Small Science Is Good Science?

 
I've been thinking a lot lately about what's wrong with science in the 21st century. Part of the problem is sloppy thinking that becomes apparent when you realize how many widely believed models are inconsistent with what we know about biology. I assume that similar problems occur in other disciplines.

One wonders if the proliferation of papers with huge numbers of authors is part of the problem. Maybe this fad of "multidisciplinary" science is part of the problem and not part of the solution? Is it possible to be an expert in two or more different disciplines?

I've seen plenty of example of biochemists and molecular biologists who publish papers about evolution without knowing much about evolution. Is this an isolated example?

Speaking of "big science," I was reminded of a paper published by Bruce Alberts back in 1985 in Cell. The title was "Limits to growth: In biology, small science is good science" (Alberts 1985).

These days, many people grow up believing that bigger is better. Giant factories that produce Wonder Bread have replaced thousands of corner bakeries, driven by the increased efficiency of scale. There is an unfortunate tendency to extend this view to the biological research community, and I have on occasion heard a major symposium speaker introduced in glowing terms as the coauthor of more than fifty papers per year. While I can admire the energy and management skills required to maintain a very large laboratory, the best biology is rarely done in this way. With a few notable exceptions, the biochemists and molecular biologists I most respect run relatively small laboratories and publish when they have something important to report. As I shall argue here, doing good science is very different from producing bread, and there are compelling reasons why large laboratories are in general less efficient and less interesting than smaller ones. To reflect this fact, I believe that changes in funding patterns and expectations would be useful in the biological sciences.

Some "big science" is good. The sequencing of the human genome, and other genomes, for example, was a big science project that benefited the entire biological community. But I'm not sure that significant advances in our understanding of how life works come from big labs. Does anyone have examples? What are the most significant conceptual advances to come out of big labs?

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Alberts, B.M. (1985) Limits to growth: In biology, small science is good science. Cell 41:337-338. [PubMed] [doi:10.1016/S0092-8674(85)80001-5]

Ignore, Reject, Answer? What to Do about Student Email Messages

 
Some of my colleagues are running courses where they ask students to write essays on science subjects. Part of the assignment is to contact a Professor in the discipline and get them to help with the scientific content of the essay. The idea is for the students to make sure they have their facts correct. A side benefit is that it gets the students in touch with active researchers.

Some of us object to this procedure on the grounds that if it became widespread there would be hundreds of students looking for Professors to help them on their assignment. Most Professors have other priorities, like teaching their own classes. To some extent, our colleagues who engage in this practice are downloading their teaching responsibilities onto others.

From 1992-2000 I ran a molecular biology course where the students had to write a major essay. They were told to do the research themselves but the instructors would be available if they need help with the interpretation of some papers. If necessary, we would put them in touch with an expert but only after the student had done enough work to ask intelligent questions on difficult material.

Here's an email message that was sent to my Sandwalk address last night. How should I respond? I don't feel comfortable ignoring the message. I will feel awkward if I refuse to help. I don't had time to answer the question—it's complicated and, besides, it's not my area of expertise.

Dear Professor Moran,

As part of a University assignment, I have been asked to email a group of experts to request their professional opinion on a particular question.

I have come to understand that a child with Dyspraxia should supplement their diet with a high dose of essential fatty acids. However, as non-Dyspraxic people age it is advised that they also should supplement their diet with these oils to combat age-related memory loss. Does this mean that people with Dyspraxia should augment their intake yet again when they age? If so, could this have an adverse effect on their health?

As your organisation came up in an internet search as being reputable, your answer to this question would be much appreciated.

I would like to thank you for taking the time to read this email and I hope to hear from you soon.

Yours sincerely,

This makes me angry. No matter what I do, I'm going to be disappointing a student who might really benefit from a reply. In my opinion the student's Professor is at fault for assigning such a task to the students.

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Barack Obama Will Save Religion in America

 
Frank Scaheffer writes in The Huffington Post [President Obama: Bad News For the New Atheists and Other Fundamentalists].

The Obama presidency is great news for almost everyone. It's bad news for some odd ideological bedfellows: the Religious Right and the so-called New Atheists.

Into the all or nothing culture wars, and the all or nothing wars between the so-called New Atheists and religion the election of President elect Obama reintroduces nuance. President elect Obama's ability to believe in Jesus, yet question, is going to rescue American religion in general and Christianity in particular, from the extremes.

There is no way to understand President elect Obama's victory as anything less than the start of not just a monumental political change but a spiritual revolution as well.

Who knew? I bet all atheists and agnostics are feeling pretty stupid right now knowing that they've been tricked by the slick-talking Obama.

And what is the "nuanced" spiritual revolution going to look like?

To the New Atheists who think that with the resounding defeat of the Religious Right, we are entering a secular age, think again. Obama will block your path. He'll do it for the same reason he'll make the Religious Right's paranoid fantasies about him soon seem shamefully ridiculous. That's because President elect Obama is that rarest of all rare people: a thoughtful, compassionate and likable statesman who also is a thoughtful, compassionate and likable religious believer.

Sounds like trouble. President Obama is going to block the path to a secular society. Gosh. I knew that American Presidents were leaders of the free world and the most powerful men (no women so far) on the planet but even I had no idea they were that powerful.

President-elect Obama brings another perspective to faith . It goes something like this:

How do cultures define themselves if not through ritual? In the "big moments" of life; birth, marriage, sickness, death "who" -- in the inimitable words of Ghost Busters -- "you gonna call?" As President elect Obama has said, and I paraphrase: Strip the human race of our spiritual language and what do we tell each other about hope?

As President elect Obama has pointed out, a world of all math but no poetry is not fit for human habitation. If everything feels flat and dull, stripped of mystery and meaning who will bother to do the science? Why bother, if all we're doing is serving those selfish genes for another round of meaningless propagation?

So does this faith always make "sense?" No. Because our perspective is from the inside, something like paint contemplating the painting of which it's a part. We're all in the same boat, all stuck on the same "canvas."

Ohmygod. Frank Shaeffer and Barack Obama have discovered the atheist dirty little secret. All of us atheists are flat and dull—we can't be born, get married, or die without calling upon God to help us.

Does anyone actually believe this stuff?

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[Hat Tip: RichardDawkins.net]

Evolution by Gene Duplication

Chymotrypsin (Monday's Molecule #95), trypsin, and elastase are enzymes that digest proteins in the stomach and intestine. All three enzymes have a similar mechanism of hydrolysis characterized by the presence of a catalytic triad of amino acid side chains consisting of aspartate, histidine, and serine residues. The serine side chain is directly involved in catalyzing the cleavage of proteins and that's why these enzymes are called serine proteases.

The three enzymes differ in specificity. Chymotrypsin cleaves foreign proteins primarily at tyrosine (Tyr) resides, trypsin is specific for cleavage at arginine (Arg) or lysine (Lys) resideus, and elastin cleaves at alanine (Ala) residues.

The genes for the three enzymes are homologous and the structures of the three enzymes are very similar as shown below (left: chymotrypsin [PDB 5CHA], middle: trypsin [PDB 1TLD], right: elastase [PDB 3EST]).


The active sites of the enzymes are slightly different so that specificity depends on which amino acid side chains of the substrate protein fit into the binding pocket.


It's reasonable to suppose that the primitive enzyme could bind weakly to many different substrates and cleave many different kinds of proteins inefficiently. An ancient gene duplication allowed one copy of the gene to evolve toward a much more active enzyme that cleaved only at certain residues. A second gene duplication gave rise to a third enzyme that cleaved at another residue. Finally the remaining gene evolved into a very active enzyme that cut at a third position.

The end result was a set of three enzymes that could cut up any protein into small peptides that can be taken up by the cells lining the intestine. The original non-specific enzyme was slower and less efficient.

This is an example of evolution by gene duplication and the important point is that the ancestral gene probably encoded a non-specific enzyme that could carry out several different reactions with different substrates. It's not a question of the duplicated copy evolving an entirely new specificity. Instead, the duplicated gene usually "perfects" an already existing minor activity by becoming more specific. Meanwhile, the other copy can also be selected for enhanced specificity for another substrate.

This model also explains the evolution of lactate dehydrogenase and malate dehydrogenase (Evolution and Variation in Folded Proteins) and the pyruvate dehydrogenase family (Pyruvate Dehydrogenase Evolution).

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Nobel Laureate: John Howard Northrop

 

The Nobel Prize in Chemistry 1946.

"for their preparation of enzymes and virus proteins in a pure form"



John Howard Northrop (1891 - 1987) was a renowned protein chemist who developed techniques for purifying and crystallizing enzymes.

He shared the prize with James Sumner, who first showed that proteins could be crystallized and with Wendell Stanley who crystallized tobacco mosaic virus.

Most biographers note that Northrop was very interested in genealogy and was proud to point out that he was a direct descendant of Joseph Northrop who settled in New Milford Connecticut in 1636 (John H. Northrop). I don't know if any other Nobel Laureates can trace their North American ancestors back 400 years.

The significanc of Northrops work is summarized in this excerpt from the presentation speech on the Nobel Prize website.

THEME:
Nobel Laureates

Doctor John Northrop. You and your collaborators have developed the crystallization of enzymes and other active proteins into an art, of which you are the masters. The conditions for successful work in this field were explored by you, and in the course of that work interesting relationships between enzymes and related proteins were discovered, which may ultimately afford a clue to a fuller understanding of the mode of action of these substances.

We now know that trypsin, pepsin, and chymotrypsin are similar proteases that cleave other proteins. We also know that the active enzymes are derived from inactive precursors called zymogens. The zymogens (pepsinogen, trypsinogen, and chymtrypsinogen) are cleaved to remove part of the protein making the remainder into an acive enzyme. It's interesting to see how John H. Northrop described this discovery in his acceptance speech.

Formation of enzymes from their precursors. Pepsin, trypsin, and chymotrypsin are derived from inactive precursors. These precursors were isolated and crystallized and the formation of the active enzyme studied. The formation of pepsin from pepsinogen and trypsin from trypsinogen are autocatalytic reactions. These enzymes may therefore be "propagated", just as are bacteria. The formation of trypsin from trypsinogen may also be catalyzed by enterokinase, an enzyme of the digestive tract, or by an enzyme produced by a mold (Penicillium.) The formation of chymotrypsin from chymotrypsinogen is catalyzed only by trypsin, so far as is known. In all these reactions the increase in enzymatic activity is accompanied quantitatively by the appearance of the new enzyme protein which is quite different in all its properties from the original precursor. It seems to me that these results are perhaps the most convincing evidence that the enzymatic activity is actually a property of the protein molecule.

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What Does Change Look Like?

 
I'm glad Barrack Obama won the election. He is much less conservative than John McCain and much more likely to do good things for America.

Change is in the air, everybody is talking about a new direction for America under Barack Obama. What kind of changes can we expect? Here's a sample from last night's vote on several propositions [CNN.com].

This measure would amend the state constitution so that only a union between one man and one woman would be valid or recognized as a marriage in the state. A similar measure was on the ballot in 2006 but failed.

According to the exit poll [Arizona Prop.102], 67% of Protestants voted to ban gay marriage as did 51% of Catholics. About 13% of voters said they had no religion and 69% of them voted against Proposition 102.

This measure would prohibit unmarried "sexual partner[s]" from adopting children or from serving as foster parents. The measure specifies that the prohibition applies to both opposite-sex as well as same-sex couples.

According to the exit poll [Arkansas Initiative 1], the voters are evenly split between Democrats, Republicans, and Independents. Democrats voted against the initiative (52%) but the other two groups voted in favor of the ban. A majority of college graduates (52%) and those with postgraduate education (54%) voted in favor of the ban on adoptions.

This measure would amend the state constitution to specify that only marriages between one man and one woman would be recognized as valid in the state. If passed, the measure would trump a May 2008 ruling by the California Supreme Court that legalized same-sex marriage.

According to the exit poll [California Proposition 8], a majority of whites (53%) and Asians (53%) voted against Proposition 8 while a majority of African-Americans (70%) and Latinos (51%) voted in favor of the ban. Democrats (65%) and Independents (56%) were against the ban but 81% of Republicans voted in favor of the ban on gay marriage.

This measure would amend the state constitution to define the term "person" to include "any human being from the moment of fertilization." This definition would be applied to all aspects of the state constitution, including the provisions that ensure that no person has his or her life, liberty, or property taken away without due process of law. Thus, the measure would essentially have the effect of banning abortion.

According to the exit poll [Colorado Amendment 48], this amendment should have been approved by a substantial majority.

This measure would amend the state constitution to define marriage as a union between one man and one woman. In order to amend the Florida constitution, 60 percent of voters must vote in favor of the amendment.

According to the exit poll [Florida Amendment 2], 71% of Protestants and 66% of Catholics voted in favor of the amendment to ban gay marriage. A majority of Whites (60%), African-Americans (71%), and Latinos (64%) voted for the ban.

This measure would prohibit all abortions in the state except in cases where mother's life or health is at risk or in cases of rape or incest for pregnancies of less than 20 weeks. A similar measure that did not include exceptions for rape or the health of the mother was on the ballot in 2006, but was rejected by voters 44 to 56 percent.

According to the exit poll [South Dakota Initiative 11], only evangelical born-again Christians and conservative Republicans supported the initiative. A majority of all other groups voted against it.

This measure would allow terminally ill, competent, adult residents of the state to request and self-administer lethal medication prescribed by a physician. The person requesting to end his or her life must be medically predicted to have six months or less to live.

According to the exit poll [Washington Initiative 1000], this initiative was supported by liberals (81%) and moderates (63%) and opposed by conservatives (66%). There are more liberals (29% of the voters) than in most states. Republicans (63%) voted against the initiative while Democrats (75%) and Independents (59%) voted for it.

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Asses on Panda's Thumb

 
It's probably not a coincidence that Panda's Thumb published a photo of a pair of asses today. See them at Equus asinus.

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Ken Ham and Jesus Visit Toronto

 
I forgot to mention that "Ken Ham" and "Jesus" were at P.Zed's talk on Friday night. Theo Bromine has photographic proof on the blog Thinking for Free [PZed Myers comes to TO].

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Anonymous Students and Their Grades

 
In Ontario we have to conform to the Freedom of Information and Protection of Privacy Act (FIPPA). What this means is that we cannot publish student names and grades. The University of Toronto guidelines are very clear on this matter [Q and A for Instructors under FIPPA]. We shouldn't even be publishing student numbers with grades.

I just checked with one of my colleagues to find out what the policy was when she graduated in 1949. She showed me the booklet put out by the university in 1949. Her name and grades were listed there. Furthermore, the names and rankings of all student were published in the newspaper.

I asked one of my students who attended high school in Europe. Her name and grades were published in the newspaper. I'm told that this practice continues in some European countries. Another of my colleague learned his medical school grades by reading the Glasgow newspaper in the early 1950s.

Assuming that FIPPA does not apply to the publication of university grades (an invalid assumption), should we publish student names and grades? What are the non-legal arguments for and against this policy?

I like the idea of publishing student's names and grades because it helps make them take responsibility for their activities at university. Very few people agree with me. They all think that a student has a right to privacy. Most of these people don't have a problem with publishing Professor's salaries and course evaluation results because the public has a right to know this information.

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[Photo Description: This is a photograph of the wall on the ground floor of my building. You can see the names and photographs of every student in the medical school graduating class.]

Today Is a Very Important Day

 
It's Sandwalk's second birthday. It was two years ago today that I posted the first message on Sandwalk [Welcome to my Sandwalk].

I started Sandwalk when PZ Myers convinced me that blogging wasn't just a fad. There was a real opportunity to discuss science, and other things, in the blogosphere. Since Nov. 4, 2006 I have published 2,253 postings—some of them have been quite popular and a few of them have been quite good (IMHO).

Sandwalk has grown into a moderate-sized blog with a number of regular readers. I'm particularly excited about the people who comment. They teach me a lot. I'm impressed by the quality of the discussion that goes on in the comments section of Sandwalk postings. This was something that I was hoping for when I started this blog.

A big thank-you to everyone who reads and comments. You've made it all worthwhile.

Here are the latest numbers.

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Please Help Me with My Homework

 
I get email messages like this on a regular basis ...

Hi Mr. Moran, My name is XXX and I am a student at YYY and I would like your help in my English Research Paper.

My task is to write a research paper about something that matters in America today, and I believe the situation surrounding the ID movement is something that really matters. I was wondering where would I be able to get the best information pretaining to the anti-ID, and I thought, why not get it from talk origins?

So Mr. Moran, I would greatly appreciate you helping me in my research paper by outlining and detailing why ID should not be allowed in classrooms or directing me to some one who can.

Thank you for your time, it is greatly appreciated.

I wonder how his teachers define "research"? Back in the olden days we used to read books and articles in order to prepare to write a research paper. Some of you may be familiar with books.

Why have things changed? Why do today's students think they can ask someone else to do all the work for them? Has it got something to do with entitlement, or is it more closely related to intelligence?

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A Canadian Perspective on Tomorrow's Victory

 
Read Is It Wednesday Yet? by psa on Canadian Cynic.

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Goodbye PZ Myers

 
There were about eighteen people at the farewell dinner for PZed and Skatje on Saturday night. We really enjoyed his visit.

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In Search of Spandrels

While looking for postings on the Maynard Smith fumble (Maynard Smith on Stephen Jay Gould) I came across this one, posted on talk.origins on Aug. 20, 1998. I had forgotten about my second search for the Spandrels paper.

This is a paper that every student of evolution should read. I can't think of a paper by Maynard Smith that falls into that category.

I recently found myself in the catacombs of the library archive far away from the stress of students writing their summer exams. It was very peaceful. It was also a place where creationists never go.

I must confess that my primary motivation for being there was work avoidance - I hate marking exams - but there was another reason as well. My secondary mission was to retrieve a pristine copy of the "Spandrels" paper so I could hand it out to my students. (My own copy had some embarassing margin notes that weren't fit for young eyes.)

There were many bound volumes of the Proceedings of the Royal Society of London (Series B). Did you know that this journal goes back over one hundred years? (That's even before I was born.) Did you know that you have to look in the stacks under "R", for "Royal", and not "P", for "Proceedings"? Did you ever wonder why librarians do that? My own theory is that they really don't want us to take out their books so they make it as difficult as possible to find something.

I was looking for volume 205 (1979). As usual, it was on the bottom shelf; way down at the level of my shoes. I had to get down on one knee and that's a lot of work. But at least volume 205 wasn't missing. With trembling hands I flipped the pages looking for the sacred text. Would it be there or would the pages have been cut out with a razor blade? Chances were good - pre-med students don't read about evolution.

Yes! There it was: "The Spandrels of San Marco and the Panglossian paradigm: a critique of the adaptionist programme" by S.J. Gould and R.C. Lewontin. They even spelled "programme" correctly! Off I went to the photocopy machine. Off I went to buy a new photocopy card. Back I came to the photocopy machine. Let's see now ... how much magnification will I need to fill an 8x11 page so I don't have to close the damn lid every time I copy a page? 125% should do it. Wrrrrr .... flash .... swish .... splat.

Maybe 120% would work ...

At last, page 598 was perfect. (Anyone want extra copies of the references from this paper?) I worked my way forward to page 581 fending off the librarian who insisted that I had to close the lid or I would ruin the photocopier - and my eyes (I'm not sure which was more important to her).

I was lucky there were three or four students to distract her. Behind my back I heard some mumblings about "eccentric" and "stubborn" but unfortunately I couldn't see exactly what was going on.

Hope I didn't miss anything interesting.

I knew that Gould had presented the paper at a meeting in London in December, 1978. Lewontin wasn't there because you have to fly to get to England and Lewontin thinks that if humans were made to fly then we would have evolved wings. So, who else was at the meeting? Did they publish papers in the same issue of the journal? Let's see ...

My thoughts were interrupted by some shouting in the line behind me. Guess I'd better get away from the photocopier. The machine seems to be making people angry.

Off I went to find a desk to sit down at. Found one. Off I went to the photocopier to retrieve my photocopy card. Back I came to the desk.

Someone was there. Found another desk. It had a banana peel on it.

Cool. All the papers are here. The meeting was called "The Evolution of Adaptation by Natural Selection" and it was organized by John Maynard Smith and R. Holliday. Orgel has a paper on evolution in vitro. The Charlesworths write about sex in plants. There's a paper by Maynard Smith on game theory and the evolution of behaviour. George Williams was present (more about him later). And guess who else? - Richard Dawkins!

The Dawkins' paper is titled "Arms races between and within species" (R. Dawkins and J.R. Krebs). It goes on and on about the adaptive significance of arms races and the optimization of animals. I bet the Gould talk was not well received by Dawkins in 1978. :-)

The Williams paper is very interesting ("The question of adaptive sex ratio in outcrossed vertebrates"). He examines two popular theories of the adaptive control of sex ratio (why there are 50% males and 50% females). After looking at the detailed models and the available data he concludes,

Evidence from vertebrates is unfavourable to either theory and supports, instead, a non-adaptive model, the purely random (Mendelian) determination of sex.

Good for him. I wish I could have been at the meeting. Maybe there was a discussion. Flipping to the back of the book I find a petulant summary of the meeting written by A.J. Cain. You can tell he's really annoyed at something that went on in the meeting,

Ever since natural selection appeared on the scene, there have been those who voiced an a priori and dogmatic dislike of it. One classic example is George Bernard Shaw ... I suspect from my own work that natural selection may have been very much more important than anyone has realized up to now. If so, can these emotional and other rejections of it, or, more generally, the tendency of the human race to take a non-objective view of evolution and kindred topics, be explained by natural selection?

There is a possible evolutionary explanation, as yet untested, and no other scientific one that I know of.

Whew! The discussion must have been exciting. Let's see, it should be right at the end. Ah, here it is,

[It has not been possible to include the general discussion in this publication.]

Damn.

Gotta go, the banana peel is making me ill - it looks like it's been here since the day before yesterday. Is that a fruit fly? Off I go.

Back again. (Forgot my pen.) See ya.

Larry Moran

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Maynard Smith on Stephen Jay Gould

 
Someone resurrected an old quotation by John Maynard Smith in a comment on Good Science Writers: Stephen Jay Gould.

Here's how I replied on March 26m 2002 on the newsgroup talk.origins. It was at least the tenth time I had addressed this silly comment by Maynard Smith.

This is not a universally held view. LAM is no doubt familiar with John Maynard Smith's famous remarks about Gould:

"Gould occupies a rather curious position, particularly on his side of the Atlantic. Because of the excellence of his essays, he has come to be seen by non-biologists as the preeminent evolutionary theorist. In contrast, the evolutionary biologists with whom I have discussed his work tend to see him as a man whose ideas are so confused as to be hardly worth bothering with, but as one who should not be publicly criticized because he is at least on our side against the creationists. All this would not matter, were it not that he is giving non-biologists a largely false picture of the state of evolutionary theory."

As an aside, isn't that beautifully written?

Genes, Memes, & Minds JOHN MAYNARD SMITH November 30, 1995, New York Review of Books (the essay was a review of "Darwin's Dangerous Idea: Evolution and the Meanings of Life" by Daniel C. Dennett).

Unfortuantely JMS drops the issue at that point and has, so far as I know, never taken it up again.

He probably thought he had better things to do.

Either that, or he was very embarrassed by his inappropriate remarks and hopes that most people will forget about them. I wonder what Maynard Smith thinks of all those idiots in the AAAS who elected Gould President of the largest scientific society in the world? What in the world could Maynard Smith have been thinking when he invited Gould to Oxford to give a prestigious series of lectures on evolutionary theory?

For those interested in the background to all this, I can do little better than suggest reading Segerstråle's book "Defenders of the Faith", where she discusses the history of all this, the arguments between people like Lewontin, E.O. Wilson, Gould, Dawkins, etc. JMS comes out of it well - he was sat in the middle trying to makes sense of both sides.

Do you really think that Maynard Smith's remarks quoted above represent someone who's trying to make sense of Gould's side? Maynard Smith is firmly on the side of Dawkins in this debate. Like Dawkins, he has never given any indication that he understands the main issues. When Maynard Smith says that Gould is presenting a "largely false picture of the state of evolutionary theory" you should appreciate that what Maynard Smith is really saying is that Gould presents a picture that Maynard Smith disagrees with. Only Maynard Smith and his friends know about the *true* picture of evolutionary theory.

Gould is not nearly as arrogant as his opponents.

I've also noted on several occasions that just because Maynard Smith can't understand the complications of modern evolutionary theory doesn't mean that his simplistic version is correct.

In addition I've pointed out that Gould is often referenced in evolution textbooks for his contributions to pluralism, heterochrony, punctuated equilibria, progression, disparity, the tape of life, species selection, and spandrels. You have to look hard to find references to Maynard Smith.

To me that suggests that Maynard Smith is a man hardly worth bothering with.

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[Image Credit: Photograph of Stephen Jay Gould by Kathy Chapman from Lara Shirvinski at the Art Science Research Laboratory, New York (Wikipedia)]