Thursday, May 31, 2007

The Bora Zivkovic Rules of Science Communication

Bora Zivkovic ("Coturnix") has posted on the Bloom and Weisberg article and on the issue of Do You Trust Scientists?. Naturally Bora has some ideas on this and (surprise) they involve framing.

Since he specifically mentions me [More than just Resistance to Science], I thought I might as well respond.
That is why, Larry's protestations notwithstanding, we desparately need the advice of people whose job is to study communication. We have no idea how to talk to people with hierarchical worldviews and the phatic use of language and we better listen and be prepared to learn.
Name some names. Show me these mythical communications experts who are doing such a good job of communicating science to the general public. Where in the world did you come up with this ridiculous idea that scientists have no idea how to talk to the average person?
All the examples that Larry points out - teaching science majors in college, talking to other scientists, writing popular science books, writing science blogs - are aimed at the audience that already is rational and uses language to get and impart information. It just does not work in persuasion and education of the irrational folk. The way to frame the science is completely different.
Bull. The way to talk to irrational people is not to get down in the gutter with them and behave irrationally. How in the world do you expect people to trust you, Bora, if you abandon the core principles of science?
So, what do we do?

Phase 1 is to attain authority (that is why science reporters will not do for this - it has to be scientists themselves). In doing so, the scientists have to do more than just assert equal authority as the priest, sheriff and mayor. For a hierarchically-minded audience, the only way to rise in authority is for someone else's authority to diminish at the same time ("How can the UN tell MY President what to do?"). It is a ladder they think of and only one person or group can be at any single rung of it. Thus, scientists have to displace clergy, lawyers and politicians as sources of authority on scientific matters.
I agree with this. Scientists need to challenge religion since in the USA that's the dominant authority. The first step is to get their attention by making some noise. So far it's working.
How does one do this? When dealing with kids (and adults who have not yet made the change to a rational worldview), the only way is to appear to be 100% sure. This is not the audience that gets error-bars, confidence intervals, fine points of philosophy of science, and alternative hypotheses. You tell it how it is (even if inside you cringe, knowing that what you are saying is only 98% sure). You tell it with conviction. No need to lie. Just get out of the science-paper mindset. The studies mentioned in the Edge piece confirm this notion as well.
You do that and you've lost my respect. What do you get in return? You get the same kind of respect as politicians and everybody else who's prepared to sacrifice truth for spin. What you're advocating is not "framing," it's surrender.

"Truth" is something like "pregnancy." Something is either true or it is not true. There's no such thing as 98% true. That's just a polite word for a lie. "Spin" is another polite word for a lie and so, it appears, is "framing."
Phase 2 is to gain trust. As Sara Robinson explained in her series "Tunnels and Bridges" and "Cracks in the Wall" (both found in the sidebar here), this is a slow and gradual process. No looking down at people. Not calling them stupid or evil. Giving them a helping hand and encouragement. Perhaps promise an induction into a secret powerful society of scientists. Even if one makes small steps, reward them even if you do not like where they got in the process: smile when the individual moves form YEC to OEC, and again when he moves from OEC to IDC, and again when he moves from IDC to Theistic Evolution, and again when he moves from Theistic Evolution to a genocentric, hyperadaptationist form of naturalistic evolution and give them a damned PhD when they understand and accept the modern evolutionary theory.
Whatever. You do it your way and I'll do it my way. There's plenty of room for all kinds of personalities in this battle. For the time being I'm impressed with the Dawkins approach. People have been trying it your way for decades and look at what kind of success they've had in America.

For over a century, the creationists have been mocking, criticizing, and demeaning scientists from the pulpit, in books, on television and in newspapers. Not only do they call us stupid but evil as well. Guess what? That strategy has been working for them. It's time to fight back. Think of it in terms of attack adds if that makes you feel better. Except that our attack adds are truthful.
While phases 1 and 2 can, to some extent, be done simultaneously, Phase 3 can be attempted only once the person has already passed the first two phases. The Phase 3 is science education as we understand it. It can only be applied to the audience that is already rational and uses language for the exchange of information, not emotions. Actually understanding the world, not just taking your word for it (phases 1 and 2 are pretty much getting people to trust you on your word, not understanding any science yet) is something that we want them to achieve and traditional science education can do so. I am sure that Larry is really good at this phase, even though he refuses to acknowledge that the first two phases are necessary or even existent before a person can understand and accept what Larry is teaching.
Oh come on, Bora, I'm not nearly as stupid as you imagine. If the other phases are to establish trust and gain authority then I'm perfectly aware of the fact that these are important. Just because I think that your tactics will do the exact opposite does not mean that I reject the goal.

The problem is, you can't have it all. You can't expect to get "respect" by lying about science, or framing it in ways that are unacceptable to scientists, and then expect to turn around and teach good science. By the time you've spun your way to "respect" you lost the moral authority to teach.

Does Sandwalk Own Me?

 
25 %

My weblog owns 25 % of me.
Does your weblog own you?


[Hat Tip: Shalini]

Darwin and Design by Michael Ruse

 
In Darwin and Design Michael Ruse tackles a tough problem; namely "Does evolution have a purpose?" Unfortunately the correct answer is "no" but Ruse muddles, misdirects, and misunderstands so thoroughly that by the time you reach the end of the book you just want to throw it against the wall.

The main theme of the book is teleological thinking or the idea that things happen in order to achieve a goal. We are familiar with this way of thinking in religion. Ruse spends some time describing the history, culminating in the natural theology of William Paley.

Paley and others argued that the presence of design in nature demanded a God who was the designer. The teleological part of this argument is the recognition that designed species, especially humans, represent a clear goal that needs an explanation. Life has meaning and purpose, according to believers, and it is God who gave it to us.

A teleological argument, or argument from design, is an argument for the existence of God or a creator based on perceived evidence of order, purpose, design and/or direction in nature. The word "teleological" is derived from the Greek word telos, meaning end or purpose. Teleology is the supposition that there is purpose or directive principle in the works and processes of nature.
"Teleological Argument" Wikipedia
Charles Darwin explained how life could appear to be designed by invoking natural selection, thus removing God from the equation. Nevertheless, teleology remains an important part of science, according to Ruse, because nature is designed by natural selection. It is quite appropriate, he says, to argue from design (the eye for example) to cause (adaptation).
This then is the paradox to which Darwin and Design is directed. Darwin seems to have expelled design from biology, and yet we still go on using and seemingly needing this way of thinking. We still talk in terms appropriate to conscious intention, whether or not we believe in God. In biology we still use forward-looking language of a kind that would not be deemed appropriate in physics or chemistry. Why is this?
Ruse seems to be at his best when describing the history of philosophy—as long as that history pre-dates Charles Darwin. His book is worth reading if you want a good summary of the design argument up to 1859. From that point on things begin to fall apart because Ruse does not understand modern evolution and he does not understand the controversies over evolutionary theory that persist to this day. Consequently, all of his history from Darwin on is biased and wrong.

The essence of Ruse's argument is as follows. Life evolves by natural selection. This leads to species and characteristics that are well-adapted. These characteristics have the appearance of design because they are, in fact, designed by natural selection. Because we know that everything is an adaptation it's perfectly legitimate to look at a species or an organ and assume that it as been designed by natural selection. While this adaptationist program may seem teleological because it assumes a purpose, it is, in fact a very legitimate way to do biology because design is a fundamental part of biology.

There are times when one thinks that Michael Ruse must have slept through the last half of the twentieth century. Has he never heard of Gould & Lewontin and The spandrels of San Marco? Is he unaware of the controversy over the validity of the adaptationist program?

Yes and no. He's heard of the controversy but he just wasn't listening. Everyone else who has addressed this question recognizes that the Gould & Lewontin challenge is not going to go away. They attempt to deal with it—usually not very successfully.

To his credit, Ruse seems to have picked up on the rumors that something important was going on so he does mention the spandrels paper and the attack on the adaptationist program. It's right there on pages 234-239. Five pages on structural constraints as introduced by Gould & Lewontin in their famous 1979 paper. Structural constraints? Surely there's more to the argument than that? Yes, there is but Ruse can easily dismiss it,
The point is whether they [Gould & Lewontin] introduce a whole new dimension into the discussion, by showing that much in the organic world is fundamentally nonadaptive. Darwinians have failed to see this and still continue not to see it.
That's it. Ruse is blind to modern evolutionary theory and quite proud of it. According to Ruse everything is an adaptation and "Darwinism" and "evolution" are synonyms.

The rest of the five pages on Gould & Lewontin are no more enlightening. Lest you think I'm being too harsh on Ruse, I assure you I'm not. He really doesn't get it. There are two pages devoted to random genetic drift. Two pages! After acknowledging that drift can sometimes cause evolution he dismisses it out of hand with,
Over time, however, random drift would be expected to average out more smoothly than differences due to the ever-changing forces of selection. For this reason the hypothesis that most molecular difference is due to drift has not been well received. Time and time again, measurements have shown that molecular differences are not what we would expect were drift the sole or main cause of change. In fruit flies, we see how random drift was ruled out as a significant factor in changing levels of the Adh gene.(p. 201)
Having summarily dismissed all objections to the ubiquity of adaption, Ruse can defend the argument from design by invoking adaptation as the sole driving force of evolution. In a chapter on "Design as Metaphor" he outlines his version of the adaptationist program. It's not only appropriate to attribute design to living things but it's a very productive way of advancing scientific knowledge.
Organisms produced by natural selection, have adaptations, and these give the appearance of being designed. This is not a chance thing or a miracle. If organisms did not seem to be designed, they would not work and hence would not survive and reproduce. But organisms do work, they do seem to be designed, and hence the design metaphor, with all the values and forward-looking, causal perspective it entails, seems appropriate.(p. 276)
Critics of the adaptationist program—I am one—argue that it begs the question. When you see something in nature it is reasonable to assume that it arose by evolution. The question we want to answer is what kind of evolution gave rise to that particular characteristic?

Take the fact that some people can roll their tongue as a simple example. We know there is a genetic basis to tongue-rolling. Some people have the allele that allows it, and some don't. We want to know why tongue-rolling exists.

     Once you have the metaphor of design in play, then of course you can ask questions about borderline instances and extensions and so forth. The real question, though, is whether, in the first place, the metaphor itself is an appropriate one. The question is not whether metaphors should be used at all but whether the specific metaphor of design should be used to explain evolution.

     Darwinians argue strenuously that it must be used. Richard Dawkins speaks to precisely this issue, asking what job we expect an evolutionary theory to perform. ... Dawkins agrees with John Maynard Smith that the "main task of any theory of evolution is to explain adaptive complexity, i.e. to explain the same set of facts which Paley used as evidence of a Creator."

Michael Ruse p. 278
If you are a modern evolutionary biologist then you are aware of several possibilities. It could be just an accident that has no great significance at all. Maybe tongue-rollers and non-tongue-rollers have an equal chance of leaving offspring and the alleles will be fixed or eliminated by random genetic drift. Or maybe one of these groups has a selective advantage. Maybe tongue-rollers are more successful at having children and that's why the allele persists in the population. Eventually everyone will be a tongue-roller because natural selection is operating.

If you are a committed adaptationist then you begin by assuming that the ability to roll your tongue is designed. Your task is then to explain how this design arose and you have only one choice—evolution by natural selection. Thus, your choice of the design metaphor has blinded you to the possibility that tongue-rolling may not be an adaptation at all. This is a very restrictive research program because the question pre-supposes the answer. In other words, by imposing design and purpose on the natural world—albeit natural and not divine purpose—Ruse and his colleagues are avoiding the very question they should be asking; namely, "is this an adaptation?" This bias leads to fanciful just-so stories as the adaptationists struggle to come up with imaginary ways of explaining the design that they think they see in nature.

Does Ruse have an answer to this objection? Yes he does,
The critic might respond that one has here a circular situation: Darwinians make searching for adaptation central to their program, and then when they find the adaptations they so fervently seek, they use them as support for Darwinism. But a better term than "circularity" might be "self-reinforcement." Darwinism is a successful theory—our scientific examples show that—and at the moment (and for the foreseeable future, whatever the qualifications) it is the only game in town, on its own merits. Fruit flies, dunnocks, dinosaurs, fig wasps—this is a theory on a roll. It has earned the right to set the agenda. (p. 280)
As far as I'm concerned this is dead wrong. Darwinism is not the only game in town and we've known that for almost fifty years. At the very least you have to consider fixation of alleles by random genetic drift. If this is how a character actually evolved then there is no design. The metaphor is inappropriate. The program is useless. (There are other non-Darwinian processes.)

The entire thrust of Ruse's argument for design and purpose in evolution is absolutely dependent on one critical assumption: that natural selection is the only significant mechanism of evolution. If this isn't true then his whole argument falls apart. It isn't true.

I accept Ruse's challenge when he says,
Of course, Lewontin and his school do not care for many of the findings of the adaptationists. But to say that we should not play the game at all, or that we should count all as equal, requires some persuasive arguments. Better than arguments would be examples. Let those who worry about explanatory adaptationism show their dunnnocks and dinosaurs and fig wasps. When they demonstrate that they can do science which explains and predicts without invoking adaptation even implicitly, then we can start taking their position seriously. (p. 281)
There are literally dozens of examples of non-adaptive evolution that have been widely discussed in the scientific literature. It is more than "silly" of Ruse to issue a challenge like this. It's just plain ignorant.

Scientists who study junk DNA, for example, are doing very legitimate science when they predict that junk DNA sequences will not be conserved between species. Scientists who study blood type in humans are doing real science when they test the null hypothesis by asking whether the alleles conform to the Hardy-Weinberg distribution. (They do, suggesting strongly that they are not under selection.) Scientists who study speciation in birds ask whether the founder effect is real. (It is, and this shows that morphological changes during speciation are not due to adaptation.) The late Stephen Jay Gould and his colleagues have done good science by developing theories of punctuated equilibria and species sorting without assuming that natural selection and adaptation are essential. Ruse needs to take their position seriously. Meanwhile Ruse has demonstrated that we don't need to take him seriously.

The entire field of molecular evolution is based largely on explanations and predictions that rely on random genetic drift of neutral alleles. As far as I know, the people who work in that field are good evolutionary biologists even though they don't assume design when constructing their phylogenies.

And lets not forget about one of Lewontin's favorite examples. The African rhinoceros has two horns while the Indian rhinoceros has only one. Why? If you accept the modern theory of evolution then your choices of explanation can range from adaptive to accidental. If you restrict yourself to Darwinism then you must assume design and your explanation has to invoke natural selection. Somehow you have to come up with ways to explain why African rhinos were better off with two horns while Indian rhinos were better off with only one.

Using the metaphor of design and purpose forces you to assume the answer to the very question you are asking. It forces you to reject known evolutionary mechanisms such as random genetic drift. This may be good philosophy but it's not good science.

Getting back to the title of the book. Is nature designed? Partly, but there are lots of things that don't look designed and are not the end product of natural selection. Our genome is a good example. It's more like a Rube Goldberg apparatus than a well-tuned machine. It is not particularly helpful to say that living things are designed, or even that they have the appearance of design. If we stop saying that everything is designed then we will be better prepared to consider other possibilities, like evolution by accident.

Hypothesis: A Journal for the Discussion of Science

 
Hypothesis is a journal for the the discussion of science [Hypothesis].

The journal is supported by the Department of Biochemistry, Department of Immunology, Department of Medical Biophysics, and Department of Medical Genetics & Microbiology at the University of Toronto. Most of the editors and contributers are graduate students in one of those departments. You may have heard about Hypothesis before if you read Eva Amsen's blog [easternblot]. She is one of the editors-in-chief.

The May 2007 issue contains several interesting articles and a provocative editorial on Food Science Gone Bad. Let me quote the last paragraph of the editorial in order to tempt you into reading the whole thing.
The fact that science is complicit in a food philosophy detrimental to public health presents an ethical dilemma for researchers. Whereas health products based on pseudoscience are reflexively disparaged among scientists, the use of nutrients to build healthy foods is seemingly founded in peer-reviewed research published in reputable journals. Scientists must address this problem by being vocal outside the scientific community, where journalists and product developers stretch the conclusions of nutritional studies well beyond their intended context. While it would be naïve to suggest that scientists ought to downplay the significance of their research, the ease with which research findings are misused implies a responsibility to demand balanced reporting. A more practical reason to speak out is that exaggeration in science journalism slowly erodes the credibility of the scientific enterprise in the public eye. Unfortunately, the promise of diet fads and myriad weight loss products makes it even harder to digest the sober truth about the scientific study of nutrition: progress is slow, true breakthroughs are rare, and you still have to eat your vegetables. [my emphasis, LAM]
Other articles are ...
North Carolina Science Blogging Conference. Eva Amsen

Environmental Factors can Modify Genotype Risks by Slight Changes in Protein Conformation: The Role of Water. Shahram Shahabi, Zuhair Muhammad Hassan, Nima Hosseini Jazani, and Massoumeh Ebtekar

Fun with Microarrays Part II: Data Analysis. Paul C. Boutros

Normalizing Endophenotypes of Schizophrenia: The Dip and Draw Hypothesis. Béchara J. Saab and John C. Roder

Wednesday, May 30, 2007

Lessons from Science Communication Training

 
"Lessons from Science Communication Training" is the title of a letter appearing in the May 25th issue of Science magazine [Lessons from Science Communication Training].

The letter is from a group at Cornell University who developed a science communication course for graduate students. According to the letter,
... the goal of this course was to improve our ability to discuss our research with both the general public and the professionals writing and reporting on science in the media.
The authors have three key recommendations that I'll discuss below but before getting to them let's set the stage.

Matt Nisbet recommends the article on his blog [At Science, a Focus on Media Training for Scientists]. I assume he endorses the message because it fits with his idea of framing science. Chad Orzel is a little bit skeptical but he accepts the principles laid out in the Science letter [Framing Science: Look Inside the Sausage Factory].

What is the problem that the Cornell group is trying to solve? Here's how they put it,
However, a cultural shift is under way, reflecting the higher stakes of research, and an increased recognition by scientists, stakeholders, and policymakers that (i) scientists need to get their message out, (ii) scientists need training to learn how to do so, and (iii) training should begin at the graduate level.
Now, I don't want to be accused of claiming that all scientists are excellent communicators but as far as I can tell they don't do such a bad job. After all, communicating is extremely important in science whether it be writing a scientific paper or lecturing to undergraduates. It's not at all clear to me that we scientists are doing such a bad job of communicating science.

But we all know that's not really the issue. The issue is the fixation of some people on the idea that scientists need special training in order to communicate to the general public. Apparently the skills needed to communicate within the scientific community are just not good enough when it comes to writing popular science. But is this true? Do scientists really fall down when it comes to communicating to non-scientists?

I don't think so. I have several selves full of books by scientists. You may be familiar with some of the names: Richard Dawkins, Ken Miller, Carl Sagan, Ernst Mayr, Ed Wilson, Jim Watson, Francis Crick, Jared Diamond, George Williams, John Maynard Smith, Lynn Margulis, David Raup, Niles Eldredge, David Suzuki, Richard Lewontin, and Stephen Jay Gould. Many of these scientists have also written newspaper articles and reviews in the New York Times. They've been interviewed on television and they've given public lectures all over the world.

Not bad for scientists, eh? Of course not every scientist can be good at this but that's surely not the point. The important point is whether there's a serious problem when it comes to scientists communicating with the general public. Frankly, I don't see it. The scientists are communicating science very effectively. Maybe some people aren't listening, or maybe some people don't understand science when they hear it.

I think the so-called "problem" here is not about communicating good science. It's about using science language as a tool to persuade people to change their minds. This is what Nisbet and Mooney are on about. They don't really care about the science, they take that as a given. What they want is for scientists to move out of the science sphere into the political sphere. They want scientists to adopt their particular political perspective and fight on their side for the policy changes that they believe in. They don't really want scientists to explain stem cell research. Scientists have already done a good job at that. Nisbet and Mooney want scientists to fight against the pro-life people who would shut down stem cell research. That's not science communication. It's politics. Perhaps you need framing in politics but it's wrong in science.

Let's, for the sake of argument, agree that scientists can do better at communicating science (not politics) to the general public. Who's going to teach them? If you were being logical you might assume that the best teachers would be scientists with a proven track record, like the ones mentioned above. Or perhaps another group of lesser luminaries who have some experience with the media.

Well, if that's what you think you then haven't been listening to the conversations. Did you know there's a large group of people out there who think that scientists need lessons from science journalists, reporters, and people in the press office? Apparently these guys have been doing a much better job than the scientists when it comes to communicating science to the general public. I guess they're better framers. Who knew?

Back to the original letter in Science. Here are the three bits of advice that the Cornell group teaches.
First, involve people from multiple fields across your college or university. In particular, we highly recommend involving staff from the press relations office. These specialists have a unique perspective on what topics are newsworthy and on the challenges scientists face in communicating effectively. Include scientists who have personal experience communicating their research to the public and journalists from your campus or local newspaper.
I like the idea of getting advice from scientists who have personal experience. I'm very skeptical about advice from the staff of press relations offices. My experience with the results coming out of those offices does not inspire confidence. I'm not sure that scientists should be taking lessons on how to communicate to the general public from a group that doesn't seem to be very good at it. I think that press relations offices are part of the problem, not part of the solution.
Second, visit a news room (radio, print, or television) and talk to reporters--not just science reporters, but reporters in all fields. Ask to sit in on a meeting where reporters and editors pitch stories to each other. This process reveals what stories interest reporters and how those stories are developed. Understanding this process will help scientists identify and explain the newsworthy attributes of their own research.
What evidence do we have that a group of reporters sitting around a table is able to distinguish good science from bad science? None whatsoever [SCIENCE Questions: Asking the Right Question]. Clearly the goal here is not to focus on good science communication—it's how to spin good science to conform to what the newspapers want to print. We know what that is. Shave your head, commit a crime, exaggerate your claims. Is this really what we want our graduate students to learn?

The group that needs lessons here is the reporters, not the scientists. That ain't gonna happen but it's no reason for us to lower ourselves to their standards.
Third, get hands-on experience communicating science as part of the class. Do not just set up a series of lectures and field trips: write press releases, write articles, conduct interviews, get interviewed, create a Web page, and set up a science blog. Ask your collaborating journalists and PR specialists to facilitate and critique student projects. Hands-on experience with feedback from media professionals and other students provided some of the most useful learning experiences in our course.
Experience is important. Nobody questions that. The important question is who is going to be the judge of good science writing? If it's going to be journalists, PR specialists, and media professionals then I want to see evidence that they are doing a good job right now. Are they worthy of trust?

Canada, Australia, Europe, and Japan Are Blue States

 

From the website Vision of Humanity,
The Global Peace Index is a ground-breaking milestone in the study of peace. It is the first time that an Index has been created that ranks the nations of the world by their peacefulness and identified some of the drivers of that peace. 121 countries have been ranked by their ‘absence of violence’, using metrics that combine both internal and external factors. Most people understand the absence of violence as an indicator of peace. This definition also allows for the measuring of peacefulness within, as well as between, nations.

Peace is a powerful concept. However, the notion of peace, and its value in the world economy, is poorly understood. Historically, peace has been seen as something won in war, or else as an altruistic ideal. There are competing definitions of peace, and most research into peace is, in fact, the study of violent conflict.

Vision of Humanity contains the results from the Global Peace Index and other material of interest on peace. It also contains a section on institutions that need help to fund peace-related initiatives. Over time this source will be updated to combine more relevant material that will demonstrate the linkages between peace and sustainability.
[Hat Tip: John M. Lynch]

Nobel Laureates: Robert W. Holley, Har Gobind Khorana, and Marshall W. Nirenberg

 
The Nobel Prize in Physiology or Medicine 1968.

"for their interpretation of the genetic code and its function in protein synthesis"


Robert W. Holley (1922-1992), Har Gobind Khorana (1922- ), and Marshall W. Nirenberg (1922- ) received the Nobel Prize in Physiology or Medicine for their work in cracking the genetic code.

Holley identified and sequenced the first transfer RNA. Khorana developed techniques for synthesizing polynucleotides that could be used to program translation in cell free extracts and Nirenberg identified the amino acids that were incorporated when synthetic RNAs were used.

The presentation speech highlights the significance of this work. It ranks as one of the classic achievements in biology.
In this situation Nirenberg arrived at a very simple and ingenious solution: he realized that the biochemist had a decisive advantage over the archeologist since he could construct in the test tube a system which uses a nucleic acid as template for the formation of a protein. Such a system can be compared with a translation-machine which is fed by the scientist with a sentence written in the alphabet of nucleic acids; the machine then translates the sentence into the protein alphabet. Nirenberg synthesized a very simple nucleic acid, composed of a chain of only a single repeating letter. Using this nucleic acid the system produced a protein which also contained a single letter, now written in the protein alphabet. In this way Nirenberg had both deciphered the first hieroglyph and shown how the machinery of the cell can be used for the translation of the genetic code in general. After that, the field moved extremely rapidly. Nirenberg reported his first results in August 1961. Less than five years later all the details of the genetic code were established, mainly from the work of Nirenberg and Khorana.

Much of the final work was done by Khorana. During many years he had systematically devised methods which led to the synthesis of well defined nucleic acids, giant molecules with every building block in its exact position. Khorana's synthetic nucleic acids were a pre-requisite for the final solution of the genetic code.

What is the mechanism for the translation of the code within the cell? This question was successfully attacked by Holley. He is one of the discoverers of a special type of nucleic acid which has been called transfer-RNA. This nucleic acid has the capacity to read off the genetic code and to transform it to the protein alphabet. After many years' work Holley succeeded in preparing a transfer-RNA in pure form and, finally, in 1965, established its exact chemical structure. Holley's work represents the first determination of the complete chemical structure of a biologically active nucleic acid.

The interpretation of the genetic code and the elucidation of its function are the highlights of the last 20 years' explosive evolution of molecular biology which has led to an understanding of the details of the mechanism of inheritance. So far the work can be described as basic research. However, through this work we can now begin to understand the causes of many diseases in which heredity plays an important role.

Dr. Holley, Dr. Khorana, Dr. Nirenberg. At the end of his Nobel lecture, Edward Tatum in 1958 looked into his crystal ball and tried to predict some of the future developments in molecular biology. He suggested among other things that the solution of the genetic code might come during the lifetime of at least some of the members of his audience. This appeared to be a bold prophecy at that time. In reality it took less than three years before the first letters of the code were deciphered and, because of the ingenuity of you three, the nature of the code and much of its function in protein synthesis were known within less than eight years. Together you have written the most exciting chapter in modern biology.
This award is somewhat controversial since there are those who think that Heinrich Matthaei should have shared the Nobel Prize [see Cracking the Genetic Code: The polyU Experiment of Nirenberg and Matthaei]. At the time of the discovery, Matthaei was a post-doctoral fellow under Nirenberg. By the time he left to go back to Germany, Matthaei and Nirenberg were not on good terms.

Resistance to Science

 
In my previous posting [Do You Trust Scientists] I referred to an article by Paul Bloom and Deena Skolnick Weisberg who discussed the reasons why some adults resist science and opt instead for pseudoscience or religion. Bloom and Weisberg said,
The developmental data suggest that resistance to science will arise in children when scientific claims clash with early emerging, intuitive expectations. This resistance will persist through adulthood if the scientific claims are contested within a society, and will be especially strong if there is a non-scientific alternative that is rooted in common sense and championed by people who are taken as reliable and trustworthy.
Along comes GilDodgen who is exactlythe sort of person we are talking about. He posts a message on the Intelligent Design Creationism blog Uncommon Descent [More Silly Psychobabble About “Resistance to Science”]. Believe it or not, this is what he said.
I’m not quite sure what the “developmental data” are, but I do know something about science, and I am certainly not resistant to it, which is precisely why I am an intelligent-design proponent.

I use the hard sciences all day long in my work as (primarily) a software engineer in the aerospace research and development field. These sciences include: physics, mathematics, electrical and mechanical engineering, computational algorithms, detailed computer program design and debugging, and information processing. The end products of all this highly integrated science must work in the real world, and this is the only measure of success in my professional field. Vague, unsupported philosophical ruminations, like those of psychologists, don’t cut the mustard when it comes to real science and scientific endeavor.

It is precisely because of my knowledge of science, in a number of scientific disciplines, that I reject blind-watchmaker Darwinism and materialist explanations for all that we observe. Psychologists, especially the evolutionary kind, should become more familiar with real, hard science, before they make sweeping, unsupported claims about others’ motivations for rejecting their definition of “science.”
And you wonder why we call them IDiots?

Do You Trust Scientists?

 
Last September (2006) John Wilkins wrote a series of posting on why Creationists reject evolution/science. I highly recommend that you read all four essays right now.
  1. Why are creationists creationist?
  2. Why are creationists creationist? 2 - conceptual spaces
  3. Why are creationists creationist? 3: compartments and coherence
  4. Why are creationists creationist? 4: How to oppose anti-science
John explains that much of science is not intuitively obvious and children have a natural tendency to resist notions that go against what they see as common sense. They will encounter serious problems if the authority figures in their lives, such as parents and pastors, are telling them stories that conflict with what they hear in school—especially if these anti-science authority figures are reinforcing their naive common sense notions of the natural world. John outlines the various defensive mechanisms that people adopt when faced with such a dilemma.

Part of the problem is how we present science in a culture that is pre-disposed to mistrust it. As John points out in essay #4, we need to work on making science more trustworthy.
The crucial way to get people to trust science is to show them, by letting them do it, that science is the premier way to learn about the world. Science is a learning process that relies on no single person, but which each individual can engage in. I'm sure science teachers have been trying to get this message across for years, but have been swamped by the demands of curricula designed to make students tertiary ready. A better bet would be to educate the population first, and offer ways in which those who are really committed to science, and are therefore much more likely to actually become scientists or otherwise benefit from it, can become ready for the later education.

This will have a benefit - the policy makers, usually elected from the general population of non-scientists, will understand that even if they do not understand the particular discipline that is cognitively relevant to a given social issue, like global warming or HIV AIDS, that the reasons why the specialists assert these claims is not a matter of simple social construction or dogmatic faith. They may even be better able to assess these claims on their merit, and to critically reject those that are fashionable among scientists but lack the necessary evidentiary support.
I agree that this is a problem. It's more of a problem in some cultures than in others but everyone who is interested in promoting rationalism over superstition should pay attention. Where I might disagree slightly with John is that I think we need a two-pronged attack. Not only do we need to increase the status of science but we need to weaken the hold of religion.

In today's posting, John reiterates these themes [Antiscience is learned in childhood] by referring to a recently published article by by psychologists Paul Bloom and Deena Skolnick Weisberg. Here's the link to their article in The Edge [WHY DO SOME PEOPLE RESIST SCIENCE?].

Bloom and Weisberg make some of the same points that John makes about how children learn. Those are interesting points but I want to focus on whether scientists can be trusted. Here's what Bloom and Skolnick say,
In sum, the developmental data suggest that resistance to science will arise in children when scientific claims clash with early emerging, intuitive expectations. This resistance will persist through adulthood if the scientific claims are contested within a society, and will be especially strong if there is a non-scientific alternative that is rooted in common sense and championed by people who are taken as reliable and trustworthy. This is the current situation in the United States with regard to the central tenets of neuroscience and of evolutionary biology. These clash with intuitive beliefs about the immaterial nature of the soul and the purposeful design of humans and other animals — and, in the United States, these intuitive beliefs are particularly likely to be endorsed and transmitted by trusted religious and political authorities. Hence these are among the domains where Americans' resistance to science is the strongest.

We should stress that this failure to defer to scientists in these domains does not necessarily reflect stupidity, ignorance, or malice. In fact, some skepticism toward scientific authority is clearly rational. Scientists have personal biases due to ego or ambition—no reasonable person should ever believe all the claims made in a grant proposal. There are also political and moral biases, particularly in social science research dealing with contentious issues such as the long-term effects of being raised by gay parents or the explanation for gender differences in SAT scores. It would be naïve to ignore all this, and someone who accepted all "scientific" information would be a patsy. The problem is exaggerated when scientists or scientific organizations try to use their authority to make proclamations about controversial social issues. People who disagree with what scientists have to say about these issues might reasonably infer that it is not safe to defer to them more generally.

But this rejection of science would be mistaken in the end. The community of scientists has a legitimate claim to trustworthiness that other social institutions, such as religions and political movements, lack. The structure of scientific inquiry involves procedures, such as experiments and open debate, that are strikingly successful at revealing truths about the world. All other things being equal, a rational person is wise to defer to a geologist about the age of the earth rather than to a priest or to a politician.

Given the role of trust in social learning, it is particularly worrying that national surveys reflect a general decline in the extent to which people trust scientists. To end on a practical note, then, one way to combat resistance to science is to persuade children and adults that the institute of science is, for the most part, worthy of trust.
So here's the problem. How do we convince people that scientists are worthy of trust? It's clear that the front lines are at the interface between what scientists know and what the general public knows about science. This is often framed as an issue about communicating science. Many non-scientists think that scientists need to do a better job. Is this really the problem?

The "burden" of communicating science is often assumed to fall on the shoulders of science writers and science journalists. They are the ones who write the press releases and increasingly they are the ones who write about science in newspapers and magazines. The leading "science" figures on television today are not scientists but science journalists. Even in the leading science journals such as Nature and Science it's the science journalists and not scientists who write the articles that will be read by a wide audience.

In today's world we have a rather paradoxical situation where non-scientists who write about science are proclaiming themselves to be experts on science communication, yet they call upon scientists to learn from them how to manipulate the media to get the science message across. But if science journalists are doing such a good job then why do we need scientists? Is it possible that the failure to make science a trustworthy enterprise is due, in part, to the failure of science journalism?

I'd like to explore this question further.

Tuesday, May 29, 2007

How to Get Into Medical School

 
Here's some advice on how to get into medical school here in Ontario. It includes tips on how to get into medicine at the University of Toronto [Medical School Applications].

How to Get Into Graduate School

 
Shelley Batts has all the right answers [Guide to Getting Into Graduate School for the Sciences]. You need to read her entire posting but here's the short version to tempt you ...
  1. Spend your spare time doing research.
  2. Cultivate awesome letters of recommendation.
  3. Take the relevant classes, but have a few other interests too.
  4. Have a reason why you want to do research.
  5. Read the literature, know the basics, and a few tough surprising facts.
  6. Know your interviewers, and their research.
  7. Shell out the money for a GRE tutor if you are a nervous test-taker.
  8. Apply to schools based on labs, not the US News and World Report Rankings.
  9. Email professors you are interested in working with.
  10. Follow the funding.
  11. Good scientists don't always make good mentors.
  12. Don't be afraid to get out if it isn't working.
  13. Stand up for yourself, and keep at it.
  14. Share most of your ideas, but keep a few to yourself.
  15. Apply for NRSAs.
  16. Be curious.
  17. Know some science lineage.
  18. Know who won the Nobels that year, in your field.
  19. Email the students in the program, and in the lab.
  20. Find out where/what students from that program are doing now.
  21. No second-choices. Nothing but science will do.
  22. Be professional, talk shop, ask what projects their students are doing.
Some of these only apply to Americans but on the whole it's excellent advice for everyone. Be sure to pay close attention to #21. Ignoring that advice is problably the second most common mistake that applicants ever make. The most common mistake is ignoring #2 or thinking that there's no relationship between #2 and #21.

Cracking the Genetic Code: The polyU Experiment of Nirenberg and Matthaei

 
By 1960 it was widely recognized that DNA was transcribed to yield messenger RNA (mRNA) and mRNA was translated to yield proteins. The translation step could be carried out in vitro by using extracts from E. coli cells that had been primed with purified RNA. Some of the favorite messages were RNAs from viruses such as TMV or yeast cells. By measuring the amino acids that were incorporated into protein it was possible to show that the RNAs from different sources were making different proteins.

The relationship between the RNA and the protein product was obvious. There was something about the sequence of nucleotides in the RNA molecule that determined the sequence of amino acids in the protein. The RNA encoded the amino acid sequence. What was this genetic code?

Marshall Nirenberg was a scientist working at the NIH labs on the outskirts of Washington D.C. He and his post-doc Heinrich Matthaei realized that they could program their cell free extracts with synthetic RNAs and crack the genetic code.

Their first attempt was with a synthetic RNA called polyU because it was composed entirely of uridine residues [Monday's Molecule #28]. They added polyU to various test tubes containing one amino acid that was radioactively labelled. They then looked for incorporation of this labelled amino acid into high molecular weight protein that could be precipitated from the extract.

Here's how the experiment is described on the NIH website [The poly-U Experiment]
On Saturday, May 27, 1961, at three o'clock in the morning, Matthaei combined the synthetic RNA made only of uracil (called poly-U) with cell sap derived from E. coli bacteria and added it to each of 20 test tubes. This time the “hot” test tube was phenylalanine. The results were spectacular and simple at the same time: after an hour, the control tubes showed a background level of 70 counts, whereas the hot tube showed 38,000 counts per milligram of protein. The experiment showed that a chain of the repeating bases uracil forced a protein chain made of one repeating amino acid, phenylalanine. The code could be broken! UUU=Phenylalaline was a breakthrough experiment result for Nirenberg and Matthaei.

The two kept their breakthrough a secret from the larger scientific community–though many NIH colleagues knew of it –until they could complete further experiments with other strands of synthetic RNA (Poly-A, for example) and prepare papers for publication. They had solved with an experiment what others had been unable to solve with theoretical explanations and mathematical models.
Shortly after discovering the very first codon, Matthaei returned to Germany. Nirenberg assembled a team of scientists to crack the rest of the genetic code by adding various synthetic RNAs to the cell free extract. The first few codons were simple; polyA stimulated incorporation of lysine and polyC stimulated incorporation of proline. (PolyG didn't work.) A random mixture of U and C, poly(U,C), incorporated leucine and serine.

Eventually, with the help of Gobind Korhana, the team was able to synthesize RNAs with defined triplets of nucleotides and the entire genetic code was worked out. Nirenberg, Korhana, and Robert Holley (for determining the structure of tRNA) received the Nobel Prize in 1968.

It's important to note that the cracking of the genetic code for E. coli proved to be universal (almost). All species use the same genetic code. It's also important to note that cracking the genetic code, which was done forty years ago, is not the same as sequencing a genome ["Cracking the genetic code" and "mapping the genome"].

The standard genetic code is shown below. The column on the left represents the first nucleotide in a codon, the row on top (2nd position) represents the middle nucleotide, and the column on the right is the third position. You can see why poly(U,C) encoded serine and leucine because one of the codons for serine is UCU and one of the leucine codons is CUC.

Shhh. Don't tell Larry.

 
The Tim Horton's fans have all migrated to Pharyngula [Shhh. Don't tell Larry]. I'm not sure but I think some of the comments are making fun of Canadians. Get on over there and teach those Yankees about good coffee and a good country.

Besides, PZ could use the traffic. He's down to less than 25,000 per day.

Oh, and don't forget to tell all those pharyngulites about all the other yummy things at Timmy's. Mmmmm ... honey crullers , timbits, chili, turkey bacon club sandwich, cream of broccoli soup.

Monday, May 28, 2007

SCIENCE Questions: How Can a Skin Cell Become a Nerve Cell?

 
"How Can a Skin Cell become a Nerve Cell?" 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 Can a Skin Cell Become a Nerve Cell 309: 85.
[Text] [PDF]
Gretchen Vogel is a contributing correspondent for Science magazine. She is based in Berlin.

This question is really about developmental biology but it's framed as a question about how (animal) oocytes can reprogram somatic cell nuclei.
Scientists have been investigating the reprogramming powers of the oocyte for half a century. In 1957, developmental biologists first discovered that they could insert the nucleus of adult frog cells into frog eggs and create dozens of genetically identical tadpoles. But in 50 years, the oocyte has yet to give up its secrets.

The answers lie deep in cell biology. Somehow, scientists know, the genes that control development--generally turned off in adult cells--get turned back on again by the oocyte, enabling the cell to take on the youthful potential of a newly fertilized egg. Scientists understand relatively little about these on-and-off switches in normal cells, however, let alone the unusual reversal that takes place during nuclear transfer.
Now developmental biologists may disagree, but I think we pretty much know the answer to this question. Oocytes contain the right transcription factors to activate the genes required for early development. Somatic cells don't have these proteins. When you isolate nuclei from somatic cells and put them in an oocyte you dilute out the various transcription factors than maintained control of gene expression in the differentiated cell. This makes the somatic cell chromatin competent for transcription that's under the control of oocyte factors.

I disagree with Gretchen Vogel when she says, "scientists understand relatively little about these on-and-off switches in normal cells." I think we understand a great deal about the regulation of gene expression. I doubt very much whether there are any mysteries than need to be explained.
Scientists are just beginning to understand how cues interact to guide a cell toward its final destiny. Decades of work in developmental biology have provided a start: Biologists have used mutant frogs, flies, mice, chicks, and fish to identify some of the main genes that control a developing cell's decision to become a bone cell or a muscle cell. But observing what goes wrong when a gene is missing is easier than learning to orchestrate differentiation in a culture dish. Understanding how the roughly 25,000 human genes work together to form tissues--and tweaking the right ones to guide an immature cell's development--will keep researchers occupied for decades. If they succeed, however, the result will be worth far more than its weight in gold.
This is just one more example of confusion about the difference between knowledge and technology. Observing what goes wrong when a gene is mutated has led to huge advances in our knowledge of development. It's fair to say that we understand the basic principles. For some of us that's enough to answer the most important question. But for some Science journalists it's only the beginning. They won't be happy until we can use that knowledge to cure human diseases or repair injuries.

If we were to ask a general question like "What Are the Fundamental Concepts in Development and Differentiation?" then I might agree that it ranks in the top 25 science questions. But this particular question, like so many others, is misguided and anthropomorphic. Furthermore, in terms of fundamental principles, it overlaps extensively with several other questions such as "What Controls Organ Regeneration?", "How Does a Single Somatic Cell Become a Whole Plant?", "What Genetic Changes Make Us Uniquely Human?", and "Can We Selectively Shut Off Immune Responses?"

Department of Biochemistry Research Day

 

SCIENCE Questions: What Controls Organ Regeneration?

 
"What Controls Organ Regeneration?" is one of the top 25 questions from the 125th anniversary issue of Science magazine [Science, July 1, 2005]. The complete reference is ...
Davenport, R. John (2005) What Controls Organ Regeneration 309: 84.
[Text] [PDF]
John Davenport is Science magazine's editor for the Science of Aging Knowledge Environment (SAGE KE).

He writes,
Unlike automobiles, humans get along pretty well for most of their lives with their original parts. But organs do sometimes fail, and we can't go to the mechanic for an engine rebuild or a new water pump--at least not yet. Medicine has battled back many of the acute threats, such as infection, that curtailed human life in past centuries. Now, chronic illnesses and deteriorating organs pose the biggest drain on human health in industrialized nations, and they will only increase in importance as the population ages. Regenerative medicine--rebuilding organs and tissues--could conceivably be the 21st century equivalent of antibiotics in the 20th. Before that can happen, researchers must understand the signals that control regeneration.
This is another example of a "fundamental" science question that's put in the context of technology development. I find this disappointing. Rather than simply expressing an interest in organ regeneration for the sake of understanding developmental biology, the writer assumes that the question has to be rationalized by making it relevant to medicine.
Animals such as salamanders and planaria regenerate tissues by rekindling genetic mechanisms that guide the patterning of body structures during embryonic development. We employ similar pathways to shape our parts as embryos, but over the course of evolution, humans may have lost the ability to tap into it as adults, perhaps because the cell division required for regeneration elevated the likelihood of cancer. And we may have evolved the capacity to heal wounds rapidly to repel infection, even though speeding the pace means more scarring. Regeneration pros such as salamanders heal wounds methodically and produce pristine tissue. Avoiding fibrotic tissue could mean the difference between regenerating and not: Mouse nerves grow vigorously if experimentally severed in a way that prevents scarring, but if a scar forms, nerves wither.

Unraveling the mysteries of regeneration will depend on understanding what separates our wound-healing process from that of animals that are able to regenerate. The difference might be subtle: Researchers have identified one strain of mice that seals up ear holes in weeks, whereas typical strains never do. A relatively modest number of genetic differences seems to underlie the effect. Perhaps altering a handful of genes would be enough to turn us into superhealers, too. But if scientists succeed in initiating the process in humans, new questions will emerge. What keeps regenerating cells from running amok? And what ensures that regenerated parts are the right size and shape, and in the right place and orientation? If researchers can solve these riddles--and it's a big "if"--people might be able to order up replacement parts for themselves, not just their '67 Mustangs.
These are interesting questions but they're hardly fundamental question on the frontiers of scientific knowledge. The article alludes to the answers—it's a question of regulating gene expression. There are no profound mysteries here. What controls organ regeneration is almost certainly the same thing that controls other aspects of development; namely, signals (such as hormones), and transcription factors.

We may not know the details but it sure looks to me like we already know the principles. Recall that the special issue was introduced by an essay on "In Praise of Hard Questions" [see: SCIENCE Questions: Asking the Right Question]. The type of questions were defined as,
Science's greatest advances occur on the frontiers, at the interface between ignorance and knowledge, where the most profound questions are posed. There's no better way to assess the current condition of science than listing the questions that science cannot answer.
So the question is whether understanding organ regeneration is really on the frontier or whether it's part of a mopping up exercise behind the front lines.

Monday's Molecule #28

 
Today's molecule looks a little complicated but all we need is the trivial name. If you can supply the correct chemical name that would be impressive

As usual, there's a connection between Monday's molecule and this Wednesday's Nobel Laureate(s). This one is an indirect connection but it should be obvious to anyone who has studied biochemistry/molecular biology.

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. (A feeble excuse, in my opinion. )

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

Sunday, May 27, 2007

"Cracking the genetic code" and "mapping the genome"

 
Dear scientists and science journalists. Next time a genome sequence is published please do not refer to it as "cracking the genetic code" (that was done back in the early 60's) or "mapping the genome" (it's not the same as sequencing).

For a more complete explanation of why these terms are wrong see Cracking the Code by Ryan Gregory. I agree with his take on science journalism...
I think this is another symptom of too much journalism and not enough science in science journalism. Instead of resorting to the standard catchphrases and clichés, why not introduce your readers to some accurate terms and concepts with which they may not be familiar? You can catch the interest of readers and educate them on the basics rather than appealing to their misconceptions or lack of prior knowledge.

SCIENCE Questions: How Much Can Human Life Be Extended?

 
"How Much Can Human Life Be Extended?" is one of the top 25 questions from the 125th anniversary issue of Science magazine [Science, July 1, 2005]. The complete reference is ...
Couzin, Jennifer (2005) How Much Can Human Life Be Extended? Science 309: 83.
[Text] [PDF]
Jennifer Couzin is a San Francisco-based news writer for Science magazine. She also wrote on "To What Extent Are Genetic Variation and Personal health Linked?".

With respect to the sort of fundamental questions that are described in the lead article [SCIENCE Questions: Asking the Right Question], this is a stupid question. It isn't really a science question at all; it's a question about technology, or the application of science. If a leading magazine like Science can't get the difference between technology and fundamental science questions then we're in a lot more trouble than I thought.

Compare this question to one of the valid questions that is asked, "What Is the Universe Made of?" Does anyone really think that a question about how to prolong human lifetimes is in the same category as a question about dark matter?

Not only is this not a "science" question, it's a question that reflects a huge bias in favor of a single species, Homo sapiens. If our goal is to teach science literacy then surely one of the most important ways to advance this goal is to convince people that there's a lot more to science than just it's interface with medicine. As long as the general public continues to treat science as a means to an end then we're never going to convince them that knowledge for its own sake is valuable.

SCIENCE Questions: To What Extend Are Genetic Variation and Personal health Linked?

 
"To What Extend Are Genetic Variation and Personal health Linked?" is one of the top 25 questions from the 125th anniversary issue of Science magazine [Science, July 1, 2005]. The complete reference is ...
Couzin, Jennifer (2005) To What Extend Are Genetic Variation and Personal health Linked? Science 309: 81.
[Text] [PDF]
Jennifer Couzin is a San Francisco-based news writer for Science magazine. She writes mostly on health-related issues and received the 2003 Evert Clark/Seth Payne Award for excellent science writing by a young journalist [Science Writers Honor One of Their Own].

The question may seem strange at first but don't be misled. Nobody is questioning whether there's a link between human diseases and genes/alleles. The question is exactly what it seems—how much linkage is there? It's the nature vs nurture question and that's surely an interesting question.

As Couzin writes,
These developments have led to hopes--and some hype--that we are on the verge of an era of personalized medicine, one in which genetic tests will determine disease risks and guide prevention strategies and therapies. But digging up the DNA responsible--if in fact DNA is responsible--and converting that knowledge into gene tests that doctors can use remains a formidable challenge.

Many conditions, including various cancers, heart attacks, lupus, and depression, likely arise when a particular mix of genes collides with something in the environment, such as nicotine or a fatty diet. These multigene interactions are subtler and knottier than the single gene drivers of diseases such as hemophilia and cystic fibrosis; spotting them calls for statistical inspiration and rigorous experiments repeated again and again to guard against introducing unproven gene tests into the clinic. And determining treatment strategies will be no less complex: Last summer, for example, a team of scientists linked 124 different genes to resistance to four leukemia drugs.

But identifying gene networks like these is only the beginning. One of the toughest tasks is replicating these studies--an especially difficult proposition in diseases that are not overwhelmingly heritable, such as asthma, or ones that affect fairly small patient cohorts, such as certain childhood cancers. Many clinical trials do not routinely collect DNA from volunteers, making it sometimes difficult for scientists to correlate disease or drug response with genes. Gene microarrays, which measure expression of dozens of genes at once, can be fickle and supply inconsistent results. Gene studies can also be prohibitively costly.
I like the sound of this. It shows that she's skeptical of the exaggerations in the scientific literature and that's good. It's what a science writer should be doing.

The problem is, this isn't one of the top 25 mysteries in science by any stretch of the imagination. We don't know the answer but that's because we don't yet have enough data. I don't think there's any profound scientific problem here. Some links between genes and disease are very clear [e.g., Glycogen Storage Diseases] and some will be more difficult to work out. Some diseases may not have a genetic component at all.

It's good to be skeptical about the rhetoric that comes out of the medical literature but the top questions in science should not be about medicine of technology and they should not be about things where we're just waiting for more data.

Friday, May 25, 2007

Towel Day

 

Towel Day :: A tribute to Douglas Adams (1952-2001)


Today is Towel Day in honor of Douglas Adams. You're supposed to carry your towel with you all day but I left mine at home because I forgot what day it was. Thanks to my favorite daughter for reminding me, but next year try and remind me the day before.

If you don't know about towels, here's a reminder from the website ...
To quote from The Hitchhiker's Guide to the Galaxy.

A towel, it says, is about the most massively useful thing an interstellar hitch hiker can have. Partly it has great practical value - you can wrap it around you for warmth as you bound across the cold moons of Jaglan Beta; you can lie on it on the brilliant marble-sanded beaches of Santraginus V, inhaling the heady sea vapours; you can sleep under it beneath the stars which shine so redly on the desert world of Kakrafoon; use it to sail a mini raft down the slow heavy river Moth; wet it for use in hand-to-hand-combat; wrap it round your head to ward off noxious fumes or to avoid the gaze of the Ravenous Bugblatter Beast of Traal (a mindboggingly stupid animal, it assumes that if you can't see it, it can't see you - daft as a bush, but very ravenous); you can wave your towel in emergencies as a distress signal, and of course dry yourself off with it if it still seems to be clean enough.

More importantly, a towel has immense psychological value. For some reason, if a strag (strag: non-hitch hiker) discovers that a hitch hiker has his towel with him, he will automatically assume that he is also in possession of a toothbrush, face flannel, soap, tin of biscuits, flask, compass, map, ball of string, gnat spray, wet weather gear, space suit etc., etc. Furthermore, the strag will then happily lend the hitch hiker any of these or a dozen other items that the hitch hiker might accidentally have "lost". What the strag will think is that any man who can hitch the length and breadth of the galaxy, rough it, slum it, struggle against terrible odds, win through, and still knows where his towel is is clearly a man to be reckoned with.

SCIENCE Questions: What Is the Biological Basis of Consciousness?

 
"What Is the Biological Basis of Consciousness?" is one of the top 25 questions from the 125th anniversary issue of Science magazine [Science, July 1, 2005]. The complete reference is ...
Miller, Greg (2005) What Is the Biological Basis of Consciousness? Science 309: 79.
[Text] [PDF]
Greg Miller is a news writer for Science. He begins by describing the classic mind/body problem in philosophy. Rene Descartes claimed that mind and body were two separate things.
Recent scientifically oriented accounts of consciousness generally reject Descartes's solution; most prefer to treat body and mind as different aspects of the same thing. In this view, consciousness emerges from the properties and organization of neurons in the brain. But how? And how can scientists, with their devotion to objective observation and measurement, gain access to the inherently private and subjective realm of consciousness?
This is a slippery slope. The real question is "Does Consciousness Exist?" There's no point in asking about the biological basis of something until you establish that the "something" actually exists. As Miller hints in his introduction, consciousness could be just an epiphenomenon—a kind of illusion that's produced when a brain operates.

If that's true then the right question would be something like "How Are Memories Stored and Retrieved?" As it turns out, that is one of the top 25 questions, but it's not this one.

The article ends by pointing to promising lines of research that might arise from asking the "right" question.
Ultimately, scientists would like to understand not just the biological basis of consciousness but also why it exists. What selection pressure led to its development, and how many of our fellow creatures share it? Some researchers suspect that consciousness is not unique to humans, but of course much depends on how the term is defined. Biological markers for consciousness might help settle the matter and shed light on how consciousness develops early in life. Such markers could also inform medical decisions about loved ones who are in an unresponsive state.
This is begging the question (in the old-fashioned sense of the phrase). The question we should be answering is not "why does consciousness exist?" but "does consciousness exist?" I don't think it does exist, so naturally this ranks as a very silly question as far as I'm concerned.

The statement that "some researchers suspect that consciousness is not unique to humans" is very disturbing. It implies that most workers think otherwise, as does Greg Miller. Personally, I'm not aware of any serious research scientist who thinks that "consciousness" (if it exists) is something that only a human possesses and not a chimpanzee or even (gasp!) an octopus. (Readers are invited to post the names of anyone who thinks otherwise.)

And the idea that there might be "biological markers for consciousness" seems to portray sloppy thinking at best and profound misunderstanding at worst.

Questions about how the brain works rank right at the top of my list of important questions. This question is not one of those. It is badly formulated and the explanation in the article makes it even worse.

SCIENCE Questions: Why Do Humans Have So Few Genes?

"Why Do Humans Have So Few Genes?" 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) Why Do Humans Have So Few Genes? Science 309: 80. [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.

Pennisi begins with the usual mythology about how surprised scientist were to discover that humans had fewer than 30,000 genes [see Facts and Myths Concerning the Historical Estimates of the Number of Genes in the Human Genome]. She continues by using most of the standard excuses for the Deflated Ego Problem [The Deflated Ego Problem].
That big surprise reinforced a growing realization among geneticists: Our genomes and those of other mammals are far more flexible and complicated than they once seemed. The old notion of one gene/one protein has gone by the board: It is now clear that many genes can make more than one protein. Regulatory proteins, RNA, noncoding bits of DNA, even chemical and structural alterations of the genome itself control how, where, and when genes are expressed. Figuring out how all these elements work together to choreograph gene expression is one of the central challenges facing biologists. [Numbers 1,2,5,6,7]
It's downhill from then on. Pennisi goes on to briefly describe the leading contenders for solving the imaginary problem. Not once does she mention that these have all been challenged in the scientific literature and not once does she mention that they are not specific to humans even though they must be if they're going to get you out of the pickle.

Is this one of the "right" questions that I talked about earlier? [SCIENCE Questions: Asking the Right Question] Nope. Not even close. In fact, it's a very "wrong" question that reflects an ignorance of the scientific literature and a profound misunderstanding of evolution, developmental biology, and gene expression. Humans have exactly the number of genes that we expect. They don't need to have many more genes than fruit flies or worms because a small number of unique genes are all that's required to make significant differences in development. They don't need to have special complexity mechanisms to "explain" anything because there's nothing that needs explaining. Human genes are fundamantally the same as those in Drosophila melanogaster (fruit fly), Caenorhabditis elegans (nematode worm), and Arabidopsis thaliana (a small flowering plant).

This "top 25 question" illustrates exactly the problem that I alluded to earlier. You don't recognize the important questions in science by polling science writers and editors. The "right" questions are the ones being asked on the frontiers by the creative experts who are thinking outside the box. This is an "inside the box" question and very few of those ever turn out to be important.

The right question would have been "Why Were You Surprised?"

SCIENCE Questions: Asking the Right Question

 
In July 2005 Science magazine published a list of the top questions in science [Science, July 1, 2005]. I was reminded of this list when I attended a meeting last month because the publishers of Science were handing out a special isue devoted to those questions. There are two categories; the top 25 questions, and 100 other questions. (It was the 125th aniversary of the magazine, hence 125 questions.)

I'd like to spend some time discussing those questions because not only are they interesting from a scientific point of view but they also reveal a great deal about science journalism and the public perception of science.

The issue began with an essay titled "In Praise of Hard Questions." The author, science writer Tom Siegfried, notes that hard questions stimulate science. He says,
The pressures of the great, hard questions bend and even break well-established principles, which is what makes science forever self-renewing—and which is what demolishes the nonsensical notion that science's job will ever be done.
Everyone agrees with the sentiment behind this statement. We all know that asking the right questions is the essence of good science. We all know that hard questions challenge prevailing models. On the other hand, we also know that there is such a thing as a stupid question in spite of what your Professors might have told you. Stupid questions can mislead scientists and stiffle creativity.

The opening article quotes David Gross, the 2004 Nobel Laureate in Physics who says,
One of the most creative qualities a research scientist can have is the ability to ask the right questions.
So, what are the "right" questions to ask? In my experience, the "right" questions are not immediately obvious. As stated above, they often challenge the prevailing dogma and this means that in the beginning they are dismissed as silly questions. Over time, the idea that this is a good question becomes more and more acceptable until finally it starts to stimulate active research.

What this means is that at any given point in time the "right" questions are only known to a few scientists on the cutting edge. These are ones who have begun to understand that the old questions aren't working any more. The vast majority of scientists will be sticking with the paradigm that's about to be overthrown. If you were to take a vote they would overwhelmingly dismiss the very questions that need to be asked.

Now, don't get me wrong. This is the way science is supposed to work. We all know that 99.9% of all attacks on orthodoxy deserve to be dismissed. The wonderful thing about science is that the 0.1% of "right" questions will almost certainly bubble to the surface. The real tricky part is picking out that 0.1% in advance.

So, if you were the editors of Science magazine how would you identify the important questions in science without falling into the trap of reinforcing orthodoxy and missing those very questions that a small group of experts are beginning to pay attention to? One way would be to seek out those experts and ask their opinion. This seems to be what is being advocated in the lead article where Tom Siegfried says,
Science's greatest advances occur on the frontiers, at the interface between ignorance and knowledge, where the most profound questions are posed. There's no better way to assess the current condition of science than listing the questions that science cannot answer.
But, Science magazine did not ask the experts at the frontiers. The actual procedure is explained in the editorial accompanying the July 1, 2005 issue. According to editors Donald Kennedy and Colin Norman, here's what they did.
We began by asking Science’s Senior Editorial Board, our Board of Reviewing Editors, and our own editors and writers to suggest questions that point to critical knowledge gaps. The ground rules: Scientists should have a good shot at answering the questions over the next 25 years, or they should at least know how to go about answering them. We intended simply to choose 25 of these suggestions and turn them into a survey of the big questions facing science. But when a group of editors and writers sat down to select those big questions, we quickly realized that 25 simply wouldn’t convey the grand sweep of cutting-edge research that lies behind the responses we received. So we have ended up with 125 questions, a fitting number for Science’s 125th anniversary.
The "right" questions were selected by editors and science journalists. I'm going to examine some of these questions in the next few days, concentrating exclusively on biology questions. Let's see how well they did when asked to identify the top "hard" questions in science.

Thursday, May 24, 2007

The Deflated Ego Problem

"How humans get away with having a small genome"

Believe it or not, that's actually the subtitle of a short article in this month's issue of SEED (June, 2007). Who knew that humans have a small genome?

The author, Yohannes Edemariam, is a frequent contributor to SEED. He lives here in Toronto. Edemariam begins with the usual mythology designed to make you think there's a problem with the human genome [see Facts and Myths Concerning the Historical Estimates of the Number of Genes in the Human Genome]. This "problem" cries out for an explanation ...
Given our complexity—our capabilities for abstract thought, language, the building of civilizations—biologists were surprised at the relatively small number of genes we possess when they first began studying the human genome. It has since been become clear that our 20,000 to 25,000 genes can be manipulated by processes that statistically enhance the variety of ways in which each gene becomes manifest in our physical makeup.
This is typical of the rhetoric that pervades the popular science literature and, more importantly, the real scientific literature. The scientific evidence shows that our genome has about 25,000 genes and that's not much more than nematode worms or fruit flies. What this tells us is the same message that developmental biologists have been shouting for 35 years—small changes can have big effects. Clearly, some people haven't been listening.

The human chauvinists are disappointed that our genome isn't as complex as our brains and behavior suggest (to them). They expected to see tangible evidence that humans were at the top of the heap. I call this "The Deflated Ego Problem." The question before us is whether this is a real scientific problem or whether it stems from an incorrect understanding of evolution and development.

Having barely survived a major blow to their ego when the human genome turned out to have fewer than 30,000 genes, the deflated ones have fought back with various schemes to explain the "paradox." What they look for is some special mechanism that we humans possess in order to get a bigger bang for our buck. In other words, they're looking for their missing complexity in other places.

Ironically, the chauvinists don't realize that their "problem" can only be solved by discovering hithertofore unknown mechanisms that are confined to humans, or possibly mammals. The reason is obvious. If the mechanism is universal then fruit flies and worms have it as well and we can't use the new-found genome complexity to rationalize why we have so few genes compared to them. After all, the goal here is to explain why we only have a few thousand genes more than those "simple," "primitive," species and the explanation won't work if we all have the same complexity-generating mechanisms. I say "ironically" because many of the special mechanisms being proposed were first discovered in these "primitive" species. Now they're being used to solve the Deflated Ego Problem.

So, what are these magical complexity-generators that "statistically enhance the variety of ways in which each gene becomes manifest ...?" Are they going to solve the Deflated Ego Problem?

I'm not going to tell you which one is being promoted in the SEED article. You'll have to buy the magazine—which I highly recommend in spite of its flaws—to find out the answer. Here's the latest list of the sorts of things that may salvage your ego if it has been deflated.
1. Alternative Splicing: We may not have many more genes than a fruit fly but our genes can be rearranged in many different ways and this accounts for why we are much more complex. We have only 25,000 genes but through the magic of alternative splicing we can make 100,000 different proteins. That makes us almost ten times more complex than a fruit fly. (Assuming they don't do alternative splicing.)
2. Small RNAs: Scientists have miscalculated the number of genes by focusing only on protein encoding genes. Our genome actually contains tens of thousands of genes for small regulatory RNAs. These small RNA molecules combine in very complex ways to control the expression of the more traditional genes. This extra layer of complexity, not found in simple organisms, is what explains the Deflated Ego Problem.
3. Pseudogenes: The human genome contains thousands of apparently inactive genes called pseudogenes. Many of these genes are not extinct genes, as is commonly believed. Instead, they are genes-in-waiting. The complexity of humans is explained by invoking ways of tapping into this reserve to create new genes very quickly.
4. Transposons: The human genome is full of transposons but most scientists ignore them and don't count them in the number of genes. However, transposons are constantly jumping around in the genome and when they land next to a gene they can change it or cause it to be expressed differently. This vast pool of transposons makes our genome much more complicated than that of the simple species. This genome complexity is what's responsible for making humans more complex.
5. Regulatory Sequences: The human genome is huge compared to those of the simple species. All this extra DNA is due to increases in the number of regulatory sequences that control gene expression. We don't have many more protein-encoding regions but we have a much more complex system of regulating the expression of proteins. Thus, the fact that we are more complex than a fruit fly is not due to more genes but to more complex systems of regulation.
6. The Unspecified Anti-Junk Argument: We don't know exactly how to explain the Deflated Ego Problem but it must have something to do with so-called "junk" DNA. There's more and more evidence that junk DNA has a function. It's almost certain that there's something hidden in the extra-genic DNA that will explain our complexity. We'll find it eventually.
7. Post-translational Modification: Proteins can be extensively modified in various ways after they are synthesized. The modifications, such as phosphorylation, glycosylation, editing, etc., give rise to variants with different functions. In this way, the 25,000 primary protein products can actually be modified to make a set of enzymes with several hundred thousand different functions. That explains why we are so much more complicated than worms even though we have similar numbers of genes.
I don't think any of these explanations are valid because I don't think there's a problem that need explaining in the first place. I wish scientists and science writers would stop pretending that the Deflated Ego Problem is a real scientific problem and I wish they'd stop promoting their favorite, logically flawed, arguments to defend it.

Since that ain't going to happen, I'd like to offer a bit of advice designed to spare us from rhetorical overload. Here's a little template that all science writers can use next time they're tempted to write about this "problem."
(I/we/the authors) believe that the Deflated Ego Problem is a real scientific problem. (I/we/the authors) propose that explanation number (1/2/3/4/5/6/7) will account for the fact that we have too few genes.