Thursday, May 31, 2007

Thoughts from our appallingly ignorant national leadership...

Blogging around here really will resume soon, as soon as my talk is over after tomorrow. Right now I don't have time to comment on two appalling expressions of ignorance, one on evolution by Republican Senator and Presidential candidate, Sam Brownback, and the other on global warming by NASA administrator Michael Griffin; I'll just direct readers to some other good blog responses.

For a critique of Griffin's claim that global warming, although real, is not something we need to be worried about (a claim I heard him repeat on NPR this morning), check out this piece by Chris Mooney.

For a response the Brownback's affirmation of creationism, check out Pharyngula.

Friday, May 25, 2007

My dirty secret...

It's been a little busy around the lab and home, but more science is coming up soon: The new technique of ChIP-seq, the opossum genome, book reviews of Uncertainty and I am a Strange Loop, and hopefully this weekend a piece on quaternions and vectors in Pynchon's Against the Day.

And now for my confession:

OK, I watched the American Idol finale. In fact, I've watched much of the American Idol season. The show isn't exactly filled with my style of music, but hey, it's entertaining. And as a Green Day fan, I lucked out - Green Day gave an electrifying performance of John Lennon's "Working Class Hero" on the American Idol finale; by far the best performance of the night.

I never thought Green Day would be caught dead on a show like American Idol, but I suppose it was a good way to publicize the humanitarian Instant Karma project. I was struck by the irony of the whole thing though: to the cheering crowd Billie Joe Armstrong sang

"Keep you doped with religion and sex and TV
And you think you're so clever and classless and free
But you're still fucking peasants as far as I can see..." [with 'fucking' bleeped out of course],

while one of the show's executive producers told an interviewer that this year's American Idol finalists "are some of the most commercial finalists we've had since Carrie Underwood... Either one will make a great winner for the show and the brand. They both have the potential to sell many records."

Wow - Lennon's lyrics vs. Marketspeak - if it got any more dissonant than that the universe would explode.

Sunday, May 20, 2007

It's not just the pet food...

Why is the US so driven by greed? Somehow we care so much about corporate profits that we can't even effectively make sure that our food is safe. This story in Sunday's Washington Post (free registration required) details the tainted food (human food - not just pet food) shipments from China that the underfunded and understaffed FDA is trying to keep out of the US food supply. The foods that the FDA turns back are unsanitary, stored in carcinogenic preservatives, filled with antibiotics banned in the US, and much more.

In spite of numerous recommendations from the National Academy of Sciences and various other expert panels to institute more serious efforts to protect our food supply, corporate interests and the large potential Chinese market for US exporters have been higher priorities than the safety of US consumers.

Here's how the Washington Post puts it:

"Dead pets and melamine-tainted food notwithstanding, change will prove difficult, policy experts say, in large part because U.S. companies have become so dependent on the Chinese economy that tighter rules on imports stand to harm the U.S. economy, too.

"'So many U.S. companies are directly or indirectly involved in China now, the commercial interest of the United States these days has become to allow imports to come in as quickly and smoothly as possible,' said Robert B. Cassidy, a former assistant U.S. trade representative for China and now director of international trade and services for Kelley Drye Collier Shannon, a Washington law firm."

The US economy always ends up being the sacred cow that must not be harmed at any cost - such as our health or our environment. And it is unfortunate that in a nation where much of the world's very best science is done, and where at one time we made groundbreaking advances in modern society by establishing agencies that were charged with protecting our citizens based on the best science available, we can't put together the political will to actually make use of our considerable expertise to keep our food safe.

Wednesday, May 16, 2007

Studying General Principles of Biological Systems - How flies make sense of smell

About two months ago I was in Steamboat Springs, Colorado, attending the Keystone Symposium on Systems Biology and Regulatory Networks. I went hoping to hear about forward-looking research that deals with some of the most fundamental outstanding questions in biology - fundamental in the sense of being relevant not just to a particular cell type or organism, but to most cells, developmental systems, or biological systems in general.

I not sure whether I really got a glimpse of the future at this meeting, but I did get a good view of the present. Many of the speakers at this meeting are running labs that have made steady contributions to what is currently being called systems biology. I think these labs are producing good research, but I'm not so sure that this is what systems biology should look like. Much of the work presented at the conference was high-throughput data collection and analysis; in other words, genomics. This type of research can help obtain a global picture of what's going on in the cell - such as where all of the transcription factors (DNA-binding regulatory proteins) are under a given set of conditions, or which genes or proteins interact with each other (physically or genetically), forming an 'interaction network.' Unlike a lot of stuff out there that's billed as systems biology, much this stuff was quite good - the organizers did a good job of selecting worthwhile speakers.

However, there are two primary reasons I don't think this type of research is really what systems biology should ultimately be:

- What we learn isn't fundamental enough - it only applies in certain limited cases, where there are directly homologous systems in other cell types or organisms; it's not about biological systems in general.

- The arguments aren't quantitative enough - we may learn quantitative things about many individual genes and proteins, but what we say about the big picture is still only qualitative. In other words, we can't yet reason about biological systems in the same way we reason about engineered, nonliving systems like circuits.

These are hard challenges to meet, but unless we meet them, systems biologists will only be saying the same types of things about cells that molecular biologists have been saying for decades, except that they'll be saying them about larger and larger datasets.

My favorite talk of the conference was by John Carlson, from Yale, who spoke about how fruit flies smell what's in their environment. Or, in Carlson's words (co-written with Elissa Hallem):

"Sensory systems produce internal representations of external stimuli. A fundamental problem in neurobiology is how the defining aspects of a stimulus, such as its quality, quantity, and temporal structure, are encoded by the activity of sensory receptors."

Basically, Hallem and Carlson wanted to figure out how a fly's odor sensing machinery is able to discriminate among the many different odors a fly encounters in its environment. An odorant is an often complex molecule, one that binds to odorant receptors (proteins in the cell membrane), which in turn activate a neural signal. Flies (and humans) possess many different odor receptors, but not nearly enough to have one receptor for every odor they can perceive. Instead, flies have to make do with receptors that can detect a variety of odorants, and their neural systems have to integrate this data to produce a useful internal representation of the odors in the environment.

Hallem and Carlson took some of these fly odorant receptors and expressed them in special neural cells which harbored no other odor receptors. They would then expose the neural cell to an odorant; if that odorant activated the receptor, there would be an electrical pulse in the neural cell that they could measure. These researchers managed to actually measure this in live flies instead of just using neurons in tissue culture. They would suck up a fly into a pipette, leaving only its head sticking out, and then expose the fly to various odors.

In this way they tested over 100 different odors on several dozen different odorant receptors. Not surprisingly, some receptors were activated by a broad spectrum of odors, while others were sensitive to only a few odors. Furthermore, each receptor was sensitive to a unique combination of odors; that is, no two types of receptor responded to exactly the same odors, although there was a lot of overlap in the sensitivity of receptor types.

Carlson reported much more data, which I am skipping over here, but to make sense of it all, Carlson and Hallem represented their data in a 24-dimensional 'odor space' (one dimension for each receptor in the analysis). By analyzing the data this way, they were able to categorize the various odorants: certain groups of odors activated very similar sets of receptors; certain odors produced a complex response (that is, they activated many different receptors) while others produced a simple response (by activating only a few receptors). In essence, they were able to characterize classes of odors by the combinatorial neural response the odors produced.

In the paper I linked to above, Hallem and Carlson end with this tantalizing sentence:

"This analysis provides a foundation for investigating how the primary odorant representation is transformed to subsequent representations and ultimately to the behavioral output of an olfactory system."

At the conference, Carlson made good on this promise. Since this is unpublished work, I can't write publicly about what he shared yet. But essentially, he has been able, using his odorant data, to build a fairly predictive model of fly behavior that actually works. When I see his paper come out, I'll post an update here.

This is good systems biology. Carlson is doing more than just laying the foundation for a better bug-repellent; he is tackling a fundamental problem of how complex environmental signals are processed by limited numbers of neurons in an animal to produce a coherent behavioral response.

Thursday, May 10, 2007

A Bad Mix: Psychiatric Drugs, Money, and Children

I gripe about the poverty of postdoctoral scientists, but I'd rather be poor and keep my professional integrity than be lavishly paid by drug makers and lose my conscience. The NY Times has a story about psychiatrists who receive payments from drug makers, and who also just happen to have a tendency to frequently prescribe 'atypical drugs' for children. (Atypical here means prescribed for an unconventional use or patient population, one for which the drug was not initially designed. Atypical prescriptions are not necessarily bad - physicians are allowed to use their professional judgment to write such prescriptions.) This isn't a new issue by any means, but the NY Times story reemphasizes its importance.

The story described physicians who are paid thousands of dollars by drug makers to lecture on or write about (in other words, promote) potentially best-selling anti-psychotic drugs. Those same physicians just happen to prescribe these drugs much, much more frequently than physicians who are not paid by pharmaceutical companies. Often the patients receiving these prescriptions are adolescents or children - populations on which these drugs have not been well tested.

Amazingly, these physicians think that this massive conflict of interest can be dismissed simply by denial. According to the NY Times:

"Doctors... maintain that payments from drug companies do not influence what they prescribe for patients."

Yeah, right.

Even without any malicious intent, a conflict of interest can exert an influence on someone's behavior. The NY Times quotes Dr. Steven Hyman, the provost at Harvard:

"There’s an irony that psychiatrists ask patients to have insights into themselves, but we don’t connect the wires in our own lives about how money is affecting our profession and putting our patients at risk."

If a drug works well for a certain class of patients, it should be promoted by physicians who give lectures because they are leaders in their field, not because they have been selected by marketing executives to push the drug. These physicians should show some integrity and not accept lecture fees or other honoraria from drug makers.

No matter how fervently these physicians believe that their professional judgment is not affected, at the very least they should care about maintaining the trust of their patients. Would you be concerned if your child's physician was being paid thousands of dollars to promote an anti-psychotic drug, not officially approved for use in children, that had just been prescribed for your child? I sure as hell would.

Saturday, May 05, 2007

Darwin Among Republican Presidential Contenders

One third of the Republican presidential candidates, when asked in their recent debate whether they believed evolution, admitted that they don't buy it. The blogosphere has already said much about this, and today the NY Times picks up the story.

The NY Times includes this appalling quote by Larry Arnhart, a poli sci professor at Northern Illinois University:

"The intellectual vitality of conservatism in the 21st century will depend on the success of conservatives in appealing to advances in the biology of human nature as confirming conservative thought."

How convenient when science can confirm one's preconceived notions! That's exactly the opposite approach an intellectually honest person (not to mention someone who calls himself a scholar) should be taking, and it's not helpful for the intellectual vitality of any movement that embraces such an outlook.

This whole debate - whether evolution (not 'Darwinism' - evolution is much more than Darwinism) supports conservative thought - brings to mind something Richard Feynman said when discussing the philosophical implications of the Uncertainty Principle:

“In any case that I have ever seen of any of the philosophical ideas of the sciences dragged out into another field, it's completely distorted, a trivial shadow of its original idea, and it seems in some respects to be quite silly..." - and quite wrong, I should add.

(Feynman quote is from the audio recording of Feynman's second lecture on quantum mechanics in his Lectures on Physics.)

Friday, May 04, 2007

Will the real systems biologist please stand up?

According to the NIH, you can't be a systems biologist and an experimental geneticist at the same time. The NIH has issued a call for applications to:

"use systems biology approaches to investigate the mechanisms that underlie genetic determination of complex phenotypes.  These projects will combine computational modeling approaches and experimental validation of predictive models."

This is exactly the kind of thing our lab is working on. We have expertise in both mathematical modeling and experimental genetics and biochemistry. But according to the NIH, my boss would have to find someone else to collaborate with if he wanted to apply for this particular grant:

"It is expected that a team of at least two principal investigators (PIs), one with expertise in systems biology and the other with expertise in the genetics of humans or model organisms, will apply for funding under this FOA.  Applications from a single investigator or that propose solely data production and accumulation will be considered non-responsive and will not be reviewed."

At this point, systems biology is such a chaotic, diverse field (you can't really call it a discipline) that it is really an absurd exercise to try to define who has "expertise in systems biology." Almost all of the people publishing what is called systems biology were trained in other disciplines - math, physics, engineering, computer science, and yes, biochemistry, genetics, and molecular biology. (Just check out the faculty in Harvard's Department of Systems Biology.)

Computational biologist Sean Eddy (who trained as a molecular biologist) had the following to say about the team appraoch adovcated by the NIH:

"It's also depressing to read that the National Institutes of Health thinks that science has become too hard for individual humans to cope with, and that it will take the hive mind of an interdisciplinary “research team of the future” to make progress. But what's most depressing comes from purely selfish reasons: if groundbreaking science really requires assembling teams of people with proper credentials from different disciplines, then I have made some very bad career moves."

He goes on to talk about the biologist Howard Berg (who trained as a physicist):

"He's successfully applied physical, mathematical, and biological approaches to an important problem without enlisting an interdisciplinary team of properly qualified physicists, mathematicians, and biologists. As he recently wrote, perhaps he'll have to start collaborating with himself."

It is depressing to see that talented investigators who have skills in both areas are barred from applying under this application request.

Tuesday, May 01, 2007

Douglas Hofstadter is a Strange Loop

If you liked Godel, Escher, Bach, you'll be happy to see that Douglas Hofstadter has a new book out - I Am a Strange Loop. This new book, according to Hofstadter, gets to back to the heart of the subject that Hofstadter dealt with in GEB, much more so than his other books. I never read any of his other books after GEB - I loved GEB, but somehow the other books just didn't catch my interest.

I Am a Strange Loop, however, looks very compelling. It's Hofstadter's take on how consciousness arises - a problem that I see as closely related to systems biology. The big common question is: how does a coherent system (and consciousness is the coherent system par excellence) arise from the complex interactions of it's usually non-hierarchical parts?

Hofstadter is also one of the most literary authors of science books, and it looks like he's true to form in this latest one.