hat Tip: Canadian Cynic]