The 2008 Nobel Prize in Chemistry

 
I'm not a big fan of giving out Nobel Prizes for technological achievements although I do recognize that some of them are noteworthy. This one goes too far in the direction of technology, in my opinion. The technique is useful and has led to many advances in the field but I don't think it's Nobel Prize work.

There were many other worthwhile candidates who made significant advances in the study of basic science, leading to a direct contribution to our understanding of how nature works. None of the names commonly discussed on the science blogs got the prize.

The Chemistry prize was announced today: The Nobel Prize in Chemistry 2008. Here's the press release from the Nobel Prize website.

8 October 2008

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2008 jointly to

Osamu Shimomura, Marine Biological Laboratory (MBL), Woods Hole, MA, USA and Boston University Medical School, MA, USA,

Martin Chalfie, Columbia University, New York, NY, USA

and

Roger Y. Tsien, University of California, San Diego, La Jolla, CA, USA

"for the discovery and development of the green fluorescent protein, GFP".

Glowing proteins – a guiding star for biochemistry

The remarkable brightly glowing green fluorescent protein, GFP, was first observed in the beautiful jellyfish, Aequorea victoria in 1962. Since then, this protein has become one of the most important tools used in contemporary bioscience. With the aid of GFP, researchers have developed ways to watch processes that were previously invisible, such as the development of nerve cells in the brain or how cancer cells spread.

Tens of thousands of different proteins reside in a living organism, controlling important chemical processes in minute detail. If this protein machinery malfunctions, illness and disease often follow. That is why it has been imperative for bioscience to map the role of different proteins in the body.

This year's Nobel Prize in Chemistry rewards the initial discovery of GFP and a series of important developments which have led to its use as a tagging tool in bioscience. By using DNA technology, researchers can now connect GFP to other interesting, but otherwise invisible, proteins. This glowing marker allows them to watch the movements, positions and interactions of the tagged proteins.

Researchers can also follow the fate of various cells with the help of GFP: nerve cell damage during Alzheimer's disease or how insulin-producing beta cells are created in the pancreas of a growing embryo. In one spectacular experiment, researchers succeeded in tagging different nerve cells in the brain of a mouse with a kaleidoscope of colours.

The story behind the discovery of GFP is one with the three Nobel Prize Laureates in the leading roles:

Osamu Shimomura first isolated GFP from the jellyfish Aequorea victoria, which drifts with the currents off the west coast of North America. He discovered that this protein glowed bright green under ultraviolet light.

Martin Chalfie demonstrated the value of GFP as a luminous genetic tag for various biological phenomena. In one of his first experiments, he coloured six individual cells in the transparent roundworm Caenorhabditis elegans with the aid of GFP.

Roger Y. Tsien contributed to our general understanding of how GFP fluoresces. He also extended the colour palette beyond green allowing researchers to give various proteins and cells different colours. This enables scientists to follow several different biological processes at the same time.

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[Photo Credit: GFP Glowing Genes]

Steve Jones Says Human Evolution Is Over

There's so much wrong with this article by Steve Jones that I don't know where to begin. So I'll leave it up to Sandwalk readers to comment. Steve Jones is a Professor of genetics at University College, London (UK) and the author of Darwin's Ghost.

From Times Online via RichardDawkins.net.

Leading geneticist Steve Jones says human evolution is over
By Julia Belluz

Human evolution is grinding to a halt because of a shortage of older fathers in the West, according to a leading genetics expert.

Fathers over the age of 35 are more likely to pass on mutations, according to Professor Steve Jones, of University College London.

Speaking today at a UCL lecture entitled "Human evolution is over" Professor Jones will argue that there were three components to evolution – natural selection, mutation and random change. "Quite unexpectedly, we have dropped the human mutation rate because of a change in reproductive patterns," Professor Jones told The Times.

"Human social change often changes our genetic future," he said, citing marriage patterns and contraception as examples. Although chemicals and radioactive pollution could alter genetics, one of the most important mutation triggers is advanced age in men.

This is because cell divisions in males increase with age. "Every time there is a cell division, there is a chance of a mistake, a mutation, an error," he said. "For a 29-year old father [the mean age of reproduction in the West] there are around 300 divisions between the sperm that made him and the one he passes on – each one with an opportunity to make mistakes.

"For a 50-year-old father, the figure is well over a thousand. A drop in the number of older fathers will thus have a major effect on the rate of mutation."

Professor Jones added: "In the old days, you would find one powerful man having hundreds of children." He cites the fecund Moulay Ismail of Morocco, who died in the 18th century, and is reputed to have fathered 888 children. To achieve this feat, Ismail is thought to have copulated with an average of about 1.2 women a day over 60 years.

Another factor is the weakening of natural selection. "In ancient times half our children would have died by the age of 20. Now, in the Western world, 98 per cent of them are surviving to 21."

Decreasing randomness is another contributing factor. "Humans are 10,000 times more common than we should be, according to the rules of the animal kingdom, and we have agriculture to thank for that. Without farming, the world population would probably have reached half a million by now – about the size of the population of Glasgow.

"Small populations which are isolated can evolve at random as genes are accidentally lost. World-wide, all populations are becoming connected and the opportunity for random change is dwindling. History is made in bed, but nowadays the beds are getting closer together. We are mixing into a glo-bal mass, and the future is brown."

Be sure to keep in mind the definition of evolution [What Is Evolution?].

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My Friend Publishes a Book

 
Many years ago I had a friend who lived just up the street. We didn't get to see each other very much because we went to different high schools. But we did go on one date—to a Simon and Garfunkel concert. It didn't make much of an impression on her because she doesn't even remember it!

Later on she became a well known radio and TV personality including a stint as the co-anchorwoman on the CBC National and a interviewer on "As It Happens" on CBC Radio and NPR.

Now she's written a book and I'm sure it's going to be an excellent read.

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Framing Science

 
Matt Nisbet recently posted the following message under the title Framing Science Ranked Among Top 15 Science Blogs.

For the fourth straight month, Framing Science ranks among the top 15 science-related blogs, as tracked by Wikio. The position of a blog in the Wikio ranking depends on the number and weight of the incoming links from other blogs. (Blogrolls are not taken into account and Wikio only counts links from the last 120 days.)

I submitted a comment in which I noted that several famous science blogs such as Bad Astronomy, The Panda's Thumb, and RichardDawkins.net are not included in the Wikio rankings.

Since this has been discussed many times on the blogs, it's safe to assume that Matt knows about it. I think he understands that his ranking among the top 15 blogs is not quite what it seems. So I asked in the comment whether he was deliberately trying to deceive his readers or was this an example of framing?

Unfortunately, my comment must have gone astray in the ether since it didn't survive moderation. Isn't that strange?

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Monday's Molecule #91

 
Identify this molecule. You need to describe what you see as accurately as possible and name the species from which this protein was purified. I don't think any of you can do it without a hint but I've received complaints that the hint makes it too easy. We'll see how you do without a hint.¹

There's a direct connection between today's molecule and a Nobel Prize. I'm looking for the person(s) who discovered the significance of the molecule—not necessarily the structure.

The first one to correctly identify the molecule and name the Nobel Laureate(s), wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are four ineligible candidates for this week's reward. You know who you are.

THEME:

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

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

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

UPDATE: The molecule is a fragment of bovine prion protein and the Nobel Laureate is Stanley Prusiner. Four people got it right but the winner is Haruhiko Ishii.

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1. OK, maybe one little hint ... this week's Nobel Laureate(s) on Sandwalk were inspired by this week's 2008 winners.

The 2008 Nobel Prize in Physiology or Medicine

 
This one is going to cause a stir in the scientific community. Nobody predicted this [The 2008 Nobel Prize in Physiology or Medicine].

6 October 2008

The Nobel Assembly at Karolinska Institutet has today decided to award The Nobel Prize in Physiology or Medicine for 2008 with one half to

Harald zur Hausen

for his discovery of "human papilloma viruses causing cervical cancer"

and the other half jointly to

Françoise Barré-Sinoussi and Luc Montagnier

for their discovery of "human immunodeficiency virus"

Summary

This year's Nobel Prize awards discoveries of two viruses causing severe human diseases.

Harald zur Hausen went against current dogma and postulated that oncogenic human papilloma virus (HPV) caused cervical cancer, the second most common cancer among women. He realized that HPV-DNA could exist in a non-productive state in the tumours, and should be detectable by specific searches for viral DNA. He found HPV to be a heterogeneous family of viruses. Only some HPV types cause cancer. His discovery has led to characterization of the natural history of HPV infection, an understanding of mechanisms of HPV-induced carcinogenesis and the development of prophylactic vaccines against HPV acquisition.

Françoise Barré-Sinoussi and Luc Montagnier discovered human immunodeficiency virus (HIV). Virus production was identified in lymphocytes from patients with enlarged lymph nodes in early stages of acquired immunodeficiency, and in blood from patients with late stage disease. They characterized this retrovirus as the first known human lentivirus based on its morphological, biochemical and immunological properties. HIV impaired the immune system because of massive virus replication and cell damage to lymphocytes. The discovery was one prerequisite for the current understanding of the biology of the disease and its antiretroviral treatment.

Discovery of human papilloma virus causing cervical cancer

Against the prevailing view during the 1970s, Harald zur Hausen postulated a role for human papilloma virus (HPV) in cervical cancer. He assumed that the tumour cells, if they contained an oncogenic virus, should harbour viral DNA integrated into their genomes. The HPV genes promoting cell proliferation should therefore be detectable by specifically searching tumour cells for such viral DNA. Harald zur Hausen pursued this idea for over 10 years by searching for different HPV types, a search made difficult by the fact that only parts of the viral DNA were integrated into the host genome. He found novel HPV-DNA in cervix cancer biopsies, and thus discovered the new, tumourigenic HPV16 type in 1983. In 1984, he cloned HPV16 and 18 from patients with cervical cancer. The HPV types 16 and 18 were consistently found in about 70% of cervical cancer biopsies throughout the world.

Importance of the HPV discovery

The global public health burden attributable to human papilloma viruses is considerable. More than 5% of all cancers worldwide are caused by persistent infection with this virus. Infection by the human papilloma virus is the most common sexually transmitted agent, afflicting 50-80% of the population. Of the more than 100 HPV types known, about 40 infect the genital tract, and 15 of these put women at high risk for cervical cancer. In addition, HPV is found in some vulval, penile, oral and other cancers. Human papilloma virus can be detected in 99.7% of women with histologically confirmed cervical cancer, affecting some 500,000 women per year.

Harald zur Hausen demonstrated novel properties of HPV that have led to an understanding of mechanisms for papilloma virus-induced carcinogenesis and the predisposing factors for viral persistence and cellular transformation. He made HPV16 and 18 available to the scientific community. Vaccines were ultimately developed that provide ≥95 % protection from infection by the high risk HPV16 and 18 types. The vaccines may also reduce the need for surgery and the global burden of cervical cancer.

Discovery of HIV

Following medical reports of a novel immunodeficiency syndrome in 1981, the search for a causative agent was on. Françoise Barré-Sinoussi and Luc Montagnier isolated and cultured lymph node cells from patients that had swollen lymph nodes characteristic of the early stage of acquired immune deficiency. They detected activity of the retroviral enzyme reverse transcriptase, a direct sign of retrovirus replication. They also found retroviral particles budding from the infected cells. Isolated virus infected and killed lymphocytes from both diseased and healthy donors, and reacted with antibodies from infected patients. In contrast to previously characterized human oncogenic retroviruses, the novel retrovirus they had discovered, now known as human immunodeficiency virus (HIV), did not induce uncontrolled cell growth. Instead, the virus required cell activation for replication and mediated cell fusion of T lymphocytes. This partly explained how HIV impairs the immune system since the T cells are essential for immune defence. By 1984, Barré-Sinoussi and Montagnier had obtained several isolates of the novel human retrovirus, which they identified as a lentivirus, from sexually infected individuals, haemophiliacs, mother to infant transmissions and transfused patients. The significance of their achievements should be viewed in the context of a global ubiquitous epidemic affecting close to 1% of the population.

Importance of the HIV discovery

Soon after the discovery of the virus, several groups contributed to the definitive demonstration of HIV as the cause of acquired human immunodeficiency syndrome (AIDS). Barré-Sinoussi and Montagnier's discovery made rapid cloning of the HIV-1 genome possible. This has allowed identification of important details in its replication cycle and how the virus interacts with its host. Furthermore, it led to development of methods to diagnose infected patients and to screen blood
products, which has limited the spread of the pandemic. The unprecedented development of several classes of new antiviral drugs is also a result of knowledge of the details of the viral replication cycle. The combination of prevention and treatment has substantially decreased spread of the disease and dramatically increased life expectancy among treated patients. The cloning of HIV enabled studies of its origin and evolution. The virus was probably passed to humans from chimpanzees in West Africa early in the 20th century, but it is still unclear why the epidemic spread so dramatically from 1970 and onwards.

Identification of virus−host interactions has provided information on how HIV evades the host’s immune system by impairing lymphocyte function, by constantly changing and by hiding its genome in the host lymphocyte DNA, making its eradication in the infected host difficult even after long-term antiviral treatment. Extensive knowledge about these unique viral host interactions has, however, generated results that can provide ideas for future vaccine development as well as for therapeutic approaches targeting viral latency.

HIV has generated a novel pandemic. Never before has science and medicine been so quick to discover, identify the origin and provide treatment for a new disease entity. Successful anti-retroviral therapy results in life expectancies for persons with HIV infection now reaching levels similar to those of uninfected people.

Harald zur Hausen, born 1936 in Germany, German citizen, MD at University of Düsseldorf, Germany. Professor emeritus and former Chairman and Scientific Director, German Cancer Research Centre, Heidelberg, Germany.

Françoise Barré-Sinoussi, born 1947 in France, French citizen, PhD in virology, Institut Pasteur, Garches, France. Professor and Director, Regulation of Retroviral Infections Unit, Virology Department, Institut Pasteur, Paris, France.

Luc Montagnier, born 1932 in France, French citizen, PhD in virology, University of Paris, Paris, France. Professor emeritus and Director, World Foundation for AIDS Research and Prevention, Paris, France.

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Obama, Biden, McCain and Palin Agree on One Thing

 
Same-sex marriage is the law of the land in Canada and in many (most?) other Western industrialized nations. It's against the law in most states in the USA.

I was aware of the fact that John McCain and Sarah Palin were opposed to legalization of same-sex marriage. Last night I was shocked to learn that Barack Obama and Joe Biden also oppose legalization of same-sex marriage.

Unless the following is incorrect ...

IFILL: Let's try to avoid nuance, Senator. Do you support gay marriage?

BIDEN: No. Barack Obama nor I support redefining from a civil side what constitutes marriage. We do not support that. That is basically the decision to be able to be able to be left to faiths and people who practice their faiths the determination what you call it.

The bottom line though is, and I'm glad to hear the governor, I take her at her word, obviously, that she think there should be no civil rights distinction, none whatsoever, between a committed gay couple and a committed heterosexual couple. If that's the case, we really don't have a difference.

IFILL: Is that what your said?

PALIN: Your question to him was whether he supported gay marriage and my answer is the same as his and it is that I do not.

IFILL: Wonderful. You agree. On that note, let's move to foreign policy.

Isn't this the 21st century? Isn't Obama supposed to be a progressive?

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Vote

 
There's an election coming up in Canada and the USA. Canada's is first.

No matter what you think about the candidates it's important to go out and vote. I plan on voting several times at least once for somebody. I don't know who, yet.

This is a really, really cool video made by a bunch of people you may recognize. Even if you've already voted in the advance polls you should watch this video. It will make you laugh (unless you're offended by four letter words and women removing their bras).

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[Hat Tip: Phil Plait of Bad Astronomy]

Tangled Bank #115

 
The latest issue of Tangled Bank has been published on Evolved and Rational [The Tangled Bank #115: The awesome level is over 9000!].

Welcome to the 115th edition of the Tangled Bank, a biweekly blog carnival featuring the best science and medicine posts in the blogosphere. The name of this carnival was taken from Charles Darwin's famous metaphor:

"It is interesting to contemplate a tangled bank, clothed with many plants of many kinds, with birds singing on the bushes, with various insects flitting about, and with worms crawling through the damp earth, and to reflect that these elaborately constructed forms, so different from each other, and dependent upon each other in so complex a manner, have all been produced by laws acting around us."

If you are new to Evolved and Rational, this blog deals with science, evolution, creationism, skepticism, atheism, and internet culture; albeit with a generous serving of lulz. If you like what you see, please subscribe to the RSS feed.

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

Armor of God Pajamas

 

Hands up all of you who think that these armor pajamas are going to make the kids feel safe and secure at night?

I didn't think so.

The pajamas alone simply won't do. They'll also need semi-automatic handguns.

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[Hat Tip: Friendly Atheist]

Any Questions?

 
David Scott Springer (DaveScot) is one of the IDiots who post on the Intelligent Design Creationism websites. One of his latest is an example of Google Trends, a nifty way of tracking Google search terms over a period of five years.

DaveScot posted a graph on Uncommon Descent showing the trend for "Intelligent Design" (blue), "Darwinian Evolution" (red), "Scientific Creationism" (orange), and "Theological Evolution" (green) [Fun With Google Trends - ID vs. Darwinism vs. Creationism]. Here it is ...


He ended the posting with the enigmatic "Any questions?"

Yes, as a matter of fact, I have many questions. For starters, why is there only a temporary blip in "Intelligent Design" in the Fall of 2005? That's when the Dover trial was in full swing so you might expect there to be an upswing in interest as the trial went on. After all, the daily reports were highlighting the destruction of Intelligent Design as a credible phenomenon and everyone likes a train wreck.

But why was there no significant interest before 2005 or after?

And why did he use "Darwinian evolution" as his query when he knows full well that this is mostly a creationist term.^(Update) The only people searching for articles on "Darwinian evolution" would be creationists. Wouldn't it be more informative to find out who was interested in just plain "evolution?" Wouldn't it be fun to see if that search term outranked "Intelligent Design?" You bet.

So here's the result: the top graph is for the USA and the bottom one is for the United Kingdom.




Any questions? I didn't think so.

Those of us who are involved in the creation/evolution debate tend to forget how little the general public knows about Intelligent Design Creationism. I'm teaching a class on scientific controversies and one section is about the evolution/creation debate. The 50 students in my class probably are there, in part, because they have an interest in this debate. When I asked them to explain "Intelligent Design" only a handful (~5) had any idea what it was and most of the students claimed they had never heard of it.

It looks like the wedge strategy isn't working very well.

Update: DaveScot was asked on Uncommon Descent why he used the term "Darwinian evolution" instead of just "evolution." His reply? .... "ID doesn’t dispute all “evolution”. It disputes Darwinian evolution." Is anyone still wondering why we call them IDiots?

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Walking with Charles Darwin

 
Stavros Isaiadis posted this photograph of Darwin's walking stick on his blog Journey Through a Burning Mind [Damn those Immoral Darwinists!].



I'm sure Darwin used it while strolling on the Sandwalk. Undoubtedly the skull reminded him of his evil plan to destroy religion by publishing a book about evolution.

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The New Model Organisms

 
A model organism is one that is amenable to a variety of studies. It often means that it has a well established genetics and that it is relatively easy to maintain in the laboratory.

Back in the late 1960s and early 1970s, scientists who were part of the 'phage group began to look around for new model organisms—especially eukaryotes. I decided to move from bacteriophage T4 to an already existing model organism, Drosophila melanogaster. Some workers set up entirely new systems, such as Caenorhabditis elegans [Nobel Laureates: Sydney Brenner, Robert Horvitz, John Sulston].

The research scientists who I knew at the time were having fierce debates over the proper choice of a new model organism and some of them choose systems that did not pan out. The ones that caught on were species like mouse, human, Arabidopsis, Tetrahymena, Dictyostelium, zebrafish, and some stange little fungus called Saccharomyces cerevisiae.

Now there's a whole new group of model organisms on the market and Cold Spring Harbor Laboratory has decided to publish protocols for each one of them [Emerging Model Organisms].

Here's the complete list. Some of them are new to me.

* Nematode (Pristionchus pacificus)
* Opossum (Monodelphus domestica)
* Planarians
* Snapdragon (Antirrhinum)
* Spider (Cupennius salei)
* Amphipod (Parhyale hawaiensis)
* Bichirs (Polypterus)
* Blind Cave Fish (Astyanax mexicanus)
* Butterfly (Bicyclus anynana)
* Choanoflagellates
* Comb Jellies (Ctenophora)
* Cricket (Gryllus bimaculatus)
* Demosponge (Amphimedon queenslandica)
* Dogfish (Scyliorhinus canicula)
* Finches
* Fruit Bat (Carollia perspicillata)
* Lamprey (Petromyzon marinus)
* Leech (Helobdella)
* Moss (Physcomitrella patens)
* Quail (Coturnix coturnix japonica)
* Snail (Ilyanassa obsoleta)
* Social Ameba (Dictyostelium discoideum)
* Tomato (Solanum lycopersicum)

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Nobel Laureate: Severo Ochoa

 

The Nobel Prize in Physiology or Medicine 1959.

"for their discovery of the mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid"

Severo Ochoa (1905 -1993 ) received the Nobel Prize in Physiology or Medicine for his discovery of an enzyme that synthesizes RNA from ribonucleotide triphosphates. The enzyme, polynucleotide phosphorylase [Monday's Molecule #90], was first isolated from the bacterium Azotobacter vinelandii. At the time it was thought to be the enzyme responsible for the synthesis of RNA in cells as described in the excerpt from the presentation speech below from the Nobel Prize website [1959 Presentation Speech].

Ochoa shared his prize with Arthur Kornberg who discovered a DNA polymerase [Nobel Laureate: Arthur Kornberg].

THEME:
Nobel Laureates

Ochoa's enzyme produces ribonucleic acids from ribonucleotides having twice the ratio of phosphoric acid residues as that contained in ribonucleic acid. The ribonucleic acid is formed by splitting out half of the phosphoric acid residues, and linking the nucleotides together to form large molecules, which, as far as we can prove today, do not differ in any way from natural nucleic acids. Kornberg's enzyme produces deoxyribonucleic acids in a similar, but not identical fashion. Both have arrived at the same, principally important result that in order to make the reaction start, it is necessary to add in the beginning a small amount of nucleic acid to act as a template. Otherwise the enzymes do not «know» which kind of nucleic acid they are to produce. As soon as they get a template to act as a guide, they start, just like a skilled type-setter, to copy the «manuscript» they have received. Here one recognizes life's own principle that like creates like. Even though several research workers had earlier suspected that such a mechanism was involved, the actual experimental proof is of greatest importance. Furthermore, Ochoa's enzyme has given us the possibility of enzymatically synthesizing simplified nucleic acids of great interest

Within a short time, scientists began to realize that polynucleotide phosphorylase did not require a DNA template. The enzyme synthesized random polymers of ribonucleotides in a reaction that is now recognized as a way of salvaging RNA in bacterial cells.

Within a few years Marshall Nirenberg, Gobind Khorana, and others began to exploit this enzyme to synthesize synthetic RNAs that were used to crack the genetic code [Nobel Laureates: Robert W. Holley, Har Gobind Khorana, and Marshall W. Nirenberg].

This is one example of a Nobel Prize that was awarded for the wrong reasons but few people begrudge Ochoa since he was widely recognized as an outstanding scientist. Arthur Kornberg worked with him for one year (1946) in New York where he (Kornberg) purified his first enzymes and fell in love with enzymes (Kornberg, 2001).

Ochoa was born in Spain and graduated from the University of Madrid with an M.D. degree in about 1925. He worked with Otto Meyerhof [Nobel Laureates: Otto Fritz Meyerhof] for a few years on metabolic enzymes before joining a series of labs in Europe. Eventually the civil war in Spain and the outbreak of World War II in Europe led him to join Carl and Gerty Cori in St. Louis, Missouri (USA) in 1942 [Nobel Laureates: Carl Ferdinand Cori and Gerty Theresa Cori]. From there he moved to New York University School of Medicine where he remained until his retirement in 1974.

Ochoa did not return to Spain until the year Franco died (1975). He celebrated his 70th birthday in spectacular manner according to Arthur Kornberg (Kornberg, 2001).

To celebrate his 70th birthday in 1975, Ochoa chose as guests the scientists he most respected worldwide. Symposia and celebratory dinners, starting in Barcelona, were followed by a visit with Salvador Dali in his museum in his hometown in Figueras and culminated in a gala of events in Madrid. It was a party, the likes of which has not been seen in scientific circles before or since.

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[Photo Credits: Top: Kornberg (2001), Bottom: Severo Ochoa: La Conquista del Nobel]

Kornberg, A. (2001) Remembering Our Teachers. J. Biol. Chem. 276:3-11. [JBC Online]

Tamoxifen and Breast Cancer

 
When you get to my age, more and more of your female relatives, friends, and acquaintances will be diagnosed with breast cancer. They will be undergoing more or less radical surgery followed by chemotherapy and/or drug treatment. One of the most common drugs for the treatment of breast cancer is tamoxifen.

Tamoxifen is a chemical that binds to a protein called estrogen (or estradiol) receptor. The estrogen receptor is a protein that binds to DNA to increase (activate) or decrease (repress) gene expression. Its DNA binding properties are influenced by its interaction with the hormone estradiol (estrogen)—a discovery first reported by my friend Keith Yamamoto back in 1972 (Yamamoto and Alberts, 1972).

In normal cells, estrogen can stimulate the growth of tissues by turning on the genes that promote cell division. This is a good thing. However, it turns out that most of the breast cell cancers arise from cells that have estradiol receptors and in that case the presence of estrogen in your blood stream makes the cancer cells grow. These forms of cancer are called estrogen receptor positive (ER+) breast cancers.

That's the bad news. The good news is that such cancers respond well to tamoxifen. The effectiveness of tamoxifen is due to the fact that it binds to the estradiol receptor but doesn't convert it to the active regulator of gene expression.¹ When you take tamoxifen there's so much more of it in your bloodstream that it out-competes all of the estrogen. As a result the cancer cells can't grow, (but neither can any of the other tissues that need estrogen).

Hormone therapy (tamoxifen) is often combined with radiation or chemotherapy to reduce the risk of recurring cancer for women who have undergone surgery to remove tumors. However, if the cancer has not spread to the lymph nodes then hormone therapy by itself is effective against ER+ breast cancer. This is especially true for pre-menopausal women 40 years of age or older where chemotherapy does not add significantly to the effectiveness of tamoxifen [see tamoxifen].

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1. This isn't quite true. Tamoxifen itself doesn't bind to the estradiol receptor protein, instead it is converted inside your body to other chemicals that do bind.

Yamamoto KR, Alberts BM. 1972 In vitro conversion of estradiol-receptor protein to its nuclear form: dependence on hormone and DNA. Proc. Natl. Acad. Sci. USA. 69:2105-2109. [PubMed]

Words That Should Not Be Used Together in the Same Sentence: PETA + Ethics

 

PETA stands for "People for the Ethical Treatment of Animals." Apparently this group is unaware of the fact that human beings are animals because their treatment of humans is far from ethical.

Their latest outrage is a billboard in New Jersey that promotes a link between milk and autism. This is part of their aggressive promotion of vegetarianism. The reasoning—if you stoop to calling it that—is described on their website at Got Autism?.

Orac at Respectful Insolence has taken time off from his campaign against alternative (i.e. non-evidence based) medicine to take a whack at PETA [see PETA: Even more impossible to parody than ever!]. The take-down is impressive. PETA is exposed as bunch of kooks hiding behind the veneer of science in order to promote their special brand of woo. If they harm people by spreading lies, then so much the better, as long as those people are carnivores.

Toward the end of his posting, Orac backs off a little so that he doesn't appear to be too nasty to the PETA fools.

I know, I know. Beating up on PETA is like beating up on a helpless puppy dog, except that puppy dogs are cute and lovable, and PETA is anything but either of the two. It's also too damned easy, leaving me feeling vaguely guilty when I'm done for not going after a more challenging target. I do it anyway because the level of sheer irrationality demonstrated by PETA with each and every one of its campaigns just irritates the hell out of me. I hate having my intelligence insulted in such a manner. Also, the sheer publicity whoring for which PETA is so well known irritates me. It's painfully obvious that PETA doesn't give a rodent's posterior about helping autistic children. It just knows that autism has been in the news a lot lately and decided a good way to get publicity would be to latch onto autism somehow, no matter how tenuous the link they come up with to justify their billboard. Not that it will matter to most PETA supporters or to the "biomedical:" (translation: antivaccinationist) movement. Indeed, this latest campaign is so idiotic that I almost expect to see it touted on autism quackery websites soon.

There, now. I feel better. Slapping down PETA is always a fine diversion when my workload gets too heavy and I need a break. Hopefully, I can pick a more challenging target next time. On the other hand, so much woo is no better than this; so I'm not sure there really is a much more challenging target in that realm.

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Nobel Prize: 2008?

 
Chad Orzel at Uncertain Principles has started a contest to guess this year's Noble Prize winners [Guess the Nobels, Win a Prize]. The Nobel Prize in Physiology or Medicine will be announced next Monday (Oct. 6) and the Nobel Prize in Chemistry will be announced two days later on Wednesday, Oct. 8.

Read the list of blogger nominees from last year and the year before on The Daily Transcript. I'm sticking with Ernest McCulloch and James Till (see photo) for the discovery of stem cells.

Other possibilities include Harry Noller, Tom Steitz (+ other) for the structure of the ribosome and Elizabeth Blackburn, Carol Greider & Jack Szostak for telomeres.

It would be a scandal if Francis Collins and Crag Ventor won for the human genome.

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Canada's Do Not Call List

 
Today is the day Canada's DO NOT CALL (DNCL) list comes into effect. If you register your phone number with the Canadian Radio-television and Telecommunications Commission, telemarketers will not be allowed to call you without breaking the law ($15,000 fine).

Unfortunately there are some notable exceptions ...

There are certain kinds of telemarketing calls and faxes that are exempt from the National DNCL, including those made by or on behalf of:

• registered charities seeking donations
• newspapers looking for subscriptions
• political parties and their candidates, and
• companies with whom you have an existing commercial relationship; for example, if you have done business with a company in the previous 18 months––such as a carpet-cleaning company––that company can call you

Telemarketers making exempt calls must maintain their own do not call lists. If you do not want to be called by these telemarketers, you can ask to be put on their do not call lists. They are obliged to do so within 31 days.

The new legislation that comes into effect today stipulates how telemarketers are supposed to behave when you are called.

Among other things, telemarketers must:

• identify who they are and, upon request, provide you with a fax or telephone number where you can speak to someone about the telemarketing call
• display the telephone number that they are calling from or that you can call to reach them, and
• only call or send faxes between 9:00 a.m. and 9:30 p.m. on weekdays and between 10:00 a.m. and 6:00 p.m. on weekends

Telemarketers must not use Automatic Dialing and Announcing Device (devices that dial telephone numbers automatically and deliver a pre-recorded message). However, these devices can be used by police and fire departments, schools and hospitals, as well as for appointment reminders and thank you calls.

You can put your phone number on the list at DNCL or by calling the toll-free numbers 1-866-580-DNCL (1-866-580-3625) or 1-888-DNCL-TTY (1-888-362-5889).

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Monday's Molecule #90

 
Identify this molecule. You need to describe what you see as accurately as possible and name the species from which this protein was purified. I don't think any of you can do it without a hint so here's a clue.¹

There's a direct connection between today's "molecule" and a Nobel Prize. I'm looking for the person(s) who discovered the molecule as won the Nobel Prize for the discovery.

The first one to correctly identify the molecule and name the Nobel Laureate(s), wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are four ineligible candidates for this week's reward. You know who you are.

THEME:

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

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

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

UPDATE: Alex Ling of University of Toronto is this week's winner. We was able to identify the PDB file as 1whu, part of the structure of polynucleotide phosphorylase from Mus musculis (mouse). Once you've identified the enzyme the Nobel Laureate is obvious: it's Severo Ochoa. Congratulations Alex, I now owe you two lunches.

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1. It is NOT the flying spaghetti monster. GSSGSSGPQKIFTPSAEIVK YTKIIAMEKLYAVFTDYEHD KVSRDEAVNKIRLDTEEHLK EKFPEVDQFEIIESFNIVAK EVFRSIILNEYKRCDGRDSG PSSG

Strategic Voting

 
I probably need to explain strategic voting to those people who don't have the "advantage" of living in a multiparty democracy. Strategic voting is where you deliberately vote for someone who is not your first choice in order to prevent another candidate from winning in your riding.

In the context of the current election, it means that a Liberal could vote for an NDP candidate if it was the NDP candidate who had the best chance of defeating the Conservative candidate in a particular riding. The idea being floated right now is that all Liberal, NDP, and Green Party supporters unite behind the candidate who has the best chance of defeating the Conservative candidate and preventing the Conservatives from getting a majority.

There are many good reasons for opposing strategic voting, not the least of which is that it's fundamentally dishonest.¹ Jennifer Smith of Runesmith's Canadian Content has always been opposed to strategic voting but in today's posting she announces that she's changed her mind [By Any Means Necessary].

My name is Jennifer, and I support strategic voting.

I know other people who are going to hold their nose and vote Liberal even though they are dissatisfied with the Liberal Party and with their leader Stéphane Dion. They realize that by switching their vote to the NDP, Bloc, or Green Party, they will make it more likely that Stephen Harper could remain Primie Minister with a majority government.

I'm not there yet. I want to make absolutely sure that Stéphane Dion gets the message that he should resign on October 15th. I'm not sure he will get the message unless I vote for someone else. On the other hand, a majority Conservative government could be a disaster for Canada.

If a lot of Canadians vote strategically to elect Liberals and prevent a Conservative majority do you think Stéphane Dion will understand what happened and do the right thing?

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1. Everyone with an I.Q. over 50 realizes that we need to change our voting system from first-past-the-post to some sort of proportional system. But that's not going to happen for many years. First, a lot of stupid people have to die. Meanwhile, we're stuck with the debate over strategic voting.

Discussing Junk DNA with an Adaptationist, Again

Nils Reinton is a molecular biologist working in the field of medical diagnostics and he has been challenging the concept of junk DNA in the comment section of a recent posting. The title of that posting, Everything Is There for a Reason?, was direct response to an earlier posting from Nils where he claimed that we shouldn't label DNA as "junk" because it's a science stopper.

During the discussion in the comment to my posting, I challenged Nils to answer a number of questions. He has responded on his blog SciPhu with Hey junk people, I accept your challenge (part I). I resonded to his answers in Discussing Junk DNA with an Adaptationist.

Now Nils has weighed in with Hey junk people, I accept your challenge (part II).

Q: Why is the Fugu genome so much smaller than that of other fish?

and

Q: When two similar species differ in genome size by a factor of two—probably due to an ancient polyploidization—is the majority of DNA in both species functional?

A: His argument is that since the genome size differs between species, much of it must be junk. But, you could easily use the same argument towards a function, by saying that the difference in genome size is a defining (functional) difference between species. We just do not know do we ! And, why does the difference in size not give you reason to speculate on function at least in parts of these regions ? Others have however, speculated far better than me on this topic, and a thorough introduction to such research can be found at junkdna.com and following this link to “The Principle of Recursive Genome Function“.

No, my argument was not that the extra DNA has to be junk just because there are two similar species that differ in the sizes of their genomes.

The question was directed at adaptationists who postulate a function for everything. I wanted to know the adaptationist explanation for those observations. What is it? Following a polyploidization is it possible that most of the DNA in the larger genome becomes non-junk right away?

Incidentally, by linking to the HoloGenomics website (junk.dna), Nils does not enhance his credibility.

Q: In the human lineage there are over one million Alu sequences. They all look like degenerate versions of 7SL RNA. Are all of these sequences functional? If so, what function could they be doing? And why do the human Alus look so different from the mouse ones?

A: I am not saying all Alu-elements are functional. On the “what is junk” scale, one extreme is that everything that hasn’t been ascribed a function is junk (Larry Moran’s position !?) and on the other end is “nothing is junk”. My position is somewhere in the middle: Some of the DNA in our genome is possibly junk. A number of individual Alu-elements will undoubtedly end up in the “junk”-category when more is known about our genome. That said, it has been shown that Alu-elements can constitute (parts of) regulatory and functional elements. It’s rather hard to tell which ones are functional by just looking at them. I therefore refuse to call them “junk” by default, - I strongly feel that the “junk”-label is a dismissal of any possible function(s) and should be used with caution if at all, - even for Alu-elements.

My position is that a huge amount of the DNA in our genomes is junk. That position is based on many different lines of evidence as well as on rational extrapolation from what we know and don't know about molecular biology and evolution.

Nobody is arguing that every single Alu element is junk. That would be stupid because we know for a fact that some of them have secondarily acquired a function. The point is whether most of this repetitive sequence can be reasonably assumed to be functional, and if so, what kind of function does the adaptationist imagine for most of these sequences?

In the absence of any reasonable functional explanation, and in the face of evidence that most Alu elements are degenerate retrotransposons, it is reasonable to adopt the working hypothesis that they are junk. That's not a science stopper. It's just common sense.

Q: Most intron sequences do not seem to have a function. Why does the size of introns in the same gene vary so much in related species and why isn’t the sequence conserved in most cases?

A: This argument is similar to the genome size argument above, and the answers for bullet 5 and 6 are equally valid here. Thus, there may be many reasons for a variation in intron size and this variation is not a very good argument to support the “junk” hypothesis. Also, the intron can contain regulatory elements and the c-gamma example above goes to show that introns can even contain functional (as in transcribed) genetic elements.

The fact that we have a few examples of functional intron sequences is no reason to assume that most of them are functional in the face of abundant evidence that they are not. That's a position that only a confirmed adaptationist would take.

This is a case where the exceptions tend to prove the rule not that the exceptions make a new rule.

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Remembering Paul Newman

 

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Sleepy Hollow

This is a view of the cemetery of the Old Dutch Church of Sleepy Hollow. It was taken by a visitor who posted it on the Friends of the Old Dutch Burying Gorund website.

The church, which you can see in the background of the photo, was built in 1697 in what was then called Phillips Burgh. It is now located in Tarrytown, New York, north of New York City on the east bank of the Hudson river. Sleepy hollow was made famous by Washington Irving, who is buried in this cemetery [The Legend of Sleepy Hollow].

From the listless repose of the place, and the peculiar character of its inhabitants, who are descendants from the original Dutch settlers, this sequestered glen has long been known by the name of SLEEPY HOLLOW, and its rustic lads are called the Sleepy Hollow Boys throughout all the neighboring country. A drowsy, dreamy influence seems to hang over the land, and to pervade the very atmosphere. Some say that the place was bewitched by a high German doctor, during the early days of the settlement; others, that an old Indian chief, the prophet or wizard of his tribe, held his pow-wows there before the country was discovered by Master Hendrick Hudson. Certain it is, the place still continues under the sway of some witching power, that holds a spell over the minds of the good people, causing them to walk in a continual reverie. They are given to all kinds of marvellous beliefs; are subject to trances and visions; and frequently see strange sights, and hear music and voices in the air. The whole neighborhood abounds with local tales, haunted spots, and twilight superstitions; stars shoot and meteors glare oftener across the valley than in any other part of the country, and the nightmare, with her whole nine fold, seems to make it the favorite scene of her gambols.

The dominant spirit, however, that haunts this enchanted region, and seems to be commander-in-chief of all the powers of the air, is the apparition of a figure on horseback without a head.

Phillips Burgh was settled in the late 1600s, mostly by Dutch settlers from New York (New Amsterdam). The original Dutch colony was lost to the English in the Second Anglo-Dutch war, which ended in 1667 and the Dutch territory was permanently ceded to England after the Third Anglo-Dutch war ending in 1674.

One group of settlers were not Dutch but Canadian. The David sibship consisted of Carel David, David David, Angelica David, Mathys David, Margaret David, and Daniel David. They were born in Laval, Quebec (Canada) and moved to New York with their parents Guillaume David and Marie (Armand)¹ David. As the children reached adulthood they migrated north to become farmers in Phillips Burgh and they joined the Dutch Church of Sleepy Hollow.

The David family was originally from France and their ancestors can be traced back to Julien David of St. Etienne who was born about 1200. By the time they emigrated to Canada they were Hugenots.²

I am directly descended from Margaret David who married a French soldier named Pierre Montras (Montrose). They moved to Kingston, New York, just up the river from Phillips Burgh. That's where their daughter Margaret Montras was born in 1691. Pierre died in 1703 leaving Margaret with several children who she farmed out to her brothers and sisters in Phillips Burgh. Many of the Montras (Montrose) children also joined the Dutch Church of Sleepy Hollow.

Margaret Montras was probably living with her uncle Carel Davids (name change) when she met and married Harmen Harmse, the son of the Dutch settler Capt. Jan Harmse and his wife Aeltje (Abrahams) Harmse. Jan Harmse was an elder in the Dutch Church of Sleepy Hollow. We can trace Aeltje Abrahams' ancestors (and mine) back to 1555 in Holland.

When Harman married Margaret Montras he took her name as his surname and became known as Harmen Montras. Their fourth child, Peter (Petrus) Montras, was baptized on March 6, 1715 in the Dutch Church of Sleepy Hollow. He is my great- great- great- great- great- great-grandfather. Peter's descendants changed their last name to Montrose or Montross.

Harmen Montras and his wife Margaret Montras are almost certainly buried in the Old Dutch Church of Sleepy Hollow cemetery in unmarked graves and so are Harmen's parents Jan Harmse and Aeltje. That's four direct ancestors of mine. Part of the house built by Jan Harmse is still standing in Irvington, New York.

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1. The maiden name of Guillaume David's wife Marie is not known for certain. It was probably "Harmens" or some variant of that name. She appears to be from New Holland, possibly Manhattan. She was NOT a french "filles à marier" or a "filles du Roi."

2. There is no evidence to support a connection between Guillaume David and the David line in France. In fact, there's no evidence to support the clam that David was French.

The Oldest Non-Living Things on Earth

 
First we had a link to the oldest living thing on Earth [Botany Photo of the Day and the Oldest Living Organism] and now we link to the oldest thing on Earth [Oldest Rocks on Earth Discovered?].

These rocks are found in the Nuvvuagittuq region of Hudson Bay in Northwestern Quebec (Canada). As part of the Canadian shield they have long been known to be among the oldest rocks on Earth. Some of the rocks from this region have now been reliably dated to 4.28 billion years ago making them the oldest rocks known.

The dating technology is based on the decay of samarium to neodymium-142 and the work is published in this week's Science magazine (O'Neil et al. 2008).

These rocks are not the oldest things, however, because there are zircon inclusions from rocks in Western Australia that date back to 4.38 billion years. The zircon crystals probably formed somewhere else and were incorporated into the Australian rocks.

The Canadian rocks might also be much younger, having incorporated bits of older sediment, but for now, it looks like the Canadian shield may actually have formed over four billion years ago.

One thing is clear, Canada and Australia are the oldest countries in the world, by far.

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J. O'Neil, R. W. Carlson, D. Francis, R. K. Stevenson (2008). Neodymium-142 Evidence for Hadean Mafic Crust Science, 321 (5897), 1828-1831 DOI: 10.1126/science.1161925

Botany Photo of the Day and the Oldest Living Organism

 
The oldest known organism on the planet is about 4,800 years old. Find out what that has to do with the Botany Photo of the Day.

It is often very hard to tell the difference between various species of pine. One of the distinguishing characteristics of this species (left) is that it has five needles per cluster. Other species have one, two, or three. I don't know if there is a species with four needles per cluster, or six.

Here's a question for all the adaptationists, is number of needles per fascicle an adaptation or is it just an allele that was fixed by accident? Is it an example of a morphological characteristic that is not an adaptaion?

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One Hundred Words of Science

 
Check out Biocurious where PhilipJ has posted on One hundred words of science. I've suggested a few changes. Look over the list and see whether you agree.

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Unrealistic Expectations

 
Harold Varmus was in town recently to receive the Henry G. Friesen International Prize in Health Research. He made some interesting comments that were reported in last Thursday's issue of the Globe and Mail [Cancer expert warns of too-great expectations]. Bayman spotted it and reported on Balblab [Varmus on "The Cure" for Cancer].

Here's what Varmus said,

Nobel laureate Harold Varmus, head of New York's Memorial Sloan-Kettering Cancer Center, said one of the inherent difficulties in continuing to raise funds for cancer research is to explain to people how difficult the problems are that still lie ahead.

“These problems are really, really tough, and they're going to be knocked off more or less one by one,” he said in an interview in Toronto, where he received one of Canada's highest-profile medical awards, the Henry G. Friesen International Prize in Health Research.

Unrealistic expectations of an imminent cure for cancer have been around since former U.S. president Richard Nixon declared war on the disease in his 1971 State of the Union address, Dr. Varmus said.

They have been fuelled, he said, by a continuous stream of media articles that trumpet some initiative such as the completion of the genome project and then predict a payoff never matched by reality.

And he argued that the culture of unrealistic expectations is encouraged by the way science is taught in schools, with a focus on outcomes rather than process.

This is part of a growing backlash against hype in the media. I think most of us realize that in the past we exploited the naivety of the media in order to advance our pet projects. As we get older we realize that we were wrong to make this pact with the devil and now we want to turn the clock back and emphasize the purity of science and the search for truth.

We want the general public to understand how science is really done and not how we pretended it was done. One of the reasons for this change in attitude is that science has lost credibility for not living up to the hype. Another reason is that we see the problems with a society that doesn't understand how science really works. It makes fighting creationism and other superstitions much harder.

I hate to bring up framing again but I think these two issues are related. For those of us who want to teach the truth about science, framing sounds too much like the old ways that we are trying to put behind us.

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[Photo Credit: In addition to being a Nobel Laureate and President & Chief Executive of Memorial Sloan-Kettering Cancer Center, Varmus is also Co-founder and Chairman of the Board of PLoS: Public Library of Science.]

Nature's Evolution Question

 
The British science magazine Nature asked the following question of each US Presidential candidate [US election: Questioning the candidates].

Do you believe that evolution by means of natural selection is a sufficient explanation for the variety and complexity of life on Earth?

My answer, of course, is "no"; natural selection is not a sufficient explanation. You also need random genetic drift and a host of other things that are part of evolutionary theory.

How would you answer the question, dear readers?

Both candidates did a pretty good job of answering this question.

Obama: I believe in evolution, and I support the strong consensus of the scientific community that evolution is scientifically validated.

McCain said last year, in a Republican primary debate: "I believe in evolution. But I also believe, when I hike the Grand Canyon and see it at sunset, that the hand of God is there also."

They both avoided answering the direct question. Instead, they interpreted the question to be whether they believe in evolution. They both believe in evolution.

Since this is one of the leading science magazines in the world I'm certain that the question was not about believing in evolution. It was designed to discover whether McCain and Obama were adaptationists. There's no other reasonable explanation since it's impossible that Nature wouldn't know the difference between "evolution" and "natural selection." At least I think it's impossible ...

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Joe Who?

 
According to CBS News,

Washington - Vice presidential candidate Joe Biden says today's leaders should take a lesson from the history books and follow fellow Democrat Franklin D. Roosevelt's response to a financial crisis.

"When the stock market crashed, Franklin D. Roosevelt got on the television and didn't just talk about the, you know, the princes of greed. He said, 'Look, here's what happened,'" Barack Obama's running mate recently told the "CBS Evening News."

Except, Republican Herbert Hoover was in office when the stock market crashed in October 1929. There also was no television at the time; TV wasn't introduced to the public until a decade later, at the 1939 World's Fair.

I would have thought the bloggers would be all over this. Have I been reading the wrong blogs?

Lately I've been wondering what happened to Joe Biden. You don't see much about him on television. Now I know why. Maybe he and Sarah should take a very long trip to Afghanistan and let the big boys run for President.

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Howler Monkeys

 
Back in the olden days before blogs, we had the newsgroup talk.origins where the battle between evolution and creation was fought. The newsgroup still exists and it's still very active.

One of the most famous anti-evolutionists on talk.origins was a man named Ted Holden. He was witty and prolific, as well as being a famous internet kook. Ted didn't like the fact that he had to defend himself against attacks from scores of people so he coined the term "Howler Monkeys" to describe the chorus of evolutionists who joined in whenever a creationist appeared. (Ted wasn't exactly a creationist in the traditional sense. There was very little about Ted that was "traditional.")

Here's a posting from Ted Holden in 1995 ...

The clique which dominates talk.origins sees themselves as heroes, doing battle with the powers of darkness in an effort to prevent a return to the dark ages. I once noted that, to any outsider attempting to present anything other than the standard lock-step glop on t.o, they present what amounts to a sort of a tribal reaction, what one might expect from a tree-full of crows confronting a hawk or a tree of howler-monkeys encountering a leopard. The crew has since adopted the term "howler-monkeys" as a heraldic device, or metaphor, and refer to themselves as "howler monkeys" as a badge of honor.

Ted is right about the term "Howler Monkeys." Many people on talk.origins were proud to call themselves Howler Monkeys and meetings of talk.origins participants were called Howlerfests. We had a Toronto Howlerfest in 2005 that brought talk.origins regulars like the Canadian cousin of Prof. Steve Steve (see photo), PZ Myers, Canadian Cynic, John Wilkins, and Jeffrey Shallit who have gone on to to become bloggers. You may have heard of some of these talk.origins alumni.

Many of you don't know about Howler monkeys. Ms. Sandwalk just sent along this National Geographic video of Howler monkeys in action. I don't think she meant it as a compliment.

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How Many Genes Do Nematodes Have? - Pristionchus pacificus Genome

 

Nematodes are small wormlike creatures that live almost everywhere. Many of them are parasites but there are thousands of species that live in the soil. "... it is said that if everything on the earth were to disappear except the nematodes, the outlines of everything would still be visible: the mountains, lakes and oceans, the plants and the animals would all be outlined by the nematodes living in every habitat."¹

The free-living species Caenorhabditis elegans was chosen by Sydney Brenner as a model organism for the study of development [Nobel Laureates: Sydney Brenner, Robert Horvitz, John Sulston]. It turned out to be an excellent choice and by the mid 1990s this small metazoan (multi-cellular animal) was selected as the best metazoan candidate for genome sequencing.

The complete genome sequence was published in 1998. The genome is 100 Mb in size (= 100 million base pairs). This was smaller than the predicted size of the fruit fly genome (165 Mb) or the human genome (3,200 Mb). The first estimates of the number of genes were over 19,000 and at the time this was thought to be a reliable estimate although there were many, including me, who though that it was probably too high.

Over the years we have become more skeptical of these initial gene counts because there are many problems. The location of genes is determined by sophisticated computer programs that are trained to recognize the important characteristics of gene sequences (protein coding genes). This year marks the tenth anniversary of the publication of the C. elegans genome sequence and most people will be surprised to learn that the annotation of this sequence is just beginning to be complete.

A recent paper by James Thomas summarizes the result so far (Thomas, 2008).

Thomas points out that gene prediction suffers from the presence of false positives. One of the complications is pseudogenes, which are not easy to distinguish from real genes. Another complication is proving that a predicted gene is actually functional and not just a computational artifact. There is no better way to resolve these issues than by having real live people look at every potential gene. This is why annotation takes so long.

The latest estimate is 20,140 protein coding genes in the Caenorhabditis elegans genome. The coding regions (exons) would take up about 40 Mb of DNA or 24% of the genome. Most of the remainder is junk DNA.

The number of genes is remarkably close to the original prediction although it should be noted that estimates of the number of genes went up after the initial draft sequence was published. Nevertheless, unlike the gene count in humans, the number of genes has held pretty steady.

The number of genes can be compared to the number in the Drosohila melanoaster genome (~15,000) and the human genome (20,500). These are the only two other eukaryotic metazoan genomes² that have been extensively annotated.

There are about 23,000 distinct transcripts from these genes. What that means is that roughly 18,000 genes produce a single transcript and about 2,000 produce two or three different transcripts by alternative splicing.

The C. elegans genes can be divided into two categories. About 8,000 of them are unique and the remainder belong to gene families. A gene family consists of multiple copies of the same gene in the same genome. The copies (paralogues) may be identical or they may be quite different but still related. Some of the gene families are very large and some have only two members.

There seem to be about 3,000 genes families contributing to the 12,000 genes that are not unique. The bottom line is that there are about 11,000 (8K + 3K) different kinds of gene in C. elegans. Interestingly, only 1800 of these genes are found in both insects (Drosophila) and primates (humans). The rest are restricted to just insets and nematodes or just nematodes (10,000 are found in other nematode species).

James Thomas points out that the determination of orthology (same genes in other species) is much more difficult than one might imagine. Many of the online databases, for example, contain erroneous entries based on faulty predictions. These false predictions propagate so that it often isn't reliable to use the database to confirm that a predicted gene actually exists. That's why he restricts his comparisons to well-annotated genomes wherever possible.

Partially annotated genome sequences of Caenorhabditis brigsae and Caenorhabditis remaneri are available. Orthologous gene comparisons indicate that the three species are remarkably dissimilar for species within the same genus. They probably diverged at least 20 My ago.

A new nematode genome sequence was published this week. The species is Pristionchus pacificus, a parasite of the oriental beetle Examala orientalis (Dieteridh et al. 2008). The authors note that there is a different species of parasitic nematode associated with almost every species of beetle, which means that there are at least as many nematodes as insects.

The Pristionchus pacificus genome is 169 Mb in size, which is considerably larger than the size of the Caenorhabditis elegans genome (100 Mb). P. pacificus has 23,500 genes.

Some of the increase in genome size is due to more genes but this is only a minor difference. Some of it is due to the presence of additional copies of repetitive DNA sequences in P. pacificus but the increase doesn't account for the extra 69 Mb of DNA.

The differences in gene number are almost entirely due to increases in the members of gene families in the P. pacificus genome. Several specific examples were given, notably 250 extra copies of ribosomal protein genes compared to C. elegans.

Another remarkable difference is in the number of genes involved in detoxification, or removal of poisonous substances. There are about 250 extra copies of gene family members in this category. The authors speculate that this expansion may be selection for detoxifying enzymes in parasites as opposed to the free-living C. elegans.

In addition to the various Caenorhabditis species, we now have a complete genome of the nematode Brugia malayi the parasite responsible for filariasis in humans. Pristionchus diverged from Caenorhabditis about 350 My (million years) ago and Brugia diverged from the others about 900 My ago according to Dietrich et al. (2008). Thomas (2008) cautions that these divergence times are based on an underestimate of mutation/fixation rates and that nematodes may be evolving more rapidly than other phyla. Nevertheless, it is clear that nematodes are an ancient, diverse, and abundant group of animals.

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1. Nematoda.

2. See the discussion in the comments for examples of other well-annotated eukaryotic genomes. Yeast is obvious but what about Arabidopsis?

[Photo Credit: Christina Beck]

Christoph Dieterich, Sandra W Clifton, Lisa N Schuster, Asif Chinwalla, Kimberly Delehaunty, Iris Dinkelacker, Lucinda Fulton, Robert Fulton, Jennifer Godfrey, Pat Minx, Makedonka Mitreva, Waltraud Roeseler, Huiyu Tian, Hanh Witte, Shiaw-Pyng Yang, Richard K Wilson, Ralf J Sommer (2008). The Pristionchus pacificus genome provides a unique perspective on nematode lifestyle and parasitism Nature Genetics DOI: 10.1038/ng.227

J. H. Thomas (2008). Genome evolution in Caenorhabditis Briefings in Functional Genomics and Proteomics, 7 (3), 211-216 DOI: 10.1093/bfgp/eln022