Here I go...

... like a lamb to the slaughter.

I guess I'm one of the last of PZ's sacrificial students. As you may have gathered from my clever alias my name is Katie and I'm a senior biology major. I've actually known PZ for a number of years--I'm a Morris native and went to high school with his son, Connlann. When I was thirteen I met Connlann in an upper level math class (something esoteric called "algebra") and learned that Connlann's dad was a biologist (cool!) and an atheist (he puts people to sleep before surgery??) I soon adopted him as my personal biological encyclopedia and would pester PZ with questions of science any chance I got. When I decided to stay in Morris for college, PZ became my academic advisor and I've been harassing him for knowledge ever since.

This year I am applying to medical school and busy preparing my senior seminar on hypothermic treatments in preserving brain cells in cardiac arrest patients. This new treatment is already in use in some hospitals across the country and completely revolutionizing the way we manage cardiac arrest victims. If you've come across studies on this in the literature, I'd appreciate your input. I'm especially interested in research on the way brain cells die. Apparently cells that have been oxygen deprived commit apoptosis even after re-oxygenation. For some reason, induced hypothermia after or during resuscitation increases brain cell viability.

Well that's all I've got. Now go ahead. Eviscerate me (bleat!).

More like this

If you want to study how brain cells die, you should conduct field research in a church. More brain cells die there than anywhere else. I think most of them commit suicide or die of boredom.

I love the way you write. You should come to southern California for medical school. It's nice here, and we have good schools.

By cureholder (not verified) on 14 Sep 2007 #permalink

Can't speak for everyone, but I see no reason to eviscerate. Look forward to hearing more about your research. You're so lucky having a personal biological encyclopaedia - I used to hero-worship my friend's dad, because he was a conservation biologist and had an aquarium with seahorses.

(he puts people to sleep before surgery??)

That one earned an easy smile-and-a-half! :-) :-j

Is there a way to distinguish cells that destroy themselves from cells that succumb to injury? How can you tell the difference? (I've always wondered this, BTW.)

By Caledonian (not verified) on 14 Sep 2007 #permalink

Good luck, doc!

-jcr

By John C. Randolph (not verified) on 14 Sep 2007 #permalink

I'm sure you're already aware of this, but: Football player Kevin Everett received hypothermic treatment for his recent spinal cord injury.

"Green said the key was the quick action taken by Cappuccino to run an ice-cold saline solution through Everett's system that put the player in a hypothermic state. Doctors at the Miami Project have demonstrated in their laboratories that such action significantly decreases the damage to the spinal cord due to swelling and movement."

http://sports.espn.go.com/nfl/news/story?id=3014742

Fascinating stuff.

And the doctor doing the procedure, I think it was Dr. Andrew Cappuccino, said something to the effect that there was nothing miraculous about it -- that the treatment was something PEOPLE had discovered and worked to perfect. Sounded to me like he was staking out ground against the claim-to-come that God had a hand in healing Everett.

When I was a young Paediatric resident I had to put an intravenous line in a wee lad; his dad told me: "You'll never get the line in; last time they had to call an atheist to do it."

Got it first time, of course.

Incidentally, there is a new series of DVDs on Evolution in Medicine from Henry Stewart Talks. We need biologically-minded medics; good luck in your studies!

By Amenhotep (not verified) on 14 Sep 2007 #permalink

Nobody who has known Herr Doktor Meyerz for any length of time need fear his minions. They will only hurl insults. He will eviscerate you in a non-metaphorical way.

Incidentally, there's been reports of a new method of performing CPR by regular abdominal massage - apparently it is measurably better than chest compression, and send more blood to the heart than the old technique. It also doesn't break ribs or sternums.

By John Wilkins (not verified) on 14 Sep 2007 #permalink

Is there a way to distinguish cells that destroy themselves from cells that succumb to injury? How can you tell the difference? (I've always wondered this, BTW.)

Basically when a cell dies it, well, dies. Cellular functions stop and it gets mopped up by leukocytes (or not). The cell self-destruct mechanism is different. Basically the cell chops its DNA into short segments, packages it, then splits itself into neat little chunks for easy disposal. It is a very highly regulated and very "neat" process that leaves the cell in perfect little pieces for leukocytes to eat up. It would be sort of akin to you cutting yourself into 1-inch cubes, putting each of those cubes into a little box and then leaving the boxes on the curb for the garbage man to pick up.

By TheBlackCat (not verified) on 14 Sep 2007 #permalink

#6:

Hank, get out of my brain (no neurobiology pun intended) :)

There was actually a discussion on the Bills' message board about whether or not Everett's condition is an act of Gawd, and too many people over there said that, yes, it was more a miracle from Gawd than good medical care.

http://boards.buffalobills.com/showthread.php?t=9452

I guess if Everett had taken that same hit before the hypothermia treatment was developed, God wouldn't have had anything to do with his paralysis, but since he benefited from modern medicine, the touch of the divine is present. Not so much a god of the gaps as a god of the anything good.

Getting back on topic, though, I think the whole concept is fascinating. It would be interesting to figure out what sort of evolutionary mechanisms or selection pressures would develop cells that die after they're re-oxygenated, rather than while they're being starved of oxygen. Unless I'm not being very imaginative, it almost seems like it would be detrimental rather than beneficial for it to work that way.

I have a tip that would make for the introduction less perplexing: observe where your name/moniker is actually posted when visitors are reading the main page. I found myself confused when you stated "As you may have gathered" since there were only two prior sentences to observe and neither led me to know what your name might possibly be.

It seems to this non-biologist like it would be a good thing to artificially expose neurons to reduced oxygen levels until we find a level that reliably makes them commit apoptosis, then expose them and immediately look at circulating mRNA to see what changes in gene expression have happened, i.e. by what pathway apoptosis is activated. Until you know that, it seems to me to be somewhat hopeless to try to block it.

(I bet someone did this years ago and I didn't notice.)

Hi Katie. Welcome!

Nothing here to indicate evisceration as a treatment.

(PZ - man, you have some sharp ones, don't you? But then I'm sure you already knew that!)

That IS interesting, about how neurons (and other cells in general) seem to avoid damage under hypothermic treatment, isn't it?

I'm not very well informed on the biochemical details behind the phenomenon (biochemistry being a might too densely complex for one of my bent, in physics and astrophysics, to wrap my clumsy mind around) but it does seem to me that a good look into first principles could well proffer some further insight into the mystery. At least I think it wouldn't hurt (besides presenting a potentially tedious waste of time - but who can say without doing the work? ;)

From my perspective, for example, I might also look at it from a thermodynamic standpoint (attending to the "forest" as well as the "trees", so to speak): how the motions and speeds and general jiggling-about of atoms and molecules are reduced with declining temperature, and how the rates of chemical reactions in general are reduced, perhaps with some surprising deviations, considering certain peculiarities in ensymes and other catalysts involved in reactions and such phenomena as giant-molecule (like protein) folding, etc. may depart from the expected rates of decline with temp.

Along this vein one may also consider how certain species manage to avoid catastrophic cell damage with "antifreeze" when temps go down far enough to otherwise cause water to crystalize.

Of course I may have just exposed my vast ignorance on this topic, but as complex as biochemistry surely is, I expect there's still a world of research to be done there.

After all, so much of ground-breaking research comes from a reexamination of what we all think we already know...and that kind of self-testing "reality checking" is exactly what science is famous for.

I, for one, would like to hear back from you on the course of the thinking on your interest! One can learn very much indeed by seeing how others learn and arrive at knowledge.

Good luck in your endeavors!

By Arnosium Upinarum (not verified) on 14 Sep 2007 #permalink

I'm especially interested in research on the way brain cells die. Apparently cells that have been oxygen deprived commit apoptosis even after re-oxygenation. For some reason, induced hypothermia after or during resuscitation increases brain cell viability.

There's still a lot of research to be done on the details of that. The important thing with cooling the brain is to get deep enough into the affected tissues (they've been experimenting on rats).

The reason cooling works at all though is apparently down to the release of chemical signals when the brain is damaged. Those are what tell neighbouring cells to kill themselves. Cooling slows down the release and spread of those chemicals (along with other metabolic processes - so it's not a very specific treatment!). This gives time for the damage to be fixed so that further cells then see no reason why they should succumb to apoptosis and don't.

Ongoing research for spine and brain injuries is about finding more specific blockers of the apoptosis mechanism. Partially specialised stem cells, "progenitor cells", have been found to have some protection against it.

PS Risking just the one link to see if I can still get the post through.

Hi SEF...your post serendipitously ammends my clumsy effort. Thank you much!

By Arnosium Upinarum (not verified) on 14 Sep 2007 #permalink

(he puts people to sleep before surgery??)

No, all the time, mostly during lectures; it would be a good research project to see whether this effect is more closely related to the stuff he drones on about, or the activities of the victim the night before.

(This is a fascinating experiment, P.Z. I wish there were some way to survey your readers to see whether it helps them out, and how.)

Katie, you almost made me spit beverage all over the keyboard with the "puts people to sleep before surgery" comment. Nice work - sounds exactly like something my students would say :) Kind of like "he's a veteran - you know, a doctor for cats and dogs". Good luck!!

Ho there, Katie.

I recall a study in the NEJM regarding this issue, relatively recently (a few months ago?). I believe they specifically mentioned the hypothesis that it was not that cells were dying during re-oxygenation, though they were, but that during re-oxygenation they were oxygenating at such a rapid rate that they were being mistaken for being hyperoxygenated.

Hyperoxygenation is generally a good sign of malignancy, and so tends to set off apoptosis.

Let me just rattle off the relevant studies here, and if you're interested in getting some of the PDFs, don't hesitate to e-mail me. I don't mind sharing my NEJM access with PZ's bastard science spawn.

Lack of Effect of Induction of Hypothermia after Acute Brain Injury; http://content.nejm.org/cgi/content/abstract/344/8/556

Treatment of Traumatic Brain Injury with Moderate Hypothermia
http://content.nejm.org/cgi/content/full/336/8/540

Hypothermia for Traumatic Brain Injury -- A Good Idea Proved Ineffective
http://content.nejm.org/cgi/content/extract/344/8/602

Hypothermia to Protect the Brain
http://content.nejm.org/cgi/content/full/346/8/546

And some helpful papers you ought to be able to get via institutional access (hopefully):
Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_ui…

Apoptosis after traumatic human spinal cord injury.
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_ui…

Death in normal and neoplastic cells.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&T…

Apoptotic and anti-apoptotic mechanisms following spinal cord injury.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&T…

By James Stein (not verified) on 15 Sep 2007 #permalink

(bleat!).

Uh-uh, we know the line about a wolf in lamb's clothing.

This year I am applying to medical school and busy preparing my senior seminar on hypothermic treatments in preserving brain cells in cardiac arrest patients. This new treatment is already in use in some hospitals across the country and completely revolutionizing the way we manage cardiac arrest victims.

Try Pubmed. They have hundreds of articles that are narrow enough to be very helpful and thousands that are broad enough to give you a broad understanding.

Of course everybody turns this into creationist bashing!

Not everybody (I cite myself for starters). Looking back at the thread though, "nobody" would be a more accurate assessment (apart from the vaguest of hints). Perhaps you meant a different thread entirely.

Excellent post Katie!

"If you want to study how brain cells die, you should conduct field research in a church. More brain cells die there than anywhere else. I think most of them commit suicide or die of boredom."
This does not work. As Dawkins has said, "if you are going to church you have to hang your brains up at the door."

who is this Connlann guy - all we ever hear about is Skatje and the Trophy wife?

who is this Connlann guy

There have been pictures ...

Hi Katie: I was impressed with your advanced knowledge and reasoning. If you're looking into neuron cooling, you might check the Safar Center in Pittsburgh. They do emergency ultraprofound hypothermia for trauma and hemorrhage. I did some work with them, and my husband (Mr Science Goddess?) also has interactions with them. They are really great people using hypothermia (cooling to 5 degrees C) for brain preservation. After med school, you could be a fellow there. (http://www.safar.pitt.edu/), or, if you go to med school at U Pitt, you could also work on a project.

SG

By Science Goddess (not verified) on 15 Sep 2007 #permalink

Katie, that's an interesting topic. I wonder: has there been any research on similar technique for stroke? Both a heart attack and thrombotic stroke present similar insult to the brain: inadequate circulation. So at a gross level, if hypothermia protected the brain in one, it should protect the brain in the other.

Hemorrhagic stroke is different, of course. There, much of the damage occurs not from the initial bleeding, but from the lesion that is formed.

Anyway, welcome! Study hard and get into med school.

Hi! I work in a lab that studies insects at low temperatures. By hypothermia, are we talking below zero/0-10 degrees/slightly below room temperature? Because there's all kinds of interesting things that go on at different temperatures, likely with different gene expression and physiological mechanisms.

Now excuse me, I've gotta go supercool some Drosophila larvae...

Hey, Katie, excellent first post -- enough to move me, a rare commenter, to comment! I look forward to reading your posts with particular interest, as I have a special interest in the subject.

[Oh, and I hate Dr. Cappuccino. He has made my life harder. (I'm director of categorization for an information company. All the articles about Everett were getting Coffee as a topic.)]

Nice post.

Are you sure you want to waste your talents by going to med school? Then again, you seem far too intelligent to get suckered into doing a PhD.

You write with clarity, wit & style. If only any of the one-trick ponies who do 90% of the 'eviscerating' around here could say the same; they tend to rely on pompous verbiage and boring their enemies to death through repetition.

Says the creative writing teacher:

I approve of this one's style!

I'm especially interested in research on the way brain cells die.

Girlfriend, if you're in college and haven't already done mountains of hands-on research on this very subject, well, I just don't know what to tell ya.

"I'm especially interested in research on the way brain cells die."

Hmm, i've been dead from the neck up for years and no ones noticed.

Might I suggest you also include in your study firefighters who decide to become cops. We ( firefighters ) happen to think our misguided breatheren have suffered some form of brain damage but we are unable to find a scientific reason for it.

By firemancarl (not verified) on 15 Sep 2007 #permalink

Girlfriend, if you're in college and haven't already done mountains of hands-on research on this very subject, well, I just don't know what to tell ya.

LOL @ that!

I think Connlann would make a great Inigo Montoya.

Katie: Nice first post (and I never met a Katie I didn't like, truly!) and if the rest of PZ's food supply students do nearly as well, it'll be a fun semester for all of us here.

Someone already posted on my thought, which had to do with heat/energy accelerating physical processes, especially gas transport and swelling. The body gets damaged, it heats up, fluids and gases start migrating (for a lot of reasons), injured areas swell up, and you have a problem. 'Under a Flaming Sky', a great book about the Hinckley firestorm, has really ghastly descriptions of the body's response to burns. I wonder if some of the same things don't happen in response to other catastrophic injuries. Perhaps high-pressure environments would help also.

John had mentioned a new CPR method (regular abdominal massage instead of compression). My husband dives and has taken several CPR classes. Although I can google it myself, does anyone have a link for this?

Go to Edinburgh University in Scotland for med school. It's a great school (one of the best in the world), and PZ has already acknowledged our superior accents!
Oh, and fees are cheaper, too!

For some reason, induced hypothermia after or during resuscitation increases brain cell viability.

This review paper may be useful to you on that question. I think, as someone mentioned it in the posts above, the reason is simply physiochemical. The low temperature slows down the enzymatic processes involved in cellular damage and apoptosis. This works not only for neurons and glial cells, but also for endothelial cells, smooth muscle cells, cardiomyocytes and so forth. Hypothermia also slows down leukocyte migration to the site of injury (and therefore, inflammation as well as phagocytosis), and may also cause the release of anti-inflammatory cytokines. This demonstrates the caveat with hypothermic treatment; in order to be effective it needs to be controlled and localized. By running ice-cold saline (with a great presence of mind) in Everett's body, Dr. Capuccino achieved exactly that.

By Kausik Datta (not verified) on 15 Sep 2007 #permalink

Does anyone else think Katie's research sounds like the pre-credits sequence to a zombie movie?

Doctor: Congratulations, Dr. Glasrud! This patient is still alive!

Katie: Not exactly, Doctor. His brain cells are still alive. The patient himself is perhaps better described as ... undead.

Doctor: Undead?

Katie: Yes. And to remain undead, he'll need to constantly resupply those cells with fresh hemoglobin, cerebrospinal fluid, and glucose. Taken orally.

Patient: Glurgh. Aaaargh. Braiiiiiins!

It would be no fun to eviscerate you, as you seem to be familiar with the methods of the inter-tubes and aren't a complete n00b to our ways. We only like to eviscerate unsuspecting people!

Personally, I could never even dream of eviscerating anyone who actually knows how to spell "eviscerate"!! A bit of good writing goes a long, long way. Good luck to you, Katie.

By PuckishOne (not verified) on 15 Sep 2007 #permalink

I see a fascinating opportunity for some other research. You're becoming a doctor. Doctors (like engineers) have a long and embarrassing track record of claiming to be scientists who embrace creationism. Could you report to us the exact moment when they come for you to inject the parasite into your brain?

Katie, dont be afraid - here we beat up people, slaughter is only on a first come, first served basis. Nice post, btw!

Nobody who has known Herr Doktor Meyerz for any length of time need fear his minions. ... He will eviscerate you in a non-metaphorical way.

:-) In a match between Mayharz Minions against Willikins Willies, I bet on the former any day.

By Torbjörn Larsson, OM (not verified) on 15 Sep 2007 #permalink

Hi Katie,

I read a news story relating to this topic a while back...I can't quite remember now, but I think the story was about this. Hope that gives you some useful links you can follow.

"Glasrud"? As if "Skatje" wasn't curious enough. Is Morris rich in Norwegian emigrants?

I like the "put's people to sleep" quib. But now I wonder. There are already examples of people attacking and vandalising the homes of paediatricians. How long will it be before they start to burn anaesthesists at the stake?

[Oh, and I hate Dr. Cappuccino. He has made my life harder. (I'm director of categorization for an information company. All the articles about Everett were getting Coffee as a topic.)]

Heh. The dangers of automatic categorization...

Katie, you're a keeper! I really loved your post and I look forward to seeing you regularly.

I can't help you with your topic of interest, but I'll be very interested to see what you turn up.

And good luck in med school--I hold out every hope for that to happen for you.

Completely OT, butI can't help this. Every time I see the "Here I go..." thing on the side bar, this pops into my head:

Here I go
Here I go
Here I go again.

Girls, what's my weakness?
MEN!

What's to eviscerate?

I have seen these ideas before (I read a lot of science news), but they're very interesting and worthy of discussion.

Ditto on southern California. I just moved here for medical school. It rocks.

Nice startoff, indeed!

I find myself thinking about the reports I've heard of inducing "suspended animation" effects with hydrogen sulfide. Not sure how relevant that is, but I wonder if that would have a similar effect regarding cell death.

By David Harmon (not verified) on 15 Sep 2007 #permalink

Oh ma gawd! You gonna freeze my head? What the hell you freaky scientists gonna come up wit next?

By Elizabeth (not verified) on 15 Sep 2007 #permalink

"Glasrud"? As if "Skatje" wasn't curious enough. Is Morris rich in Norwegian emigrants?

Ummm... Minnesota? Hello? ;-)

This might be of peripheral interest to you:

TherOx
Aqueous Oxygen therapy

By Reginald Selkirk (not verified) on 16 Sep 2007 #permalink

God.

You guys get a Christian, and you shred the poor bugger. Get a definative girl, and you swoon.

The internet really does turn guys into dorky 8th graders, doesn't it?
:/

By SmellyTerror (not verified) on 16 Sep 2007 #permalink

ahem, not all of us are "swooning"

I don't see a need for evisceration here. I'm an aspiring medical researcher myself and your seminar sounds like interesting stuff.

And yes (the 'puts people to sleep before surgery' comment made me smile) Which is somewhat painful at the moment as I'm recovering from surgery on my jaws.

By anti-nonsense (not verified) on 19 Sep 2007 #permalink

Katie, dont be afraid - here we beat up people, slaughter is only on a first come, first served basis. Nice post, btw!

Nobody who has known Herr Doktor Meyerz for any length of time need fear his minions. ... He will eviscerate you in a non-metaphorical way.

:-) In a match between Mayharz Minions against Willikins Willies, I bet on the former any day.

By Torbjörn Larsson, OM (not verified) on 15 Sep 2007 #permalink