The Daily Transcript

Richard Dawkins The Root of all Evil Part I

2006-08-27T13:41:00.000-04:00


yup

The blog is moving

2006-03-02T12:40:00.000-05:00

Yes, I had mentioned this to some of you, and now it's finally come to fuition - my blog is moving to Science blogs. The new address is:

http://scienceblogs.com/transcript/

Enjoy!

Eye Candy

2006-02-28T09:27:00.000-05:00

Well writing a paper makes you feel beaten-up. But now that it's done I feel better. (Hope the reviewers like it).

PS Guess what's I've captured in this image.

The Picture of a Happy Scientist!

2006-02-27T16:08:00.000-05:00

So my blog's been suffering from neglect. (I'm writing up a paper.)

Hopefully it'll get in some journal, then I'll be a happy scientist!

Speaking of happy scientist, check this photo out (to the right).

And why is he happy? He not only just published a paper but is on front page of Harvard's website. Check out the Harvard article, and the original article in Nature Chemical Biology. What a golden moment!

{Update}

I've been asked to save the actual webpage cover for future reference ... I've done one better and pasted it on the blog:

Notice that Brian's paper is a bigger news story than Larry Summers' departure. Ah success!

{Update 2/28/06}

Basic summary: Brian found that Gold, platinum, and some other heavy metals can bind and inactivate MHC II and thus be used to treat autoimmune disorders.

Brian told me that when he discusses his results with many western doctors they are not that interested, while doctors from the developing world are enthralled. Not only is this treatment cheap, but it turns out that many local remedies for arthritis and other autoimmune diseases involve heavy metal administration.

Ref: Stephen L De Wall et al., Noble metals strip peptides from class II MHC proteins. Nature Chemical Biology, Published online: 26 February 2006

Mimivirus

2006-02-24T09:04:00.000-05:00

While reading, Keat's Telescope, I read an interesting entry on Mimivirus.

I've been reading a bit on this weird creature. Last year its genome was sequenced (see the Science article). It is 1.2Mbp (longer than some eubacteria) and has over 10,000 genes, some of which are house keeping genes such as tRNAs and amino-acyl transfer RNA synthetases (proteins that load up the tRNAs with amino acids). Infact it was originally thought to be a bacteria, you can see it by light microscopy ... then someone looked at it in an EM (electron microscope) and saw it's true nature. In comparing it's house keeping genes to homologues in bacteria and eukaryotes, it's thought that Mimvirus is so ancient that it may represent a fourth branch in the tree of life (along with eubacteria, archaebacteria and eukaryotes).

To read more, check out the March edition of Discover Magazine.

Refs:
Bernard La Scola et al., A Giant Virus in Amoebae. Science (2003) 299:2033
Raoult et al., The 1.2-Mb Genome Sequence of Mimivirus. Science (2004) 306:1344 - 1350

Some General Comments about Larry Summers

2006-02-22T08:40:00.000-05:00

So the news is all over the papers. Of all the articles I've read this morning, the most appropriate is Alan Dershowitz's OpEd in the Boston Globe.

I didn't agree with everything our President said, but in the end his goals were to provoke debate. Yes there were other problems ... his relationship with Cornell West, his confrontational style ... but in the end his comments about women in Science did him in.

But just as I hated the review by Leon Wieseltier (see here) it pains me to read the comments of all those who wanted Larry to step down due to the comments on sex. It is worth it to go and read what Larry actually said. He wanted to open debate and stimulate research concerning this topic. I do believe that Academia has a duty to investigate why the differences between men and women in many endeavors, but my guess is that both those of the right and left of the political spectrum would be surprised by the potential findings.

We may not agree with what Larry said, but the proper answer is to study the matter further not stifle debate (and use personal attacks to change the subject). My biggest guess is that to get to the top of Academia, takes a lot of (ridiculous) sacrifice and here is why more women than men opt out. As postdocs we get next to nothing to help support families etc. it's hard to justify staying in Academia ... and I don't have to worry about pregnancy. And in my opinion, something has to be done about it. The problem is not Larry, and it's not men vs women, IT'S THE SYSTEM.

For the record ... I've copied an entry from my old blog about the speach in question.

---------------------------------------

Friday, 18 February 2005

Larry Releases Transcript

Well here is the transcript!

This was part of a speech on gender ratio imbalance in Math and Engineering. What is the ratio of men to women in other fields? High up, it's not much better.

Well he starts off with a strange comment:

It is after all not the case that the role of women in science is the only example of a group that is significantly underrepresented in an important activity and whose underrepresentation contributes to a shortage of role models for others who are considering being in that group. To take a set of diverse examples, the data will, I am confident, reveal that Catholics are substantially underrepresented in investment banking, which is an enormously high-paying profession in our society; that white men are very substantially underrepresented in the National Basketball Association; and that Jews are very substantially underrepresented in farming and in agriculture. These are all phenomena in which one observes underrepresentation, and I think it's important to try to think systematically and clinically about the reasons for underrepresentation.

What a bizarre mix of things to say!

And the relatively few women who are in the highest ranking places are disproportionately either unmarried or without children, with the emphasis differing depending on just who you talk to. I agree! A career in the Sciences (or most professions) is not compatible with raising a family. But I think that this is also true for fathers.

Larry may have a point in that usually women bare the brunt of the child rearing. However I believe that it's easier for husbands to dump this responsibility on their wives and this maybe facilitated by the type of society we live in.

... and the work that Claudia Goldin and Larry Katz are doing will, I'm sure, over time, contribute greatly to our understanding of these issues and for all I know may prove my conjectures completely wrong.

I'll have to look in to these studies ... Now on to IQ ...

I looked at the Xie and Shauman paper-looked at the book, rather-looked at the evidence on the sex ratios in the top 5% of twelfth graders. If you look at those-they're all over the map, depends on which test, whether it's math, or science, and so forth-but 50% women, one woman for every two men, would be a high-end estimate from their estimates. From that, you can back out a difference in the implied standard deviations that works out to be about 20%. And from that, you can work out the difference out several standard deviations. If you do that calculation-and I have no reason to think that it couldn't be refined in a hundred ways-you get five to one, at the high end. Now, it's pointed out by one of the papers at this conference that these tests are not a very good measure and are not highly predictive with respect to people's ability to do that. And that's absolutely right. But I don't think that resolves the issue at all. Because if my reading of the data is right-it's something people can argue about-that there are some systematic differences in variability in different populations, then whatever the set of attributes are that are precisely defined to correlate with being an aeronautical engineer at MIT or being a chemist at Berkeley, those are probably different in their standard deviations as well.

Well it's hard to say whether these 5th graders are already "socialized". Also why are there more women (than men) enrolling in college. Does US society affect this? In Canada medical school is dominated by WOMEN!

So my best guess, to provoke you, of what's behind all of this is that the largest phenomenon, by far, is the general clash between people's legitimate family desires and employers' current desire for high power and high intensity, that in the special case of science and engineering, there are issues of intrinsic aptitude, and particularly of the variability of aptitude, and that those considerations are reinforced by what are in fact lesser factors involving socialization and continuing discrimination.

Well that's still up for debate. My own opinion is that the clash between family and career, and socialization (the two of which ARE related) are probably the main cause. The lack of support from institutions (such as Harvard which due to its prestige can get away with throwing scraps to it's professors) is also a big problem. Here at the Medical campus the "new research building" was recently completed. I was told that when asked what facilities should be included, most faculty and staff replied "daycare facilities". What did they build? A gym!

I would like nothing better than to be proved wrong, because I would like nothing better than for these problems to be addressable simply by everybody understanding what they are, and working very hard to address them.

Cute Larry... Well if anything this episode will be good in the longterm. These are issues that need to be discussed.

The only other question is: Will Larry survive?

Larry's Gone

2006-02-21T16:07:00.000-05:00

Well rumors were flying around all morning. Then we heard something on the radio. Now sitting down at my laptop this afternoon to check my email ... this:

From: Lawrence Summers [official@harvard.edu]
Sent: Tue 2/21/2006 1:05 PM
Subject: Message from President Summers
Attachments:

Dear Members of the Harvard Community,

I write to let you know that, after considerable reflection, I have
notified the Harvard Corporation that I will resign as President of the
University as of June 30, 2006. I will always be grateful for the
opportunity to have served Harvard in this role, and I will treasure the
continuing friendship and support of so many exceptional colleagues and students
at Harvard.

Below are links to my letter to the community, as well as a letter from the
members of the Corporation and a related news release.

Sincerely,
Larry Summers

http://www.news.harvard.edu/gazette/daily/2006/02/21-summers.html
http://www.president.harvard.edu/speeches/2006/0221_summers.html
http://www.news.harvard.edu/gazette/daily/2006/02/21-board.pdf

I guess that's the end of the Summers Saga.

Why rant when the blogosphere can rant for you

2006-02-21T10:43:00.000-05:00

This Sunday in the NY Times Book review section, I read a horrible review of Daniel Dennett's book Breaking the Spell: Religion as a Natural Phenomenon. I wanted to write up a blog entry or a letter to the editor, but I had too much stuff to do.

I haven't read it, but I've read several interviews (one in the NY Times Saturday Magazine) about the book. Dennett's has two proposals ... first that academia should study the reason why humans have religion - as in the biologically/evolutionarily based reason why we've developed religion, and second, does religion confer any benefits to individuals or to society.

In other words, did the belief (or predisposition) in religion offer some benefit to our ancestors? And today, is religion making you happier, healthy ... ?

Instead of a critique, the review by Leon Wieseltier offers an incoherent analysis of the whole endeavor of academic research. In addition, the review is laced with personal attacks, as in

In his own opinion, Dennett is a hero.
...
Dennett is the sort of rationalist who gives reason a bad name; and in a new era of American obscurantism, this is not helpful.
Dennett flatters himself that he is Hume's heir.
...
In the end, his repudiation of religion is a repudiation of philosophy, which is also an affair of belief in belief. What this shallow and self-congratulatory book establishes most conclusively is that there are many spells that need to be broken.

And there's more ... Dennett has "naturalist superstitions" and spreads "Scientism". Wieseltier attacks Dennett's reasoning by reasoning that reason can't be used to study religion. What the bloody hell??? In other words, please don't ask rational questions.

Do I need to write more? Yesterday, I was amazed by all the fuss generated in various blogs on the subject of the book. So instead of repeating what they said, go and read them.

Brian Leiter
Silly Humans
Pharyngula
Stumblings in the dark
The Little Green Blog
Shotgunfreude
The Secular Outpost
Science and Politics

Scientists Taking Holidays?

2006-02-20T10:28:00.000-05:00

Yes it's President's Day, but does that stop the lab from filling up?

If you are concerned that Holidays may slow down the pace of Science, fear not, Scientists have lost the ability to take time off! (or perhaps to identify major holidays/weekends)

This fact was seared into my brain last night. I had to stop by the lab to poly-adenylate some RNA I needed for an experiment, and who do I see in the lab at 10:30PM on a Sunday night of a three day holiday? Not a desperate postdoc, or some struggling grad student, (well that's not true, I found one of those in the computer room), but a lab technician. When I asked him, "what's up?" his reply was, "concentrating protein and reading my novel".

Amazing.

A Slice of Life Scarves

2006-02-18T08:10:00.000-05:00

As a microscopist you are often are stunned by the beauty of what's on your microscope slide. I remember as a grad student showing this technician (a former doctor from China) a slide where cells were stained by immunofluorescence against microtubules. After peering into the microscope he turned to me and said, "there must be a God". Yes quite beautiful stuff.

So it came as no surprise when a good friend of mine sent me a link to A Slice of Life Scarves. This company uses motifs from the life sciences as patterns for their scarves and ties. Besides Golgi scarves (left) and centriole ties, they even have sarcomere ties (for those power meetings!)

Bimolecular Fluorescence Complementation

2006-02-16T14:11:00.000-05:00

Just read an article in the last issue of JCB, where the authors used a nifty new technique to investigate when and where certain RNA binding factors associate together.

What's neat, is that this technique, bimolecular fluorescence complementation (or BiFC) works by fusing each half of a fluorescent protein (in this case yellow-fluorescent protein; YFP) to two proteins of interest (in this paper the RNA export factor TAP/NXF1 and the RNA binding factor Y14). To regenerate the intact YFP molecule the two proteins in question must come together. Since the fluorescence can be monitored without fixatives you can mow monitor this potential interaction in living cells.

In the past researchers used a related technique called FRET, or fluorescence energy transfer, to demonstrate the interaction of proteins in live cells. It works by fusing one type of fluorophore (say fluorophore "A") to protein #1 and a second type of fluorophore (say fluorophore "B") to protein #2.

If the two proteins came close enough, when excited, fluorophore A can donate (or transfer) it's energy to fluorophore B.

Stimulate A, measure B.

The problem is that when you stimulate fluorophore A, a fraction of it's emitted light overlaps with the fluorophore B's emission spectrum. In addition when you excite fluorophore A, some of fluorophore B will get excited directly (i.e. not by energy transfer) and emits some light. These sources of non-FRET fluorescence contribute to background or noise, and limits your detection. As any good microscopist knows detection = signal/noise. So the only way to determine the amount of fluorescence caused by FRET, is to perform very precise measurement to get the values for the noise (background fluorescence) and total fluorescence (FRET + background) of the experiment. Often FRET changes the fluorescence by as little as 10% of the total fluorescence ... not a very high signal to noise ratio!

With BiFC, fluorescence will only occur once the two YFP halves come together ... thus reducing the backgroud and increasing the signal to noise ratio. The authors provide data that the two YFP halves don't interact on their own, so BiFC can only result if TAP and Y14 get close to each other. One nice result from these experiments was that although the TAP protein is found primarily at the nuclear rim, the BiFC fluorescence (and hence TAP-Y14 association) was seen in another part of the nucleus, in speckles. When the authors swapped which YFP half was attached to TAP and Y14, BiFC wasn't observed indicating that for BIFC to occur, the two halves of YFP have to be not only close to each other but also correctly aligned. In addition the authors only observed fluorescence when the RNA binding motifs of both TAP and Y14 werefunctional, suggesting that the two proteins associate together when bound to a transcript (i.e. mRNA).

So in summary here's another tool to monitor protein interactions in cells. We'll have to see whether this technique can be used for other protein combinations. OK that's enough flashy science for today ...

{Update 2/18/06}

Here is image 1 from the paper described above. They show BiFC fluorescence, staining against the C-terminal half of YFP (YC), DNA (DAPI) and a color merge. This as a good example of using black and white images to present data. If you wonder why the image looks strange, the authors have inverted the B&W picture (i.e. black=fluorescence, white=no fluorescence). This type of data presentation can often help to display very faint patterns. If you look in "B" Y14 is found in speckles while TAP/NXF is localized to the nuclear rim.

Ref: Ute Schmidt, Karsten Richter, Axel Bernhard Berger, and Peter Lichter, In vivo BiFC analysis of Y14 and NXF1 mRNA export complexes: preferential localization within and around SC35 domains JCB (06) 172:373-381

Postgenomic: The Biomedical Science Blog Clearinghouse

2006-02-15T10:36:00.000-05:00

Just read a post from Evolgen, about this new biomedical blog aggregator started by the Flags and Lollipops blog. It's called Postgenomic.

Once in the site you'll find links to blogs entries that review papers, science meetings and hot discussion topics. Also this site features lots of stats, like "the wordiest science blogs". Incidentally according to the stats on that page I'm pretty wordy 373 words/post or #15 out of 66 listed blogs ... I'm not sure whether this is good or bad.

(BTW This post will definitely lower my word count!)

More Media

2006-02-13T18:55:00.000-05:00

No, not he type used to feed cells (or gradstudents), but webcasts, podcasts and films.

First, Robert Write has an interview with Edward O. Wilson at his site meaning of life tv (which incidentally has lots of great interviews). I like Wilson's take on the difference between Science and all other human organizations ... IDers take note. [From the Gene Expression blog.]

Next Science magazine finally got it's act together and are now producing a weekly podcast (a little more in the style of NPR than Nature's podcast). Interestingly they us a piano riff (between segments) that's yanked off one of my favorite albums, Medeski Martin Wood's Notes from the Underground. [For MMW fans, this is their first and only TRUE jazz album before they did hokey techno-infused pseudojazz - to get a feel of this album listen to this clip.]

Finally I saw a great movie, Cache ... it's comprehendable if you do see it keep in mind West/Middle East relations and the Iraq war. To read more (including a spoiler) see my analysis at the Cache website.

Further Differentiation within the ER

2006-02-12T09:52:00.000-05:00

OK this week I've been obsessed with the endoplasmic reticulum (ER). This organelle is comprised of a continuous network of membranous tubes (and sheets) that extends to the cell periphery. In addition ER sheets also envelopes the nucleus - forming a bilayered nuclear envelope with an outer nuclear membrane and inner nuclear membrane.

Here's a pic of the ER from a previous post:

The extended part of the ER though is mostly tubular, as I displayed in an earlier post on Immunofluorescence images:

So the question becomes ... how do you form tubular organelles?

Well Gia Voeltz, from our lab just published a paper in Cell on how a class of proteins (Reticulons and DP1-related proteins) are responsible for this architecture. Reminiscent of an earlier post where I described how Nesprins are confined to the outer nuclear membrane (and thus help to differentiate that portion of the ER), reticulons and DP1 define another part of the ER, the reticular or tubular part. So reticulons are excluded from the nuclear membrane. But there's more, Gia used an assay to form tubules in vitro (i.e. in a testube) from ER vesicles derived from frog eggs. She could inhibit the tube formation by modifying reticulons or by adding antibodies against reticulons. In addition the way reticulons are inserted into the membrane is not typical of most membrane proteins, and this strange "topology" may help them to curve membranes and thus help to form tubes.

Here are a black & white images with a color overlay (from Gia's paper), that demonstrate the unique distribution that reticulons adopt. Notice how a general ER marker (Sec61-beta) is in the tubular portion and in the nuclear envelope, but that reticulon4a (also called NogoA) is only found in the tubular ER. Note how the black and white image of Rtn4a (but not the color overlay!) clearly demonstrates how reticulons are excluded from the nuclear envelope.

To read more check out the paper.

Ref: Gia K. Voeltz, William A. Prinz, Yoko Shibata, Julia M. Rist and Tom A. Rapoport, A Class of Membrane Proteins Shaping the Tubular Endoplasmic Reticulum Cell (2006) 124:573-586

Interview with Bil

2006-02-10T19:50:00.000-05:00

It's Friday night, I'm in the lab writing my paper when who pops up in an IM chat screen? Bil the man. He's starting up a new lab in California. We chatted a bit ...

Mad Scientist: man I should do a blog "interview" with you

Bil the Man: Right.

MS: (just another excuse not to work on the paper) ok here goes

BtM: Dude, I have sht to do.

MS: so do I

BtM: Yeah, well, if you don't need quick answers. I'm writing my first e-mail to an undergrad interviewing next week.

MS: What's the best thing about becoming a PI?

BtM: The best thing is that I get to make all the decisions. The worst thing is that I have to make all the decisions.

MS: Anything you didn't anticipate?

BtM: As a PI there is a lot of administration, a lot of politics, and lots of decisions. It is really easy to stay busy. I'm only taking baby steps and it is already very complicated. The money also goes really fast.

MS: Really, out of money ... what are the big ticket items?

BtM: Centrifuges burn the money fast. I regret buying one of them already but hopefully it won't be a big mistake. Also, they come with rotors at over 5K each. That package cost me nearly 200K. Incidentals add up fast too. I'm looking at a 20K order from Fisher/VWR.

MS: That's why Tom is constantly obsessed with rotors ... so what's the status on the lab? When will you be pippetting away in there?

BtM: We'll be starting in about 2 weeks I hope. All the big stuff should be here by then. That will be almost exactly 2 months from day 1. My Tech is aching to start pippetting. I hope he feels the same way in 2 months.

MS: Are you excited? Anxious?

BtM: I'm anxious. I really want to get started. I don't want to rely exclusively on others supplies so I'm waiting a bit. We'll be moving pretty fast once we get started. I think the two people I have so far are capable of a lot of output.

MS: I'm impressed that you don't feel (or appear to feel) overwhelmed. Do you ever think to yourself "man I'm responsible for all this money, people etc."?

BtM: Not really, I feel a lot or responsibility but I don't feel like that is complicated. I've made a few mistakes but those were learning mistakes. ie If you don't know for sure get advise. I have a lot of support from the other faculty. I feel overwhelmed that little of what I've been doing involves the details of the science. So far it has all been about setting up the lab and administration. I'm looking forward to talking science in a real way again. Hopefully my lab will give me that.

MS: Ok I should be going for dinner soon so one last question. If you were to guess, when is the first big paper coming out?

BtM: Oh man, I don't want to jinx anything. I'm hoping the next interesting paper will be SecY mutants....

MS: Thanks ... one of the best interviews I've had so far ... well thought answers, I guess that's why they hired you (well not really)...

BtM: Man, you have no idea how serious this job makes you. I'm looking forward to relaxing once we are focusing on research.

MS: That's why you're always talking about the beach ...

BtM: Have a great weekend. Give our best to your missus.

MS: Thanks you too, say hi to {wife - not sure if Bil wanted his wife's name on the net}

Immunofluorescence

2006-02-09T08:55:00.000-05:00

OK here's a post geared mostly to cell biologists. My big pet peeve about reading the scientific literature is ... colored fluorescent images.

Why do people insist on pseudo-coloring their images? I know that you want pretty pictures and as every kid knows the more colorful the picture the more adoration one gets from approving parents ... but we're talking about data and instructing/convincing your fellow peers about new findings.

So why is color bad for data presentation?

Your eye is better at detecting various shades of grey than shades of any hue. Or to rephrase, it's easier to detect details in a black & white image.
Your eye can also simultaneously detect many more shades of grey than any hue. This is sometimes called dynamic range. If your protein is enriched in one area of the cell and sparse in another location, it's easier to convey the range of concentrations in black & white.
Then there is the famous green/red overlays. I hate those! You can never tell whether an area is green (just protein 1) or yellow (protein 1 & 2).

So let me illustrate (literally!) what I mean:

Here is the same image (of a protein localized to the endoplasmic reticulum) in black white, and the 3 colors commonly used:

You're thinking, well it isn't so bad ... but in a journal article these images are usually scaled down ... lets do that.

Besides the blue pic, they're still not too shabby ... but go ahead and print these 4 images and all detail will be lost in the red and blue images. Greens tend to fair a bit better, but the black and white will be just fine and clear. Yes clarity is the aim of data presentation, not pretty pictures.

Blog pains

2006-02-08T19:01:00.000-05:00

Just had a long conversation with a good friend from NY. We talked about science, careers, how the locals back at Columbia University are faring ... and of course about blogs.

It's funny, back in grad school, we had many conversations about reaching out to the public and spreading the gospel of science (and no I'm not implying that science is like a religion). In a way, I guess that's what this blog is about. Although I have the suspicion that most of the readers are scientists themselves (or even biologists).

This inkling that no non-scientists ever come to my blog is compounded by the fact that I've been banished from Google.

It use to be that you could type in "daily transcript blog" and my site was hit #2, now it's something like hit #700. I used to get lots of traffic from Google from people who would perform searches on "blog mRNA" or "central dogma of biology", but no longer. Now my traffic from Google has gone to zero (although Google's blog search lists my entries just fine). So plain unsuspecting folk can only get to my site by searches in Yahoo and MSN (something also happened to my Technorati entry), or via direct links.

I've read up on why Google may ban your site, and I'm quite sure that this is indeed what happened. In fact listed in the top 10 as a hit in Google for "daily transcript blog" is another site "Daily Transcript Q&A". This was a site I accidentally set up when blogger told me that the ribonucleicacids URL was not available (which it wasn't). So I had registered this site without knowing it. Well instead of deleting this second site, I decided to add some info to it (hence the "Q&A").

Actually the VERY first URL I entered was "ribonucleicacid.blogspot.com". Again blogger told me that this URL was taken, but again it in fact registered this site under my user name. For a while this URL just sat there. Then one day I posted an entry directing traffic from that URL to this site "ribonucleicacids.blogspot.com" (singular vs. plural) - why not. Well I'll tell you why not ... this was probably the cause of the Google (and Technorati) ban. Creating websites to boost your links.

Oh well, who needs Google anyway?

(and yes I know, they own blogger)

Science in Action

2006-02-07T15:13:00.000-05:00

Portuguese (tissue) culture:

Looks like she's mouth pipetting, or drinking (we're not sure) some yummy tissue culture media. I hope that this newspaper clipping won't spark riots.

Article on Peer Review

2006-02-05T07:51:00.000-05:00

I read an interesting article in The Scientist on how the NIH wants to evaluate the peer-review process for NIH grant applications.

Some facts about NIH grants:

Average age a researcher gets his/her first R01 grant: 42 (as I've mentioned in a recent post).
Time between grant submission and grant acceptance: average of 9 months.
Percent of R01 grants that go to new investigators: 6%.

This article is a partial follow up of a commentary (also published in The Scientist) by David Kaplan of Case Western on the peer review process in general. If you've had bad experiences with the whole review process, you'll applaud Kaplan.

Eye Candy

2006-02-03T18:44:00.000-05:00

It's Friday ... here's a cell stained against mRNA from an artificial gene.

Flock of Dodos

2006-02-02T19:30:00.000-05:00

Got this email ... sounds interesting.

Event Details: Flock of Dodos: The Evolution-Intelligent Design Circus
Presented By Harvard Museum of Natural History
Description: Filmmaker and former biologist Dr. Randy Olson's new film probes the great communications struggle around evolution vs. intelligent design being waged in today's mass media. Olson's humorous, enlightening and sometimes sobering journey includes in-depth interviews with proponents of intelligent design, school board members, and lawyers, and footage from an evening with evolutionists who gather for a game of poker and evolution debate. (Screening to be followed by a question-and-answer with the filmaker and panel discussion with Harvard biologist James J. McCarthy and New York Times Science writer ornelia Dean.)

Date/Time Monday, February 06, 2006 at 7:00 PM
Regular: $8.00; HMNH Members: $6.00 (2 tickets per person per ID); Harvard ID: $6.00 (2 tickets per person per ID)
Location: Geological Lecture Hall, 24 Oxford St. Cambridge

Class is in for Congress

2006-02-01T21:17:00.000-05:00

Wow, I just read an article that Donald Kennedy was leading a science class for congress. From a NY Times article:

Mr. Boehlert (NY House Rep.) said, "everyone boasts that they are for science-based policy until the scientific consensus leads to an unwelcome conclusion, and then they want to go to Plan B."

So now, when scientific questions pervade legislation on issues like climate change and stem cell research, there is growing concern that Congressional misunderstanding can produce misguided policy.

To fight such misunderstanding, Mr. Boehlert and others sponsored the Jan. 23 briefing, organized by the Center for Health and the Global Environment at Harvard.

This coupled with the President's commitment to basic research (in his State of the Union address) means that Washington is waking up (I hope).

What did Bush say is the state of the union? Here are some key points:

Train 70,000 high school teachers over five years to lead advanced-placement classes in math and science.
Encourage up to 30,000 math and science professionals over eight years to become adjunct high school teachers.
Provide $50 billion to double over 10 years the investment in federal agencies that support basic research in the physical sciences and engineering.
Support making the research and development tax credit permanent to give companies certainty in tax planning.

Now all we need is an attendance card for those house members and senators. Better yet a mandatory standardize test on science ... with the results published online!

New NIH Grant for Postdocs: K99/R00

2006-01-31T17:29:00.000-05:00

The official title is the NIH Pathway to Independence (PI) Award (K99/R00). Note the use of the initials "PI" in the grant title ... very cute. This new grant was announced by the NIH Jan 27th. Here is the link.

Key points (from the NIH website):

The Pathway to Independence Award will provide up to five years of support consisting of two phases. The initial phase will provide 1-2 years of mentored support for highly promising, postdoctoral research scientists. This phase will be followed by up to 3 years of independent support contingent on securing an independent research position. Award recipients will be expected to compete successfully for independent R01 support from the NIH during the career transition award period. The PI Award is limited to postdoctoral trainees who propose research relevant to the mission of one or more of the participating NIH Institutes and Centers http://www.nih.gov/.

It is anticipated that 150 to 200 PI Awards will be issued for this program in the initial year.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the number, quality, duration, and costs of the applications received.

Applications must be submitted on or before the receipt dates described at http://grants.nih.gov/grants/funding/submissionschedule.htm

The average age that an independent investigator get his/her first R01 grant (NIH biomedical research grant) is 42! Translation: junior faculty are having a hard time getting money. This initiative by the NIH will help out young postdocs get funding to help them finnish up their postdoctoral work and to help setup a lab at a period in their life when it's traditionally hard to get an R01. Hmm sounds familiar. Everything you need to know about this funding resource can be found here.

Want to See a Mad Scientist at a Food Orgy?

2006-01-29T08:12:00.000-05:00

Well this is what you might see:

And what is the viscosity of melted chocolate?

If you want to know what was in the big glass with the creamy residue, the remains of soursop vodka.

For more pictures of our massive food experiment visit the SocArt blog. All will be explained ...

Debate on THE SCIENCE OF GENDER AND SCIENCE

2006-01-28T08:17:00.000-05:00

Here is a link to a great debate/lecture between Steven Pinker and Elizabeth Spelke.

(From Gene Expression blog.)

BTW Blogger has been down - this post is via MS Word and a nifty attachment that allows you to post to blogger directly.

Update ... 1/28/06

This past week I heard this great interview on WBUR's On Point, where Norah Vincent discusses how she posed as a man for 18 months to see "the other side". And judging by these pics of Norah as a man (left), she looks the role. Calling the episode an anthropological experiment, she discovers that men and women seem to inhabit separate cultures ... very interesting stuff. Her biggest surprise - she now understands why the two sexes often miscommunicate and misinterpret each other's actions.

Her book Self Made Man, was on the cover of the NYTimes book section from a couple of weeks ago. I'll have to check it out ...

Differentiation within organelles

2006-01-27T18:55:00.000-05:00

Non-cell biologists have often viewed the cell as a bag of molecules. Over the years as cell-biology has developed, it became clear that this was a simplistic generalization. Cells are organized by a dynamic cytoskeletal network that can organize the cellular architecture. Cells are also subdivided into membrane bound organelles. The deeper we look into the cell the more we find that each cellular component is subdivided into specialized regions.

Now it would seem that organelles themselves are subdivided. As all good cell biologists know, the endoplasmic reticulum (ER) is a large continuous network of tubes and sheets responsible for synthesizing secreted protiens, metabiolize lipids and store calcium. Part of the ER extends and wrap around the nucleus to form the nuclear membrane. The inner nuclear membrane (INM) and outer nuclear membranes (ONM) are connected by specialized pores (nuclear pore complexes; NPCs) that allow only certain proteins to enter/exit the nucleus. The INM contains a specialized group of proteins that regulate several aspects of nuclear function.

I’ve been reading recent work on a group of proteins called Nesprins that localize exclusively to the ONM. Nesprins are some of the biggest proteins made by the cells. The nesprin proteins are anchored to the outer nuclear membrane by one end of the molecule, called the KASH domain. This domain extends across the the space between the outer and inner membranes (called the perinuclear space) to bind to a group of inner nuclear membrane proteins called SUNs. The other Nesprin end binds to various cytoskeletal elements and probably mediates how the Nucleus gets dragged around the cell. It looks like other proteins have KASH domains as well and may define an entire fauna of proteins that reside on the nuclear surface. So the outer nuclear membrane is further subdivided from the rest of the ER. There is the great spatial complexity that lies within cells, and we’ve only scratched the surface (I know corny pun).

Refs: Worman, H and Gundersen, G. Here come the SUNs: a nucleocytoskeletal missing link. Trends Cell Biol. 2006 (E-Published)

Update ... some trivia!

So it looks like Nesprins are some of the biggest proteins in the cell. Nesprins are members of the plakin family, all of which are huge. Here is a list of some of the biggest proteins encoded in the human genome (# of amino acids in parenthacies).

Some big proteins:
Giantin (3259)
Titin (33423)

Some plakins:
Nesprin-1 (8797)
Nesprin-2 (6883)
Nesprin-3 (975)
MACF (7412)
Dystonin (5497)
Plectin (4684)

Canadian Election Results

2006-01-24T10:56:00.000-05:00

Here are the facts and interpretations of last night's elections in Canada.

Liberals got the boot. Canadians punished those who have remained in power a bit too long.
Conservatives won a minority government. Canadians still don't trust the conservatives enough to give them full control.
The NDP (left of the Liberals) does not hold the balance of power. NPD did gain a lot of seats and this is a good sign that the Canadian public has not veered to the right.
Conservatives won seats in Quebec. This is the most important event in the elections. The major change in Canadian politics last night was that the Liberals AND the separatists lost votes to the conservatives in my home province. In fact the Liberals had their weakest showing in Quebec in 20 years. Also note that Conservatives won SEPARATIST ridings! Previously the Tories were not seen as viable in Quebec ... if you wanted to boot out Liberals you voted BQ (separatist) ... but after last night this is no longer true. There is a now a viable federalist (i.e. non-separatist) option for French Canadians.

Canadian Elections

2006-01-23T10:59:00.000-05:00

Yes it's that time again. Unfortunately I couldn't go back home to vote ... and it looks like the separatists will win my riding (damn).

Having lived in the US for almost 9 years I can probably compare the two systems. Canadian elections are shorter (about 2 months of campaigning). Canadian elections are more unpredictable. Canadian elections cost less and the televised election debates probably play a bigger role. And Canadians vote with a pencil and paper AND still have quicker results and fewer problems than American elections. On this last point, some may say, "the Canadian population is smaller". All I can say is that there are 30 million Canadians (about half the size of France) and that although we're 1/10 the size of the US, each polling station probably has the same number of voters - if they can count paper ballots in Canada, they can do it in the US.

What can I say about what's happening (politically) in the True North Strong and Free? You can probably read up on it. Surprisingly all the major papers here have articles on the Canadian elections.

However if you really want to know what's going on, this video clip (click on "Buckley's Ad") probably sums up the mood in Canada right now.

Bravo Paul Nurse

2006-01-22T08:50:00.000-05:00

I finally got around to reading the much talked about comment by Paul Nurse that appeared in the last issue of Cell. Some background ... Paul Nurse (or should I say Sir Paul Nurse) won the Nobel Prize along with Lee Hartwell and Tim Hunt for the discovery of the cell cycle, arguably one of the biggest discoveries in the past 100 years. He recently moved from London to New York to head Rockefeller University.

Nobel Website Bio.
Rockefeller homepage.

In his commentary, Nurse identifies 3 major problems with academic research in the US today:

Academic funding and the pyramid scheme.
The attack of science by various religious groups.
Recruitment (i.e. the lack of American scientists + the miserable way foreign scientists are treated in the US)

Yes these are all issues that I and others seem to insensately write about on our little blogs. I highly recommend that you read the whole commentary. It's available for free to the general public on Cell's website.

(thanks BC)

Yet another Interview

2006-01-21T11:37:00.000-05:00

I recently had a conversation with my father. He has a degree in Nuclear Physics and was a teacher for over 20 years. Although he is now retired he still keeps up with the latest developments in physics and keeps up a blog on physics called Stings of Ideas. We talked about String Theory, the Big Bang Theory and other things …

Mad Scientist: Could you briefly explain string theory (ST)?

Man from Zohra: Basic idea: everything - quarks, electrons, photons - are made of tiny strings.

MS: Why do many believe that ST is the key to deducing the grand unifying theory?

MfZ: By accident, when it was proposed as a theory for the nuclear force, the graviton appeared in the theory. Up until then gravity was a force outside the scheme that Quantum Mechanics has for all the other forces.

MS: So the elusive graviton can be predicted by ST ...

MfZ: Absolutely, if it were discovered, it would be a great boost to ST.

MS: It is often said that ST can predict 10^500 different types of universes, what strategy do String theorists have to figure out which theory belongs to our present universe?

MfZ: ST relies on mathematics that employs 10 dimensions. The main problem in ST is to go from 10 dimensions ( 9 spatial plus time) to 3 spatial plus time. In other words, we get too much information, and the trick is to try to weed out the useless information. Now what has been identified are Calabi-Yau manifolds which divide higher dimensional space neatly into 4 and six.

MS: So what in our universe is represented by a Calabi-Yau manifold?

MfZ: Nothing that I know, right now it is basically a mathematical structure that theorists are using to break down a 10-D equation into a 4- and 6-space.

MS: So is our universe a Yau-Calabi manifold floating in a 10D reality?

MfZ: Too soon to tell.

MS: What does ST have to say about the cosmological constant?

MfZ: Cosmology theories are separate but ST also might include supersymmetry, which would have a lot to say about the fundamental particles and how the universe was formed in the early stage, but that is another story.

MS: What is supersymmetry and why is it so important for ST?

MfZ: A good definition of supersymmetry can be found here. It is not vital to ST, but a main concern is the Higgs field, in which particles acquire mass. Supersymmetry would be nice if it turned out to be true.

MS: An alternative to the big bang theory has been floating around recently, could you explain what this is all about?

MfZ: The cyclic theory incorporates the big bang theory but it proposes no beginning. The Universe undergoes an endless sequence of cycles in which it contracts in a big crunch and re-emerges in an expanding big bang, with trillions of years of evolution in between.

MS: So the universe is contracting and expanding indefinitely.

MfZ: The seeds for galaxy formation were created by instabilities arising as the Universe was collapsing towards a big crunch, prior to our big bang.

MS: How do they explain that the expansion in our universe is accelerating? Shouldn't it be slowing down?

MfZ: In the initial phase, think of a spring compressed and released, it would accelerate then slow down. If the spring is attached to a wall, it will then reverse direction. The universe is believed to behave in that fashion.

MS: But if gravity acted as the accelerating force during the big crunch, shouldn't it be the deaccelerating force during the expansion?

MfZ: Dark energy would fueling our expansion. Eventually, we will slow down as gravity caught up. For the next trillion years or more, the Universe undergoes a period of slow cosmic acceleration (as detected in recent observations), which ultimately empties the Universe of all of the entropy and black holes produced in the preceding cycle and triggers the events that lead to contraction and a big crunch. Note that dark energy is not simply added on -- it plays an essential role.

MS: So what is this dark energy?

MfZ: If I knew, I would win the nobel price.

MS: Do they have any idea at how far out the universe will expand before the forces of gravity start to over come the dark energy and start contracting the universe?

MfZ: No, this is beyond our measuring capacity. According to the latest theory, the universe would be expanding for trillions of years, who knows how far it will reach is anyone's guess.

MS: One last question ... what will be the next big idea in cosmology? (if you were to guess)

MfZ: That a trick question?

MS: No - it's the big guess question. BGQ

MfZ: Maybe our latest probe to Pluto might tell us we are wrong on gravity???

MS: Wow.

MS: Ok thanks for the interview.

MfZ: Bye.

Lots of work = few posts

2006-01-20T20:09:00.000-05:00

Tending a blog can be a bit like having a pet. Fun to play with, and when you're busy easy to ignore (and let die).

OK so the word of the day is ... antediluvian. It refers to the period before the biblical flood. It can also refer to an oldfashion or antiquated person ... a remnant from a long ago era.

Reading Thomas Freidman's OpEd in the paper today makes me wonder whether the we are living in a period just before "the flood" ...

From his article:

Friends, we are in the midst of an energy crisis - but this is not your grandfather's energy crisis. No, this is something so much bigger, for four reasons.

First, we are in a war against a radical, violent stream of Islam that is fueled and funded by our own energy purchases. We are financing both sides in the war on terrorism: the U.S. Army with our tax dollars, and Islamist charities, madrasas and terrorist organizations through our oil purchases.

Second, the world has gotten flat, and three billion new players from India, China and the former Soviet Union just walked onto the field with their version of the American dream: a house, a car, a toaster and a refrigerator. If we don't quickly move to renewable alternatives to fossil fuels, we will warm up, smoke up and choke up this planet far faster than at any time in the history of the world. Katrina will look like a day at the beach.

Third, because of the above, green energy-saving technologies and designs - for cars, planes, homes, appliances or office buildings - will be one of the biggest industries of the 21st century. Tell your kids. China is already rushing down this path because it can't breathe and can't grow if it doesn't reduce its energy consumption. Will we dominate the green industry, or will we all be driving cars from China, Japan and Europe?

Finally, if we continue to depend on oil, we are going to undermine the whole democratic trend that was unleashed by the fall of the Berlin Wall. Because oil will remain at $60 a barrel and will fuel the worst regimes in the world - like Iran - to do the worst things for the world. Indeed, this $60-a-barrel boom in the hands of criminal regimes, and just plain criminals, will, if sustained, pose a bigger threat to democracies than communism or Islamism. It will be a black tide that turns back the democratic wave everywhere, including in Iraq.

Julia, Queen of EMBO Covers

2006-01-18T12:28:00.000-05:00

Every year, Julia from our lab submits photo art to EMBO (European Molecular Biology Organization) Journal's cover art contest. Last year they chose this great fall image for their November 16th issue.

And this year they chose another one of her photos. It's on the cover of their current issue.

I was going to post something on the contest (it ended Jan 11th), but I guess I didn't get around to it. Maybe next year ...

What's your h-index?

2006-01-17T10:56:00.000-05:00

About a month ago I had a conversation with my thesis advisor about the h-index. It is a new method, proposed by Jorge E. Hirsch of UCSD to quantitatively measure a scientist’s influence. His proposal was published in PNAS and Nature had a little report on it. Here's a publically available link to the paper (for those who don't have institutional access to PNAS).

The Abstract from the original PNAS paper:

I propose the index h, defined as the number of papers with citation number is [equal or greater than] h, as a useful index to characterize the scientific output of a researcher.

And here is the rationale from the paper:

Why would you try to quantitatively measure a scientist’s influence? For the few scientists who earn a Nobel prize, the impact and relevance of their research is unquestionable. Among the rest of us, how does one quantify the cumulative impact and relevance of an individual's scientific research output? In a world of limited resources, such quantification (even if potentially distasteful) is often needed for evaluation and comparison purposes (e.g., for university faculty recruitment and advancement, award of grants, etc.).

So what is my h-index? To find out log into Thomson Scientific's ISI Web of knowledge, find all your papers and sort them based on citations. Scroll down the list until your paper rank is equal or greater than the citations for that paper. In my puny grad-student/postdoc career, I’ve only published 9 peer-reviewed papers. What follows is a bar graph of the number of times each paper was cited (citation number), and the paper rank where rank=citations, is paper #8.

Benefits of the h-index:
- It is quantitative.
- It takes into account not just the number of publications or how well a couple of publications are cited, but the QUANTITY of well cited publications.
- Older, well established professors will have accumulated many citations for initial work that is still relevant. Thus h-index goes up with time.
- As you increase your h-index number, it becomes harder to increase it further. Take my h-index: all i need to get to h-index=9 is to publish another paper and hope that it gets cited at least 9 times (and that my current #8 gets cited an extra time). So right now my h-index will roughly grow with the number of publications. Eventually as my h-index grows (to say 50), each new paper has to be cited at least as many times (in this example, 51 citations) to boost my h-index.

Problems:
- Self citations. Although this could easily be eliminated.
- Papers which are wrong. This is not so bad. If you are influential, by definition, people will have to confront and address your "bad data" and explain why it is wrong.
- Cross field comparison. Currently biologists have much higher h-indexes than physicists, simply because there are more scientists who study biology (and thus more individuals who can cite you). Even within biology, it looks like researchers studying signal transduction and oncogenes get a boost to their h-index.

Some h-indexes for notable biologists:

Francis Crick: 53
James Watson: 43
Sydney Brenner: 92
George Palade: 105
Keith Porter: 70

Some people in our vicinity ...

Marc Kirschner: 90
Tim Mitchison: 59
Tom Rapoport: 60
John Blenis: 64
Joan Brugge: 67
Tom Maniatis: 115
Lew Cantley: 97
Steve Harrison: 74
Jack Szostak: 63

other big guys ...

Gunter Blobel: 120
James Rothman: 92
Randy Schekman: 76
Ian Mattaj: 65
Rudolf Jaenisch: 96
Elaine Fuchs: 93
Richard Hynes: 94
Michael Sheetz: 65
Ron Vale: 56
Bert Vogelstein: 143
Bob Weinberg: 113
Susan Lindquist: 74
Harold Varmus: 103
Michael Bishop: 112
Phil Sharp: 115
Joan Steitz: 91
Tom Steitz: 85
Thomas Cech: 82
Alexander Varshavsky: 62
Eric Kandel: 117
Richard Axel: 80
Paul Nurse: 90
Lee Hartwell: 61

One problem with these lists ... we did the searches on ISI, but could not account for papers where the middle initial was omited so the true values for some researchers may be slightly higher ...

OK I've wasted enough time. I'll end with this quote from Hirsch's PNAS paper:

In summary, I have proposed an easily computable index, h, which gives an estimate of the importance, significance, and broad impact of a scientist's cumulative research contributions. I suggest that this index may provide a useful yardstick with which to compare, in an unbiased way, different individuals competing for the same resource when an important evaluation criterion is scientific achievement.

But of course this is all bxxl sxxt ...

{Update 1/28/06}

Acme Scientist informs me that Michael Behe's h-index is 15 ... interesting. Someone should compile the h-index of all these so-called experts ...

Another Victory for Idiocy

2006-01-15T09:30:00.000-05:00

I just read a disturbing OpEd in the NY Times by Robert L.Park form the University of Maryland. It tells how the Bush administration killed the Deep Space Climate Observatory (aka Triana), a satelite wich would monitor Earth's energy balance ... and thus inform us on the rate of global warming. This is another example of government squashing good science in the name of big oil interest. From the article:

Development began in November 1998 and it was ready for launching three years later. The cost was only about $100 million. For comparison, that is only one-thousandth the cost of the International Space Station, which serves no useful purpose.

Before Triana could be launched, however, there was a presidential election. Many of the industries favored by the new Bush White House were not anxious to have the cause of global warming pinned down. The launching was put on hold.

The disdain of the Bush White House for Triana goes much deeper than just a desire to avoid the truth about global warming. Triana began life in early 1998 as a brainchild of Al Gore, who was then the vice president. Mr. Gore, the story goes, woke up one morning wondering if it would be possible to beam a continuous image of the full Earth back from space to inspire people with the need to care for our planet. The 1972 portrait of the full Earth, taken from the Moon, had inspired millions with the fragile beauty of our blue planet. Why not beam the image live into classrooms, allowing students to view weather systems marching around the globe?

Scientists had dreamed of such an observatory for years. They hoped Mr. Gore's influence would make it happen. Mr. Gore's support would end up destroying it. Those who hated him, hated Triana. His dream of inspiring environmentalists and schoolchildren served only to trivialize the project. It was ridiculed as "Gore's screen saver."

Triana is terminated, but global warming is not. Someday, there will have to be an observatory at L1. Perhaps the most important lesson from our exploration of the solar system is that the most terrible place on Earth is a Garden of Eden compared to the best place anywhere else. We must find out how to keep it that way.

For more on Robert Park click here. Triana's NASA webpage used to be here.

Podcasts Podcasts Podcasts

2006-01-14T09:24:00.000-05:00

Over the holidays we got an iPod.

My wife (a non-scientist) has used it to listen science podcasts.

Science Podcasts? It would seem that any large institution/media outlet/media program that specializes in Science news/reporting has a podcast. Science based media is ahead of the curve on this technology. Here is a short list of science podcasts.

Nature (hey Science, wake up! Although Science Magazine also has the occasional podcast.)
The Naked Scientist (BBC)
Science Fridays (NPR)
Quirks and Quarks (CBC)
The New Scientist
The Scientist
Seed Magazine
NOVA (PBS)
This Week in Science (UCDavis)

Authorship Disclosure

2006-01-12T10:42:00.000-05:00

Due to the whole stem cell scandal, both Science and Nature are considering changes in the mechanisms of publishing scientific results . One "reform" is authorship disclosure. From an article in yesterday's NY Times:

One change Science is considering is to require a statement from each author describing his or her contribution to an article. These statements would be published, probably online, Dr. Kennedy [editor of Science] said.

And it's about time. This idea that the actual contributions of authors be disclosed has been bouncing around for a while. There are too many authors whose sole contribution was the donation of an antibody, DNA plasmid, or other PREVIOUSLY published reagent.

Ben Lewin, the former publisher of Cell had this to say:

If this proposal took hold, it wouldn't be a bad thing since you would have a better sense of people's contributions.

For more on the stem cell affair, link to the latest articles in Science and Nature ... and a nice time line of all the events.

[Update 1/14/06]

There is nice discussion on ethical behavior in the scientific community on the Scientific American (SciAm) blog. (Thanks Gaw3)

Likelihood Statistics

2006-01-11T09:15:00.000-05:00

I was just reading this great post from Mike the Mad Biologist (I know ... a much more original name than my nom de plume).

In this entry, he discusses Falsification (as in the theory of scientific theories espoused by Karl Popper) and likelihood Statistics (a much more realistic description of how science works).

From his post:

The difference between the two approaches is that falsification tests data against an a priori model, while likelihood uses the data to build the most likely model given the existing data. The strength of likelihood is that it does not assume how the world works. It also allows you to judge the relative likelihood of different models (or processes). The disadvantage is a garbage-in garbage-out problem: 92% of the time, an unbiased coin would yield an observed ratio that is not 50:50.

It's worth reading the whole entry - and if the detailed discussion frightens you, Mike also incorporated cuddly pictures of baby pandas and puppies.

Occupational Names for Scientists

2006-01-09T17:19:00.000-05:00

Not much happening - reading quite a bit of papers. As I was perusing the literature on nuclear export, I came across a paper by a researcher named Cumming. This reminded me of a passage in Jared Diamond's The Third Chimpanzee about scientists whose surnames reflect their area of expertise (I'll post it when I have the time). Off the top of my head, here is a list of researchers whose name say quite a bit about what they study:

Polymeropoulos Mihael is one of the world's leaders in analyzing the genome, in particular to sequence, map and analyze many mRNAs (or ESTs - expressed sequence tags).

Here's a good question for you ... who identified the taste receptor that recognizes sugars? Charles S. Zuker of course!

Then there is the famous (now retired) ornithologist Mitchell Byrd.

I guess I should have been an archaeologist ...

Interview with a Crazy Scientist

2006-01-07T10:06:00.000-05:00

I interviewed a former colleague of mine, the crazy scientist. We discussed the next big thing in cell biology, his outlook for 2006 and his prospects at finding a job as a PI (principal investigator i.e. professor) ...

Mad Scientist says: How long after a vacation does it take before you are able to perform experiments?

Crazy Scientist says: Well, that is a very interesting question. When I leave, I plan ahead so that I can start an experiment as soon as I get back. The problem is that normally those experiments don't work because I end up making stupid mistakes. So in the end, only after 3-4 days, or a stupid mistake, am I able to run a decent experiment.

MS: It takes me about a week. As hard as I try it would seem that the forces of Nature are against me.

CS: For example I arrived Wednesday evening from Europe with a 5 hr jet-lag. Thursday morning I was running gels to test some serum I received during the holidays. Tuesday I realized I screwed up the experiment. Friday I had the result.

MS: At least the rabbit was working hard while you were away. How do you think this year (2006) will go for you?

CS: Very exciting. Since I'm in the job market, I am very excited to know where I will get the next interview, will I like the place, when will I move, etc.

MS: I'm glad that you are optimistic.

CS: Also, I am finishing up some exp for the next paper .

MS: So it sounds like 2006 will be a good year for you. Speaking of the new year, what do you predict will be the biggest discovery (in 2006) in Cell Biology?

CS: Uhm, that's easy. RNA transport from the nucleus (just kidding...)

MS: Wow I chose the right field!

CS: Ok, now for the right answer. I think a lot will be discovered about local regulation of cellular functions by small hairpin RNAs (shRNA), also known as micro RNAs (miRNA). These activate the turnover of mRNAs. Right now this field is very hot, but the field is limited to the role of shRNAs in development. There is some cell biology being done, but some questions such as whether degradation of mRNAs within a region of the cell can allow for local regulation of protein turnover are not yet addressed. This local protein control may contribute to generating different cell shapes and other morphological aspects. This will be very cool.

(Post interview note: for more on shRNAs and miRNAs, click here.)

MS: So RNA is the place to be!

CS: It is a good place, however, remember that all starts in the nucleus, and that big ball is very fascinating ... and what do you think?

MS: I think that we've seen the genome, we've seen the transcriptome, the kinome, the proteome ... now it's time for the glycosylome! (as in glycosylation ... or the compiling of how sugars are added to proteins, and the different functions of each type of sugar modification)

CS: What about the phosphorylome? Can you imaging knocking-out one kinase at a time a measure phosphorylation of 100-1000 proteins?

MS: I think that too many people study phosphorylation. Two groups (one in our department) are doing that just that (the phosphorylome). The one in our department did mass spec and pulled out every phosphopeptide enriched in mitosis. There is also the ubiquitinome - but it's an oversaturated field as well.

CS: Good. They'll hopefully repeat it for each knock-down kinase.

MS: Maybe they can hire you! I think that if those systems biologists can get their act together, maybe getting some insights into how signaling "modules" work could be big in 2006. Speaking of jobs - what is the thing you look for when interviewing for positions?

CS: Critical mass. How smart and how interesting is the work of my future colleagues. That is the key thing.

MS: So interaction is the most important feature - is it better in large institutions, or smaller ones?

CS: You can find good group of people in small institutions and you can be completely alone in large ones. My experience with Columbia (a huge institution) is that you end up talking with the same 4-6 labs. So I think we cannot make a rule for that. The next important factor is the working conditions (space, core facilities, startup package, funding). The perfect situation is a big institution with a good core of 4-6 groups.

MS: I see - do you feel that as a scientist with a background in "live cell imaging" you have an advantage over other scientists (in that you have more to offer in your interactions with colleagues)?

CS: Not necessarily. I think every scientist have their "background" and their specific "advantage to offer". My background is not better than someone that has a protein-interaction background.

MS: But getting back to biggest areas in 2006 - more and more people are adapting their assays to microscopy - such as single molecule enzymology ... you do have some technical expertise that is not that widely spread.

CS: I guess depending on your question, some backgrounds are more suitable than others depending on the colleagues you find yourself with. Again interaction plays a very important role. (I have to go soon, one more question)

MS: What is the next big thing in cytoskeletal research? (I had to ask a big question since it's my last one)

CS: I think it will be the connection between actin and microtubules, and how this is involved in regulation of both cytoskeletons and their function. Some call it cytoskeletal cross-talk.

MS: I guess you're in the right field! It's funny, because this question has been studied for years, and we've made lots of progress, but it is one of the trickiest questions in all of Cell Biology.

CS: I guess so!

MS: Thanks for chatting. Have a good weekend.

CS: Thanks, you too.

Positive Entry

2006-01-05T10:57:00.000-05:00

OK I promised people that I would write a positive entry today, so here goes ...

Want to see a crazy scientist? Here's many pictures of a former colleague of mine, taken by his wife Claudi (who is also a scientist). For more amazing and fun filled photos, visit her blog aroundaboutme ... and they say scientists aren't fun. Whoo-hoo!

Want to read more on RNA? Visit Bartholomew Cubbins' blog (Bartholomew Cubbins on RNA) ... the blog in his words:

Ribonucleic Acid - it's not just for transferring genetic information between DNA and proteins anymore. This blog will discuss current gossip, news, and major papers within the field. The level of discussion will be quite detailed, yet I hope that non-scientists who are interested in RNA will be able to follow.

And to all the nay-sayers that may dismiss a blog on RNA, this is what BC has to say:

It is my hope that there are legions of non-scientist men and women out there frothing at the mouth to learn more about RNA. And I'm not talking about the RNA drops therapy variety (I'd link to it but I just ran out of Purell).

The Final FY 2006 Appropriations Bills for Federal R&D

2006-01-04T18:08:00.000-05:00

From a statement released by the AAAS:

On December 30, nearly three months into the fiscal year, President Bush signed the last two FY 2006 appropriations bills into law, bringing the FY 2006 appropriations process to a close. AAAS estimates that the federal R&D portfolio totals $134.8 billion in 2006, a $2.2 billion or 1.7 percent increase. But 97 percent of the increase goes to just two areas: defense weapons development and human space exploration technologies. Funding for all other federal R&D programs collectively will barely increase, and will fall nearly 2 percent after adjusting for inflation.

...

Many flagship federal science agencies have disappointing budgets in 2006: the National Institutes of Health (NIH) budget falls for the first time in 36 years; the National Science Foundation (NSF) wins a small increase but has less in real terms for its research portfolio than in any of the last three years; the Department of Energy (DOE) Office of Science budget declines, and despite big increases in development funding the Department of Defense (DOD)’s basic research funding declines.

...

...the bill also contained a 1 percent across-the-board cut for all discretionary programs, even those whose budgets had already been signed into law earlier. Even before the across-the-board cut appeared, the President and Congress had agreed to cut overall domestic discretionary spending by nearly 1 percent, but now it appears that domestic spending will fall almost 2 percent in 2006.

And now time for some data. Funding of several federal R&D agencies over the past 10 years (adjusted for inflation):

R&D (deffence and basic research) funding as a percent of GDP:

The future of funding for federal R&D programs? Here's the last paragraph of the report:

Although many lawmakers of both parties have called on the U.S. to dramatically boost its investments in basic research in order to ensure U.S. innovative capacity and therefore future economic competitiveness, these proposals have run into a brick wall of tight budgets. Looking back on 2005, there finally appeared to be bipartisan and widespread recognition that the U.S. leadership in science and technology, innovation, and technology-based competitiveness were under threat from emerging economic competitors, especially India and China, but instead of boosting R&D investments policymakers cut them to meet restrictive budget targets. And things could get worse before they get better: the Bush Administration’s FY 2007 budget proposal, due in February, is primed to continue the same combination of tax cuts, declining discretionary spending, and modest entitlements reforms that have characterized past budgets, resulting in what is likely to be another year on the downward slope for most parts of the federal R&D portfolio.

Anxiety

2006-01-03T08:33:00.000-05:00

A new year, full of hope ... and anxiety.

During our trip to Seattle, anxiety was a common topic discussed.

Now back home I just read in the NY Times an obituary of Dr George Gerbner. From the article:

He founded the Cultural Indicators Research Project in 1968 to track changes in television content and how those changes affect viewers' perceptions of the world. Its database has information on more than 3,000 television programs and 35,000 characters.

Mr. Gerbner said people no longer learned their cultural identity from their family, schools, churches and communities but instead from "a handful of conglomerates who have something to sell."

He coined the phrase "mean world syndrome," a phenomenon in which people who watch large amounts of television are more likely to believe that the world is an unforgiving and frightening place.

"Fearful people are more dependent, more easily manipulated and controlled, more susceptible to deceptively simple, strong, tough measures and hard-line postures," he testified before a Congressional subcommittee on communications in 1981. "They may accept and even welcome repression if it promises to relieve their insecurities. That is the deeper problem of violence-laden television."

Biomedical Science, Pressing Issues for 2005/2006

2005-12-30T09:43:00.000-05:00

Well we're at the end of the year ... and as others do, I will try to list the most important issues facing the Biomedical Science community in the coming year.

1) Doing Science with Less Funding.

Yes for the first time in over 3 decades, 2007 will see a cut in appropriations to the NIH budget. Get it straight - the NIH is the world's largest source of financing for biomedical science. As the NIH goes, so goes basic research in the life sciences.

Over the past decades, the NSF budget has not increased much, but the NIH budget had been growing with help from big Pharma lobbyists. Then under the Bush administration, the increase in funding to all the basic sciences (including the NIH) slowed down while money towards defense research increased (as this graph from a Boston Globe article demonstrates). From the AAAS website:

The National Institutes of Health (NIH) budget will fall in 2006 for the first time in 36 years because of a modest appropriation combined with the 1 percent across-the-board cut. The $28.6 billion NIH budget is 0.1 percent below 2005. After adjusting for inflation, NIH has a smaller budget in 2006 than it did in 2003, erasing the small gains of the last two years. All but two institutes suffer budget cuts in 2006, with most institute budgets falling between 0.4 and 0.7 percent.

The AAAS is giving a daily update of the 2006 appropriations ... click here to see the latest. This slowdown in the NIH's budget increase has been exacerbated by an expansion in the number of principal investigator positions at major research centers. Already I've heard of several labs closing down in the past year as NIH funding is stagnating. So there are more researchers vying for less money. Things do not look good for young professors starting up their own lab (that will be me in a couple of years!)

2) Science Outsourcing.

First economics has pushed much of the computer technology to Asia, and now it seems as if the pharmaceutical industry and maybe even much of academic research may follow. It's the extension of Science by kits. It's neither good nor bad, but will have a dramatic influence on how we do Science. I've already wrote extensively on this subject. Here are some of those entries:

Outsourcing Science.
More on the Rise of Chinese Technology.
Thanksgiving Dinner Talk & Outsourcing.
America, Foreigners, and Academic Science.
Scientific Establishment to the US: Shape Up!

3) Science Education.

Yes there is all this talk of intelligent design ... blah blah blah. The bigger problem is that all these "evolution critics" DON'T UNDERSTAND HOW EVOLUTION WORKS! You can see it in how the whole subject is discussed in various public forums and in the mass media. The problem here is that the public needs better science education.

On that front there is good news: Americans

have a high opinion of scientists
want better science education in schools
are very "science literate" when compared to citizens of other nations

But what are the obstacles? Anti-intellectualism is still highly prevalent in American society. Science literacy, although high by international standards, is very poor (click here for some scary stats), and this is due to the fact that science literacy is dependent on college education. High schools just don't cut it. Bottom line: we need to improve Science education in high schools.

4) Studying Biology on the Next Level.

Many biologists have come to the conclusion that reductionism can only go so far. (Want proof? ask a physicist how cells divide.) Biology must expand from studying how a single gene/protein works in the context of a biological system to understand how a whole chunk of the system works. To address this, two new lines of research have been created, Systems Biology and Synthetic Biology. Will they succeed or are they just the new trendy fields? We'll have to wait and see.

Not on the list ... The Culture Wars.

Look, despite all the stem cell critics and problems in South Korea, stem cell technology will happen (although perhaps not in the US).

Evolution? As stated above, the main problem is confusion in minds of the general public. The problem is not that certain people are hostile to evolution, but that the majority of Americans (and some so-called biologists) can't even explain how the "theory" they're against works, let alone criticize it.

Well that's it for 2005. Have a happy New Year.

Biggest Finding of the Year

2005-12-25T13:43:00.000-05:00

Yes everyone has his/her lists ... but it's oh-so-fun. So here goes, the biggest finding of the year. (This might be a little RNA-centric!)

Central Dogma of Biology overturned! (???)

Have a near-lethal mutation in your DNA? Researchers from Robert Pruitt's lab at Purdue suggest that in Arabidopsis thaliana (the model organism for studying plant genetics), mutants can attempt to alter upto 10% of the genome so that the next generation may rid itself of the deleterious gene. The reversion process is stimulated by stress - it's as if the organism knows that something is wrong, and attempts to correct the error so that the next generation is free of potentially bad (or deleterious) mutant gene. Since the organism does not know what is the bad gene, it willy-nilly reverts upto 10% of the genome. Consequentially 10% of the offspring have fixed the offending gene. The altered genes often contain sequences found in the grandparent's DNA that were not inherited in the parent's genome. So where did the extra genetic information come from? These researchers suggest that the parents store extra-genomic information from grandparents. Since the researchers could not find any of this information in the parental DNA, it may be stored in RNA versions of the genes that are retained between generations. Of course for the theory to be proven, the team from Purdue need to identify this inherited RNA.

So it use to be thought that information in biology flowed in one direction: DNA => RNA => protein (i.e. the Central Dogma of Biology). But in this case RNA is the potential source of the backup genes. In the case of stress, backup-RNA => DNA.

As with all great findings, there are controversies. Abed Chaudhury has claimed an alternative "fix" for the poor arabadopsis mutant, where bad genes may be turned off using RNAi. How are 10% of the genes reverted? ... Dr Chaudhury postulated that sick individuals may fix genes by soaking up DNA from the environment ... this alternative theory needs to be tested and would be as remarkable as the RNA-backup theory.

And a second researcher, Animesh Ray, postulated that mersitem cells may store parental-DNA- fragments. These DNA fragments may be used to revert genes in the gametes of sick individuals. Again, someone should be asking "show me the DNA".

So yes my finding of the year is a big question mark, however this line of investigation has shown that our current understanding of inheritance is flawed ... somehow organisms can fix mutant genes. Hopefully 2006 will bring us closer to how this really works.

Lolle S.J. et al., Genome-Wide Non-Mendelian Inheritance of Extra-Genomic Information in Arabidopsis Nature (2005) 434: 505

Chaudhury A., Plant genetics: Hothead healer and extragenomic information Nature (2005) 437:E1

Ray A., Plant genetics: RNA cache or genome trash? Nature (2005) 437:E1-E2

Artichokes & that sweet taste

2005-12-22T11:26:00.000-05:00

Well here I am in rainy Seattle visiting the inlaws. Last night we prepared artichokes for dinner. Naturally the conversation turned to how the consumption of artichoke has a curious effect on the sense of taste: everything tastes sweet even water. If you've never experienced this before it's because you've never had fresh artichoke. Pickled artichoke hearts don't have this property.

So entering "Artichokes and Sweet Taste" into Pubmed what do you get?

Bartoshuk LM, Lee CH, Scarpellino R, Sweet taste of water induced by artichoke (Cynara scolymus). Science. 1972 178(64):988-9.

The authors commented that their research was catalyzed by an AAAS dinner which featured artichokes. Using a tasting assay, the researcher discovered two substances in artichoke that stimulate a sweetening of subsequent ingested substances (such as water), chlorogenic acid (3-caffeoylquinic acid) and cynarin (1,5-dicaffeoylquinic acid).

From the original paper:

In other reseach, these two phenolic compounds have been proposed to

have antimicrobial activities
act as anti-oxidants
upregulate Nitrous Oxide Sythetase in exposed tissue

Searching a bit further, I found this other fruit, miracle fruit (Synsepalum dulcificum), that has similar effects on altering taste. However this time the culprit is a protein, miraculin.

Kurihara K, Beidler LM. Taste-modifying protein from miracle fruit. Science.
1968 161:1241-3

What else could there be? ... searching more I stumbled into this review:

Kurihara Y. Characteristics of antisweet substances, sweet proteins, and
sweetness-inducing proteins. Crit Rev Food Sci Nutr. 1992 32:231-52.

Abstract.

Recent studies on structures and functions of sweetness-inhibiting substances (gymnemic acid, ziziphin, and gurmarin); sweet proteins (monellin, thaumatin and mabinlin); and taste-modifying proteins (miraculin and curculin) were reviewed. Several gymnemic acid homologues and gurmarin were purified from the leaves of Gymnema sylvestre and their structures were determined. Ziziphin was also purified from leaves of Ziziphus jujuba. Gymnemic acid and ziziphin are glycoside of triterpenes that suppress sweetness in human, while gurmarin is a peptide having antisweet activity in rat. Mabinlin is a heat-stable sweet protein. The whole amino acid sequence and the position of disulfide bridges of mabinlin were determined. Miraculin has the unusual property of modifying a sour taste into a sweet taste. Curculin elicits a sweet taste. In addition, water and sour substance elicit a sweet taste after curculin. Their amino acid sequences and subunit structures were determined. These proteins are expected to be used as low-calorie sweeteners.

OK enough Pubmed for me. Have a ... sweet ... holiday.

The best things about science

2005-12-20T11:15:00.000-05:00

After having written about the worst (parts I and II), why not write about the best things about science?

Here goes:

1) Discovery. One of the greatest feelings I've ever had as a researcher was peering down at the microscope and seeing something that I know has never been seen in the history of mankind. It's funny, the first thing you want to do is ... tell somebody. When my thesis advisor discovered that cells have different types of microtubules (a truly unexpected finding) it was the middle of the night. Apparently, he rushed off to explain the big discovery to the only other person in the floor at that time, a janitor. Science literally means standing at the edge of knowledge ... and looking beyond. What a thrill.

2) Discussion. One great part of Science is that scientists love talking about ideas. I never tire of speaking to fellow scientists - we are a very curious group. It reminds me of this quote I once heard (I'm not sure of the source):

"People of high intelligence talk about ideas...
People of average intelligence talk about things...
People of no intelligence talk about other people!"

Although in my opinion I would substitute "intelligence" with "curiosity". There is a bias that scientists are a very reclusive and unsociable group. I would strongly disagree. We are constantly discussing and exchanging ideas - and the freedom to explore, invent and analyze ideas within the scientific forum is unlike anything else I've ever experienced. Due in part to this type of social interaction, I believe that scientists are trained to be very clear thinkers and very CAREFUL thinkers. But more importantly, a good scientist makes careful assumptions. This is the difference between Darwin and say Freud ... or Marx. Many non-scientists have this strange habit of not checking their assumptions. In the course of analyzing the world around them, this type of error magnifies itself and leads these individuals to strange and often erroneous interpretations of phenomena. As a scientist I often question non-scientists' assumptions and sometimes find that they confuse this line of inquiry as an attack on their ego (although many scientists also fall into this category - see "worst things about science", item #8). So as a summary I would say that good scientists love discussion and are non-judgmental in what they discuss (as long as the discussion is about ideas!), but scientists are judgmental in how they discuss ideas. This is where many non-scientists could learn from scientists.

3) Creativity. Good scientists are very creative. Think of it, you are at the cutting edge of knowledge, you read the scientific literature, there is a problem you would like to address, and then you ask (hopefully) a very insightful question, and come up with a model of how nature works. What to do next? Well you want to test your model ... usually by performing experiments, while covering all your bases (i.e. with appropriate controls). But of course you can't perform the "perfect experiment", because you are limited by the current technology. What to do? Most scientist use the latest techniques ... but the best scientists modify these techniques slightly to perform innovative experiments that are closer to the "dream experiment".

If you've managed to invent a really good technique that is capable of addressing a particular type of question, this is referred to as an assay. Working out the bugs of an assay is hard and can take a long time, but once the assay is up and running, you can collect tons of data in very short time spans. In addition, you've become the world's expert at this novel technique. Great scientists always come up with innovative assays, and then use the assay to gain new insights into old problems. Even better than that is to use an assay to address problems that people haven't even begun to think about. I love this part of science - call it MacGuyverism.

OK that's enough for today, but as usual other suggestions are welcome.

Dead cell art!

2005-12-19T10:41:00.000-05:00

As promised, weird pics of the remains of dead cells (due to microinjection induced explosion):

Images from gradschool

2005-12-18T10:39:00.000-05:00

While my wife is at Spanish class I was rummaging through some old data CDs from gradschool. I had lots of great pics in there.

Picture #1 is of the microtubule cytoskeleton of a migrating cell. I took this picture when I was investigating how migrating cells modify their microtubules (yellow/green microtubules here) when they crawl (in this picture towards the woundedge on the right). In red are the unmodified microtubules. If you get the impression that there is a circular structure to the left that is devoid of microtubules, you're right, that's the cell's nucleus. For more on microtubule modification, click here. For more on how the nucleus gets nudged to the back of the cell during migration (a topic I worked on as well), click here.

Picture #2 is of a fibroblast in the act of re-adhering to a fibronectin coated coverslip. I took this picture while studying how cellular adhesion stimulates the modification of tubulin. Blue is the phase image, red is the cell's unmodified (or tyr) microtubules, yellow/green is the cell's modified (glu) MTs.

Picture #3 random salt crystals:

Invented Results

2005-12-17T10:16:00.000-05:00

Wow the whole stem cell debacle is all over the press. And in the process Science is scarred in the public's imagination.

(On the other hand, scientists are conservative when it comes to the belief in other peoples work. Science is a brutal place. There is always someone who is re-evaluating, re-dissecting, re-examining, your ideas/results. Many times these same people are advocating that your ideas be discarded. After a while, if an idea is repeatedly confirmed by others, it MAY be accepted by everyone.)

Since we are on the topic of ideas and results, I've updated the Worst things about science II. While we are so pessimistic, you can also check out the Worst things about science (part I).

What I've been doing for the past couple of days

2005-12-16T11:14:00.000-05:00

Microinjecting and snapping photos ...

Here are some weird things that I've been seeing (or as they say IMAGING) in the nucleus. I wont explain much ... so view it as nano-art.

First up are two nuclei microinjected with Fluorescein coupled 70-KiloDalton Dextran (basically a large fluorescent molecule). The injected fluorophore redistributes throughout, but can't escape, the nucleus. Why can't it leave? It's too big. Notice the darker splotches within the nuclei, these are dense zones are called nucleoli, and are centers for ribosome assembly. Look at the multi-lobular nuclei on the left, how can a nuclei be deformed in such a manner? The answer is totally unknown.

OK next up is a coinjection experiment. Two pictures of the same cell. Top picture is of RNA, stained with a red fluorophore, bottom picture is fluorescein (green) 70-kD dextran (see previous paragraph). Notice the cool looking dots of RNA that SURROUND THE NUCLEOLI - very weird. Notice how these dots are regularly spaced.

Again how or why these dots/granules/bodies are formed - totally unknown. If anyone ever tells you that we understand biology or cells - they obviously haven't been looking very hard.

So much to look at, so little time (to blog) ...

I'll post pictures of exploded cells next ...

Farewell Bil

2005-12-13T09:44:00.000-05:00

It's been a strange week - full of experiments and great results. And full of parties. Sunday we met for our monthly Bookclub meeting (or as one member calls it, our monthly food and drink orgy). Saturday we were over at Bil's, who is leaving us to start up his own lab on the west coast.

First we lost U. Now Bil ...

Scientists are always on the go. 4 years here, 5 years there. It's exciting but at the same time disorienting. My wife and I feel like we have no real base. Is it Seattle where her family is from? Is it where my roots are in Montreal? Is it New York where we lived for 6 years?

It reminds me of this great book I read a couple of years ago - The Global Soul, by Pico Iyer. In it, this Indian born, English and American educated, now resident of Japan, describes a new class of countryless individuals. These educated citizenless people take part in a nebulous global culture. A true phenomenon of life in the 21st century.

Word of the day

2005-12-09T10:55:00.000-05:00

A very short post for today:

Karochi: Japanese for death by overworking.

In a related topic – I have more microinjections planned for tomorrow. Wish me luck.

Microinjecting my brains out ...

2005-12-08T16:38:00.000-05:00

I've been microinjecting cells like a madman recently (or perhaps a mad scientist?)

Microinjection is a very useful technique - you can basically shove anything into a cell. Antibodies, DNA, RNA, quantum-dots ...

One question that fellow scientists ask me is whether microinjection damages cells in anyway. You would be surprised how resilient cells are. As far as we know microinjected cells display normal functions. They can transcribe DNA into RNA. They can translate the RNA into protein. They can migrate. In the case of neurons, they can form axons.

One of the classic microinjection papers is Yuli Wang's microinjection of fluorescent actin, a component of the cytoskeleton. Another was Tim Mitchison's injection of fluorescent tubulin, another cytoskeletal component. Both papers led to major discoveries as it allowed the researchers to monitor how cells and molecules change over time. In cells the cytoskeleton could be remodled and reorganized in minutes - it's a dynamic rather than than a solid scafold for the cell. Visualizing molecules inside of living cells was a big deal as the behavior of biological molecules over time - the illusive dimension - could now be analyzed.

Ok I've got another time-point to take care of ...

Refs:

Taylor DL, Wang YL. Molecular cytochemistry: incorporation of fluorescently labeled actin into living cells.
Proc Natl Acad Sci U S A. 1978 Feb;75(2):857-61.

Mitchison T, Kirschner M. Dynamic instability of microtubule growth.
Nature. 1984 Nov 15-21;312(5991):237-42.

One man's garbage is another man's gold ...

2005-12-07T11:17:00.000-05:00

It's strange how within the Biological community different fields of research have different views.

I just completed experiments where I've inhibited a cellular process by microinjecting (into cells) antibodies raised against a key molecular component. To researchers that study the cytoskeleton, such antibody injection experiments are routine. However, in the "RNA field" such experiments are taboo. One collaborator (from an RNA lab) claimed that my experiment was the equivalent of injecting phenol into cells.

My graduate training was from a lab that specialized in studying microtubules, a component of the cytoskeleton, and as a postdoc I now am studying mRNA. Funny thing is that in the cytoskeletal fields, microinjection experiments are much more common. Antibody injections have been performed for decades. No one has ever reported any adverse effects of the antibodies. Infact it is common practice to mix non-specific antibodies with an active protein and inject the mixture into cells. The injected cells can then be identified by performing immunofluorescence against the injected antibody.

But would those in the RNA field trust decades of standard practice? This is a prime example of how different biological fields are totally oblivious to what is standard in other biological fields. I guess it's a side-effect of such divergent areas of research within biology.

Bravo Nicolas Kristof

2005-12-06T09:13:00.000-05:00

In today’s OpEd Nicolas Kristof skewers the right, and the left, for their scientific illiteracy.

As I’ve posted on before, the US will no longer maintain its title as the world leader in technological innovations. Why? First, with respect to higher (i.e. graduate education in the sciences), eastern countries such as India and China are catching up. I applaud their efforts. Second, scientific illiteracy and anti-intellectualism are rampant in the US. As Kristof puts it:

In the U.S. and most of the Western world, it's considered barbaric in educated circles to be unfamiliar with Plato or Monet or Dickens, but quite natural to be oblivious of quarks and chi-squares. A century ago, Einstein published his first paper on relativity - making 1905 as important a milestone for world history as
1066 or 1789 - but relativity has yet to filter into the consciousness of otherwise educated people.

"The great edifice of modern physics goes up, and the majority of the cleverest people in the Western world have about as much insight into it as their neolithic ancestors would have had," C. P. Snow wrote in his classic essay, "The Two Cultures."

So the dumb-dumbs in the west remain (or become) clueless, and scientific proficiency (and technical know-how) spreads in the east. What will the outcome be? There are many possibilities. And some of what I've speculated has started. As I’ve writen before, if trends continue ALL SCIENCE WILL BE SHIPPED ABROAD (infact it seems almost as if Kristof reads my blog).

This disregard for science already hurts us. The U.S. has bungled research on stem cells, perhaps partly because Mr. Bush didn't realize how restrictive his curb on research funds would be. And we're risking our planet's future because our leaders are frozen in the headlights of climate change.

But a science illiterate citizenry also is ill-equipped to deal with many current day issues.

Without some fluency in science and math, we'll simply be left behind in the same way that Ming Dynasty Chinese scholars were. Increasingly, we face public policy issues - avian flu, stem cells - that require some knowledge of scientific methods, yet the present Congress contains 218 lawyers, and just 12 doctors and 3 biologists. In terms of the skills we need for the 21st century, we're Shakespeare-quoting Philistines.

So what’s to be done – western society must realize that hubris (from all parts of the political spectrum) and anti-intellectualism (or ANTI-SCIENCE-ism) will hurt us in the long run.

Intellectuals have focused on the challenge from the right, which has led to a drop in the public acceptance of evolution in the U.S. over the last 20 years, to 40 percent from 45 percent. Jon Miller, a professor at the Northwestern University medical school who has tracked attitudes toward evolution in 34 countries, says Turkey is the only one with less support for evolution than the U.S.

It's true that antagonism to science seems peculiarly American. The European right, for example, frets about taxes and immigration, but not about evolution.
But there's an even larger challenge than anti-intellectualism. And that's the skewed intellectualism of those who believe that a person can become sophisticated on a diet of poetry, philosophy and history, unleavened by statistics or chromosomes. That's the hubris of the humanities.

Will the US be selected against?

The Control of Nature

2005-12-04T12:36:00.000-05:00

While my column is washing, and my brain is fried, I should finally write this entry ...

A while back, right around the time of Katrina, I read a spectacular book, The Control of Nature by John McAfee (Amazon site).

When man's interests conflict with an ever changing environment, what does man do? He/she fights change.

(All images were hijacked from maps.google.com.)

Part 1

The Army Corps of Engineers vs the Mississippi River.

As time goes on rivers carry sediment from their sources to their deltas. The sediment settles, the riverbed rises until the river overflows and takes a new steeper route to the sea. But not the Mississippi. After the war of 1812, the Army Corps of Engineers was commissioned to protect New Orleans and the mouth of the Mississippi from future sieges. Eventually the Army Corps took control of the whole river. From Baton Rouge to the big easy, millions now depend on this great river, but the river wants to switch course to the Atchafalaya. Old River (see map) connects the Mississippi to the Atchafalaya, is now dammed. Walls that are longer, wider and taller than the great wall of China, hold the Mississippi in it's current itinerary. The elevated river has become an aqueduct. To read this part of the book, click here.

Part 2

Vestmannaeyjar, Iceland vs the Mid-Atlantic Ridge

Your home is right where two tectonic plates rip apart. A nearby volcano erupts, the lava is heading to your town and the only harbor in your country. What do you do? Water the lava of course (or as the locals call it, "pissing on the lava"). And those crazy Icelanders managed to stop the lava in the nick of time (see map). This crazy tale is too incredible to believe. The Icelanders were even walking on the lava to water it from the top. If the lava-watermen stood still, their boots would catch on fire. At some point a chunk of the volcano (Eldfell) broke off and drifted on the lava towards their town. Migrating Mountains?? Read the book to find out what happened next. Here's a nice website on the whole affair.

Part 3

Los Angeles vs. the Sierra Madre

You city fills an entire valley and is creeping towards an incredibly high (and young) mountain range to the north. Due to tectonic plate movement (see arrows) this mountain range is growing. Every couple of decades avalanches from the growing mountains turn into mud slides that engulf whole sections of the city. But that's not all. The climate is very arid and the vegetation is highly combustible. Driven by evolution, many plants emit flammable oils to encourage the scorching of themselves and competing plants turning these new mountains into fire drenched infernos every 10-30 years. Once the area is reduced to ashes, their heat resistant seeds sprout. Mudslides, wild fires, and still people want to live in L.A.?

Having examined these 3 examples, I had many questions. But one principle stood out,

Sometimes, progress = resistance to change.

Look at the Kyoto protocol. Look at our unsustainable business practices. What will happen if the sea levels rise? It looks like instead of moving our coastal cities, we will erect huge dikes. We humans use technology to find quick fixes ... but such a strategy may lead to our eventual downfall.

Cool things for Friday

2005-12-02T10:07:00.000-05:00

Nature has something on Synthetic Biology, in cartoon form.

Someone from Seed Magazine alerted me to this new toy they have (now available to the public), called Phylotaxis. Speaking of Seed Mag, check out their Podcasts.

Here is an interview with the author William Gibson. Here's a link to his blog where he gives a link to this great movie clip from 1946 (Tall Medstudent, you'll love this one!) on how to tell whether you're community is under the influence of despotism.

Here are incredible (and fun) movies of Listeria monocytogenes infecting tissue culture cells from Julie Theriot's Lab.

If you missed it, here's a link to the Picower Institute's inaugural seminar (not too interesting, according to coworkers that watched it).

My Dad keeps on getting his letters published in the Montreal Gazette and Time Magazine.

And a coworker sent me link to this crazy site ... Creationists looking for pterosaurs??? Look at the map (right) of possible pterosaur migration routes from Noah's Arc to present day sightings. We weren't sure whether this was a hoax or the real thing. Fellowship University? (as one blog pointed out it's initials are FU). The site is quite extensive and the links (as far as we can tell) are legit. But it's too wacky. It has a great kidz page. Wikipedia lists this organization (Objective Ministries) as a parody.

The Worst Things About Science II

2005-12-01T10:15:00.000-05:00

So here is part 2 of my whiney post. I've had lots of suggestions about this topic but I only have time to enter a couple of points:

The Worst Things about Science Part II

8 - The Model (or the Ego and the Id). Inspired from personal experience and two comments. Science is all about models - how does a cell know when to divide? The current model of the cell cycle with it's check points explains it. Good scientists generate good models which fit the experimental evidence and give further insight into the processes studied. However some scientists view their "model" as their own child, fiercely defending it with every psychological means necessary. A subset of those researchers go as far as substitute the model with their own credibility and thus defending the model (in their mind) is equivalent to defending their standing within the scientific community. Data that does not fit is easily discarded and opponents are belittled. As more people subscribe to the model, the model's champion experiences ego inflation. Finally if enough people believe this idea and will irrationally fight for it, that's when the model becomes dogma. Woe is the one to challenge this.

{Update: 12/14}

This whole model thing reminds me of a JCS T-Shirt I once received. The caption was:

Owner of the Idea
Chanpion of the Model
Victim of the Dogma

9 - The "Last Experiment" syndrome. About a quarter of all scientists at anytime are performing the famous "last experiment". This elixir supposedly will solve all the researcher's problems. Often it has been catalyzed by mentors, reviews or thesis committees (often with the chant of "just try this") and often looks deceptively simple. If the experiment gives a negative result, the researcher duefully repeats the experiment with additional "tweaks" in a futile attempt to get the damn thing to work. Often the desired result is needed to prove the "model" (see # 8) and so a negative result is greeted with a "just try it one more time, but this time why don't you try ..." Conversely if the experiment works, magically a NEW last experiments appears. Like a black hole, weeks and months disappear with nothing to show for it. Like a drug habit the thing just won't go away. To all those out there on their "last experiment" all I can say is "good luck".

10 - The artifact. Non-scientists may be asking, what is an artifact (in the context of science). Here is a good definition from Wikipedia. These artifacts have plagued scientists for a long time. Want to detect a protein? Use an antibody that "specifically" binds to your protein of interest. But whatchout, this antibody also recognizes (artifactually) a second unrelated protein. Have an assay to see if your protein polymerizes actin by measuring light scattering of the actin sample? Little did you know that the cuvet (i.e. container) that you are using has a scratch in it that can catalyze actin polymerization ALL ON ITS OWN. In the best case scenario, proper controls are performed and you catch the anomaly early. Worse, you spend 3 years on a project only to learn that the premise is based on an artifact. Worst case scenario ... you publish a paper using the artifactual results and your career is over. Artifacts that support the model (see worst thing #8) are hard to catch and harder to overturn. Moreover, results that disprove the model are often disregarded by the model's champions with the quip "those results are artifactual".

Ah, isn't science fun ...

Unfortunately I'm in the last experiment mode (for a publication), so I really should not waste anymore time with blogging (oh no! this last comment will surely provoke comments from some coworkers ...)

Facts and Models

2005-11-29T12:24:00.000-05:00

Got a response to the Ernst Mayr Quote:

"Some scientific studies are based on pure facts..while others stand on theory alone."

Actually that's not true. Science generates models (i.e. theories) that predict how the world works. To verify that your model is the "best available model", you must perform experiments (or make observations) to test the model's predictive power. The results of these experiments (i.e. facts, or empirical results) either support your model or go against your model. The latter scenario is called falsification. If your model is falsified, you either have to alter your model or throw it away and come up with a better model. This is the scientific method.

Do not confuse empirical results with models (or "theories"). They play very different parts within the scientific process. The rock that falls towards the earth with a certain acceleration is an empirical result, and gravity is the model. Gravity would predict that a rock falling towards the moon has a different velocity, and so it does ... thus our current model of gravity is supported by the facts (i.e. the theory of gravity is not yet falsified).

Some models can't be falsified. These models are "bad" because they do not have predictive power. For example if I believe the model that God created the universe, it does not predict anything WITH CERTITUDE. It does not predict "If you dig here you will find X" ... in other words, there is never a chance that you would dig and find "not X" and thus proclaim, "ah, I guess this falsifies God". This is not to say that God does not exist, but that the question of whether God created the universe lies beyond the realm of Science.

In other words good models exclude many potential results. A fantastic model would predict A and not B, C, D, E, F, G or H. A weak model would predict either A, B, C or D, and not E, F, G or H. Non-falsifiable models would not give any clear prediction (A to H are possible). Many people believe that string theory is not a good model because it's details can be molded to fit any empirical result and thus string theory (in it's current form) has almost no predictive power. Evolution on the other hand has very strong predictive power and those predictions are seen within every sequenced gene.

To sum this up,

1) Science builds models (i.e. theories).
2) Models (i.e. theories) have a certain degree of predictive power with regards to the empirical results (i.e. facts) you accumulate through experimentation and observations. The better the model the more accurate the predictions.
3) Fantastic Models usually give insight. This means that you acquire a deeper understanding of the underlying principals at play. Some may argue that good models encourage reductionalism.

Eye Candy

2005-11-28T20:13:00.000-05:00

I was analyzing my injected cells, while listening to this interview of William Gibson, and I bumped into this photo I took over the weekend:

It's an injected Hela cell nuclei - but looks like a jack-o-lantern. Very nice.

Thelonius Monk & Asperger's Syndrome

2005-11-27T10:01:00.000-05:00

For oncetoday's entry will be on a muscician, Thelonius Monk.

This great artist has been in the news lately - recently someone acting on rumors found a recording of a Carnegie Hall concert given by the Thelonious Monk Quartet and John Coltrane. This new recording is of great importance as John Coltrane spent 6 pivotal months with Thelonious in 1957. In that time he kicked heroin and "found God". Until this discovery there were only a hand full of songs recorded by this partnership. I've been listening to this phenomenal recording for 2 weeks straight, it's fantastic.

Monk's music is incredible. Paraphrasing Wynton Marsalis, he has the spirit of a wise guru trapped inside the mind of a five year old. When I've made my parents listen to his stuff, they exclaimed that his songs sounded like Sesame Street on LSD.

His unorthodox music, fully of seemingly simple yet complex and melodies, and his personality (Monk seems oblivious to the world - totaly foccused on his music) are all reminiscent of Asperger's syndrome. This disease has been in the news of late. Asperger's is a form of Autism, but the afflicted are usually quite gifted especially when it comes to recognizing and analyzing patterns. I've writen in the past on how Asperger's and other forms of Autism may be caused by increased prenatal exposure to testosterone. In a recent article, WIRED claimed that it was the Nerd Syndrome:

Kathryn Stewart, director of the Orion Academy, a high school for high-functioning kids in Moraga, California, calls Asperger's syndrome "the engineers' disorder." Bill Gates is regularly diagnosed in the press: His single-minded focus on technical minutiae, rocking motions, and flat tone of voice are all suggestive of an adult with some trace of the disorder. Dov's father told me that his friends in the Valley say many of their coworkers "could be diagnosed with ODD - they're odd." In Microserfs, novelist Douglas Coupland observes, "I think all tech people are slightly autistic."

...

These days, the autistic fascinations with technology, ordered systems, visual modes of thinking, and subversive creativity have plenty of outlets. There's even a cheeky Asperger's term for the rest of us - NTs, "neurotypicals." Many children on the spectrum become obsessed with VCRs, Pokemon, and computer games, working the joysticks until blisters appear on their fingers. (In the diagnostic lexicon, this kind of relentless behavior is called "perseveration.") Even when playing alongside someone their own age, however, autistic kids tend to play separately. Echoing Asperger, the director of the clinic in San Jose where I met Nick, Michelle Garcia Winner, suggests that "Pokemon must have been invented by a team of Japanese engineers with Asperger." Attwood writes that computers "are an ideal interest for a person with Asperger's syndrome ... they are logical, consistent, and not prone to moods."

And other great muscicians, such as Glenn Gould, have been diagnossed with this syndrome. To hear about Asperger's on NPR's Infinite Mind click here.

Quote from Ernst Mayr

2005-11-26T10:16:00.000-05:00

I've been reading Ernst Mayr's This Is Biology: The Science of the Living World. In it there is this great quote:

It is often asked why we do science? Or, what is science good for? ... The insatiable curiosity of human beings, and the desire for a better understanding of the world they live in, is the primary reason for an interest in science by most scientists. It is based on the conviction that none of the philosophical or purely ideological theories of the world can compete in the long run with the understanding of the world produced by science.

Thanksgiving dinner talk & outsourcing

2005-11-25T09:36:00.000-05:00

Last night we had many coworkers over for a thanksgiving food orgy. Everything was great, although it took forever to cook our 27lb turkey. We had many things to celebrate. One coworker just got a paper accepted into a big journal. Another coworker is leaving us to start his own lab on the west coast. At dinner the talk drifted from work to my blog, then to outsourcing science, then to how some scientists who used to be communists act like capitalists, and finally how there is one lab head at Harvard Medical School who's already outsourcing all of his fly work (i.e. creating and maintaining mutant fly strains). Apparently the NIH does not fund any outsourced science work (yet).

Since today's post was already written for me, our guests then suggested a couple of entry titles, the only one that I can recall is "Some scientists are more equal than others".

Marc Kirschner to give a reading of his new book

2005-11-23T07:35:00.000-05:00

This morning someone took our paper, and so during breakfast I picked up The Improper Bostonian to check the local listings ... and who do I see listed in the Books & Poetry section? Our ex-department head Marc Kirschner. To be honest, someone had told me that he was in there - but they had a photo of him (and of his long time collaborator, John Gerhart) as well.

He'll be reading from his new book The Plausibility of Life, November 29th, 7PM at First Parish Church, Harvard Square. To read a previous entry on this book, click here.

Back from NYC

2005-11-22T07:27:00.000-05:00

Well I'm back from NYC where I once was a Grad student in the Gundersen Lab. My wife and I try to go back to "the city" once every 3-4 months to "get stimulated" (click here for a description of a previous visit).

So what did we do?

We spent Saturday night at "Chez Bushwick", watching their Shtudio Show ... from the website:

SHTUDIO SHOW offers a smorgasbord of cutting-edge dance, new music and other performance. This is not another burlesque/cabaret show, but rather an evening devoted to maintaining New York's unique legacy of experimentation and underground umph.

Although SHTUDIO SHOW seemed to be frequented by mostly modern dancers, the show included readings, performance art, music (although of the postmodern genre) and of course a dance performance (again very postmodern).

So where is "Chez Bushwick"? Well in Bushwick Brooklyn, NY of course ... from the April 1st edition of the NYTimes:

Williamsburg and neighboring Bushwick buzz with ad hoc entrepreneurship. Artists brave the area's stark postindustrial landscape, and camp out -- often illegally -- in loft spaces. Soon enough, fabulous little health food stores spring up among the carcasses of burned-out cars, rents rise accordingly, and artists push on to the next frontier, leaving in their wake a neighborhood made safe for commerce but too expensive for artists. It has happened before -- think SoHo and the East Village -- and it may well be happening again. Artists in search of affordable space have been pushing Williamsburg's eastern frontier steadily deeper into Bushwick.

Although Williamsburg is gentrifying, Bushwick is all abandoned industrial space. And Bushwick is being invaded by artists, from the same article:

The most visible addition (to the dance scene)was the Williamsburg Art Nexus, a black box theater affectionately known as WAX. A refuge for up-and-coming choreographers that opened in 2000, it reflected the neighborhood's freewheeling, do-it-yourself roots. Unlike Manhattan spaces, where a handful of gatekeepers control access to sought-after sites like P.S. 122, Dance Theater Workshop, Danspace Project at St. Mark's Church and the Kitchen, WAX was uncurated. Anyone with $1,500 and a dream could rent the theater for a weekend and put on a show, until last fall, when the theater closed to make way for luxury lofts.
No site dedicated to dance has emerged in the area with the visibility and professionalism WAX had, but Williamsburg and Bushwick are still full of dance studios that serve intermittently as theaters. Chez Bushwick, Soundance and Studio 111 all have informal monthly performance series, and there has been a flowering of mixed-use spaces, like Galapagos Art Space, the Brick and OfficeOps, offering the occasional dance performance. In addition, some choreographers use their private lofts for showings, and a few art galleries, like the Williamsburg Art and Historical Center and Cave, have regular dance performances.
This flourishing has given the dance world a much-needed boost. Cheap space and ample time have helped young choreographers push past the generic stuff they were churning out in two-hour increments at rented studios, and the multiplicity of informal performance spaces has encouraged irreverence and experimentation.

A documentary on the place is in the works. For more on Chez Bushwick here.

Another visit of note, PS1, MoMa's experimental contemporary art museum located in an industrial section of Queens (right across thr river from Bushwick). With a NYC trip, we almost always make a quick stop at PS1. The most notible installation was John Kesler's The Palace at 4 A.M.
What was it about? It's a room full of moving cameras ... filming you through paper cutouts that depict war, pornography and 9/11. Thus the viewer is viewed and all is distorted (see pic). In one instalation, post cards are slowly ramed into cameras, and on the video screen you're flying into the World Trade Center. Another camera is pointed towards a window where a carboard cutout is hanging ... and on the screen it's the Apocalypse on Jackson Ave. Is terrorism and the war, an ugly pornographic flick? How would we feal if we were there? How is the media distorting all these events?

Science Resources International

2005-11-20T20:03:00.000-05:00

I'm here in NYC for the night. I was flipping through Edgar's copy of WIRED, and what do I see?
Stats on Science R&D.

Top country in allocating resources to R&D per GDP? China (6% GDP).
How about the US and Canada? US, just over 2.5%, and Canada, just under 2.5%.

I'll post more up once the issue comes out electronically.

{update 11/22}

The WIRED article is now available online.

What a week

2005-11-18T15:57:00.000-05:00

Well this week was a mixed bag.

My microinjection experiments were painful due to the fact that the needles kept braking and that Hela cells are just hard cells to microinject (see a pic of injection bellow). These days of pain may explain the outbursts on previous posts.

While collecting the data from these injected cells, NPR had a report on Peretz, the new leader of the labor party in Israel. My day was a bit brighter. Then I listen to how the Democrats and moderate Republicans got their spine back. Hmm the week seemed not so bad after all. And then I realized that these painful injections have given me the results I've been hopping for. I guess that makes today's post cheerful. This ended in watching giant papier-mache puppets advocating for an overthrow of the government.

And just like the puppets, we're headed to NYC for the weekend. So things are looking good.

The Economics of Academic Research

2005-11-17T09:40:00.000-05:00

Interesting exchange will the Tall Medstudent. That I’d like to share as a post on it’s own. (All that follows is an elaboration of comments from yesterday-post’s).

Tall Medstudent:

When foreigner postdocs stop coming to the US, there will have to be a rise in salaries, and that will be followed by Americans reentering science.
That will be helped by the worsening of the US economy; the worse opportunities are in business, the better jobs in science will look.
This comes back to the Bush State-of-the-Union statement: America needs foreigners to do the jobs that Americans will not do. The lie in that statement was that Americans will not do the jobs, because American business would rather pay foreigners a lower wage than pay an American what he needs to survive in his economy. Anyways, I think that the US science needs a shake-up like this in order to move forward again.

I agree partly. Salaries will go up if there is a decrease in labor supply. All those that claim that “Americans don’t want to do those jobs” DON’T UNDERSTAND ECONOMICS. A truer statement is that Americans don’t want to do those jobs AT THAT PRICE. When employers can’t hire, they increase the salaries until they can fill those positions.

BUT an additional factor, that has non-monetary value, is how respected a job is. Americans don’t respect academia and so not many Americans enter research. In contrast Asian culture respects academia – that’s why many Americans of Asian descent enter academia at higher rates than other subsets of the American population. This not only has effects on how many Americans enter Science, but how much federal (or state) money is set aside for basic research, and what the NIH guidelines are to paying postdocs. The stature of a postdoc is so low in our society (and in our institutions) that they’re position on the income ladder is lower than it reasonably should be. And the high number of postdocs (due mostly to the over hiring of postdocs) applying for the limited number of PI slots is another great source of anxiety and one of the biggest problems in academia.

The solution may not be to limit foreign students, especially if other countries get their act together and the American school system continues to fail in its mission to produce well educated citizens. To build a wall around the US would only isolate America from obtaining the best minds from overseas. This is exacerbated by the fact that foreign researchers are treated like crap when they are here (in terms of getting visas and green-cards). I’ll get back to what the solution IS later, now onto part two …

I disagree with the worsening US economy will increase academic pay.

1) When this occurred earlier this decade, Americans jumped from business to the high paying professions (doctor, lawyer ...). There are too many alternatives to academia.

2) If the economy slides downhill, the government will cut money for research grants. Less postdoc openings and thus the market will favor lowering salaries even more (fewer jobs for the pool of aspiring academics).

3) Even if academia seems like a better alternative, the increase in Americans in academia will favor an even greater lowering in salaries and work conditions (as in #2 the ratio of jobs to the employment pool decreases, pushing salaries down).

Academic research is in a sense a luxury. A country has it if it can afford it. But that is deceptive. The US economy relies on basic research to generate new industry, so more and more it is a necessity. That’s why China and Singapore are investing tons of money in biomedical science. That’s why the US economy has been so strong over the last 60 years – it has the best universities and generates all the new technology. But I’m not sure that this will last. My belief is that academic investment is primarily correlated to HOW MUCH THE GOVERNMENT WANTS TO INVEST IN RESEARCH. Right now support for research funding is eroding. Academic conditions (FOR POSTDOCS AND GRADSTUDENTS) are not good, but still better than overseas. And the reliance on foreign academics allows this to continue to a certain extent. But I believe that the main problems are within American culture and academic culture.

Recently the NIH guidelines for postdoc salaries went up. Why? It wasn't because of supply and demand issues, it was because members of academia (PIs, not postdocs) lobbied the NIH to increase the salaries.

So in the end factors within the Academic establishment, and factors within American culture (as in respect for researchers, and a recognition that research is important for the future of this country) are the biggest pressures that will better conditions in Academic institutions especially for postdocs. We (POSTDOCS) need more money, and better respect within the institution and within society. And less postdocs should be hired, but those that are hired should be nutured not treated like slave labor! We can’t just rely on the market, but must change the culture as well. American culture and Academic culture. To simply rely on the market would be a disaster for postdocs, for the US, and in the end the US will lose out.

America, Foreigners, and Academic Science

2005-11-16T09:06:00.000-05:00

While most bloggers and conservatives worry about the latest front on the culture wars ... the REAL crisis in American Science continues to simmer.

From an OpEd by Stuart Anderson in today's NY Times:

Foreign graduate students, particularly those who study science or engineering,
are a boon to the American economy and education system. They are critical to the United States' technological leadership in the world economy: according to a study by Keith Maskus, an economist at the University of Colorado, for every 100 international students who receive science or engineering Ph.D.'s from American
universities, the nation gains 62 future patent applications. International students have founded many of America's most innovative companies, including Sun Microsystems and Intel.

America needs academics. We support the US economy. But grad-students and postdocs in academic labs are treated like crap here - low wages, little security. Keep in mind however that conditions in the US are much better off than elsewhere, and most of the big labs where you can get the best trainning are still American labs. Result - very few Americans are in research and thus the US relies on foreigners to fill it's academic institutions. But can this go on? The number of academics coming across the border to work in the US is falling.

Although it's easy to blame tightened post-9/11 visa policies for stagnating or declining international student enrollment figures, other factors have contributed to this unfortunate trend. Among them are fierce competition for students with Britain, Japan and other countries; improvements in the economies and universities of China and India, the countries that send the largest number of students here; the cost of an American education; and a perception that the United States is not interested in attracting international students.

So the US is having problems getting foreign workers to come. Now more science may be done outside the US (see my post on Outsourcing Science).

And furthermore, what's happening to foreign academics after they're finished with their gradstudies and postdocs at American institutions? Many, unable to get permanent status, are leaving. I personally know 4 individuals in my direct working environment who are dealing with green cards and are in limbo with regard to their current residency status.

Finally, and perhaps most avoidably, the United States makes it exceedingly difficult for our foreign-born science and engineering doctorates to stay in the country, where they might work in our private sector, conduct research in our labs or teach at our universities. It can take two years or more to gain permanent residency, and there are significant backlogs in applications for employment-based green cards.

Again the US should pay attention to all this if they wish to stay ahead of the curve.

Deforestation

2005-11-15T16:00:00.000-05:00

Good article in today's Science Section of the NY Times on recent deforestation trends (see map below). Overall deforestation is not as rapid as in the past. And a surprise! Can it be that "totalitarian China" is outplanting the other developing nations?

From the article:

"While good progress is being made in many places, unfortunately forest resources are still being lost or degraded at an alarmingly high rate," said Hosny El-Lakany, assistant director-general of forestry for the food and agriculture agency.

The slowing rate of forest loss is encouraging, some forest experts say, but biologists contend that most acreage gained by plantation forestry contains a fraction of the plant and animal diversity destroyed with virgin forests. Forest cover has generally been expanding in North America, Europe and China and diminishing in the tropics.

...

Asia has seen an extraordinary turnaround in a decade: it lost about 3,000
square miles of forest a year in the 90's but gained nearly 4,000 annually since
2000, said Mette Loyche Wilkie of the F.A.O. But almost all of that change has
occurred because of China's new forest policy, she said. Tropical forests
elsewhere in Asia are still being cleared at a rising pace, the report said.

While Africans and South Americans cut down their trees, the Chinese are planting them (as well as the Spanish and Italians). And this is less of a credit to China and more of wake up call to countries like Brazil and Indonesia. If you're going to cut trees, plant them as well! It's called renewing your renewable resources. For more info see the Food and Agricultural Organization of the UN.

OpEd in today's Boston Globe about evolution and ID

2005-11-14T14:37:00.000-05:00

Here is the link to Cathy Young's piece in today's Globe, Fact and fiction on evolution. I really have nothing more to add to it. But I do like her last paragraph:

Yes, there are people in the scientific and academic elites who fear and despise religion. Unfortunately, the battle for intelligent design will do little except reinforce their worst prejudices.

Best Places to Work in Academia??

2005-11-12T10:11:00.000-05:00

I was glossing over The Scientist, when I came across this article:

Best Places to Work in Academia, 2005

(Like the NY Times, The Scientist just doesn't get it. I don't have a personal subscription, so I can't cut & past the relevant quotes.)

So if you're an academic in the life-sciences, where is the best place to work in the US?

1- Clemson University
2- Trudeau Institute

In the rest of the world?

1- Weizmann Institute
2- University of Toronto
(Incidentally, University of Alberta and University of Calgary also made the top 15, I guess Elizabeth Blackburn was right.)

But why Clemson and Trudeau? Both have small life-science departments, both are in the middle of no-where. More importantly, both do not not have many scientists pushing the frontiers of knowledge. There are many essentials to create a good working environment, but stimulation is near the top. Sure these places may have low stress levels and great health care benefits, but stimulation? It reminds me of these stupid lists of the "best places to live in America" where Nirvana lies in some tiny town in the Midwest. Something tells me that these lists reflect the wishes of the list makers rather than some objective measurement.

There are many things I hate about Harvard Medical School, but one benefit is that you are surrounded by hard working and/or very clever people. In most labs, such an environment helps you grow as a scientist. And Boston also has quite a bit of culture and night life to help recharge your batteries.

Is Harvard Medical School in the top 15? No. Would I rank it in the top 15? Probably not.

Harvard medical school is a great place to work as a postdoc, but not as junior faculty. Unfortunately Harvard can rest on i's name and can treat it's academic staff like trash ... and get away with it. After all there will always be more high quality academics vying for those spots. But would I want to go to Clemson or Trudeau? Not anytime soon.

RNAi Multimedia

2005-11-11T10:30:00.000-05:00

From Flags and Lollipops, here is a link to an animated tour of RNA interference (for more on RNAi, see this entry on my old blog) at Nature Reviews.

Fancy stuff ... perhaps this is the only way to get the public (and some scientists) interested into the newest developements in biological sciences.

Transcriptional Activation

2005-11-10T09:34:00.000-05:00

Yes the daily transcript has an entry on TRANSCRIPTION.

Yesterday I attended a talk given by Robert Tjian from UC Berkeley (HHMI profile). So what is new in the world of transcription?

Well he gave a nice intro. He explained how his lab first thought about the problem, then conducted "promoter bashing" experiments to identify DNA regions important for activating flanking gene sequences. Then he presented the current model. Promoter and enhancer DNA regions that flank the gene, bind proteins (i.e. transcription factors or TFs) that interact with a big complex ... TFIID. This complex includes the TATA binding protein (TBP) and Tata binding factors (TAFs). Under the influence of TFs, TFIID unzips the DNA and recruits RNA Polymerase II, the enzyme that copies the gene's DNA sequence into mRNA (this copying process is called "TRANSCRIPTION").

So the big question is how is transcription spatially and temporally regulated? In other words how do different cells turn on different genes? And how does the same cell turn on different genes at different times (such as during development)?

The answer? As far as I can tell confusion. We know that different TFs and different TAFs are expressed in different cells, we know that the whole thing is complex ... but beyond these simple statements, Prof Tjian could not offer further insight. I left the talk with "a bad taste in my mouth" (sorry for the cliche).

Something needs to happen in this field for it to make some serious progress. Perhaps the idea of picking model genes or understanding how one gene is differentially activated in different cells at different times, is not the best approach. Another plan of attack is needed.

Perhaps there is some hope - a student who rotated in the lab this summer, joined another lab who's goal is to coat microarrays with small DNA fragments and probe these arrays with labeled transcription factors. In otherwords BIG BIOLOGY. Now I'm no fan of big biology, but maybe it can be used to understand how these various components work together to generate temporal and spatial differential expression of genes.

Incredible International Kits

2005-11-08T19:35:00.000-05:00

All this talk of kits, and outsourcing science ... then my boss (Tom) comes back from Japan where at a conference he met a guy who operates a biomedical company that sells purified components for in vitro translation (remember from the Central Dogma, translation = "mRNA => protein"). Anyway using this company's reagents, one can reconstitute translation with purified components, and the company will sell you each purified component separately!

Want to have ribosomes bound to mRNA and stalled after encountering a valine codon? Reconstitute the whole reaction without the valine tRNA! (Actually such experiments have been done.) Want to stall the ribosome at the stop codon, omit release factors. It's all yours if you have the $.

One catch - these reagents are not for sale overseas ... so here is another wrinkle in the whole science outsourcing issue, the transport of biological reagents over borders. Currently there are many restrictions (just ask anyone who sent/received antibodies from labs overseas) and it is not clear how these restrictions will change over time. With terrorism and the promotion of globalization, it's hard to predict the future of international biomedical business.

New Kids on the Blog

2005-11-08T10:56:00.001-05:00

Well it looks like a fellow postdoc (and soon to be PI) just ditched his old blog at Tripod (just like someone else I know) and set up a new blogspot blog. Not sure if it was due to the adds or that he was just following the rest of us. Incidentally he did not want me to link to his lab's website, I guess he's a bit embarrassed about things he's said in the past.

Speaking of new blogs, my father has been furiously writing highly technical posts concerning modern physics at his new hangout. But be careful, his entries are laced with frightful equations such as:

And now Journals are getting into the blog craze. Nature Genetics has a blog. Nature Neuroscience has a blog. And here is an editorial about Science blogs in The Scientist.

France is on Fire

2005-11-07T16:12:00.000-05:00

Well if you're not American, you probably know all about the chaos that is going on in France. You know about the two kids electrocuted by accident while hidding from police officers, who relentlessly target the minority youths in empoverished French suburbs. You know about the riots, the words of the Interior Minister Nicolas Sarkozy, the and now 10 officers injured in the latest clash. From the BBC:

FRENCH RIOTS
One man killed
4,700 cars torched
1,200 people arrested
17 people sentenced
108 police and firefighters injured
Figures as of 7 November

Of course some idioblogs think that this is "terrorism", "Islam" or "Islamofascist". If you want to know what is the cause - just look at the Watts County riots here in Uncle Sam's backyard.

One question that I have: Why isn't this story being reported in the US?

Interview With a Tall Medstudent

2005-11-05T05:48:00.000-05:00

Last night I conducted an interview with the Tall Med Student (over Microsoft Instant Messenger). Like me, the Tall Med Student is Canadian although for a while he was an ex-pat working as a postdoc in some lab at Harvard Medical School (as I am now). Currently, he is attending Medical school at the University of Calgary, and has his own blog (Tales of a Tall Medstudent). We talked about the whole US/Canada thing, Alberta, medschool, and aliens ...

Mad Scientist says:How does it feel to leave the US and be back in Canada (in ten words or less)?
Tall Med Student says:It's a pleasure to go see a doctor up here. I guess that is eleven words, technically.
Mad Scientist says:Don't worry, it's like a baker's dozen.
Tall Med Student says:Oh good. Now I am thinking about doughnuts.
Mad Scientist says:Would you ever reconsider moving back down to the US?
Tall Med Student says:Never, not in three years. NYC or nothing, I think.
Mad Scientist says:What is the major issue that prevents you from moving back down?
Tall Med Student says:Health care. And all my tax money going to bomb-making and murder for profit.
Mad Scientist says:Elizabeth Blackburn told me "If I were you I would move to Alberta and get a lab there, they'll have tons of money soon", any comment?
Tall Med Student says:Just got 1.3 billion for new health care facilities in Calgary. Every dollar of oil price represents 100 million in income for the provincial government. This year's surplus will be around 9 billion or something.
Mad Scientist says:It's often said in Canada (and in Quebec in particular) that Albertans want to be American, any comment?
Tall Med Student says:No way.
Mad Scientist says:Could you elaborate.
Tall Med Student says:Bush has stopped all that.
Tall Med Student says:People here are freaking out over the possibility of private health care getting more access to the province.
Mad Scientist says:So is there a movement against all these plans to privatize healthcare?
Tall Med Student says:The government is looking for a 'third way', by which they emphasize that it will remain a public system, just organized in new ways.
Mad Scientist says:As a doctor, are you planning to practice medicine in Alberta?
Tall Med Student says:Maybe, docs are stinking rich here. Unbelievably so. A good lifestyle, low stress.
Mad Scientist says:Why do they call it "practice"? That terminology freaks me out.
Tall Med Student says:'Cause you always need more practice.
Mad Scientist says:As a patient I wouldn't want to be practiced on I need the real thing!
Tall Med Student says:Hmm, then you need to only be subjected to tried and true techniques, like amputation or bladder surgery. Although, I suppose that current doctors don't have much experience with those anymore.
Mad Scientist says:I hear that you've suffered an injury lately - did they have to amputate?
Tall Med Student says:No, they practiced on me. A med student sewed me up after the surgery, actually. The plastic surgeon did his residency here, and has just come back to town after doing a fellowship elsewhere.
Mad Scientist says:Wow, from U of C?
Tall Med Student says:No, U of S. Which worried me a bit.
Mad Scientist says:Did you guys chat about med school stuff?
Tall Med Student says:Yeah, she was a fourth year, here on an elective.
Mad Scientist says:So everyone is flocking to Calgary.
Tall Med Student says:Well, I'm not surprised. People go where the oil is.
Mad Scientist says:I thought it was the dino bones?
Tall Med Student says:The oil is here because of the dino bones, and everyone else is here for the oil, so, I suppose that makes the dino bones the primary reason.
Tall Med Student says:Man, I have been trying to figure out who that alien who visited my blog is. I suspect he or she is a Bostonian.
Mad Scientist says:Hmm. Aliens visiting blogs - are you on morphine?
Tall Med Student says:He or she mentions Salem in his or her blog.
Mad Scientist says:Very interesting. OK Dr. J is yanking on my shoulder - it's Happy Hour. Speak to you soon.
Tall Med Student says:Okay, gotta run. Ttyl.

NY Times Downgrades Access

2005-11-04T10:15:00.000-05:00

It's a shame, but the NY Times has placed limitations on it's website access. Now to view items from the OpEd section, you need to subscribe to the paper. It's obvious why this is bad for readers, but why is it bad for the NY Times? From an interesting post on Technorati's blog:

As the chart above shows, the most influential media sites on the web are still well-funded mainstream media sites, like The New York Times, ...

Infact it's the most linked-to site. And in comparison there is the Wall Street Journal:

An interesting statistic to note is the current placement of subscription sites like WSJ.com (the Wall Street Journal). While the WSJ has begun to offer some content outside of its subscriber-only site, the policy is clearly costing them some influence and attention in the blogosphere, as bloggers find it difficult to link to articles in the subscriber-only sections. Also interesting to note is that even though The New York Times and The Washington Post require free registration to view the articles, bloggers are still linking to the stories, and this behavior hasn't changed much in the past 6 months.

Note that since this change does not affect me (I get the paper at home and have full access to the web edition) I don't write this commentary out of vindictiveness. With the rise of electronic media, institutions like the NYTimes are more accessible and have much influence than previously.

So will the current change in the NY Times' policy affect it's relatively newfound influence? And if we do move to a paperless environment, where the morning news is read through an electronic screen instead of through paper, will more electronic content be pay-per-view? Going electronic and dumping paper is in the end a smart choice for many reasons (i.e. less waste, more cost effective) ... but how will these changes affect the influence of these institutions in the public debate? We will see.

More on the Rise of Chinese Technology

2005-11-04T08:51:00.000-05:00

To gain an edge technologically, you need proficiency and creativity. With the rise of the East's Academic Institutions (see my entry on outsourcing science), will the East be able to generate NEW technology? Many have argued "No", but I think that this is mostly Western prejudice. Just look at the innovation coming out of Japan over the past 50 years. From an OpEd by Thomas Friedman in today's NYTimes:

There is a lot of truth to that. Even the Chinese will tell you that they've been good at making the next new thing, and copying the next new thing, but not imagining the next new thing. That may be about to change.

...

Check out Microsoft Research Asia, the research center Bill Gates set up in Beijing to draw on Chinese brainpower. In 1998, Microsoft gave IQ tests to some 2,000 top Chinese engineers and scientists and hired 20. Today it has 200 full-time Chinese researchers. Harry Shum, a Carnegie Mellon-trained computer engineer who runs the lab, has a very clear view of what Chinese innovators can do, given the right environment. The Siggraph convention is the premier global conference for computer graphics and interactive technologies. At Siggraph 2005, 98 papers were published from research institutes all over the world.

Nine of them - almost 10 percent - came from Microsoft's Chinese research center, beating out M.I.T. and Stanford. Dr. Shum said: "In 1999 we had one paper published. In 2000, we had one. In 2001, we had two. In 2002, we had four. In 2003 we had three. In 2004, we had five, and this year we are very lucky to have nine." Do you see a pattern?

In addition, Microsoft Beijing has contributed more than 100 new technologies for current Microsoft products - from the Xbox to Windows. That's a huge leap in seven years, although, outside the hothouses like Microsoft, China still has a way to go.

...

[Dr. Shum] "I learned mostly about how to do research right at Carnegie Mellon. ... Before you create anything new, you need to understand what is already there. Once you have this foundation, being creative can be trainable. China is building that foundation. So very soon, in 10 or 20 years, you will see a flood of top-quality research papers from China."

So it would seem that China is on the rise. (Any news from India now?)

Eye Candy

2005-11-02T09:22:00.000-05:00

A mouse fibroblast, imaged using DIC (Differential Interferance Contrast) microscopy.

A Protein Complex; The Overused Abbreviation

2005-11-01T14:42:00.000-05:00

Every subject has it's lingo and it's share of strange terms. Add abbreviations and acronyms, and certain areas of expertise can be almost incomprehensible. Then there is Biology.

Life has a diversification machine, evolution. Thus those who study life (i.e. Biologists) have lots of proteins and genes to name and to investigate. Humans have about 23,000 to 30,000 conventional genes, and many other non-conventional genetic elements such as small RNAs. On top of that these same 23,000+ genes are also found in other vertebrates and many are found in almost every eukaryotic cell. Thus the same molecular machinery in yeast may be completely renamed in humans ... and named weirdly in fruit flies (Drosophila). All this leads to a mass confusion for those that read the biology literature.

But the part that really annoys and frustrates some Biologists is the overused abbreviation - a single abbreviation that is used for several different biological components. The most famous overused abbreviation (as far as I can tell) is APC.

What is APC? Well one thing it doesn't normally stand for is "A Protein Complex".

Ask a cancer biologist, and APC stands for Adenopolyposis Coli, a gene that causes colon polyps. The product of this gene affects several cellular signals and helps organize the cell's cytoskeleton. APC is also mutated in 50-60% of spontaneous colorectal cancers.

Ask a biologist studying the cell cycle what APC stands for, and he will tell you that it stands for the Anaphase Promoting Complex. This molecular machine is responsible for tagetting the destruction of key components so that the cell can proceed along the cell division cycle.

Ask an immunologist what APC stands for, and she may state that it stands for the Antigen Presenting Cell. These cell are exposing foreign antigens to the appropriate white blood cell in order to activate an immunological response.

One abbreviation, three completely different biological items. Enter "APC" into PubMed and ... good luck.

Then one day it was reported that APC (adenopolyposis coli) interacted with the machinery that yanked the chromosomes apart during cell division. This machine is called the kinetochore (greek for moving body). Of course many components of the kinetochores also activate the other APC (the Anaphase Promoting Complex). Activated APC (Anaphase Promoting Complex) destroys the links between duplicated chromosomes so that the act of chromosome separation (i.e. ANAPHASE) can take place. In addition, the first APC (adenopolyposis coli) plays a role in how the cytoskeleton reorganizes during "polarization events". An example of a "polarization event" is when a white blood cell polarizes towards an APC (Antigen Presenting Cells). Some researchers have identified specific versions of APC (adenopolyposis coli) in certain immune cells (perhaps even in APCs!) ... are you confused yet?

The Tower of Babel was built and all those that spoke the same language could no longer communicate.

The New Video

2005-10-31T11:11:00.000-05:00

Good friends stayed over this past weekend. The main topics of conversation were blogs, google, science and anxieties over our future careers.

There I found out about Google Video Search. At some point people thought that the internet would replace television, and then more recently this idea has been ridiculed - but something tells me that the death of TV (or at least a great paradigm shift) may actually occur.

Read this interesting article from the Boston Phoenix about the Participatory Culture Foundation.

But as corporations lick their chops at the prospect of digital-video windfalls, Worcester's Participatory Culture Foundation (PCF), a small cadre of young activists and programmers, is heading in the opposite direction. The group has developed an open-source, nonprofit Internet TV platform that looks to draw the average viewer into this brave new world. Called DTV in its current Mac-only beta version (but due to be renamed when it launches for both Mac and Windows in the next few weeks), it's an intuitive, user-friendly way to find free online video, subscribe to daily video feeds, organize your video library, and, importantly, publish your own video content. It's a significant development in online television, and the first major step in the PCF's grand mission to "create an independent, creative, engaging, and meritocratic TV system for millions of people around the world."

Outsourcing Science

2005-10-28T16:09:00.000-04:00

More and more this seems to be a reality that the West will have to face. As the number of highly educated individuals in India and China increases and the currents gaps in the cost of living in the West vs. the East are maintained, it will be inevitable that a large amount of commercial (and perhaps academic) science will be outsourced to the East.

And the beginnings of that are almost at hand. From an article in today's NYTimes:

China wants to transform its top universities into the world's best within a decade, and it is spending billions of dollars to woo big-name scholars like Dr. Yao and build first-class research laboratories. The effort is China's latest bid to raise its profile as a great power.

China has already pulled off one of the most remarkable expansions of education in modern times, increasing the number of undergraduates and people who hold doctoral degrees fivefold in 10 years.

...
The model is simple: recruit top foreign-trained Chinese and Chinese-American specialists, set them up in well-equipped labs, surround them with the brightest students and give them tremendous leeway. In a minority of cases, they receive American-style pay; in others, they are lured by the cost of living, generous housing and the laboratories. How many have come is unclear.

On many occasions (and on this blog and my previous blog) the issue of importing low-wage biological science workers AND outsourcing of science has come up. Now there is a rebirth of academic science in the East. So where will this all end up in 10-20 years? Will this be one of the last generation of graduate students and postdocs who can perform research in the US?

Here are some scenarios:

a) Science will be done in the West, but the pay will be bad. Few Americans enter science, preferring more lucrative jobs (lawyer, stockbroker, florist). The only individuals willing enter biomedical research are imported from other countries. WAIT this is the current situation (and I am imported labour!)

b) Due to the fact that most research grants will continue to come from the NIH, most science will be spearheaded in Western labs, but many smaller sub-projects (constructing genes, purifying proteins) will be sub-contracted to companies in India/China. (Sounds like my entry on kits.) Labs will have a PI (principal investigator) but fewer gradstudents/postdocs. Need a knockout mouse? Call up Beijing.

c) Labs will split into two. An American lab to get grants, and an Asian lab to do most of all the gruntwork. Read about Tian Xu's lab. Just like corporations, labs will go multinational.

d) All basic (i.e. unprofitable) research will be performed in the West, while pharmaceuticals will move the majority of their operations east. Although big pharma would keep outposts here so they could cash in to collaborations with any new hot field.

e) Scientific output from Asian universities increase until it rivals/surpasses Western output. Meanwhile in an anti-evolutionary orgy, American fundies go haywire, chanting "off with their heads" and Science from the US disappears.

f) Nothing much happens. Political instability in China and India cripples government funding towards science. Other impediments include a lack of local biomedical related industries that provide reagents/equipment and other essential tools for science, a cooling down of "globalization" with it's many indirect effects (such as impeding the ability of eastern labs to import equipment from the West). And then there is war, religious strife ...

Note that I'm not saying that these changes are good or bad, but that they may happen and we have to deal with them. OK my head hurts (and my anxiety is high), Friday Happy Hour here I come ...

"The Fashion Journals" or "The Holy Trinity"

2005-10-26T13:20:00.000-04:00

Andy (another Rapoport postdoc) and I had a mini debate as to whether Nature, Science and Cell should be referred to as "The Fashion Journals" or "The Holy Trinity". Many institutions of higher learning informally require a tenure-candidate to "get into" one of these publications. In addition many hotshots can get crap into these journals - like trendy bars, once you've made the hotshot list you can come back anytime you want.

Let's evaluate these titles:

"The Fashion Journals" is self explanatory.

But there is more to the "Holy Trinity".

Nature being the oldest, would have to be The Father.

Since Cell was started by Ben Lewin, a former "Nature" guy who was upset by the other two biggies, and who then "walked the earth" to start his own journal and save science publication, Cell is definitely The Son.

That would make Science the Holy Ghost. Since it's a non-profit and the "poorer cousin" of the other two journals, it is fundamentally different thing - just like The Holy Ghost.

Not bad. OK so we're not as witty as some ... but we do keep ourselves amused.

Eye Candy

2005-10-25T18:15:00.000-04:00

Hela cell microinjected with ???

Systems Biology DNA Prep???

2005-10-24T14:15:00.000-04:00

Once upon a time, we made the necessary chemicals from scratch to purify DNA from bacterial cultures. These days, for a couple of dollars, you can get all the reagents you need all packaged in a nice box - these things are called commercial "kits".

You may ask, why do you use these kits - Is it laziness? or consistent results? A combination of these answers I guess. In the end those that never made the reagents from scratch are less likely to understand how the procedure worked, and how to trouble-shoot when the procedure fails. The latest kit (from Qiagen) had this flyer and instruction booklet (pic left). But if you read the flyer closely this is what you'll notice:

This is clearly a new all time low in kits. A kit for systems biologists?? ... it's as if the kit's label should have read: "Are you a String-Theorist and want to jump into biology? Well we have the kit for you! Use our NEW AND IMPROVED kit and you'll get your DNA faster than ever (and thought-free too). Now even a clueless Physicist can purify DNA without thinking about how this stuff actually works!". The sad thing is that the kit is EXACTLY THE SAME AS THE OLD KIT, except for some blue dye that helps to evaluate if your bacteria have lysed. But Qiagen really wants us to believe that this kit is NEW AND IMPROVED, and so they added this sentence to the cover of their NEW instruction booklet:

To all those Systems Biologists ... have fun with your blue kits!

My Father's Letters to the Montreal Gazette

2005-10-23T11:05:00.000-04:00

After publishing an article on ID (which unfortunately I do not have) the Montreal Gazette obtained and published the following letter from my father:

Dear Editor,
Regarding Janice Keane's letter (Gazette, Oct. 18, "Creation is always a leap of faith") in which she asserts that "it (evolution) still is and remains a theory, rather than a fact", disparages not only evolution but all of science. Newton's law of gravity is a theory, so is Quantum Mechanics and Einstein's famous E=mc2. Yet when it comes to evolution which encompasses well-established principles found in physics, chemistry and biology, people like Janice Keane, who can't accept its implications that life arose on this planet as a random process, resorts to this ultimate dismissive
that 'it is just a theory', meaning in the sense that it has very little value. Let it be clear and simple: an attack on the theory of evolution, not on its content which is open to debate but on its reason to exist, is an attack on all of science.
Joseph Palazzo

Then today the Gazette published a response:

Joseph Palazzo (Letters, Oct 19) is clearly confused about the difference between theory and fact. If I drop an apple, it will fall to the floor 100 per cent of the time, so gravity is a fact, not a theory. Evolution, however, cannot be proven. So saying that evolution is a theory does not disparage real science.
Intellectual honesty dictates we recognize that creation and evolution are both theories. I lack the faith to believe that order came out of chaos T the Big Bang theory) or that the complexity of nature is a result of chance development(evolution).
Rev. Rich Mellette

My father's new response (just submitted to the Gazette):

Rev. Rich Mellette's answer (Letters, Oct 23) to my letter (Oct 19) further confuses the issue. Observing an apple falling is a fact, Newton's law of gravity that explains that fact is a theory, not a fact. Nonetheless on that theory -- Newton's law of gravity -- we were able to send a man to the moon and back. That we have such much confidence in that theory might lead us to believe that it is a fact, when in reality it is not.

Now Creationism can be construed as a theory but not as a scientific theory. The danger of this misconception as led as in the case of the Kansas State Board of Education to force science teachers to give equal time in their biology classroom to Creationism. But Creationism, and its hybrid Intelligent Design, have failed on all counts on the Popper's fallibility test and have been rejected as a scientific theory by the science community. In a democratic society, the religious beliefs of any person are nobody else's business. The creationists are free to believe whatever religious tenets they like. And Creationism can be taught as a course in the religious studies or the humanities, but it has no place in a science class.

Joseph Palazzo

So why is the Gazette taking ID so seriously? Well that's easy, this newspaper is owned by Conrad Black, a newspaper tycoon and staunch conservative. Unfortunately, the Gazette (an awful paper I must add) is the only English language newspaper that delivers in the Montreal area (I'm not sure if the National Post delivers in the Montreal Area, but that paper is even more Right-wing and it's also a Conrad Black production). So as a result ID gets air time in Montreal. This is a great example of how a media monopoly can adversely affect the public debate of important issues.

Nice Profile of Tian Xu in Today's NY Times

2005-10-22T10:33:00.000-04:00

Well after complaining that Scientists are rarely featured in the American press, I found a profile of Tian Xu from Yale's Genetics Department in today's NY Times. To visit his lab's website click here.

{update 10/2/05}

Sorry I usually take out some excerpts from NY Times articles, as they are only freely accessible for about a week. Foretunately there are other bloggers who DO copy whole articles, such as Dr Xu's Profile. For a discussion related to Tian Xu's lab see my post (9/28) on outsourcing science.

Happy Hour Follies

2005-10-21T16:02:00.000-04:00

There has been an ongoing "friendly rivalry" between our lab and the neighboring lab. When ever it's one lab's turn to host the weekly happy hour, it usually advertises it in a way that ridicules the other lab.

This week it was our neighbor's turn. However instead of mocking us their poster's title was: Want Avian Flu? followed by a picture of a virus, followed by a + sign, followed by a picture of a chicken followed by "= chicken wings".

Weak.

We then decided to post this poster next to their poster ...

From: John XXX
Sent: Thursday 10/20/2005 8:11 PM
To: XXX Lab
Cc:
Subject: Happy Hour
Attachments:
-------------------------------------------------------
>>> John,
>>> We have a problem, one day left, no theme for
>>> happy hour, we're screwed.
>>
>> Dear Lab,
>>
>> Don't bother me with this crap. By the way I need a place with window
>> seats to eat dinner on Friday. Someone make reservations.
>
> Dear John,
> The situation is critical, people are going to starve, and we need an idea
> quick. You're not coming to happy hour?

Dear Lab,

Happy hour? A Harvard big-shot PI like me has better things to do on a Friday night. Chicken wings are cheap these days - build your happy hour with that - think of a good reason why we should eat chicken wings - and please MAKE YOUR POSTER APPEALING! Why aren't our posters ever as good as those from the Rapoport lab???

You're doing a heck of a job. Don't bother me about this again,
John

Random Thoughs on Big Polymers

2005-10-20T19:38:00.000-04:00

Yesterday I attended an interesting talk by Xuetong Shen from University of Texas (Smithvile, TX) about how actin, a cytoskeletal protein normally found in the cytoplasm, was a component of several chromatin remodeling complexes. For non biologists, chromatin is the DNA/protein complex that makes up our chromosomes and is found in the nucleus. DNA is wrapped around a proteinacious complex, called the nucleosome. For more on this topic click here.

Why is actin in the nucleus and why hasn’t anyone ever seen it before? (Alright some have claimed to have done so.) Perhaps actin polymerizes in short sequences and acts as a mini track thus providing a surface to push nucleosomes along the length of a DNA strand? These remodeling complexes also help fix DNA double strand brake – perhaps short actin polymers act like “splints”?

But another strange fact popped into my head – a fact we use to think about when I was in the cytoskeletal field ... DNA, membranes and the cytoskeletons are the 3 biggest continuous portions of the cell, and all three of these are highly negatively charged. There is something to that … but I’m not sure what …

David Suzuki - Canadian Icon

2005-10-19T11:03:00.000-04:00

If you grew up in Canada at any period between 1970 to 1990, seared on some corner of your brain is a photo of the geneticist, environmentalist and TV personality David Suzuki. He is so loved and well known, he was recently nominated for "The Greatest Canadian".

Growing up I remember watching his show "The Nature of Things", a program that aired on CBC. Similar in format and content to PBS' Nova, the Nature of Things was a great show and I suspect had a greater viewership (as a % of the population) than Nova ever had. Well in yesterday's NY Times Science section there is a great profile of Dr Suzuki - although contrary to certain statements in the article, I think that many Scientists from the True North Strong & Free have great respect for his tireless work of educating the population. Perhaps if the US had more personalities who were Scientists, instead of having these ID debates, we could foccus the public's attention to other issues ... like global warming.

Marc Kirschner Interview on NPR

2005-10-18T15:49:00.000-04:00

Today, Marc Kirschner, head of the Systems Biology here at Harvard Medical school was interviewed on NPR's On Point program. There Prof Kirschner talked about his new book, The Plausibility of Life, evolution and what is the fabric of what he use to call evolvability. Click here to listen.

All I can say - great interview. Prof Kirschner made a couple of points that most other Scientists in the spot light fail to mention. He clearly states that there is Science and there is faith and the two should never be mixed up. He also states that Science should never be used to explain things that we do not understand, and that it is a great disservice to Science to claim that we have "all the answers".

He also talks about the great mystery of developmental biology - that actually there is not much difference at the genetic and cellular level between us and all other animals. To make an eye is not hard - most eyeless creatures have most of the building blocks (i.e. genes) to do it. It's actually easy to come up with intermediate eyes (and many of these intermediates exist in nature). And it's easy to see how the body can foster any change when things like eyes evolve. The body of multicelllular organisms is full of buffers and self organizing systems that permit these evolutionary changes, and the core components (genes) are almost universal and interchangeable. Infact the greatest mysteries in Biology escape the general public and the ID guys' imagination - how do these self-organizing principles work and how does a cell "work" (included in this second question is how do cells communicate). In the realm of evolution the biggest questions are how did life originate, how did the first (bacterial or prokaryotic) cell come about, and how did the first eukaryotic cell come about. Excluding consciousness and the mind, you can boil down 99% of the mysteries of "life" down to the cellular level. The rest (how to make limbs, eyes and) is infact trivial in comparison.

Happy World Day of Bread

2005-10-16T14:19:00.000-04:00

Yes it's true, today is World Bread Day.

And why is the Mad Scientist so enthralled by another gimmicky "World ... blah blah blah ... Day"?

Well I was reading my good friend's blog (Tales of a Tall Medstudent) where he was describing how he was attempting to bake his own bread and succeeding. Now it turns out that I've gone down that path too. I wrote back to him:

Confession - I bake my own bread too (did I ever give some to you?) It all started with crappy bread-machine bread. I loved the freshness but could not stand the crappyness - and the crust was the worst part. One day I marched down to the library and discovered "The Bread Bible" - great book BTW - and now for almost 8 months I've been baking bread - about 1-2 times a week.

Once you start baking, it's hard to stop. It's hard to explain. Part of it is the side of me that likes to tinker around and try stuff (I've been experimenting with every loaf). Another part must be a subconscious urge to create.

Another comment to the Tall Med Student's blog was from Floyd, who has a great blog on bread baking (on the Fresh Loaf site). That's where I read about World Day of Bread. Just like academic journals, there's a blog for every topic. Anyway ... Floyd exclaims on his blog:

"Hello, my name is Floyd, and I am a bread-aholic."

I went crazy this weekend. Kaiser rolls, a french bread, oatmeal raisin cookies, pumpkin bread, ciabatta, a raspberry cheese braid, honey wheat bread. Not to mention that I made a batch of apple butter, specifically for eating on home baked bread.

Next weekend, I've gotta stop. Maybe one or two batches but that is it.

And for some strange reason I perfectly understand. And I think to myself this whole baking thing is like some strange cult of underground bakers. Reminds me of the whole MAKE phenomenon (listen to this episode of NPR's Weekday about MAKE Magazine). There is an urge for people to reconect with "everyday things", take them apart, put them back together and figure out how to do it yourself. Call it MacGuyverism.

To all those mad bread bakers out there ... have fun.

RNA World - Search for the self copying molecule (RNA)

2005-10-15T11:06:00.000-04:00

Well we're almost there!

Here is some rainy day (Saturday) reading for you. David Bartel (of RNAi fame) has an interesting article in a recent issue of the journal RNA on RNA-ligase ribozymes (link). Have fun.

Marijuana makes your brain grow!

2005-10-14T17:01:00.000-04:00

It seems like every couple of months there is a new study that reports the medical wonders of Marijuana. From the latest Nature News:

The researchers injected rats with HU210, a synthetic drug that is about
one-hundred times as powerful as THC, the high-inducing compound naturally found in marijuana. They then used a chemical tracer to watch new cells growing in the hippocampus. They found that HU210 seemed to induce new brain cell growth, just as some antidepressant drugs do, they report in the Journal of Clinical Investigation.

Cannabinoids to make your neurons grow, to treat atherosclerosis ... what's next?

Scientific Establishment to the US: Shape Up!

2005-10-13T13:21:00.000-04:00

In today's NYTimes:

A panel of experts convened by the National Academies, the nation's leading science advisory group, called yesterday for an urgent and wide-ranging effort to strengthen scientific competitiveness.

The 20-member panel, reporting at the request of a bipartisan group in Congress, said that without such an effort the United States "could soon loose its privileged position." It cited many examples of emerging scientific and industrial power abroad and listed 20 steps the United States should take to maintain its global lead.

"Decisive action is needed now," the report warned, adding that the nation's old advantages "are eroding at a time when many other nations are gathering strength."

As I've said before - in the realm of science education, the US has to shape up!

We need more and BETTER science and math teachers in the high schools if we want to increase science literacy. But that's not all, the US has to support basic research (something that's been going downhill recently).

Some recommendations (as stated in the NYTimes article):

¶An Advanced Research Projects Agency modeled after the military's should be established in the Energy Department to sponsor novel research to meet the nation's long-term energy challenges.

¶The nation's most outstanding early-career researchers should annually receive 200 new research grants - worth $500,000 each, and payable over five years.

¶International students in the United States who receive doctorates in science, technology, engineering or math should get automatic one-year visa extensions that allow them to seek employment here. If these students get job offers and pass a security screening test, they should automatically get work permits and expedited residence status. If they cannot get a job, their visas should expire.

¶The Research and Experimentation Tax Credit, scheduled to expire in December, should be made permanent and expanded. It goes to companies that increase their spending on research and development above a certain level.

To encourage private investment in innovation, the panel said, the credit should increase from 20 percent to 40 percent of qualifying investments.

Follow this link to read the original press release from the National Academies.

Systems Biology - Some Insights

2005-10-12T09:03:00.000-04:00

Yesterday, I saw a Systems Biology talk by Peter Sorger, and well there was some hocus pocus, but some insight. Professor Sorger is part of the new Cell Decision Processes Center at MIT, a fancy name for the new Systems Biology Center there.

Sorger’s strategy is to study intracellular signaling cascades with a mix in silico models with cell based experiments. The former involves identifying all the signaling components and their various states and assigning differential equations to describe how a molecule changes from one state to the next or how one molecule alters a second molecule.

Molecule changing state: A1 =(v)=> A2
Molecules interacting: A + B =(v)=> AB
Molecule changing state (catalyzed by a second molecule): A1 =(v[B])=> A2

The in vivo experiments involve the activation of cellular signals by adding various extracellular factors and/or removing signaling components (or reducing their levels) using RNAi. These cells are then analyzed by measuring various factors such as the “activation” state of a key downstream signaling molecule. Using the in vivo data points, Sorger’s group has been able to “teach” their model. After tweeking the model they attempted to generate in silico based predictions and gained some insight into how the system is rigged – and you know what? their model produced some interesting ideas.

They first studied the programmed cell-death pathway (apoptosis; read the history of this field from Nobel.se). The immediate problem with such a decision, is that the cell must either choose to die or not – you do not want a half-dead cell. By adding signaling factors that activate the death pathway and then measuring a key downstream component (caspase activity) on a cell to cell level, Sorgers group found that when the decision is made, cell death is always fast. As they reduced the level of extracellular signal, cells took longer to make the decision to go from low caspase activity to high caspase activity, but once the decision was made the kinetics of caspase activation was always the same. Thus the way this system was set up, was using a “light-switch” mechanism. Levels of signal influenced how long it took to flip the switch, but once it was flipped the pathway acted just the same. The insight is that the model predicted a "switch" and pointed that switch-components were set up in several feedback mechanisms. These switch-components at first glance seem to act redundantly - there are many loops, and several interchangegable components took part in each step of the loop. Remove components and the pathway could be activated but the switch was now not as rapid and became sensitive to the levels of other “switch factors”. You still got cell-death but the switch mechanism was altered. So the intact system is ROBUST and INSENSITIVE to the fluctuations of other components – in other words the feed back loops buffer slight changes to generate a bistable equilibrium. So molecular components of the death pathway should not be seen as “pro-death” or “anti-death” but compoenents of the switch.

I sense a paradigm shift here.

Classical biochemistry/cell biology involves determining the molecular components involved in a process. Molecule X repairs DNA damage, molecule Y helps cells to stop dividing when there is DNA damage, and molecule Z relieves the inhibition allowing cells to finally divide. The moto of our field for the last 30 years has been, “find the molecules”. But X, Y and Z are interlocking components – and a better way of looking at these is part of a module that has certain properties (it can act as a switch ...) So to understand X, Y and Z you need to understand the module. So maybe a better moto would be “understand the module”.

Some problems:

These modules act independently between cells, so by studying whole populations we may miss how the module works IN THE CONTEXT OF A SINGLE CELL. To better understand this we need to have biochemical assays at the single cell level, and preferably we would want temporal information too. So you need to look at how the molecular state evolves in a single cell over time.

There are (often too) many parameters. Sorger’s group simplified their model by excluding how the molecules are made and destroyed – with each level of complexity you get more equations, more variables and then many potential models fit the data. What Sorger’s model was good for was to indicate which molecules fit together in a module. The system was insensitive to the levels of some molecules while extremely sensitive to the levels of other molecules. Thus certain molecules were purely functioning to "make things work" and their concentrations mattered little, while other molecules acted to probe the biochemical state of the cell and their levels had great influence over how cellular decisions were being made. The key then is to figure out in which of these two groups any particular molecule falls into.

Lots of voodoo. The models are so complex that we need new ways to present how they work. It was very hard to evaluate his approach because a lot of these in silico findings ... you just have to accept what he says ... and it isn’t apparent what are the caveats (and other problems) are. This is highlighted by the fact that crucial factors (such as protein/molecular synthesis and decay) were not taken into account.

The final judge of good science is (IMHO) is the insights generated by the work. On that account, Systems Biology (despite what I've written in the past) may be good for biology after all.

Game Theory Wins Nobel

2005-10-11T09:46:00.000-04:00

So the latest Nobel for Economics was awarded to Robert J. Aumann, and Thomas C. Schelling for the development of Game Theory. Interestingly Game Theory has not only affected economics, politics (especially with regards to nuclear proliferation) but also Evolution. Gene Selection employed ideas from Game Theory to predict how genes could spread in a population by promoting altruism. Genes that promote certain "rules of behavior" that reward other individuals that play by the rules (and thus share the gene in question) while punishing those that cheat (and hence do not share this gene) can become stable in a population. Such a behavioral strategy is called (in Game Theory and Evolution Biology) an Evolutionary Stable Strategy (or ESS). One famous example is the Tit-for-Tat behavior (read this great site for more on Tit-for-tat). One offspring of gene selection is Sociobiology, which in my view has been unfairly attacked for political reasons - if you can get a hold of the last issue of Seed Magazine, it has an excellent article on the history of Sociobiology.

For more on all these related topics I highly recommend Richard Dawkin's landmark book, The Selfish Gene.

Downfall

2005-10-09T09:12:00.000-04:00

Last night we saw Downfall, which portrays Hitler's last few days before the end of WW2.

As the director, Oliver Hirschbiegel, explained "The fascinating thing is that [Hitler and the Nazis] were human, not monsters with claws and fangs." Indeed Bruno Ganz (one of my favorite actors - see Wings of Desire), was excellent in portraying the dictator. The danger in a role such as this, as he puts it, is to portray Hitler as a caricature.

Why is it dangerous to portray Hitler as not being human? Because the ideology that precipitated WW2, and the horrors of WW2 was caused by humans. By calling Hitler a monster and separate from humanity, we implicitly say, we would never cause that because we're no monster. We run the danger of not learning how Germany fell under the spell of a dangerous and crazy ideology, because we're no monster. So when Politicians are compared to Hitler, this is not simply an insult ... we should take pause that such comparisons are worthwhile and instructive. Or are we trapped in the ideology that we could never cause such atrocities ... I only wish that this were true.