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 ...

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[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.

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

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.

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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.

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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.

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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.

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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?

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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?

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[Hat Tip: Canadian Cynic]

The DNA Genealogy Scam

 
CBC News has a show on television called Marketplace. It often covers scams and commercial frauds that Canadians need to be wary of. Last week they ran a segment on home DNA testing kits and the claims of those who sell them to the general public. You can watch the entire segment on their website [Who's Your Grand Daddy?].

I don't think there's any doubt that some of these companies are making exaggerated claims. That counts as a scam in my book. You'll have to watch the show to see how the private companies avoid being interviewed by Wendy Mesley. It's a hoot watching Wendy run her own scam on the streets.

I'm disturbed by the fact that we have a number of prominent bloggers pushing DNA testing. You'd think they would be all over this story. You'd think that they would be in the front lines in the attack on unscrupulous private companies who are overselling the idea of tracing your ancestors through your DNA.

If you thought that you'd be wrong. Some of these bloggers are even denying there's a problem. Fore example, here's what Blaine Bettinger on The Genetic Genealogist says about accusations of scam [Another Questionable Article About Genetic Genealogy].

First - a scam artist is by definition a person who engages in a “fraudulent business scheme.” Although genetic genealogy can be controversial, I’ve never heard a single customer accuse a company of running a scam. To the best of my knowledge, these testing companies are using the best science available to test DNA and compare results to their databases. Are physicians running a scam if they use open-heart surgery to fix a heart, rather than a simple pill that will be invented in 5 years? All technology is based on the best developed science right now. A company might have a limited database or only test a limited number of markers, but this does not qualify them as running a “scam.”

I think Blaine is letting his enthusiasm for DNA testing get the better of him. I suggest he look at the CBC show and tell us where they are going wrong if he thinks that all of the private companies are totally honest.

I don't think Hsien-Hsien Lei at Eye on DNA has made any comment either about the scams. Why?

UPDATE: The Genetic Genealogist responds to the CBC segment. His answer? Caveat emptor. Consumers should learn more about genetic genealogy before buying.

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Castor Oil

 
Today's Botany Photo of the Day is Ricinus communis, or the castor bean plant. I don't think I've ever seen a photo of this plant even though it's very famous.

This is where castor oil comes from. When I was a child castor oil was routinely used to relieve constipation. Children soon learned to lie about their bowel movements in order to avoid the cure.

One thing I didn't know is that the plant is full of a deadly toxin called ricin. In fact, there's so much ricin in this plant that ingesting a single seed could do serious harm to a child.

Fortunately, ricin is very soluble in water and during preparation of castor oil the ricin is removed. The Wikipedia site says that workers who prepare castor oil are at considerable risk, not just from ricin toxin but also from allegenic compounds in the plant surface [Castor Oil].

Makes you wonder how our ancestors ever discovered the important and useful properties of castor oil.

The general public needs to be more aware of the dangers of natural chemicals in plants. These days, there's an implicit assumption that trace amounts of man made chemicals are bad [e.g. bisphenol] but everything natural is good. The fact is, ingesting some of the herbal remedies in so-called "health food" stores can be far more dangerous to your health than drinking water from a Nalgene® bottle.

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The Nathaniel Abraham Affair

 
Nathaniel Abraham was a post-doc in a lab working on zebrafish development. He was fired because he revealed after he was hired that he does not believe in evolution.

Almost every scientist agrees that this was proper [Slackjawed creationist surprised at his own incompetence at a scientific job]. You can't work in a field that requires an understanding of evolution if you don't accept the fundamental scientific fact of evolution.

However, knowing what's right scientifically isn't the same as winning a case in court. The creationists are more than happy to take this to court because they get a lot of traction from portraying the scientific establishment as a bunch of bigots who discriminate against religion.

John Pieret looks at the court case [The Other Guy's Court]. This may get complicated. It could easily turn into a situation where justice and the law turn out to be different things.

I don't think lawyers should be deciding what's proper science and what's not—that includes Dover—but I can't see any way out of this quagmire as long as there's confusion about the differences between science and religion.

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Impending Canadian Copyright Legislation Could Be Disasterous

 
The Government of Canada has served notice that it intends to amend Canadian copyright law to bring it more into line with international standards. The goal has widespread support but the proposed legislation goes too far. The Conservative government is looking at changes that mimic the American Digital Millennium Copyright Act (DMCA) [What Is DMCA and Why Should We Care?].

Industry Minister Jim Prentice (see photo) is the man behind this obnoxious legislation.

A consortium of 92 Canadian Colleges and Universities has issued a statement opposing many of the proposed changes (Association of Universities and Colleges of Canada, AUCC). You can read the entire document at AUCC SUBMISSION TO THE MINISTERS OF INDUSTRY AND CANADIAN HERITAGE CONCERNING COPYRIGHT LAW REFORM.

This is the part that refers to new laws governing internet service providers (ISPs) such as universities and colleges.

One legislative option to address this issue would be to introduce a “notice and notice” system under which an ISP must forward to its user an allegation by a copyright owner that material on the user’s web site infringes copyright. The ISP would be required to take steps to remove the material from the hosted web site only after there has been a finding of infringement by a court and the issuance by the court of a removal order. If an ISP failed to take the steps mandated by the court order, it would be liable for authorizing infringement. This "notice and notice" approach is the existing industry practice of ISPs in Canada and has worked well for both rights holders and for ISPs. The "notice and notice" approach is supported by the Canadian Association of Internet Providers, representing major Canadian ISPs.

An alternative legislative option promoted by some interests would see the introduction of a "notice and takedown" regime similar to the one set out in the Digital Millennium Copyright Act (DMCA) in the U.S. Under this approach, when an ISP is notified by a copyright owner that there is allegedly infringing material on a web site, the ISP must respond expeditiously to remove, or disable access to, the material that is claimed to be infringing. AUCC agrees with the view of the Canadian Association of Internet Providers that this approach has the serious disadvantage of putting ISPs in a "quasi-judicial" role that conflicts with the interests of the users of their services. A “notice and takedown” approach could create incentives for ISPs to take the path of least resistance by removing content without warning or evidence of actual infringement, and thereby harm freedom of expression. This is not a minor matter for universities given that many university faculty members maintain web sites, often related to the university courses that they teach and their research.

AUCC recommendation on the liability of ISPs for infringements by users of their services:

AUCC recommends that the Copyright Act be amended to codify a “notice and notice” system under which an ISP’s obligations would be to forward to its users any allegations of copyright infringement made by a copyright owner. An ISP should not be liable for infringing material that has been posted on a web site by a user of the ISP’s services unless, after a court has ruled that the material is infringing and orders its removal, the ISP fails to comply with the court order within a reasonable time.

This is important legislation that could have a serious impact on the internet in Canada. It's one time when we definitely do not want to copy the Americans as the present government is so fond of doing. People need to pay attention. Contact your Member of Parliament.

Read the links on Canadian Cynic [ Keep Those Cards and Letters Coming] for more information.

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Junk DNA in the Toronto Star

 
Cameron Smith is an an environmentalist who lives Gananoque, Ontario (Canada). He was written more that 500 columns for the Toronto Star. Most of them are about nature. His latest column in today's Idea section caught my attention [Getting to the root of plant life].

The column seems to be heading in the direction of promoting the "intelligence" of plants (see below). There will be a followup column soon, according to Cameron Smith.

The part that disturbs me is the following,

However, with their mapping of the human genome, they [molecular biologists] discovered that humans carry only about 25,000 protein-coding genes. This was startling, because the simple nematode worm has about 19,000 such genes – and the human body is immeasurably more complex than a worm's. So, why didn't humans have a lot more protein-coding genes – genes that instruct proteins what to do?

I've addressed this point several times [Facts and Myths Concerning the Historical Estimates of the Number of Genes in the Human Genome, SCIENCE Questions: Why Do Humans Have So Few Genes?]. It's simply not true that all scientists were surprised by the number of genes we have. For many, this result was anticipated and it poses absolutely no problems in understanding biological complexity. There's no pressing need to look for some magic bullet.

To find answers, molecular biologists had to revise their notions of the genetic code. They knew that a huge number of genes in the human genome, making up more than 98 per cent of the genome, don't code protein. These they had previously dismissed as evolutionary leftovers, or junk DNA.

In an enormous turnaround, they began looking at these non-coding genes more closely and discovered they were not junk after all.

There's a lot of nonsense in those few sentences. The most important flaw is that the basic message is completely wrong. It is simply not true that molecular biologists have discarded the concept of junk DNA. The vast majority of molecular biologists know the facts; namely that >90% (probably more) of our genome consists of junk DNA. Just because there are a few renegade scientists who don't know any better does not make these facts disappear.

They had an extremely important function. A key to the mystery lay in the nature of complexity. There was no doubt protein-coding DNA was capable of creating complexity.

It could issue instructions for creating the legions of proteins that, in the case of humans, make up half their dry weight. But regulating the process was another matter. Without regulation, the results would be mostly chaotic.

In addition, as the complexity of organisms increased, the amount of regulation that was needed increased exponentially.

Regulation, it turns out, is the job of RNA (ribonucleic acid), located in the nucleus of cells along with DNA. It's from the so-called junk DNA that RNA gets regulatory instructions.

This revelation opened the intellectual floodgates, and put to rest the notion that life was ruled by a robotic DNA ritually coding proteins, much like a machine stamping out widgets.

Here are the scientific facts in a nutshell.

• Scientists have known about regulatory sequences for at least fifty years. They were never, ever, thought to be junk DNA by any competent molecular biologist.
• There is no evidence to support the half-baked notion that the amount of DNA sequence required for regulation of "complex" organisms (i.e., humans) is exponentially more than that required for regulation of "simple" organisms (i.e., nematodes). All available evidence shows that gene regulation in all multicellular species is very similar.
• We've known about regulation by small RNA's since the 1970's. Nothing new there. There is no solid evidence to suggest that regulation of typical human genes requires RNA and much theoretical and experimental evidence against such an idea. Active imagination doesn't count in science. Scientists need real data before jumping to the extraordinary conclusion that human gene regulation is fundamentally different than other species.
• One of the many reasons for accepting that only 2% of our genome is functional has to do with the concept of genetic load [Facts and Myths ...]. If junk DNA is full of genes encoding regulatory RNAs then we're in big trouble because mutation rates are going to kill us off pretty quickly.

Cameron Smith seems to be quite taken with the ideas of Anthony Trewavas at the Institute of Molecular Plant Science, University of Edinburgh (Edinburgh, UK). Trewavas has been writing papers promoting the idea that plants have a form of intelligence. He doesn't mean they have a brain, of course, what he means is that plants have a complex form of regulation that responds to the environment.

According to Trewavas, systems biology and computer modeling have revealed a level of complexity that scientists never suspected (Trewavas, 2006). Naturally, this totally unsuspected level of regulatory complexity has been hidden from those scientists who have adopted a reductionist approach to science.

Systems approaches enable plant scientists to understand the structural stability of plants, their control and design structure, and how these lead to robust and resilient behavior. These capabilities are the result of a complex biological system in which control operates at many different levels (Figure 1). Complexity is a serious biological problem, and it is likely that biological systems are the most complex known. Increasingly, scientists are going to have to depend on computational biologists to construct models that can then be tested back in laboratory conditions. However, as indicated here, laboratory conditions are only one environmental circumstance among many in which plant systems develop. In 10 years, my own estimate is that plant molecular research groups will be half modelers and half wet investigators producing new data for modelers.

I'm getting a little tired of this sort of rhetoric. Systems biology, properly defined, can be a very useful approach to a problem but turning it into a religion isn't going to help. I'm content to wait and see whether the systems biologists are actually going to deliver something (other than rhetoric) before jumping on that bandwagon.

Trewavas believes in the power of information theory (IT). This faith him to conclude that plants have a form of intellignece (Trewavas, 2005a, 2005b, 2003).

This idea of intelligent plants should not be taken literally. Trewavas clearly means it to be controversial and clearly understands that it is a metaphor. However, the concept is based on an false premise, in my opinion. The premise is that there is a complex sophisticated (and largely undiscovered) regulatory circuit in plants that allows them to behave as though they were responding to the environment in an intelligent way. I don't think we need to go down that path. Yes, plants can control gene expression, just like bacteria, but I see no value in exaggerating that control to the extent that Trewavas does.

From the current rate of progress, it looks as though plant communication is likely to be as complex as that within the brain. (Trewavas, 2003, p.6).

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Trewavas, A. (2003) Aspects of plant intelligence. Ann Bot (Lond). 92:1-20. [PubMed]

Trewavas, A. (2005a) Plant intelligence. Naturwissenschaften. 92:401-13. [PubMed]

Trewavas, A. (2005b) Green plants as intelligent organisms. Trends Plant Sci. 10:413-9. [PubMed]

Trewavas, A. (2006) A brief history of systems biology. "Every object that biology studies is a system of systems." Francois Jacob (1974). Plant Cell. 18:2420-2430. [PubMed]

Spe Salvi - Saved by Hope

 
Last week Pope Benedict XVI issued an encyclical titled Spe Salvi, a reference to a statment made by Paul to the Romans; "Spe Salvi facti sumus"—in hope we were saved.

It probably won't come as a surprise to learn that God is the "hope" that sustains all Roman Catholics.

In this sense it is true that anyone who does not know God, even though he may entertain all kinds of hopes, is ultimately without hope, without the great hope that sustains the whole of life (cf. Eph 2:12). Man's great, true hope which holds firm in spite of all disappointments can only be God—God who has loved us and who continues to love us "to the end," until all "is accomplished"

Atheists, by definition, do not believe in God. Therefore, we cannot have hope. This makes sense if you substitute "superstition" for "hope."

It's often the case when reading these papal ramblings that some passages are difficult to understand. I wonder if this is deliberate? Here's an example,

It is not the elemental spirits of the universe, the laws of matter, which ultimately govern the world and mankind, but a personal God governs the stars, that is, the universe; it is not the laws of matter and of evolution that have the final say, but reason, will, love—a Person. And if we know this Person and he knows us, then truly the inexorable power of material elements no longer has the last word; we are not slaves of the universe and of its laws, we are free. In ancient times, honest enquiring minds were aware of this. Heaven is not empty. Life is not a simple product of laws and the randomness of matter, but within everything and at the same time above everything, there is a personal will, there is a Spirit who in Jesus has revealed himself as Love.

This seems to be more than just the passive Theistic Evolutionism of Ken Miller. It seems to be closer to a God who intervenes and guides frequently. A God who plays a much more active role than most Catholics I know would be willing to admit.

The most controversial part of the Pope's message is the following,

The atheism of the nineteenth and twentieth centuries is—in its origins and aims—a type of moralism: a protest against the injustices of the world and of world history....If in the face of this world's suffering, protest against God is understandable, the claim that humanity can and must do what no God actually does or is able to do is both presumptuous and intrinsically false. It is no accident that this idea has led to the greatest forms of cruelty and violations of justice; rather, it is grounded in the intrinsic falsity of the claim. A world which has to create its own justice is a world without hope.

Now, I understand the part about a world without hope. It must be nice to rely on your preferred superstitions to get out of dealing with the problems of the world. You can be comforted in the hope that God will eventually fix it when he turns his attention to our suffering.

The part I don't get is the claim that atheism is the source of the greatest forms of cruelty and injustice. For more than a thousand years the Roman Catholic Church dominated European culture and almost everyone was a Christian. As far as I know, cruelty and injustice didn't go away during those times.

On the other hand, since the enlightenment and the coming out of atheists in the eighteenth and nineteenth centuries, we have seen huge advances in extension of fairness and justice to all people. For example, in most secular nations women are treated with something approaching equality. Meanwhile, the true believers still haven't elected a female Pope.

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Is Your Water Bottle Killing You?

 
CTV News is reporting that Mountain Equipment Co-op is going to stop selling polycarbonate water bottles [Sporting goods chain drops bisphenol A products]. The bottles leach tiny amounts of a compound called bisphenol-A (BPA) and there have been reports out for many years that BPA is dangerous to your health. One of the products that's causing concern is Nalgene® water bottles with the number 7 in a triangle. These bottles are make of a type of polycarbonate called Lexan that contains BPA.

Concern about possible health problems due to BPA have been around for years. As is usually the case whenever the alarm is sounded, the environmentalist/green/healthfood movements will be the first to respond. They have been strongly opposed to plastic water bottles for some time. Their claims about chemical dangers tend to be exaggerated so it's often hard to know who to believe. (But see TheGreenGuide for a reasoned opinion [ The Bisphenol-A Debate: A Suspect Chemical in Plastic Bottles and Cans].)

Bisphenol A resembles steroid hormones such as estrogen and it may interact with estrogen receptors. Some studies have linked it to increased risk for cancer in humans. There's a long list of other possible diseases that are possibly associated with BPA including the usual suspects like autism. Many of these presumed linkages are not credible but there are enough real scientific studies to cause concern.

The Bisphenol A website is maintained by a consortium of chemical companies. They have a clear vested interest in proving that their plastics are safe. The site contains many interesting facts and figures about the controversy including this report just released by Centers for Disease Control and Prevention (CDC) scientists in Atlanta, Georgia (USA) [Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003-2004]. The study shows that 93% of the population has detectable levels of BPA but these levels are far below the concentrations that produce harmful effects in animal studies.

What we need in situations like this is a neutral third party to evaluate the risks. Neither the chemical industry nor the healthfood industry can be trusted.

Along comes the Journal of the American Medical Association (JAMA). The Oct. 3, 2007 issue has an article summarizing the results of two recent studies [Expert Panels Weigh Bisphenol-A Risks].

The first study was done by a group of 38 scientists in November 2006.

After reviewing more than 700 studies, the group concluded that the molecular mechanism of BPA action in humans and animals is essentially identical, said Frederick S. vom Saal, PhD, of the Endocrine Disruptors Group at the University of Missouri-Columbia. Additionally, they determined that human and animal cells respond to similar doses of BPA and that the documented responses to very low-dose exposures can be explained by BPA's interaction with estrogen receptors on the cellular membrane.

"It's through these cell membrane receptors that doses below a part per trillion in cell culture can activate changes in cells," vom Saal said. "We're talking about levels of potency that are absolutely equivalent to estradiol."

The BPA doses that have been linked with health problems in animals are actually lower than the levels of free biologically active BPA that have been documented in human blood by a variety of techniques, such as ELISA testing and mass spectrometry, vom Saal said.

"The wide range of adverse effects of low doses of BPA in laboratory animals exposed both during development and in adulthood is a great cause for concern with regard to the potential for similar adverse effects in humans," according to the consensus statement. The statement calls for more research to probe BPA's effects in laboratory animals, wildlife, and humans.

The second study was done last August by a panel of the National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction.

Although the panel rated the likelihood of human reproductive problems as "minimal" or "negligible," based on existing studies, it did have "some concern" that exposure could have neurological or behavioral effects in pregnant women, fetuses, infants, and children.

One reason for the differences in the groups' conclusions is that the NTP panel chose to exclude studies in which animals were exposed to BPA through injections. Members of the panel noted that most human exposure occurs through ingestion of the substance and that this translates to lower doses because the chemical is metabolized by the liver. But other researchers argue that such studies should have been included and that excluding them overlooks important evidence that exposure to low doses of BPA may lead to morphological and functional changes in the reproductive tracts of animals exposed early in development (Maffini MV et al. Mol Cell Endocrinol. 2006;254-255:179-186).

The bottom line is that there is enough concern to warrant trying to cut down on BPA intake. While the evidence suggests that it may be impossible to completely avoid exposure, you can still avoid the most likely sources—including those plastic water bottles.

It's probably time to switch to glass or metal, just to be on the safe side.

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Mitt Romney and Truthiness

 
I noticed the following in Mitt Romney's religion speech [Mitt Romney's Faith In America address (as prepared for delivery)].

Americans acknowledge that liberty is a gift of God, not an indulgence of government. No people in the history of the world have sacrificed as much for liberty. The lives of hundreds of thousands of America's sons and daughters were laid down during the last century to preserve freedom, for us and for freedom loving people throughout the world. America took nothing from that century's terrible wars - no land from Germany or Japan or Korea; no treasure; no oath of fealty. America's resolve in the defense of liberty has been tested time and again. It has not been found wanting, nor must it ever be. America must never falter in holding high the banner of freedom.

I don't mean to diminish the role played by the United States of America during the second half of World War II but it seems a touch arrogant to say that "No people in the history of the world have sacrificed as much for liberty."



As for not taking any land from Japan, the people of the Ryukyu Islands (including Okinawa) might disagree. America occupied those islands until they were returned to Japan in 1972. The USA still has a military base on Okinawa as far as I know.

America also gained control over the Amami, Miyako and Yaeyama Islands groups at the signing of the Treaty of San Francisco. These islands were subsequently returned. I suppose Mitt Ronmney could argue that technically these territorial acquisitions were on behalf of the United Nations but that's not going to fool anyone.

America took back its colony of the Marianna Islands (Guam) after world War II but this isn't really taking land from Japan since America had previously owned the colony after grabbing it from Spain in 1898.

I was also stuck by the following statement.

I'm not sure that we fully appreciate the profound implications of our tradition of religious liberty. I have visited many of the magnificent cathedrals in Europe. They are so inspired ... so grand ... so empty. Raised up over generations, long ago, so many of the cathedrals now stand as the postcard backdrop to societies just too busy or too 'enlightened' to venture inside and kneel in prayer. The establishment of state religions in Europe did no favor to Europe's churches. And though you will find many people of strong faith there, the churches themselves seem to be withering away.

Unlike many others, Romney seems to be aware of the implications of American tradition of religious liberty. Whereas in Europe religion is disappearing in spite of the fact that European countries have state religions, in America where "religious liberty" is the norm, religion is still so important in politics that Romney is forced to give a speech defending his version of religion. There's irony hidden in there somewhere.

In such a world, we can be deeply thankful that we live in a land where reason and religion are friends and allies in the cause of liberty, joined against the evils and dangers of the day. And you can be certain of this: any believer in religious freedom, any person who has knelt in prayer to the Almighty, has a friend and ally in me. And so it is for hundreds of millions of our countrymen: we do not insist on a single strain of religion - rather, we welcome our nation's symphony of faith.

Does this sound like someone who would respect atheists and agnostics? How abut Buddhists?

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[Photo Credits: Mitt Romney from his campaign webstite (True Strength for America's Future); WWI statistics are from Wikipedia.]
[Hat Tip: RichardDawkins.net]

Complementary and Alternative Medicine Exposed

 
Skeptics Canada is launching a year-long campaign against complementary and alternative medicine (CAM). The opening salvo will be fired tonight at the monthly meeting. Go to the Ontario Institute for Studies in Education (OISE) Building on Bloor St., just west of the St. George subway stop. The meeting is in rm 2211 from 7-9 pm.

First in a series of presentations on the topic of complementary and alternative medicine. Professor Michael De Robertis will speak on homeopathy, and award-winning journalists Paul Benedetti and Wayne MacPhail will speak on chiropractic. As well, a public test of one or more alt-med treatments is being planned.

Unfortunately, I won't be able to make it because of another commitment but I can assure you that it will be very entertaining. This is a good cause. Alternative medicine is gaining in popularity as more and more people strart looking for simple cures. Don't forget why it's called "alternative" medicine—it's because it's the alternative to rational evidence-based medicine.

The latest version of Skeptics Circle (#75) has four articles on alternative medicine.

Detox and Re-Tox: Bad Medicine and Even Worse Homeopathy at Alt-Med Mecca NewsTarget on The Bad Idea Blog.

Random reward may explain why homeopathy still exists on Med Journal Watch.

How we know what will kill or cure us on Junkfood Science.

Diluting the Profits on Skeptico.

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Irreducible Complexity

Lately I've run across several different definitions of irreducible complexity [Utterly Stupid Quote of the Day]. Most people seem to think that irreducible complexity is defined as something that cannot evolve but that's not the original definition [IDiot Logic].

Here's what Michael Behe says on page 39 of Darwin's Black Box.

By irreducibly complex I mean a single system composed of several well-matched, interacting parts that contribute to the basic function, wherein the removal of any one of the parts causes the system to effectively cease functioning. An irreducibly complex system cannot be produced directly (that is by continuously improving the initial function, which continues to work by the same mechanism) by slight, successive modifications of a precursor system, because any precursor to an irreducibly complex system that is missing a part is by definition nonfunctional.

Behe then goes on to say that an irreducibly complex system cannot evolve by natural selection.

The definition is not a problem. By this definition there are many irreducibly complex systems in biology. For example, the bacterial flagella is a pretty good example as long as you relax the criteria a little bit. (Some of the minor parts can easily be removed without affecting the overall function.)

The problem is not with the definition, it's with the conclusion. Irreducibly complex systems can easily evolve. All that's required is for the simpler intermediates to have some function other than the one seen in the final completed structure. In the case of the bacterial flagella this simpler function was secretion of large molecules. The flagella evolved from a type III secretion system by just adding a few extra components.

Thus, as Behe says above, it was not produced directly by continuously improving the initial function. Instead, there were several intermediate functions (e.g., secretion) that preceded the shift to the final function we observe today. This is how irreducibly complex systems evolve.

The citric acid cycle is another example of an irreducibly complex system for which there's an easily understood evolutionary pathway. The circular pathway arose when the ends of a forked pathway were joined by evolution of a single enzyme [Defining Irreducible Complexity].

Irreducible complexity is a concept invented by Intelligent Design Creationists. You'd think they would at least make the effort to understand something they created!

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My Moral Foundations

 
I took the Moral Foundations Questionnaire to see the basis of my morality. My score is shown in green and typical scores for liberals are colored blue. Conservatives are red. (Strange choice of colors, if you ask me.)


What does this mean? Not much really, although the people who run the test think it's important. Here's what they say ...

The scale is a measure of your reliance on and endorsement of five psychological foundations of morality that seem to be found across cultures. Each of the two parts of the scale contained four questions related to each foundation: 1) harm/care, 2) fairness/reciprocity (including issues of rights), 3) ingroup/loyalty, 4) authority/respect, and 5) purity/sanctity.

The idea behind the scale is that human morality is the result of biological and cultural evolutionary processes that made human beings very sensitive to many different (and often competing) issues. Some of these issues are about treating other individuals well (the first two foundations - harm and fairness). Other issues are about how to be a good member of a group or supporter of social order and tradition (the last three foundations). Haidt and Graham have found that political liberals generally place a higher value on the first two foundations; they are very concerned about issues of harm and fairness (including issues of inequality and exploitation). Political conservatives care about harm and fairness too, but they generally score slightly lower on those scale items. The big difference between liberals and conservatives seems to be that conservatives score slightly higher on the ingroup/loyalty foundation, and much higher on the authority/respect and purity/sanctity foundations.

This difference seems to explain many of the most contentious issues in the culture war. For example, liberals support legalizing gay marriage (to be fair and compassionate), whereas many conservatives are reluctant to change the nature of marriage and the family, basic building blocks of society. Conservatives are more likely to favor practices that increase order and respect (e.g., spanking, mandatory pledge of allegiance), whereas liberals often oppose these practices as being violent or coercive.

I love it when they talk about basic foundations of morality and the biological basis of morality and then give tests where people are all over the map. How can we have such differences between liberals and conservatives if these "foundations" are universal and innate? Does this mean that right-wing conservatives were born stupid and there's nothing they can do about it?

That's a scary thought.

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[Hat Tip: Gene Expression]

Canadian Students Are #3 in Science

 
The Organization for Economic Co-operation and Development (OECD) has a Programme for International Student Assessmant (PISA).

The first study was carried out in 2000 and it tested for reading ability. Canada ranked fourth in that survey, behind Korea, Finland, and Hong Kong–China.

The second study in 2003 measured mathematical ability and Canada was fifth. Only Chinese Taipei, Finland, Korea, and Hong Kong–China did better.

The 2006 study evaluated scientific literacy. Over 22,000 15-year-old Canadian students from more than 1,000 schools took part in the test. Canadian students ranked in third place behind Finland and Hong Kong-China. The chart (above, left) shows all countries that ranked significantly above the OECD average. The chart below lists some of the countries that were below average. In total, more than 400,000 students from 57 countries took the test.

The PISA study defined scientific literacy as ...

... an individual’s capacity to use scientific knowledge, to identify questions, and to draw evidence-based conclusions in order to understand and help make decisions about the natural world and the changes made to it through human activity.

Science competency was evaluated through a series of questions designed to elicit information on ...

1. Identifying scientific issues required students to recognize issues that can be explored scientifically and the key features of scientific investigation.

2. Explaining phenomena scientifically involved the application of the knowledge of science to describe or interpret phenomena scientifically and predict changes.

3. Using scientific evidence meant interpreting the evidence to draw conclusions; to explain them; to identify the assumptions, evidence, and reasoning that underpin them; and to reflect on their implications.

Students were assessed on two different kinds of scientific literacy ...

Knowledge of science. This entailed an understanding of fundamental scientific concepts and theories, in core scientific areas. The four content areas covered were “Physical systems,” “Living systems,” “Earth and space systems,” and “Technological systems,” representing key aspects of understanding the natural world.

Knowledge about science. This included understanding the purposes and nature of scientific enquiry and understanding scientific explanations, which are the results of scientific enquiry.

The complete Canadian Report can be found on the Council of Ministers of Education website. There's much more information about other countries on the PISA website.

In general, the study looks very good. The questions are excellent and the analysis seems scholarly and well-reasoned. There are no great surprises. Student performance is correlated with school funding levels and socio-economic level.

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The Golden Compass

 
This is a clip from The Golden Compass. It's the movie the Christians are afraid of. They want you to boycott it because it promotes atheism. It looks pretty good to me. I think I'd go see it even if it wasn't just to oppose the boycott.

BTW, I also liked The Chronicles of Narnia even though it had a Christian theme. I don't have much trouble separating fantasy from reality.

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Tangled Bank #94

 
The latest version of the Tangled Bank has been posted by Felicia Gilljam on Life before death [Tangled Bank #94].

Welcome to Tangled Bank #94! My name is Felicia and this is my blog, Life before death, in which I write about secularism, science and bees, with the occasional digression into other things. You may notice that there has been a bit of a gap in posting lately, but I’m back in the game now. Should anyone want to know more about myself (unlikely as that may seem), there’s an About link in the sidebar. But now, without further ado, let’s get on with the carnival!

For those who have difficulty submitting articles to Tangled Bank, let me remind you that you can mail URL's to host followed by the "at" symbol then tangledbank.net.

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Sandwalk Readers Are Left of Center

 
The results of last month's poll show that 70% of Sandwalk readers tend to be liberals or left wingers. I suppose that's not a big surprise. Most of us tend to read blogs that reflect our point of view on the world. This blog is not likely to appeal to those from the right wing of the political spectrum.

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Nobel Laureate: Hugo Theorell

 

The Nobel Prize in Physiology or Medicine 1955.

"for his discoveries concerning the nature and mode of action of oxidation enzymes"

Axel Hugo Theodor Theorell (1903 - 1982) received the Nobel Prize in Physiology or Medicine for his work on biological oxidation-reduction reactions. These reactions are catalyzed by oxidoreductases and they often involve the oxidation and reduction of various cofactors. One of these cofactors, FMN, was Monday's Molecule #54. Near the beginning of his scientific career, Theorell worked with "yellow enzyme." The yellow color was due to the presence of riboflavin which turned out to be the cofactor FMN. It was possible to follow the oxidation and reduction of the cofactor by observing the change in color from yellow to white as it was reduced.

Later on he worked with alcohol deydrogenase, an enzyme that couples the oxidation of organic molecules to the reduction of NAD⁺. At the time this cofactor was known as DPN⁺. Theorell developed fluorescence spectroscopic methods to measure these very fast reactions.

Theorell also worked with cytochrome c, a heme-containing electron carrier involved in oxidation-reduction reactions that transfer electrons from complex III to complex IV during membrane-associated electron transport in mitochondria. Theorell was aware of the α-helix discovered by Pauling & Corey and his first X-ray images of cytochrome c confirmed that the heme group was completely surrounded by α-helices.

The Nobel Prize is awarded by the Karolinska Institute and Theorell was the first scientist from that institute to receive a Nobel Prize.

THEME:

Nobel Laureates
The presentation speech was given by Professor E. Hammarsten of the Royal Caroline Institute.

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen.

The Collegium of Karolinska Institutet has this year awarded the Prize in Physiology or Medicine to Professor Hugo Theorell for his discoveries concerning the nature and mode of action of oxidative enzymes.

More than a hundred years ago the vast field of research within which Theorell's work has been carried out was opened up by a Swedish investigator, Berzelius, who advanced the concept of catalysis and postulated that vital reactions were brought about by means of catalysts, subsequently called enzymes.

Let us as an example consider sugar, dissolved in water. It is not acted upon by oxygen outside the organism, but in living cells it is rapidly broken down by means of oxygen and enzymes, with the simultaneous liberation of energy in a form suitable for use in further reactions.

During the latter part of the 19th century the catalysts postulated by Berzelius were detected - enzymes that quicken dull and sluggish molecules such as oxygen and sugar which will not spontaneously interact. The enzymes bring about this change in the behaviour of the sluggish molecules, called activation, by contacting them for a moment and then releasing them - now in an active form - into the whirls of the molecular dance where they originate new compounds. The enzyme will contact one molecule after another without itself being changed or directly participating in the dance. It is like a tool in a production line, activating the inert material delivered to it by the belt so that a maelstrom of rapid reaction is created beyond it. But such a maelstrom can never come to rest since other tools are soon encountered, each of which maintains the motion and adapts it to a new rhythm. Thus the substances to be metabolized are brought into a sequence of rapid transformations by a versatile machinery built up of strictly specific units, the enzymes.

It is of fundamental importance to know the nature and mode of action of everyone of these truly life-giving enzymes. Their number is still unknown but it is certainly very great - Berzelius' intuitive idea has been fully confirmed in this respect.

In this field a Swedish investigator has once again substantially enlarged our knowledge.

Hugo Theorell realized from the first the importance in scientific investigation of seizing and keeping the initiative. He has realized, too, that «live and let live» is a fertilizing principle for teamwork. The able must not for long remain mere collaborators. They must themselves show initiative and become independent activators. An enzyme can give life to sluggish material in such a way that a new independent enzyme is created. Theorell's scientific work deals with active enzymes, but he is himself an efficient activator on the more complex human level.

His first discovery was made during the period 1933-1935 which, as a Fellow of the Rockefeller Foundation, he spent with the foremost pioneer in enzyme research, Otto Warburg. He arrived with his own idea and with his own technical means of substantiating it. He now made his great classical discovery of the splitting and recombination of the yellow enzyme. «Meister der Enzymforschung», Warburg called him after this scientific achievement. Since then Theorell has illuminated and clarified our understanding of several of the enzymes necessary for life, and in a passionate search for truth and fact in science has spared neither thoroughness nor effort.

Following a logical plan of investigation and with continuous refinement of technique he has clarified and enlarged that field of knowledge in which he is an outstanding leader.

The iron atoms built into many oxidative enzymes constitute functional centres, and many aspects of their intricate linkages to other parts of the enzyme have been revealed, as well as other important routes for the transport of electrons involved in the functioning of oxidative enzymes. He and his collaborators have shed light on the iron-containing enzymes called peroxidases. Before Theorell began his investigations, our knowledge of these substances was little more than guesswork. The extremely high velocity of their reactions demanded the skilful application of a range of advanced technique. It can safely be predicted that the profound analyses thereby performed will be decisive for the future integration of the role of the peroxidase system into the pattern of action of living organisms. The function of another group of iron-containing enzymes, the cytochromes, began to emerge towards the end of the last century, and here again Theorell has achieved an incisive analysis. The nature and function of the muscle pigment were also established through his investigations. He showed it to be an oxygen reservoir which comes into action when the oxygen content of the blood is depleted. It is a source of a «second wind».

A most important part of Theorell's researches has been concerned with the velocities of enzyme reactions and the factors which influence them, factors which determine the directions into which the enzymes force the processes in living organisms. These experiments are not only of basic importance but may be considered model investigations in enzymology.

Professor Hugo Theorell. A fertile imagination. An undeviating and critical accuracy. An astonishing technical skill.

All scientists possess some of these attributes. Very few have all. You are one of these few. In accordance with your gifts you have chosen the most important of all tasks in biology. The purification and the characterization of enzymes are essential prerequisites for progress within the realm of biological research. You have managed to bring about a decisive advance in this fundamental field, and in so doing you have brilliantly taken up and tended the heritage from Berzelius.

On behalf of Karolinska Institutet I ask you to receive your Nobel Prize for Physiology or Medicine for 1955 from the hands of His Majesty the King.

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[Photo Credit: Karolinska Institute]