Militant Atheists

 
Have you ever wondered why so many atheists are described as "militant" atheists? Read why on Jeff Shallit's blog Recursivity [Why Are Atheists Always Described as Militant?].

D-Day

 

Today marks the 63rd anniversary of the invasion of Normandy on June 6, 1944. British, Canadian and American forces opened the second front against Germany.

For baby boomers it means a day of special significance for our parents. In my case, it was my father who took part in the invasions. He was an RAF pilot flying rocket firing typhoons in close support of the ground troops. During the initial days his missions were limited to quick strikes and reconnaissance since Normandy was at the limits of their range from southern England. During the second week of the invasion his squadron landed in Normandy and things became very hectic from then on with several close support missions every day.

The photograph shows a crew loading rockets onto a typhoon based just behind the landing beaches in Normandy.

Today's D-Day is very different. It's the day when Leslie (Ms. Sandwalk) and I are meeting with the people involved in my daughter's wedding on June 29th at the University of Toronto Faculty Club. This is the day when we have to lock in many of the decisions; such as flowers, cakes, music, and number of guests. Very scary.

Don't for one minute think that I have much of a role here. I'm just along for the ride. Leslie and Jane are in charge.

Nobel Laureates: Aaron Ciechanover, Avram Hershko, Irwin Rose

 
The Nobel Prize in Chemistry 2004.

"for the discovery of ubiquitin-mediated protein degradation"



Aaron Ciechanover (1947- ), Avram Hershko (1937- ) and Irwin Rose (1926- ) won the Nobel Prize in 2004 for discovering the mechanism of ubiquitin mediated protein degradation [Protein Turnover]. You can view an animation of this process on the Nobel Prize website. It's called Kiss of Death.

The presentation speech was delivered by Professor Lars Thelander of the Royal Swedish Academy of Sciences on December 10, 2004. Note that the individual contributions of the three winners are not specified. They worked together on many of the problems associated with the mechanism. You can read their individual acceptance speeches to see how they present their own work.

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,

This year's Laureates in Chemistry are being rewarded for their discovery of life's own death-labeling system and at the same time for having solved a scientific mystery.

The cells in our bodies contain about one hundred thousand different proteins. Proteins do all the work in the cell, and proteins are directly responsible for its shape and function. One of the things proteins do is to build up the molecular machines that form our muscles; another is to form the enzymes that accelerate and control the various chemical reactions that are necessary for life.

Now, how can a cell possibly keep track of all its proteins? Protein molecules are synthesized and broken down all the time at a high rate. As to the synthesis of proteins, we have a good understanding of how this is regulated at molecular level, and the research here has been rewarded with a number of Nobel Prizes. In contrast, the break down of proteins in the cell has been considered less interesting, and it has attracted few researchers.

This year's Laureates in Chemistry, Aaron Ciechanover, Avram Hershko and Irwin Rose, went against the stream. They studied precisely how the breakdown of proteins is regulated in the cell. What aroused their interest was reports in the literature that the breaking down of proteins inside living cells requires energy. This seemed a paradox since everybody knew that, for example, the degradation of proteins in the intestines – that is, outside the cell – takes place with no requirement for added energy. Why is energy needed for degradation inside cells?

By studying the mechanisms of energy-dependent protein degradation in cell extracts, this year's three Laureates succeeded at the beginning of the 1980s in identifying a completely new principle for protein degradation. They discovered a system that used a type of "death label" together with three different enzymes to attach it to the proteins to be destroyed. The energy goes to activating the label and enabling the cell to control the process accurately.

The death label itself is a small protein called ubiquitin. The name comes from the Latin ubique, which means 'everywhere' and tells us that the protein is found in the cells of almost all organisms. Among all the proteins in the cell, the enzyme system chooses a certain unwanted protein molecule and tags it with the death label. The labeled protein molecule is transported to a type of waste disposer inside the cell called the proteasome, which recognizes the label rather like a key fitting into a lock. Before the labeled protein is sucked into the waste disposer for destruction, the label is removed so that it can be used again to death label more proteins. Inside the waste disposer, the doomed protein is chopped to pieces. These can later be used for synthesizing new proteins. It was first believed that controlled protein degradation is used only to destroy faulty proteins, which may otherwise damage the cell. Prion diseases and Alzheimer's disease represent similar cases. Yet constantly growing research has shown something more: that it is at least as important for the cell, by destroying a protein with a certain function, to be able to regulate a biochemical reaction, rather like when you turn off a switch. We now know that controlled protein degradation regulates other very important processes in the cell as well. Examples are the cell cycle, repair of DNA damage and immune defense. In plants, the process is also needed to prevent self-pollination. And a failure in our degradation system may lead to disease.

The discovery of controlled protein degradation explains, at molecular level, the function of a regulation system that is very central for the cell. Among other things, the knowledge can be used to produce new medicines against different diseases.

Professor Ciechanover, Professor Hershko, Dr. Rose,
Your discovery of a system for controlled protein degradation in cells has fundamentally changed our way of thinking about protein degradation. We can now understand at molecular level how the cell controls a number of central biochemical processes. More reactions regulated by ubiquitin-mediated protein degradation are being identified every year. On behalf of the Royal Swedish Academy of Sciences, I wish to convey to you our warmest congratulations, and I now ask you to step forward to receive the Nobel Prize in Chemistry from the hands of His Majesty the King.

SCIENCE Questions: What Determines Species Diversity?

 
"What Determines Species Diversity?" is one of the top 25 questions from the 125th anniversary issue of Science magazine [Science, July 1, 2005]. The complete reference is ...

Pennisi, Elizabeth (2005) What Determines Species Diversity? Science 309: 90. [Text] [PDF]

Elizabeth Pennisi is a news writer for Science magazine. She has been publishing articles there for at least ten years. She had previously written about genes and genomes, including earlier articles about the number of genes in the human genome and one of the other top 25 Science questions [Why Do Humans Have So Few Genes?]

The question is poorly phrased because it's really about speciation.

Understanding what shapes diversity will require a major interdisciplinary effort, involving paleontological interpretation, field studies, laboratory experimentation, genomic comparisons, and effective statistical analyses. A few exhaustive inventories, such as the United Nations' Millennium Project and an around-the-world assessment of genes from marine microbes, should improve baseline data, but they will barely scratch the surface. Models that predict when one species will split into two will help. And an emerging discipline called evo-devo is probing how genes involved in development contribute to evolution. Together, these efforts will go a long way toward clarifying the history of life.

Paleontologists have already made headway in tracking the expansion and contraction of the ranges of various organisms over the millennia. They are finding that geographic distribution plays a key role in speciation. Future studies should continue to reveal large-scale patterns of distribution and perhaps shed more light on the origins of mass extinctions and the effects of these catastrophes on the evolution of new species.

This question is also related to a more fundamental question; namely, what is a species?

This certainly counts as one of the top questions in biology. If we ask it in the form "What causes speciation?" then it gets us into a discussion about punctuated equilibria, founder effects and all kinds of other controversial problems. It also brings up the issue of the role of natural selection and environment in speciation. While there may not be anything new to discover, there are many open questions concerning the mechanisms of speciation. Does sympatric speciation happen, for example?

There are many who think that natural selection plays only a minor role in most speciation events and there are many who think that environmental change is not correlated with speciation [Adaptation and Accident in PNAS, Evolution of Mammals].

Protein Turnover

 
One might assume that only growing or reproducing cells would require new protein molecules—and therefore a supply of amino acids—but this is not the case. Proteins are continually synthesized and degraded in all cells, a process called turnover. Individual proteins turn over at different rates. Their half-lives can vary from a few minutes to several weeks but the half-life of a given protein in different organs and species is generally similar. Rapid protein turnover ensures that some regulatory proteins are degraded so that the cell can respond to constantly changing conditions. Such proteins have evolved to be relatively unstable. The rate of hydrolysis of a protein can be inversely related to the stability of its tertiary structure—misfolded and unfolded proteins are quickly degraded.

In eukaryotic cells, some proteins are degraded to amino acids in the lysosomes. In these cases, vesicles containing material to be destroyed fuse with lysosomes, and various lysosomal proteases hydrolyze the engulfed proteins. The lysosomal enzymes have broad substrate specificities, so all the trapped proteins are extensively degraded.

Some proteins have very short half-lives because they are specifically targeted for degradation. Abnormal proteins are also selectively hydrolyzed. The pathway for the selective hydrolysis of these proteins in eukaryotic cells requires the protein ubiquitin. Ubiquitin is Monday's Molecule #29. It is a small, highly conserved protein of about 76 amino acid residues.

Side-chain amino groups of lysine residues in the target protein are covalently linked to the C-terminus of ubiquitin in a complex pathway that involves ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin-protein ligase (E3). This pathway is coupled to ATP hydrolysis—one ATP molecule is hydroylzed for every ubiquitin molecule attached to the target protein. The ubiquitinated protein is hydrolyzed to peptides by the action of a large multiprotein complex called the proteasome (or proteosome). This process occurs in both the cytosol and the nucleus.

Other proteases catalyze hydrolysis of the resulting peptides. ATP is required to assemble the proteasome and to hydrolyze the ubiquitinated protein. Before this pathway was discovered there was no explanation for the surprising observation that the degradation of many proteins requires ATP.


Adapted from Horton et al. Principles of Biochemistry 4th edition
©Laurence A. Moran and Pearson/Prentice Hall

SCIENCE Questions: How Does a Single Somatic Cell Become a Whole Plant?

 
"How Does a Single Somatic Cell Become a Whole Plant?" is one of the top 25 questions from the 125th anniversary issue of Science magazine [Science, July 1, 2005]. The complete reference is ...

Vogel, Gretchen (2005) How Does a Single Somatic Cell Become a Whole Plant? 309: 86.
[Text] [PDF]

Gretchen Vogel is a contributing correspondent for Science magazine. She is based in Berlin.

This question is really about developmental biology. It's closely related to the two questions that immediately precedes it in the journal: How Can a Skin Cell Become a Nerve Cell?, and What Controls Organ Regeneration?. For some reason the editors of Science seem to think that there's a fundamental difference between this question and the other two. Perhaps they think that plants control gene expression by a very different process?

The totipotency of plant cells was demonstrated half a century ago as noted in the article.

Nearly 50 years ago, scientists learned that they could coax carrot cells to undergo such embryogenesis in the lab. Since then, people have used so-called somatic embryogenesis to propagate dozens of species, including coffee, magnolias, mangos, and roses. A Canadian company has planted entire forests of fir trees that started life in tissue culture. But like researchers who clone animals (see p. 85), plant scientists understand little about what actually controls the process. The search for answers might shed light on how cells' fates become fixed during development, and how plants manage to retain such flexibility.

I really don't think it's correct to say that "plant scientists understand little about what actually controls the process." Furthermore, even if there are lots of details to be worked out, I see no indication that there's some mysterious unknown process behind plant development.

This is not a fundamental question.

bio::blogs #11

 
The 11th edition of bio::blogs, a carnival on bioinformatics, has been published at nodalpoint.org [Bio::Blogs #11].

A special edition of highlights can be found at Bioinformatics Zen [Bio::blogs 11 - special edition].

Did Dinosaurs Have Feathers?

 
An article on the National Geographic website addresses an issue in the evolution of birds ["Feathered" Dinosaur Was Bald, Not Bird Ancestor, Controversial Study Says].

The article deals with a recent report by a group at the University of KwaZulu-Natal in South Africa; University of North Carolina (Chapel Hill); and the Chinese Academy of Sciences, in Beijing. The paper was published in the journal Proceedings of the Royal Society B. The authors claim that the "feathers" seen on recent dinosaur fossils are not feathers at all but collagen fibers. This is a minority opinion and the reason why I mention the article is to point out how good science writing can put things in context. Here's an example,

Lingham-Soliar and colleagues' results support the arguments of a small but highly vocal group of scientists who say there's no evidence of dinosaurs ever having feathers.

"The existence of protofeathers in these dinosaurs was considered critical evidence that birds were derived from dinosaurs," said study co-author Alan Feduccia, a bird evolution expert at the University of North Carolina at Chapel Hill.

"What we have shown is that there's absolutely no evidence whatsoever that protofeathers existed in dinosaurs, period."

But the majority of scientists in the field are unconvinced.

The article then goes on to quote from a number of scientists who disagree with the findings of the South African group.

"These people have been flogging the same horse for a long time," said Kevin Padian, curator of the University of California Museum of Paleontology.

"It is appalling that Proceedings B chose to publish this nonsense."

We need more of this kind of reporting.

Lingham-Soliar, T., Feduccia, A., and Wang, X. (2007) A new Chinese specimen indicates that ‘protofeathers’ in the Early Cretaceous theropod dinosaur Sinosauropteryx are degraded collagen fibres. Proc. Roy. Soc. B: published online Wednesday, May 23, 2007

Monday's Molecule #29

 

Today's molecule is my first example of a protein. I've given you two different views of the molecule showing most of it as a ribbon model. A small stretch of the polypeptide is displayed as a stick model. You have enough information to identify the protein provided you have taken the appropriate courses in high school or college. All we need is the name of the protein but if you can identify the species and the PDB file that would be an impressive feat of detective work.

As usual, there's a connection between Monday's molecule and this Wednesday's Nobel Laureate(s). This one is an direct connection. Once you have identified the molecule the Nobel Laureate(s) are obvious.

The reward (free lunch) goes to the person who correctly identifies both the molecule and the Nobel Laureate(s). Previous free lunch winners are ineligible for one month from the time they first collected the prize. There are no ineligible candidates for this Wednesday's reward since recent winners have declined the prize on the grounds that they live in another country and can't make it for lunch on Thursday. There was no winner last week although several people were close.

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

Mendel's Garden #15

 
Visit The Daily Transcript for your complete list of summer reading, courtesy of Gregor Mendel Mendel's Garden #15 - Summer Reading Edition]. Of course you'll already know about what causes wrinkled peas because you've been reading Sandwalk. Don't let that put you off. There's plenty of other good stuff there.

Take the Carnegie Mellon University Survey on Ethical Standards

 
This is a survey on ethics developed by workers at Carnegie Mellon University for readers of the New York Times [Survey on Ethical Standards]. We can take the survey thanks to John Tierney and his blog TierneyLab: Putting Ideas in Science to the Test [Test Your Ethics (or Lack Thereof)].

The nice thing about this survey is that you can instantly see how you answered the questions relative to everyone else who took the survey. I was very pleasantly surprised at some of the responses. If you take the survey, make sure you do it alone and in a private place. You must answer all questions honestly and you may not want friends or relatives to know your answers. Try it, and then see how everyone else answered the questions.

I've been trying to stimulate some discussion about ethics without much success [Ethical Issues in Biochemistry]. There's a growing tendency in science education to include classes on ethics but nobody seems to be able to define ethics in a way that makes sense to me. What, exactly, is an ethical issue? [see, Ethics on Wikipedia] Take the survey to see if your sense of "ethics" agrees with others.

The other problem is how do you teach ethics to undergraduate science students? What are the basic principles of ethical reasoning? Is ethical relativism a valid philosophy or are there some "rules" that every undergraduate should memorize? [see, Moral Relativism on Wikipedia] I've encountered scientists who claim that we need to teach students that ethical relativism is a failed philosophy and there really is a "right" and a "wrong."

Here's a question that's not on the survey. Does whether or not you would have your genome sequenced [Sequencing Jim Watson] count as an ethical question? I don't think so. It's a question about personal preferences and the answer depends very much on how you feel personally about issues such as privacy. This isn't "ethics" as far as I'm concerned.

Sequencing Jim Watson

 
Jim Watson has just become the first person to have his complete genome sequenced. Craig Venter's genome sequence is not far behind.

Watson's genome was sequenced at the Baylor College of Medicine's sequencing center in collaboration with 454 Life Sciences, a private company that developed some new sequencing techniques. Apparently, the sequence was completed in two months at a cost of $1,000,000. Watson received the results on two DVDs. He promises to deposit it in the public database except for the sequence of his apolipoprotein E gene. He does not want to know which allele he carries because some of them are associated with Alzeimer's disease.

Here's the question for the day. Would you want to know the sequence of your genome if all you had to do was supply a small blood sample to get it? What are the implications? Do your children have a say if you intend to release your genome sequence into the public domain.

I can tell you that I would not do it. Perhaps the older I get the more I'm inclined not to care which alleles I carry but I would always be concerned about what effect it might have on my children—although that may be an unrealistic concern since they seem to have gotten all their good genes from me!

Watson is 79 years old and has two grown children.

[Genome of DNA discoverer is deciphered]
[Nobel Laureate James Watson Receives Personal Genome]
[Project Jim, celebrity sequencing, and the divine right of geneticists]

Ethical Issues in Biochemistry

 
The American Society for Biochemistry and Molecular Biology (ASBMB) has established guidelines for undergraduate programs in biochemistry and molecular biology (Voet et al., 2003). The society has now received a grant from the Teagle Foundation to access the relationship between the goals of a major in biochemistry and those of a liberal education (Wolfson, 2007).

Here's a list of skills that biochemistry and molecular biology undergraduates should obtain by the time they graduate.

• Understanding of the fundamentals of chemistry and biology and the key principles of biochemistry and molecular biology.
• Awareness of the major issues at the forefront of the discipline.
• Ability to assess primary papers critically.
• Good quantitative skills such as the ability to accurately and reproducibly prepare reagents for experiments.
• Ability to dissect a problem into its key features.
• Ability to design experiments and understand the limitations of what the experimental approach can and cannot tell you.
• Ability to interpret experimental data and identify consistent and inconsistent components.
• Ability to design follow-up experiments.
• Ability to work safely and effectively in a laboratory.
• Awareness of the available resources and how to use them.
• Ability to use computers as information and research tools.
• Ability to collaborate with other researchers.
• Ability to use oral, written, and visual presentations to present their work to both a science-literate and a science-non-literate audience.
• Ability to think in an integrated manner and look at problems from different perspectives.
• Awareness of the ethical issues in the molecular life sciences.

This is your chance to comment on this list. I'll make sure your comments are passed along to Professor Wolfson so she can incorporate them into the study. I don't necessarily support everything on the list.

I'd like to start with the last one "Awareness of the ethical issues in the molecular life sciences." How important is this in a biochemistry/molecular biology undergraduate program? Who do you think should teach it? What kind of issues should we cover? Should there be some instruction on ethics philosophy?

Wolfson, A.J. (2007) Biochemistry and Undergraduate Liberal Education. Biochem. Mol. Biol. Educ. 35: 167-168.

Voet, J.G., Bell, E., Boyer, R., Boyle, J., O'Leary, M. and Zimmerman, J.K. (2003) Recommended curriculum for a program in biochemistry and molecular biology. Biochem. Mol. Biol. Educ. 31: 161-162.

Biochemisty and Molecular Biology Education

 
Biochemistry and Molecular Biology Education (BAMBED) is a journal published by Wiley on behalf of the International Union of Biochemistry and Molecular Biology. The journal is linked to the American Society for Biochemistry and Molecular Biology.

BAMBED publishes papers about education and education issues. The Editors-in-Chief are Donald Voet and Judith Voet. I happen to be on the editorial board and that's why I'm blogging about this journal. More people need to know about it.

Here are some of the articles in this month's issue to give you an idea of the sorts of things that educators are concerned about.

Adele J. Wolfson Biochemistry and undergraduate liberal education (p 167-168)

Vicky Minderhout, Jennifer Loertscher Lecture-free biochemistry: A Process Oriented Guided Inquiry Approach (p 172-180)

Brian J. Rybarczyk, Antonio T. Baines, Mitch McVey, Joseph T. Thompson, Heather Wilkins A case-based approach increases student learning outcomes and comprehension of cellular respiration concepts (p 181-186)

James K. Zimmerman Proper reporting of results (p 198)

Lauren Walsh, Elizabeth Shaker, Elizabeth A. De Stasio Using restriction mapping to teach basic skills in the molecular biology lab (p 199-205)

Harold B. White Commentary: What do students say about problem-based learning? (p 211-212)

Matthew Nisbet and Chris Mooney Video on Framing Science

 
Chris Mooney has challenged me to respond to a video (see below the fold) of a talk that he and Matt Nisbet gave on framing. Over on his blog, Chris criticizes PZ Myers who couldn't sit through the whole hour [PZ, You Can Do Better Than This....]. Neither could I, but at least I got to the 50 minute mark which was more than twice as far as PZ.

Chris and Matt believe their talk is much more detailed than their short paper in Science or any of their other articles. They think that with this longer version they will have answered the objections raised by a number of scientists. This is quite in line with the position they have taken over the past few months. Their main defense has been to proclaim that we just don't understand framing and that's why we don't appreciate their opinions. That defense has the tremendous advantage (for them) of avoiding having to deal with any of the objections that have been raised. It's probably a good example of framing on their part.

Here's how Chris Mooney puts it today in addressing PZ,

So, c'mon, PZ. You've ripped the "framing science" concept based upon brief essay-style presentations of it. Now we've gone all out and produced a much more thorough presentation--one that covers, in depth, the concept of framing; evolution; stem cell research; global warming; hurricanes; and then closes by presenting policy solutions--and you won't engage.

I'm disappointed by this, but I also know you're a thoughtful guy. So I'll happily give you the benefit of the doubt here and ask you again to engage with our arguments as we have now chosen--comprehensively--to present them.

Notice how this works. PZ, and others, have already explained why they have a problem with framing science. Matt and Chris didn't listen. Now they want everyone to explain it to them once again just because they've produced an extended version of their opinions.

Well, Chris, I hate to break it to you, but there's nothing new in the video. It's just the same old fluffy rhetoric that we've seen before. I watched for 50 minutes and you never once addressed the main objections that you heard from many scientists. The ball was clearly in your court and you dropped it. You had one hour to engage our arguments and show that you were listening but you didn't do that. Why?

Have you forgotten the problem? You claim to be talking about "science education" and "science communication" but you are actually talking about politics. Scientists do not deliberately "frame" science. They tell it like it is. On the other hand, if you are trying to score political points or advocate policy change then you can use any trick in the book if you think you can get away with it. The fact that some of these political battles might be related to science is interesting but almost irrelevant. You could make exactly the same case for framing if you were engaging in political battles over the constitution, economic policy, or the war in Iraq.

As far as I'm concerned you and Matt are doing serious harm to science. You are strongly implying that it's okay to spin the science in order to achieve a political objective. Not only are you implying that, you are criticizing scientists for not learning how to spin frame science properly. One thing you could easily do to fix this problem would be to stop talking about framing science communication and substitute talk about framing political debates concerning scientific topics.

The other problem with your talk is that you continue to criticize Richard Dawkins for raising problems about religion and promoting atheism. Fine, that's your opinion and you're stuck with it. But you know damn well that many of us think you are way off base on that one. You've heard this point of view many times but you never addressed it in your talk. Why couldn't you have discussed the other point of view; the one that says arguments about religion are not the same as arguments about science? I would have had much more respect for you if you had showed me that you were listening to your opponents. At the very least you could have mentioned the difference between long-term goals and short-term goals and explained why you think Dawkins should sacrifice his long-term goal in favor of your short-term goal.

Finally, there's a problem that only concerns me and other non-Americans. Everything you say is "framed" as an American problem. You're talking about the American public, American politics, and American journalism. Your solutions only apply in that context. Your chosen frame does not resonate with me. Maybe you don't care about scientists in Canada or Europe (I'm sure you don't) but when you're broadcasting to the entire world don't be surprised if some of us don't care about you either.

You do realize, don't you, that Richard Dawkins lives in the United Kingdom? Do you understand that in terms of political debates, different spins will be adopted by people in different countries? It's just not possible for you and Matt to impose your American values on scientists in Japan, India, and Europe. But since we now live in a global village these foreigners are going to be heard in your country as well. How do you propose to maintain discipline under those circumstances? You are tying to herd cats, this strikes me as more than a little naïve.

For the benefit of readers, here's the video. The part about how to frame a political debate on evolution and creation can be found about 22 minutes into the talk at the 48 minute marker. (The timer starts at 70 minutes and counts down.)