2009 Canada Gairdner Awards

 
The 2009 Canada Gairdner Award recipients were announced last week. Each awardee gets $100,000 (CDN). The winners are ...

Richard Losick: "for the discovery of mechanisms that define cell polarity and asymmetric cell division, processes key in cell differentiation and in the generation of cell diversity"

Kazutoshi Mori: "for the dissection and elucidation of a key pathway in the unfolded protein response which regulates protein folding in the cell"

Nubia Muñoz: "for her epidemiological studies that defined the essential role of the human papilloma virus in the etiology of cervical cancer on a global level which led to the development of successful prophylactic vaccines"

David Sackett: "for his leadership in the fields of clinical epidemiology and evidence-based medicine, which have had major impacts internationally in applied clinical research and in the practice of medicine"

Lucy Shapiro: "for the discovery of mechanisms that define cell polarity and asymmetric cell division, processes key in cell differentiation and in the generation of cell diversity"

Peter Walter: "for the dissection and elucidation of a key pathway in the unfolded protein response which regulates protein folding in the cell"

Shinya Yamanaka: "for his demonstration that the key transcription factors which specify pluripotency may become reprogrammed somatic cells to pluripotent stem cells"

The awards will be presented next October at the University of Toronto. Since this is the 50th anniversary of the Gairdner Awards there will be quite a gathering. You should plan on being here.

This year The Gairdner Foundation is celebrating its 50th Anniversary in spectacular fashion.

Between March and November we will hold 7 major international symposia across the country, in Vancouver, Edmonton, Ottawa, Toronto (York), Sherbrooke, Montreal and Halifax (see under Events). The finale will occur in Toronto, where we will host 50 past Gairdner recipients, including 22 Nobel Laureates, from Oct 28-30. This will be by far the largest gathering of the world's top scientists ever held in Canada. We will also introduce the 2009 Canada Gairdner Award recipients.

Canada Gairdner Laureates will participate in lectures, panel discussions, public forums, interviews and informal talks with academics, researchers, biotech and pharma companies, government leaders, graduate and postgraduate students, high school students, the media and interested members of the general public. With the exception of the social events, all the programs will be free and open to anyone who wants to share in the excitement of leading edge biomedical science.

The 50th Anniversary will be a spectacular culmination of everything The Gairdner Foundation has achieved in becoming Canada's premier international prize, and one of the top three biomedical prizes in the world. It will be a vehicle to raise awareness of the fascinating world of biomedical science and its importance to lives.

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Nobel Laureates: Mario Capecchi, Martin Evans, and Oliver Smithies

 

The Nobel Prize in Physiology or Medicine 2007

"for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells"

Mario R. Capecchi (1937 - ), Sir Martin J. Evans (1941 - ), and Oliver Smithies (1925 - ) won the Noble Prize in 2007 for developing techniques to transform embryonic stem cells with foreign genes integrated at a specific place in the genome, then using those cells to make transgenic mice.

The Press Release describing this work is a well-written description of how the techniques was developed.

This is how to make knock-out mice.
THEME:
Nobel Laureates

Summary

This year's Nobel Laureates have made a series of ground-breaking discoveries concerning embryonic stem cells and DNA recombination in mammals. Their discoveries led to the creation of an immensely powerful technology referred to as gene targeting in mice. It is now being applied to virtually all areas of biomedicine – from basic research to the development of new therapies.

Gene targeting is often used to inactivate single genes. Such gene "knockout" experiments have elucidated the roles of numerous genes in embryonic development, adult physiology, aging and disease. To date, more than ten thousand mouse genes (approximately half of the genes in the mammalian genome) have been knocked out. Ongoing international efforts will make "knockout mice" for all genes available within the near future.

With gene targeting it is now possible to produce almost any type of DNA modification in the mouse genome, allowing scientists to establish the roles of individual genes in health and disease. Gene targeting has already produced more than five hundred different mouse models of human disorders, including cardiovascular and neuro-degenerative diseases, diabetes and cancer.

Modification of genes by homologous recombination

Information about the development and function of our bodies throughout life is carried within the DNA. Our DNA is packaged in chromosomes, which occur in pairs – one inherited from the father and one from the mother. Exchange of DNA sequences within such chromosome pairs increases genetic variation in the population and occurs by a process called homologous recombination. This process is conserved throughout evolution and was demonstrated in bacteria more than 50 years ago by the 1958 Nobel Laureate Joshua Lederberg.

Mario Capecchi and Oliver Smithies both had the vision that homologous recombination could be used to specifically modify genes in mammalian cells and they worked consistently towards this goal.

Capecchi demonstrated that homologous recombination could take place between introduced DNA and the chromosomes in mammalian cells. He showed that defective genes could be repaired by homologous recombination with the incoming DNA. Smithies initially tried to repair mutated genes in human cells. He thought that certain inherited blood diseases could be treated by correcting the disease-causing mutations in bone marrow stem cells. In these attempts Smithies discovered that endogenous genes could be targeted irrespective of their activity. This suggested that all genes may be accessible to modification by homologous recombination.

Embryonic stem cells – vehicles to the mouse germ line

The cell types initially studied by Capecchi and Smithies could not be used to create gene-targeted animals. This required another type of cell, one which could give rise to germ cells. Only then could the DNA modifications be inherited.

Martin Evans had worked with mouse embryonal carcinoma (EC) cells, which although they came from tumors could give rise to almost any cell type. He had the vision to use EC cells as vehicles to introduce genetic material into the mouse germ line. His attempts were initially unsuccessful because EC cells carried abnormal chromosomes and could not therefore contribute to germ cell formation. Looking for alternatives Evans discovered that chromosomally normal cell cultures could be established directly from early mouse embryos. These cells are now referred to as embryonic stem (ES) cells.

The next step was to show that ES cells could contribute to the germ line (see Figure). Embryos from one mouse strain were injected with ES cells from another mouse strain. These mosaic embryos (i.e. composed of cells from both strains) were then carried to term by surrogate mothers. The mosaic offspring was subsequently mated, and the presence of ES cell-derived genes detected in the pups. These genes would now be inherited according to Mendel’s laws.

Evans now began to modify the ES cells genetically and for this purpose chose retroviruses, which integrate their genes into the chromosomes. He demonstrated transfer of such retroviral DNA from ES cells, through mosaic mice, into the mouse germ line. Evans had used the ES cells to generate mice that carried new genetic material.

Two ideas come together – homologous recombination in ES cells

By 1986 all the pieces were at hand to begin generating the first gene targeted ES cells. Capecchi and Smithies had demonstrated that genes could be targeted by homologous recombination in cultured cells, and Evans had contributed the necessary vehicle to the mouse germ line – the ES-cells. The next step was to combine the two.

For their initial experiments both Smithies and Capecchi chose a gene (hprt) that was easily identified. This gene is involved in a rare inherited human disease (Lesch-Nyhan syndrome). Capecchi refined the strategies for targeting genes and developed a new method (positive-negative selection, see Figure) that could be generally applied.

Birth of the knockout mouse – the beginning of a new era in genetics

The first reports in which homologous recombination in ES cells was used to generate gene-targeted mice were published in 1989. Since then, the number of reported knockout mouse strains has risen exponentially. Gene targeting has developed into a highly versatile technology. It is now possible to introduce mutations that can be activated at specific time points, or in specific cells or organs, both during development and in the adult animal.

Gene targeting is used to study health and disease

Almost every aspect of mammalian physiology can be studied by gene targeting. We have consequently witnessed an explosion of research activities applying the technology. Gene targeting has now been used by so many research groups and in so many contexts that it is impossible to make a brief summary of the results. Some of the later contributions of this year's Nobel Laureates are presented below.

Gene targeting has helped us understand the roles of many hundreds of genes in mammalian fetal development. Capecchis research has uncovered the roles of genes involved in mammalian organ development and in the establishment of the body plan. His work has shed light on the causes of several human inborn malformations.

Evans applied gene targeting to develop mouse models for human diseases. He developed several models for the inherited human disease cystic fibrosis and has used these models to study disease mechanisms and to test the effects of gene therapy.

Smithies also used gene targeting to develop mouse models for inherited diseases such as cystic fibrosis and the blood disease thalassemia. He has also developed numerous mouse models for common human diseases such as hypertension and atherosclerosis.

In summary, gene targeting in mice has pervaded all fields of biomedicine. Its impact on the understanding of gene function and its benefits to mankind will continue to increase over many years to come.

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[Photo Credits: Mario Capecchi: Reuters,DayLife, Sir Martin J. Evans: Reuters, DayLife, Oliver Smithies: University of North Carolina, Chapel Hill.]

The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

On the Evolution of Bacterial Chromosomes

 

This is a story about two cultures; the old biologists who grew up with the 'phage group and bacterial genetics, and the younger biologists who didn't.

It's also a story about science journalism and the reporting of science in the 21st century.

We've known about plasmids in bacteria for a very long time. Plasmids are small circular DNA molecules that carry a number of genes, such as those for antibiotic resistance, or sex. Some of them are present in multiple copies while others are present in only a single copy. In the case of single-copy plasmids, their replication is coupled to that of the chromosome and the daughter plasmids segregate to the daughter cells just like the newly replicated chromosomes do.

Genes can hop from chromosomes to plasmids and back again. This phenomenon was discovered in the 1950's by Jacob and Adelberg (1959). Several well-known plasmids carrying certain chromosomal genes were studied, including a famous one known as F-lac—an F plasmid containing the lac operon.

By the time the first E. coli Bible was published in 1987, there were dozens and dozens of examples of gene transfer between chromosomes and plasmids (Holloway and Low, 1987).

During the 1970s and 80s, the DNA contents of many difference species of bacteria were published. It soon became apparent that certain classes of bacteria (e.g. Rhizobiaceae) contained large plasmids called megaplasmids. Sometimes it was difficult to tell the difference between a plasmid and a chromosome (bacterial chromosomes are usually circular).

As a general rule, plasmids were dispensable. The bacteria could be "cured" of a plasmid and still survive. When the plasmid acquired essential genes, as they did from time to time, they became chromosomes. Some species of bacteria had two or more chromosomes. It was part of general knowledge that plasmids could evolve into chromosomes as described in a 1998 review by Moreno.

Animal intracellular Proteobacteria of the alpha subclass without plasmids and containing one or more chromosomes are phylogenetically entwined with opportunistic, plant-associated, chemoautotrophic and photosynthetic alpha Proteobacteria possessing one or more chromosomes and plasmids. Local variations in open environments, such as soil, water, manure, gut systems and the external surfaces of plants and animals, may have selected alpha Proteobacteria with extensive metabolic alternatives, broad genetic diversity, and more flexible and larger genomes with ability for horizontal gene flux. On the contrary, the constant and isolated animal cellular milieu selected heterotrophic alpha Proteobacteria with smaller genomes without plasmids and reduced genetic diversity as compared to their plant-associated and phototrophic relatives. The characteristics and genome sizes in the extant species suggest that a second chromosome could have evolved from megaplasmids which acquired housekeeping genes. Consequently, the genomes of the animal cell-associated Proteobacteria evolved through reductions of the larger genomes of chemoautotrophic ancestors and became rich in adenosine and thymidine, as compared to the genomes of their ancestors. Genome organisation and phylogenetic ancestor-descendent relationships between extant bacteria of closely related genera and within the same monophyletic genus and species suggest that some strains have undergone transition from two chromosomes to a single replicon. It is proposed that as long as the essential information is correctly expressed, the presence of one or more chromosomes within the same genus or species is the result of contingency. Genetic drift in clonal bacteria, such as animal cell-associated alpha Proteobacteria, would depend almost exclusively on mutation and internal genetic rearrangement processes. Alternatively, genomic variations in reticulate bacteria, such as many intestinal and plant cell-associated Proteobacteria, will depend not only on these processes, but also on their genetic interactions with other bacterial strains.

Given this context, I was interested in a recent press release: Evolutionary origin of bacterial chromosomes revealed. "Hmmm," I thought., "I wonder what new mechanism has been discovered?"

Imagine my surprise to read ...

Most bacteria have only one chromosome. The Rhizobiaceae is an unusual bacterial family in that all of its members have either two chromosomes or one chromosome and very large plasmids. Until this study, it was not clear how such multichromosomal architectures had evolved.

João Setubal, associate professor at the Virginia Bioinformatics Institute and the Department of Computer Science at Virginia Tech, commented: "Thanks to the efforts of the Agrobacterium Genome Sequence Consortium and the wider research community, we have sufficient sequence data available from different bacterial species to allow the inference of a general model for bacterial genome evolution. It appears that the transfer of genes from chromosomes to large plasmids mediates second chromosome formation."

That's not new. The idea that large megaplasmids in Rhizobiaceae could become plasmids by acquiring essential genes has been around for three decades, at least. Surely these workers known their history? The press release must be an exaggeration of what's in the paper.

So I looked up the paper (Slater et al., 2009). These workers sequenced the genomes of a number of related bacterial species containing chromosomes and plasmids. They announce the "surprising" discovery that genes can transfer between chromosomes and plasmids.

While it has long been known that gene transfer can occur between organisms, the picture that emerges from our study shows a group characterized by composite genomes in which genes of all classes are not only migrating between organisms, but also intracellularly among chromosomal and plasmid replicons.

It sounds like they never heard of F-lac or any of the other F′ or R′ plasmids. It sounds like they are completely unaware to the fact that transfer of genes from chromosomes to plasmids is an old established fact.

The authors propose a "general model for bacterial genome evolution" in which plasmids evolve into chromosomes.

This is not an isolated phenomenon. There seem to be lots of cases where today's scientists are unaware of the history of their field. A consequence of this ignorance is that the wheel is being constantly reinvented, with all the associated hype of a modern breakthrough.

Another example is the recent "discovery" of regulatory RNAs. Bacterial and 'phage examples have been known for forty years.

Why is this happening? Why do reviewers let it pass?

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[Image Credit: Jessica Snyder Sachs]

Holloway, B. and Low, K.B. (1987) F-Prime and R-Prome Factors. in Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology. F.C. Neidhardt ed. vol.2.

Jacob, F. and Adelberg, E.A. (1959) Transfer of Genetic Characters by Incorporation in the Sex Factor of Escherichia coli. Comptes Rendus 249:189-191.

Moreno, E. (1998) Genome evolution within the alpha Proteobacteria: why do some bacteria not possess plasmids and others exhibit more than one different chromosome? FEMS Microbiol 22(4):255-275. [PubMed]

Slater, S.C., Goldman, B.S., Goodner, B., Setubal, J.C., Farrand, S.K., Nester, E.W., Burr, T.J., Banta, L., Dickerman, A.W., Paulsen, I., Otten, L., Suen, G., Welch, R., Almeida, N.F., Arnold, F., Burton, O.T., Du, Z., Ewing, A., Godsy, E., Heisel, S., Houmiel, K.L., Jhaveri, J., Lu, J., Miller, N.M., Norton, S., Chen, Q., Phoolcharoen, W., Ohlin, V., Ondrusek, D., Pride, N., Stricklin, S.L., Sun, J., Wheeler, C,, Wilson, L,, Zhu, H., and Wood, D.W. (2009) Genome Sequences of Three Agrobacterium Biovars Help Elucidate the Evolution of Multi-Chromosome Genomes in Bacteria. J. Bacteriol. 2009 Feb 27. [Epub ahead of print] [PubMed] [DOI: 10.1128/JB.01779-08]

How to Prevent Evolution in Mosquitos

 
A paper in PLoS Biology discusses How to Make Evolution-Proof Insecticides for Malaria Control. The idea is to develop drugs that only kill mosquitoes after they've reproduced. That way the population can't evolve resistance to the drug.

What's interesting about this paper is the response of two different bloggers. On adaptationist, Jerry Coyne's blog, guest writer Matthew Cobb thinks it's a great idea [Of mosquitoes and the menopause]. In fact he links his discussion of the paper to the well-known adaptationist explanation of menopause.

The pluralist, Ryan Gregory, is much more skeptical, pointing out that evolution is smarter than you are ["Evolution-proof"?].

Grab your popcorn and enjoy the fight. My money's on Gregory.

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Monday's Molecule #116: Winners

 
UPDATE:The photographs of the mouse embryos are from a paper by Kothary et al. (1989). This was a study where a lacZ (β-galactosidase) gene under the control of a strong, ubiquitously competent promoter was introduced into mouse zygotes. When the gene was induced (right) the presence of β-galactosidase was detected by a blue color assay. The foreign gene is induced in almost every tissue.

These sorts of experiments in construction of transgenic mice were later extended by the work of Nobel Lauteates Mario Capecchi, Martin Evans, and Oliver Smithies who developed techniques for using embryonic stem cells.

Several people guessed the Nobel Laureates but only two people provided an explanation of the "molecule." Dima Klenchin, who is ineligible, was the only one to pick up on the hint and find the 1989 paper.

The winner is Shumona De of Dalhousie University.

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If you look closely you'll realize that these mouse embryos aren't really "molecules" in any meaningful sense of the word "molecule." That doesn't matter 'cause I still want you to identify what's going on here. This is the first time that I've resorted to using photographs from my previous life—shows you how desperate I'm getting!

The images are supposed to remind you of the work of some Nobel Laureates. See if you can guess who they are.

The first person to identify the photographs and the Nobel Laureates wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first won the prize.

There are eight ineligible candidates for this week's reward: David Schuller of Cornell University, Adam Santoro of the University of Toronto, Dima Klenchin from the university of Wisconsin, Alex Ling from the University of Toronto, Bill Chaney of the University of Nebraska, Elvis Cela from the University of Toronto, Peter Horwich from Dalhousie University, and Devin Trudeau from the University of Toronto.

Dima and Bill have donated their free lunch to a deserving undergraduate so I'm going to continue to award an additional free lunch to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch.

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 Prizes 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.

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

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Kothary, R., Clapoff, S., Darling, S., Perry, M.D., Moran, L.A., Rossant, J. (1989) Inducible expression of an hsp68-lacZ hybrid gene in transgenic mice. Development. 105:707-14. [PDF]

Applying to NSERC? Everyone gets a grant!

 
According to a study done by Richard Gordon and Bryan J. Poulin, Cost of the NSERC Science Grant Peer Review System Exceeds the Cost of Giving Every Qualified Researcher a Baseline Grant. (NSERC is Canada's funding agency for non-medical science research.)

Using Natural Science and Engineering Research Council Canada (NSERC) statistics, we show that the $40,000 (Canadian) cost of preparation for a grant application and rejection by peer review in 2007 exceeded that of giving every qualified investigator a direct baseline discovery grant of $30,000 (average grant). This means the Canadian Federal Government could institute direct grants for 100% of qualified applicants for the same money. We anticipate that the net result would be more and better research since more research would be conducted at the critical idea or discovery stage. Control of quality is assured through university hiring, promotion and tenure proceedings, journal reviews of submitted work, and the patent process, whose collective scrutiny far exceeds that of grant peer review. The greater efficiency in use of grant funds and increased innovation with baseline funding would provide a means of achieving the goals of the recent Canadian Value for Money and Accountability Review. We suggest that developing countries could leapfrog ahead by adopting from the start science grant systems that encourage innovation.

This sounds like a good idea to me. Thanks to Bora Zivkovic of A Blog Around the Clock for finding the paper.

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Royal Protocol

 
Ever country has a protocol officer and part of their job is to specify how one is supposed to treat the Head of State. In America, for example, you must always refer to the President as Mr. President and unelected cabinet ministers are addressed as Mr./Madam Secretary [Office of the Chief of Protocol].

Visiting Heads of State are expected to conform to American protocol and when the President visits another country he is expected to conform to their rules of protocol. That's how international diplomacy works. It's a system that has evolved over several centuries to try and makes things easier when two different countries communicate. The idea is for countries to respect each other.

Postdiluvian at The Unexamined Life doesn't think that Americans need to respect the protocols and traditions of a foreign country [Is it OK to hug the Queen?]. Now, as it turns out, Michelle's hug was a breach of protocol but not that big a deal, even in England. It would be comparable to someone forgetting to say "Mr. President" when addressing Barack Obama.

That doesn't justify this kind of response ....

Now here’s the bottom line: you can have your “Queen” as a powerless (and utterly pointless) figurehead if you like. She can even keep her massive wealth that somehow came into her family’s possession over the centuries. But if you ever start this bullshit about “Royal Protocol” again, or whether or not it’s okay for people to touch her, you will be removing yourself from the realm of the Serious and joining the realm of Laughingstock, much like the concept of Monarchy did ages ago.

Americans often wonder why they have so much trouble making friends in "foreign" countries. I can't imagine why.

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Five Against One

 
It's sounds so unfair. Four Christians against one lone atheist. If you add in the moderator it's five against one.

But the atheist is Christopher Hitchens so they didn't have a chance.¹

Next time they should try half a dozen Christians—and they should look for ones that are smart.²

Christian Book Expo 2009

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1. Actually, if you watch the "debate" you'll realize that Hitchens didn't need to do or say anything. Every single one of their arguments for the existence of God has been refuted dozens of times. It's like a kindergarten class in Christian apologetics. Most of the time I wish Hitchens had kept his mouth shut.

2. Assuming that ....

[Hat Tip: Friendly Atheist]

What Is Epigenetics?

 
Berger et al. (2009) attempt to define epigenetics.

"An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence."

Sounds good to me. Just about anything wold be better than the kitchem sink definition proposed by Eva Jablonka [Epigenetics at SEED].

The main examples are "DNA methylation, histone modifications, histone variants, and nucleosome positioning." These are chromosomal alterations that are passed on to daughter cells following cell division by mitosis or meiosis.

Although the Berger et al. don't mention it, these epigenetic signals are all reversible. I still don't find the term useful. It's far more accurate to refer to each of the individual examples by name and the field is "regulation of gene expression."

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Berger, S.L., Kouzarides, T., Shiekhattar, R., and Shilatifard, A. (2009) An operational definition of epigenetics. Genes & Dev. 23:781-783. [DOI: 10.1101/gad.1787609]

[Hat Tip: Hopeful Monster]

Monday's Molecule #116

 
If you look closely you'll realize that these mouse embryos aren't really "molecules" in any meaningful sense of the word "molecule." That doesn't matter 'cause I still want you to identify what's going on here. This is the first time that I've resorted to using photographs from my previous life—shows you how desperate I'm getting!

The images are supposed to remind you of the work of some Nobel Laureates. See if you can guess who they are.

The first person to identify the photographs and the Nobel Laureates wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first won the prize.

There are eight ineligible candidates for this week's reward: David Schuller of Cornell University, Adam Santoro of the University of Toronto, Dima Klenchin from the university of Wisconsin, Alex Ling from the University of Toronto, Bill Chaney of the University of Nebraska, Elvis Cela from the University of Toronto, Paul Horwich from Dalhousie University, and Devin Trudeau from the University of Toronto.

Dima and Bill have donated their free lunch to a deserving undergraduate so I'm going to continue to award an additional free lunch to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch.

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 Prizes 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.

Comments will be blocked for 24 hours.

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Religion Wars: Linux and Mac vs. Rationalism

 
Greg Linux is disappointed that the Confliker virus didn't do more damage on April 1st [Did Conflicker Flop? Yes. Why? Nobody knows].

I wasn't worried because I checked all five of my computers and not one them were infected. If they had been, it was very easy to get rid of the worm. My Linux machine didn't have the worm either.

That doesn't stop Greg from offering this advice ...

Experts expect that the worm is going to re-awaken at some time in the future and possibly actually do something. In the mean time, you may want to get rid of it if is on your system.

If you run Windows, the best way to get rid of the computer is to get a Mac or a Linux computer. There are probably other ways to do this but I don't really care. If you are running Linux, this worm can't directly affect you.

Sheesh, those religious nuts sure can be silly.

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The End of Christian America?

 
The number of Americans who don't identify with a religion has increased from 8% in 1990 to 15% today. This is encouraging but it doesn't quite mean that the battle between rationalism and superstition has been won.

Nevertheless, the fact that a national magazine could publish an article like "The End of Christian America" is an indication that the debate is on.

If North American societies become much less religious—like those in Europe—then most of the major problems with creationism will go away. Maybe then we can concentrate on promoting good science education. That's why some of us would rather put our efforts into promoting rationalism over superstition rather than defending specific creationist attacks on schools.

Both approaches are needed but those who advocate the compatibility of science and superstition are not helping.

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[Hat Tip: Hemant Mehta who has some interesting comment.]

Last Week's Scientific Breakthroughs

 
This are stories from the past week that would make good topics for discussion. I don't have time so I'll leave it up to you.

Scientists Find 'Baffling' Link between Autism and Vinyl Flooring

Masturbation could bring hay fever relief for men

New research shows lower educational outcomes for survivors of childhood cancer

6 out of every 10 university students present mathematical anxiety or fear of this subject

Humanoid Robot Helps Scientists To Understand Intelligence

Omega-3 kills cancer cells

How probiotics can prevent disease

UBC study first to show evolution's impact on ecosystems

UT Southwestern researchers reveal how the brain processes important information

Your oral health is connected to your overall health

Penn researchers demonstrate a new model for drug discovery with a fluorescent anesthetic

Humans May Be Losers If Technological Nature Replaces The Real Thing, Psychologists Warn

Milkshakes Are Medicine For Anorexic Teens In Family-based Outpatient Therapy

Hermit Arthropods 500 Million Years Ago?

Alzheimer's Disease Linked To Mitochondrial Damage

Robot Scientist Becomes First Machine To Discover New Scientific Knowledge

Virus-built Battery Could Power Cars, Electronic Devices

Athletic Ability May Lie in a Single Gene

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Washington D.C.

 
In a few days I'll be on my way to Washington (Bethesda, actually) to attend the Center for Inquiry World Congress 2009. Let me know if you'll be there and we can meet up.

Here are the main events ....

Thursday April 9, evening: Panel: The Influence of Darwin

Friday April 10, afternoon: Science and Public Policy

Friday April 10, 5:45pm: James Randi: Search for the Chimera

Saturday April 11, morning: Skepticism and Science

Saturday April 11, 5pm: Special Feature: Separation of Church and State

Sunday April 12, morning: Secularism Around the World

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Darwin Rocks

 
Watch this video about evolution and see if you can figure out what's going on. You can check your answer here.

In the fight to increase scientific literacy, I'm not sure if this contribution is useful, useless, or counter-productive but I'm leaning toward counter-productive.

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[Hat Tip: John Dennehy, who leans toward the "useful" point of view.]

Will Universities Survive?

 
Believe it or not, there are supposedly intelligent people out there who think the internet will replace universities.¹ It didn't take Sean Caroll very long to come up with some excelent reasons why this ain't gonna happen [Will the Internet Replace Universities?].

Let me add one more—research experience. You can't learn what it's like to work in a research lab if you're sitting at your desk in the suburbs.

Why do I get the feeling that most people don't understand what a university is supposed to be like? Is it true that most people think of universities just as places where you come and listen to lectures and then go home?

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1. Back in 1970 their parents were convinced that television would mean the end of universities as we know them.

Electronic Textbooks

 
There's an article in this week's issue of Nature on The textbook of the future.

Most of the article is about a Kindle version of science textbooks.

Another drawback of current e-readers is that they have small black-and-white displays, just a little larger than 9 by 12 centimetres. This makes them unsuited to most science textbooks, which typically have large pages and colourful graphics. "The market is not likely to expand until the e-readers improve," says Hegarty.

Publishers are experimenting with ways of delivering their textbooks electronically (e.g. CourseSmart) but there are still problems to be solved.

Competing ideas, such as Wiki's that replace textbooks, have a long way to go before they become a threat to the textbook market [Wikibooks: Biochemistry]. Besides, there are other problems that need to be solved.

For now these free textbooks remain a cottage industry, says Esposito. Wikipedia-like volunteer efforts are much better suited to self-contained modules that are small enough for an individual to see through from A to Z. But a textbook demands a coherent overall structure and coordination between sections. That is why creating one has always been a major undertaking, demanding long-term commitments by publishers — who need to make a profit — and by authors who usually want to be paid for their effort.

Still, perhaps 'free' and 'profitable' need not be a contradiction in terms. One group of veteran textbook publishing executives is trying to put open textbooks on a solid commercial footing. In 2007 they created Flat World Knowledge, based in Nyack, New York, and in January 2009 rolled out the first of the 21 textbooks they have in development so far. The texts are written by some 40 domain experts who will be paid 20% of royalties. The company also plans to make its content available via Kindle and other e-readers. All its content will be free to reuse for non-commercial purposes under a creative commons licence.

Eric Frank, Flat World's co-founder, says that the strategy is to attract greater use by giving the e-textbooks away — the initial targets are the high-volume texts for first-year students — and then look for profit from students' purchase of print-on-demand versions at $29.95 for black and white, and $59.95 for colour. Students can copy and use the electronic content in any way they wish, says Frank. "Cheap prices are the most effective digital-rights management," he says. "We want to avoid a digital-rights war with students." The company also hopes to make money by licensing its content to commercial companies, such as distance-learning outfits and course-management software firms.

I think there's going to be a way to make cheaper electronic versions of textbooks and still compensate the people who do all the work. I'm not sure how it's going to work but I'd love to put my book on a website where I can make changes quickly and get instant feedback from the users.

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James Lunney: Creationist, Chiropractor, Conservative

 
Meet Dr. James Lunney a chiropractor and a Conservative Party Member of Parliament for Nanaimo-Alberni in British Columbia.

"Dr." Lunney recently made a fool of himself by making the following statement in the House of Commons as reported in Maclean's magazine [James Lunney v. Evolution].

Mr. Speaker, recently we saw an attempt to ridicule the presumed beliefs of a member of this House and the belief of millions of Canadians in a creator. Certain individuals in the media and the scientific community have exposed their own arrogance and intolerance of beliefs contrary to their own. Any scientist who declares that the theory of evolution is a fact has already abandoned the foundations of science. For science establishes fact through the study of things observable and reproducible. Since origins can neither be reproduced nor observed, they remain the realm of hypothesis.

In science, it is perfectly acceptable to make assumptions when we do not have all the facts, but it is never acceptable to forget our assumptions. Given the modern evidence unavailable to Darwin, advanced models of plate techtonics, polonium radiohalos, polystratic fossils, I am prepared to believe that Darwin would be willing to re-examine his assumptions.

The evolutionists may disagree, but neither can produce Darwin as a witness to prove his point. The evolutionists may genuinely see his ancestor in a monkey, but many modern scientists interpret the same evidence in favour of creation and a creator.

PZ Myers is making fun of Canada by posting Lunney's remarks on Pharyngula. He's right. We deserve it. Lunney is a genuine kook who quite obviously wouldn't know real science if it bit him on the backbone.

Listen up, all you people who live on Vancouver Island! Don't send this guy back to Ottawa after the next election or you're going to look very silly.

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March on Sandwalk

 
Bora's doing it and Greg Laden is doing it. They're revisiting their posts from last month.

Now I'm doing it too.

Last month Sandwalk attracted 107,747 page views and 75,156 visits from all over the world. That's a new record. I posted 123 times.



The month began with an account of my streetcar ride and the atheist sign campaign in Toronto [The Streetcar We Desire]. I also celebrated the 35th anniversary of my thesis defense.

There were three debates that took up a lot of posting time.

One of them was about positive selection in humans, especially the idea that human evolution might have accelerated in the past 10,000 years. I tried to explain why some of the data looks suspicious in Signals of Positive Selection in Humans?.

We also talked a lot about the quality of science journalism. The two topics were combined when I reviewed SEED magazine's coverage of a recent book on accelerated human evolution [SEED Reviews The 10,000 Year Explosion].

The third debate was about Canada's science minister, Gary Goodyear, and the fact that he is a creationist [Gary Goodyear "Clarifies" His Stance on Evolution].

I'm pretty proud of this posting: Casey Luskin on Junk DNA and Junk RNA. It generated some comments and got a mention on several blogs.

Speaking of comments, one other posting caught the attention of Sandwalk readers and stimulated comments. You were interested to know why I Hate Cilantro/Coriander!.

In terms of most popular postings there was nothing in March that's going to make the top 20 postings. I still get a lot of traffic from people who want to learn about The Genetics of Eye Color from a posting in February 2007. Another popular posting is The Genetics of ABO Blood Types, also from February 2007.

As usual, there were lots of people who tried to guess Monday's molecule. There are a small number of regulars who get most of the prizes, The rest of you are going to have to be faster. I think I'll try and post much earlier in the day to give my European readers a better chance. We don't need to worry about giving the Australians a chance 'cause they probably wouldn't win anyway! :-)

We had an interesting group of Nobel Laureates. These postings always get looked at but nobody leaves comments. I guess there isn't much to say. The most interesting Nobel Laureates from my perspective were Frederick Banting and J.J.R. Macleod because they're from the University of Toronto. Several of the recent prize winners were controvesial, especially Selman Waksman.

Does anyone have suggestions for future postings?

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A field guide to misunderstandings about open access

 
Want to find out what Open Access is really all about? Read A field guide to misunderstandings about open access.

Do you think that articles in open access journals aren't peer reviewed? Think again.

Do you think that all open access journals charge huge publication fees? Wrong.

Do you think that open access journals are lower quality? Nope.

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[Hat Tip: Bora Zivkovic: A Blog Around the Clock]

Dynamic Genomes

There may have been a time in the past when scientists imagined a static genome that only changed slowly over millions of years. However, beginning in the 1960's we began to see the genome as a much more dynamic entity. The first evidence of this kind of genome came with the discovery of huge amounts of variation between individuals in a species.

This was followed by the discovery of transposons and junk DNA. We began to see genomes as rather sloppy DNA molecules with lots of pieces hopping in and out on a timescales of generations. We began to realize that many genomes were full of pseudogenes.

Chromosomal rearrangements such as inversions, duplications, and translocations were documented. In mammals, many of them were associated with cancer, thalassemias, and other diseases but the general impression was that these rearrangements of genetic material were quite common. Indeed, some non-disease examples began to accumulate in the literature. Clear evidence of normal rearrangements associated with regulation and development—including mating type switching in yeast, immunoglobulin rearrangements in mammals, chorion gene amplification in Drosophila, and antigenic variation in trypanosomes—reinforced the idea that the genome was not static.

Most of this information was incorporated into the textbooks. For example, by the early 1980's Benjamin Lewin' textbook Genes had an entire group of chapters under the heading "The Dynamic Genome: DNA in Flux."

We soon learned about the expansion and contraction of repetitive sequences in the human genome. These observations eventually gave rise to DNA fingerprinting whereby every individual could be uniquely identified by variations in the genome.

By the early 1990's the concept of the dynamic genome had become so widely entrenched among molecular biologists that when Singer and Berg published "Genes and Genomes" they felt obliged to inject a note of caution. While genomes are dynamic at the scale of species evolution, the typical genome of an individual is not subject to significant rearrangements.

Outside of molecular biology, the idea that genomes were flexible never seemed to catch on. Most people thought of genomes as relatively static entities that didn't change much over millions of years. In part, they adopted this position because they still placed a great deal of emphasis on the power of natural selection. If genomes were well-adapted then why would they change? Part of the skepticism about junk DNA stems from the belief that selection will eliminate useless DNA.

Recent developments have stirred many people to re-think their concept of genomes. For example, Sandra Porter of Discovering Biology in a Digital World recently asked, "What if everything you thought you knew about the genome was wrong?."

To the extent that such questions acquaint people with the concept of a dynamic genome, they are good. On the other hand, if such questions lead to the unthinking acceptance of alternative splicing, superabundant transcription, and a plethora ot RNAs, they are bad.

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Handel's Messiah

 
One year Ms. Sandwalk took the entire family to see a full performance of Handel's Messiah. It was agony, except for one brief part of the performance where we all got to stand up. Ms. Sandwalk thought it was wonderful but, remember, she also likes some country music.

My children still talk about it. I guess it's one of those "experiences" that contribute to character building, or something.

Now there's an explanation in New Scientist: How misery inspired Handel's Messiah. I knew there had to be a reason.

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Monday's Molecule #115: Winners

 
UPDATE: The molecule is indigotin or indigo dye [2,2’-Bis(2,3-dihydro-3- oxoindolyliden)]. The Nobel Laureate is Johann Friedrich Wilhelm Adolf von Baeyer.

This week's only winner is Alex Ling from the University of Toronto.

The winners this week are Pete Horwich from Dalhousie University and Devin Trudeau from the University of Toronto.

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Identify this molecule and explain why it is useful. You must supply the common name and the formal IUPAC name.

I'm looking for the Nobel Laureate whose name is associated with this molecule.

The first person to identify the molecule and the Nobel Laureate wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first won the prize.

There are seven ineligible candidates for this week's reward: Maria Altshuler of the University of Toronto, David Schuller of Cornell University, Adam Santoro of the University of Toronto, Dima Klenchin from the university of Wisconsin, Alex Ling from the University of Toronto, Bill Chaney of the University of Nebraska, and Elvis Cela from the University of Toronto.

Dima and Bill have donated their free lunch to a deserving undergraduate so I'm going to continue to award an additional free lunch to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch.

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 Prizes 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.

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Nobel Laureate: Adolf von Baeyer

 

The Nobel Prize in Chemistry 1905.

"in recognition of his services in the advancement of organic chemistry and the chemical industry, through his work on organic dyes and hydroaromatic compounds"


Johann Friedrich Wilhelm Adolf von Baeyer (1835 - 1917) won the Nobel Prize in Chemistry for his work on the preparation of organic dyes from coal tar.

His most notable achievement was the synthesis of indigo dye and determination of its structure. A cheap industrial synthesis of indigo was soon developed, freeing Europe from its dependence on indigo from India.

He was also the first person to synthesize phenolphthalein, the well-known acid or base indicator.

The presentation speech highlights the importance of the relationship between basic science and industry.
THEME:
Nobel Laureates

The complex and unique composition of indigo, however, made this also one of the hardest of tasks. Here there could be no question of one of those casual discoveries, which by happy accident seem to achieve half the work. Years of work were required for even von Baeyer's acumen and experimental skill to achieve the necessary insight into the pigment's chemical composition and to be able to manufacture it from simpler constituents. Even after the purely scientific part of the work had been completed it still took a number of years to make the results obtained from research applicable to technology.

Von Baeyer succeeded in producing indigo synthetically in three principal ways, namely from ortho-nitrophenylacetic acid, from ortho-nitrocinnamic acid and from ortho-nitrobenzaldehyde and acetone. This paved the way for the reproduction of indigo from raw material obtainable without much difficulty from coal tar. And if the problem of producing indigo industrially has now been solved from the technical as well as the economic point of view, this is entirely due to von Baeyer's basic work in the fields in question.

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The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

2,296,911 visits?

 
It's April 1st and PZ Myers tells us that Pharyngula had 2,296,911 visits last month [What are all you people doing here?].

Problem is, I don't think this is an April Fool's joke.¹

There are already 225 comments to that posting, which is probably what PZ means when he asks what everyone is doing there. Now he knows—they're posting comments!

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Sandwalk had 107,747 visits or less than 5% of the number that visited Pharyngula.

Nobel Laureate: Michael Behe

 

The Nobel Prize in Biochemistry 2009.

"for his contributions to understanding complex biological systems"


Michael Behe (1952 - ) wins the Nobel Prize in Biochemistry for his amazing work on complex biological systems, especially the concept of irreducible complexity.

Beginning with the publication of his first book, Darwin's Black Box, Behe has written numerous articles on the organization of molecular machines such as the snare complex of Mus musculus and the bacterial flagellum. He has shown that these systems exhibit a fundamental property that previous biochemists overlooked—they are so well integrated that their origin cannot be explained by the older naturalistic theory of natural selection.

His later work, The Edge of Evolution, is a seminal contribution to modern evolutionary theory. In that book he explains how previous versions of evolution are incapable of explaining the origin of protein-protein interaction sites.

The presentation speech highlights the importance of this work.
THEME:
Nobel Laureates

The development of protein features, such as protein-protein binding sites, that require the participation of multiple amino acid residues is a profound, fundamental problem that has stumped the evolutionary biology community until the present day (and continues to do so, as I explain below). It is a fundamental problem because all proteins exert their effects by physically binding to something else, such as a small metabolite or DNA or other protein, and require multiple residues to do so. The problem is especially acute for protein-protein interactions, since most proteins in the cell are now known to act as teams of a half-dozen or more, rather than individually. Yet if one can’t explain how specific protein-protein interactions developed, then it is delusional to claim that we can explain how anything that depends on them developed, such as the molecular machinery of the cell. It’s like saying “we understand perfectly well how a car could evolve; we just don’t know how the pieces could get fit together.” If such a basic requirement for putting together complex systems is not understood, nothing is understood. Keep this in mind the next time you hear a blithe Darwinian tale about the undirected evolution of the cilium or bacterial flagellum.

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Posted on April 1st, 2009.

The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

Advice for Women: What to Do When You Discover He's an Atheist

 
Friendly Atheist found the answer on YouTube.

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Sean Eddy on "Open Education"

 
I've been thinking a lot lately about how to get my textbook online without asking everyone involved to work for free. It's not an easy problem.

There's a myth out there that some places like MIT are putting up all kinds of useful information for free. The Open Courseware project sounds really exciting until you realize that they can't publish any of the slides they use in their powerpoint presentations because they're all copyrighted. It also doesn't take much perusal to realize that many MIT professors don't know as much about their subjects as you might imagine.

There's a new book advocating the concept of "Open Education" ("Opening Up Education" T. IIyoshi and M.S.V. Kumar eds. MIT Press). The book is reviewed by Sean Eddy on PLoS Biology [Open Revolution].

Sean Eddy used to be an active participant on the talk.origins newsgroup back when he was a graduate student so I eagerly followed the link to his review. I wasn't disappointed. It's the same Sean Eddy that I knew 12 years ago. He can still recognize bullshit when he sees it.

So, while I like storming the establishment with pitchforks and torches as much as anyone, when I picked up Opening Up Education (or rather, when I downloaded the PDF to my Kindle), I was looking for pragmatism, not utopianism. After 500 pages of “the silos we all know about in higher education are under assault in the new world,” the “hated textbook publishers,” the “epistemological hegemony of higher education,” and the “noble philosophy” of making everything free—“traitors” and “patriots” and “communists,” oh my!—my hopes were beaten down. Many of the 30 essays in this collection are more manifesto than explanation, and many of the 38 authors are writing more for their fellow revolutionary comrades than for us.

Life is never as simple as the Web 2.0 fans make out. Somebody is going to have to do a lot of work before the quality of a website matches what's in the best introductory textbooks. And it's extremely naive to think that all that work is just going to be given away for free.

I'm not just talking about authors. There's a whole team of people involved in publishing my textbooks. This includes editors who correct my spelling and grammar—an onerous task in my case. It includes artists who make the figures and editors who obtain permissions and copyrights for photographs. Then there's the staff at the publishers who receive and mail out manuscripts for review and editing and who handle all the paperwork/electrons associated with a major project.

Are we going to ask all of them to work for free by putting everything on the web? Of course not.

Sean does an excellent job of bursting the bubble.

“Remix,” “collective wisdom,” “Web 2.0”—many of these essays ride a bubble of popular digital punditry enthusiastically but too uncritically. Many technologists today are infected with an idea that “community is king,” that high-quality content will rain down freely merely because we connect digital communities openly. This confuses ways of sharing ideas with ways of creating ideas. It is a kind of magical thinking that has much in common with the cargo cults that cut landing strips in the jungle and carved radios from sticks in hope that more sophisticated beings would parachute technological artifacts down upon them. With all respect to the passionate and pioneering initiatives described in this collection, building landing strips to receive open educational content will not be enough. More attention must be paid to the fact that someone still needs to spend time painstakingly developing artful ways to make difficult concepts understandable—to teach!—and that it will take even more time (thus money) to render these hard-won ideas using multimedia web technology compared with writing textbooks. Success hinges on the adoption of open licensing by the professionals who make digital educational resources, and on finding ways to finance their work.

I have some ideas. I'd like to put my book on the web so that everyone can read it but nobody can download it or print out the figures and text. If you need a printed version you can sign on to the server and print out a chapter for $3. The pages would come with your name and email address printed in the header and footer—or perhaps as a watermark. The idea is to make the material available at minimal cost to an individual user while inhibiting the distribution of photocopies.

No matter how easy it is to read something online, I think there's still a market for a printed version of the material. I know from personal experience that highlighting and scribbling in the margins on my computer monitor doesn't work.

Online textbooks have several advantages such as hyperlinks, frequent revisions and updates, and interactive learning. But we need to find a way to pay for it. If you think the work is going to be given away for free then you are living in a dream world. Check out the MIT Open Courseware site under Biology to see what the cargo cult version of Web 2.0 gets you.

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[Photo Credit: Nature]

[Hat Tip: Jonathan Eisen at The Tree of Life]

Religion and Child Abuse

 
I don't think that religious indoctrination is always an example of child abuse. However, there are other ways that count as clear examples of abuse [Taliban blocks UN polio treatment in Pakistan].

Militants had reportedly agreed to allow the [polio] vaccination program to take place as part of the peace agreements.

However, the militants had reneged on their word and despite assiduous efforts made by the increasingly irrelevant local administration, no vaccinations have taken place.

“It’s a US tool to cut the population of the Muslims. It is against Islam that you take a medicine before the disease”, said, Muslim Khan, Swat’s Taliban spokesman, speaking by telephone.

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[Photo Credit: daylife/Reuters: "A man holds his twins as he waits for them to receive polio vaccines in the southern province of Kandahar September 21, 2007. Afghan health officials said on Friday they had brokered a deal with Taliban leaders to allow the immunization of children against polio in rebel-held areas in a rare sign of cooperation between the warring sides."]

[Hat Tip: RichardDawkins.net]

Way too Sensitive?

 
The techniques for detecting DNA and RNA are extremely sensitive. This sensitivity often leads to misinterpretations because it become difficult to separate signal from noise. The idea that 90% of our genome may be transcribed into functional RNA, for example, may be due to the sensitivity of an assay that can easily detect tiny amounts of accidental transcription.

Similarly, the often proclaimed ubiquity of alternative splicing may be due to the easy detection of splicing mistakes. Other examples of problems with noise might be the presumed abundance of small regulatory RNAs and the frequency of transcription factor binding sites.

The problem is acute when it comes to analyzing DNA from fossils. There, tiny amounts of contamination can really screw things up. That's why John Hawks is also interested in this problem of over-sensitive DNA assays.

Just how sensitive is the technology? Hawks has found a very interesting and informative example [The trouble with contamination]. This example is about contamination but keep in mind that it also applies to the detection of noise in transcription, DNA binding, and splicing.

Here's the original report from the BBC ['DNA bungle' haunts German police]. Over the past few years German police have been on the lookout for a mysterious woman who was linked to several murders. Her DNA was found at over 40 different crime scenes. This woman became one of the most wanted people in Europe but nothing was known about her aside from her DNA.

Finally someone became suspicious and started to look closely at the way they were collecting and analyzing DNA. To make a long story short, the alleged murderer is a factory worker in Bavaria who works in a factory that manufactures cotton swabs. The same swabs that are used to collect samples at a crime scene. Those swabs were contaminated with her DNA.

There's a lesson here. Any technology that can detect the DNA from a factory worker on a cotton swap is quite capable of detecting tiny insignificant amounts of nucleic acids inside a cell.

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1,2,3 ... What Are We Fighting for?

 
President Obama wants to sacrifice more American in Afghanistan and Canada's Prime Minister, Stephen Harper, is suggesting that this might be something that Canada should support. This is in spite of the fact that there are times when he seems to know the right answer to the question; Can We Win in Afghanistan?.

Let's make sure everyone knows what we're fighting for: 'Worse than the Taliban' - new law rolls back rights for Afghan women.

Hamid Karzai has been accused of trying to win votes in Afghanistan's presidential election by backing a law the UN says legalises rape within marriage and bans wives from stepping outside their homes without their husbands' permission.

The Afghan president signed the law earlier this month, despite condemnation by human rights activists and some MPs that it flouts the constitution's equal rights provisions.

The final document has not been published, but the law is believed to contain articles that rule women cannot leave the house without their husbands' permission, that they can only seek work, education or visit the doctor with their husbands' permission, and that they cannot refuse their husband sex.

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Glass Knives

 
One of the best labs I ever took as an undergraduate was an advanced cytology lab where we learned to use the electron microscope.¹ Part of the process was preparing thin sectioned material and that involved making our own glass knife that would cut very thin slices from wax-embedded tissue.

Here's a video from Leica showing how it's done today.²



I was reminded of this recently when I had occasion to refer to an electron micrograph taken by Harrison Latta. Latta invented the glass knife back in 1949. You can read about his discovery in this tribute to him on the University of California, Los Angeles, website.

This is one of those simple technological innovations that made a huge difference but would never have been recognized by the Nobel Prize committee.

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1. Yes, they had electron microscopes back in those days!
2. You can also buy diamond knives but that's a lot less fun.