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

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.

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.

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. )

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"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.