because all the cool kids are doing it

I'm reading Ada. Apparently I'm not alone (well, I knew I wasn't completely alone, but...)--according to Friendly Co-Op Clerk Who Didn't Make Fun of Me For Not Remembering My Address, about five people had purchased the book in the past two days. Is Ada trendy now?   ¶
6:07 PM

  susan cures smallpox

Perhaps that's an exaggeration. But I was thinking about smallpox the other day, and I had an idea. Variola (the smallpox virus) encodes VGF (viral growth factor, presumably), a homologue to the human protein EGF (epidermal growth factor). VGF binds to the cellular EGF receptor and acts as a growth factor to cells in culture (it promotes anchorage-independent growth). (If you're interested in more and better information on this topic, including how VGF and related proteins prevent ubiquitination of the EGF receptor, thereby continuously transducing the signal, check out this excellent paper by Tzahar et al.) VGF-deficient viruses appear to have no growth disadvantage in vitro, but VGF appears to be play a large role in replication and pathogenicity in vivo. Based on these data, I wonder whether anti-EGF-receptor antibodies (or EGF analogues that would bind to, but not activate, the receptor, a la tamoxifen on the ER) could help slow the progression of smallpox.

This sort of technique--targeting human proteins that are useful to viruses--is a relatively new and extremely interesting one. An obvious advantage of this technique is that, unlike techniques directed against a virus itself, it can be used against viruses that are rarely found outside of cells, like HIV. HIV enters cells by binding to the CD4 receptor on T lymphocytes. However, the virus also needs to bind another cellular protein on the same lymphocyte (a coreceptor) to enter it. This coreceptor may be either CCR5 or CXCR4--in sexually transmitted cases of HIV, viral isolates usually begin as CCR5-binding but can mutate to bind either both CXCR4 and CCR5 or CXCR4 exclusively. Upregulation of either receptor (caused by several diseases) can increase an individual's chance of HIV infection. For a better look at this topic, check out this excellent overview. Anyway, the corresponding principle holds true: decreased expression (or availability) of coreceptors can block HIV infection (at least in cultured cells). Some people are looking for small-molecule antagonists of CCR5 (because CCR5 is the coreceptor in early infection, it's the one most people are targeting). Others have taken a more radical approach and are using RNAi to reduce or eliminate the expression of coreceptors. (I should mention that lack of these coreceptors appears to have little effect upon an individual other than a decreased chance of developing HIV. Check out the article linked above for more complete information.) I thought this experiment was especially cool (mostly because it uses two methods dear to my heart--RNAi and flow cytometry).

Similar work's being done with Ebola virus. In this case, the target is tumor necrosis factor alpha (TNF-alpha). Cells infected with Ebola secrete TNF-alpha, which, among other things, causes blood vessels to become leaky. This causes shock and eventually leads to the general liquefaction that Ebola causes. An experiment that treated Ebola-infected guinea pigs with anti-TNF-alpha antibodies found that about 50% of the guinea pigs discovered from the disease, as compared to the 100% kill rate of untreated guinea pigs. Very interesting.   ¶
5:42 PM

  cringeworthy

Some people have been criticizing Dan Brown's The Da Vinci Code for the liberties it takes with history. Having just finished it, I prefer to criticize it for the liberties it takes with literary good taste. Consider this howler, an exchange between main character Prof. Robert Langdon and a Harvard class:


----------------------------------------------------------------------------------
"The next time you find yourself with a woman, look in your heart and see if you cannot approach sex as a mystical, spiritual act. Challenge yourself to find that spark of divinity that a man can only achieve through union with the sacred feminine."

The women smiled knowingly, nodding.

The men exchanged dubious giggles and off-color jokes.

Langdon sighed. College men were still boys.
----------------------------------------------------------------------------------


I don't really have a problem with the historical inaccuracies--this is, after all, a novel, and it's a bit silly to get in a huff about that. I find it more irritating that Brown is apparently unable to discuss the sacred feminine without getting weirdly moony about it, and that he feels obliged to whack his readers over the head with it ("Look! The random female tertiary characters are wise and serene! Observe the power of the sacred feminine!") Bleargh. For a far more interesting coverage of Brown's topic (well, not the murder mystery part so much as the Jesus part), I highly recommend Robert Graves's novel King Jesus, which is refreshingly free of historical pretentions. For an extremely interesting and non-moony look at the sacred feminine, I recommend Tikva Frymer-Kensky's In the Wake of the Goddesses.  ¶
10:57 PM

  ah, non-scientists writing about science

Ed links to a Boston Globe article which discusses an article by Satoshi Kanazawa that attempts to explain why male scientists "lose steam" as they age. Kanazawa's article strikes me as kind of stupid, but the Globe article--and the question of why (and if) scientists decline as they age--is an interesting one.

Master of the obvious Spencer Weart, a historian at the American Institute of Physics (what does one do in such a job, anyway?) points out that older, tenured scientists spend less time in the lab. Teaching, administrative duties, working on grants, and attending conferences can suck up a huge amount of time. In my experience working in labs of tenured professors, the presence of the professor varies by department: in the MGCB (generally smaller, less well-funded labs), professors tend to do most of their work in the lab, have more contact with postdocs and grad students, and sometimes (gasp!) do benchwork. In biomedical labs (bigger, well-funded, and usually in the hospital, which generally means that the professor's office is not near his or her lab), professors generally work in their offices, have more limited (and structured) contact with employees, and rarely do benchwork. The different perspectives engendered by these two approaches are very interesting (especially to someone like me, who'll be working for one of these types for the next eight years, at least). While the advantages of the former type of professor are obvious, the latter type, in my experience, can have an exquisite understanding of theory and experimental design (when you work on or review grants for most of your day, this happens) that can be immensely helpful to a researcher who needs to understand the "big picture" of her work.

Going back to the article, I find it interesting that Kanazawa's sample group was all male. I'd be curious to see whether there was a difference in a largely female group. In most scientific fields, women are still under greater pressure to "prove themselves" than are their male colleagues. Even in the biological sciences, where women outnumber men in many subdisciplines and are more or less in many more, women still face this pressure. For example, I've been told that, as a woman, I need to play things completely straight when presenting data, though a man would be allowed to have a little more fun with his presentation (nb: given the presentations I've seen, I wish more men would take advantage of this option).

A final comment on the article--David Galenson, a Chicago economist, differentiates biology and archaeology from math and physics on the grounds that the latter are highly theoretical and encourage great leaps of brilliance, whereas the former are ploddingly empirical. I think it's important to point out that the most important discoveries in biology (the ones that are relevant to more than specialists) are generally more theoretical in nature, and that some even seemed ridiculously anti-empirical until years after the theory was introduced. Recent examples of this type of discovery include endosymbiosis, the RNA world hypothesis, and the (charmingly named) histone code. All of them are so fascinating that I plan to elaborate more on them later, but given my normal updating frequency, who knows if that'll happen?  ¶
5:35 PM

  oh, just read the whole journal already

After looking unsuccessfully for the Winzeler article, I poked around Science a little longer. Check out their excellent special feature on chromosomal dynamics.  ¶
6:28 PM

  bugs and drugs

Microbiologists are discovering what cancer biologists have known for ages--if you really want to kill something, target its transcription factors. A NYT article* details a research team's efforts to find new targets for antimalarial vaccines and therapy. Given that the number of transcription factors (and thus the possibilities for redundancy in transcription pathways) increases with the complexity of the organism, it looks like it should be relatively easy to use this approach in Plasmodium. (Plasmodium has fewer than ten transcription factors--in comparison, humans have more than 1000, and my formerly beloved Arabidopsis, despite being amazingly genetically simple for a plant, has upwards of 400. Plant genetics is for badasses.)

Question: is it normal for researchers to culture Plasmodium in their own blood? It seems sort of gruesome to me--also, I wonder if they have to genotype themselves for sickle-cell anemia. How much more expensive would it be to just get the blood from a blood bank, anyway? Is this lab the Trading Spaces of microbiology or something? I had thought that there was big grant money (Gates) out for malaria right now.

*For some reason, the University of Chicago's subscription to Science does not cover the article by Winzeler et al referred to in the NYT article. Huh. Anyway, in this week's Science: an article on measles outbreaks coinciding with a drop in vaccine use. Uh, not to beat a dead horse or anything.  ¶
6:02 PM

  inversions and diversions

There's an interesting review in this week's Nature of a Cell paper by Nishii et al. Essentially, they're looking at Volvox carteri, a green alga, to solve some fundamental problems in the biomechanics of developmental biology. If you remember Volvox from high school bio (it looks like a green hollow sphere with smaller, darker spheres inside it--these are reproductive cells), you may remember its unusual life cycle. Volvox embryos begin as a single reproductive cell, which undergoes five symmetric divisions. After these, an asymmetric division occurs, giving rise to sixteen large cells (reproductive cells) and sixteen smaller cells. At the end of division, the larger cells are still on the outside, while the flagella of the smaller cells are facing inward. To attain the adult body plan, the embryo undergoes inversion.

Sound familiar? It should--this inversion is not unlike that which occurs during gastrulation in animal embryos (and neurulation in vertebrates). The biomechanical processes underlying gastrulation and neurulation are horribly difficult to work out. As the review points out, we've known about flask (or bottle) cells--the elongated cells that are the first to invert in gastrulation--for over a hundred years, but we still don't really know what they do (though we do have a few models). Now, we may have a better idea, as Nishii et al have identified a kinesin (InvA), located in cytoplasmic bridges, that appears to be essential for Volvox inversion. It's expected that this will launch the search for a similar protein in animals. Reading papers like this remind me of how much I miss dev bio ... if only I could find a researcher who's looking at both dev bio and cancer bio in an organism OTHER than fruit flies. And who isn't focusing on hematopoiesis. I guess that's a tall order.  ¶
10:00 PM

  bye-bye, money!

I have discovered the heady thrill of Apple's student discounts. Hello, Mr. G5. I'm going to buy you.   ¶
4:51 PM

  saints in the modern world

During his pontificate, Pope John Paul II has canonized more saints than any previous pope. The total number (more than 460) is a bit deceptive; several large groups of martyrs** make up the vast majority--between 380 and 400, depending on what source you're using--of the total. Of the 98 individual canonizations that I could number, 3 were from the laity, 21 were martyrs, 37 were founders or foundresses, and 37 were religious (including tertiaries and lay priests). Some are questionable, some are charmingly named, and only about eleven are at all familiar to me.* In addition, the Pope has beatified some 1300 people, of whom upwards of a thousand are martyrs.

Why has John Paul II canonized and beatified so many people? (His response to this question in his address Tertio Millennio Adveniente, which I like to think is tongue-in-cheek, claims that there are more Catholics these days than there used to be.) It seems natural to link the huge number of canonizations and beatifications with his extensive traveling; according to the Vatican, 56 of his 99 trips outside Italy have included canonization or beatification ceremonies. This has been particularly evident in countries that aren't traditionally Catholic, such as Korea and Latvia. Some negatively characterize the visits and the canonizations as part of an expansionary program (I guess I don't really see this as a negative thing, though I suppose it's pretty easy if you're fairly anti-Catholic to begin with). On the other hand, it can be seen as an inclusionary policy that puts a face on holiness, so to speak, for the many Catholics who live outside Europe, whence hail most saints.

That brings up another issue; namely, what is the place of saints in the post-Vatican II Church? One of the most crucial tenets of Vatican II is the call to holiness for all Catholics. One of the most compelling responses I have found to this question is in a reflection by Cardinal Jose Saraiva Martins.

Therefore holiness, with its own special quality, also affects culture. The saints have made it possible to create new cultural models, new responses to the problems and great challenges of peoples, new developments for humanity on its way through history.

Given the current state of affairs in the Church, I'm sure we can use a few new ways to be holy. I'd be interested to see whether John Paul II's successor, whoever he may be, keeps up with JP2's rates of canonization and beatification, and whether the trends that have developed in recent years (namely, relatively large numbers of founders and foundresses being canonized) continue.

NB: It should be noted that at least a few of the canonizations have been quite controversial. For example, the beatification and canonization (both occuring during the current pontificate) of Teresa Benedicta of the Cross, born Edith Stein, a philosopher who converted from Judaism, became a Carmelite nun, and died in Auschwitz have been the subject of intense debate. The issue of whether she was killed because of her perceived Judaism or her actual Catholic faith (while it is an issue--the Church can split hairs on reasons for martyrdom when it wants to, as in the case of Oscar Romero) is secondary to the issue that Stein's canonization represented a desire on the part of the Church to "Christianize the Holocaust". At the very least, Stein's canonization in the midst of controversy over the Church's complicity in the Holocaust was a case of excruciatingly poor timing.*** Another controversial saint is Josemaria Escriva, the founder of Opus Dei, a very right-wing Catholic organization that has huge support in the Vatican. Opus Dei has been called pretty much everything from a modern, laic version of 16th-century Jesuitism to a cult that promotes mortification of the flesh. His beatifications have been no less controversial--this is, after all, the man who tried to beatify Pope Pius XII, who has been accused of complicity with the Nazis during the Holocaust. He ended up beatifying Pope Pius IX, who, despite starting out as a fairly liberal cleric, set the Church back decades with the publication of his Syllabus of Errors.

Recommended reading: Kenneth Woodward's excellent book Making Saints: How the Catholic Church Determines Who Becomes a Saint, Who Doesn't, and Why.

*The 101 companions of Andrew Kim Taegon and Paul Chong Hasang, the thirteen companions of Lorenzo Ruiz, Domingo Ibanez de Erquicia, and Jacobo Kyushei Gorobioye Tomonaga, the 116 companions of Andrew Dung-Lac, the eight companions of Cirilo Bertran and Inocenco do la Inmaculata, the 24 companions of Cristobal Magallanes, and the 119 companions of Augustine Zhao Rong.

**Maximilian Kolbe, Andrew Kim Taegon, Paul Chong Hasang, Andrew Dung-Lac, Mary Marguerite Dufrost de Lajemmerais, Rose Philippine Duchesne, Edith Stein, Katharine Drexel, Padre Pio, Juan Diego Cuauhtlatoatzin, and Josemaria Escriva, if you were curious.

***This wasn't the last time JP2 chose to push the wrong issue at the wrong time--viz his denunciation of gay marriage and adoption (which he linked to child molestation) during the clerical sex abuse scandal.
  ¶
7:36 PM