No such thing as a dumb question

OK, at the time I was somewhat staggered by the dumbness of this question. I gave a talk about my work, in which I described how various ion channels could be inhibited and potentiated by a selection of anesthetics. Then someone asked, essentially: If a drug has the capability to depolarize a neuron, potentially leading to increased firing, it can't act as an anesthetic, can it?

Now, this dude, given that he must be in anesthesiology research if he was at my talk, should have known better. And definitely should have known better than to ask it as if he had stumbled across a trick question that would unravel all my research, because that's just jerk-y.

But it actually isn't a dumb question. Unconsciousness is much more complicated than simple suppression of all neuronal activity. During anesthesia, some neurons fire more and some neurons fire less. And the hard truth is - we're not totally sure which neurons do what or how that leads to anesthetic endpoints. In general what changes is firing PATTERN, which causes changes in how neurons talk to each other ("integration" for those wanting a more technically accurate term).

Consciousness and anesthesia are so much more complicated than simple reduction in total brain activity, but that's what makes it fun!

Federal regulations (a.k.a why your IACUC seems totally unreasonable)

It is a generally accepted belief that IACUCs as a whole and as individuals thrive on making animal use as annoying and difficult as possible, and derive great pleasure from rejecting, revising, rehousing and otherwise annoying animal users. I can assure you that, with rare exceptions, this is not the case.

Now, don’t get me wrong, there are a few animal users I’d like to have a little chat with. Like the pompous nitwit last month who sent me a one page “rebuttal” to my request for modification. I totted up his animal numbers, came up with 517, looked at his total of 617 and requested that he review his numbers. I got this >500 word rebuttal full of tables and equations and needlessly snotty language, I added them up again, still got 517.  I re-requested modification stating that his total was 517, the total on the rebuttal was 517 and the total on the protocol still said 617. Total waste of my time, total waste of his time, and totally his fault.

*Sidenote rant concluded*

The real reason our procedures are so darn convoluted is that we have to enforce federal regulations from multiple agencies, and they don’t always match. A priceless example of this emerged today.

1)   Animal users use gamma irradiators on some protocols. We are required to know where all animals go when they leave the animal facility, and to inspect all these places twice a year.

2)   Gamma irradiators are subject to increased controls, such that no one except for those certified as “Trustworthy and Reliable” (T&R) are allowed to know where the irradiators are, or who is certified to use them.

Long and the short of it, to uphold their laws, radiation safety wants us to permit irradiation users to avoid stating room locations and transit paths and to avoid inspection of these areas. We said no.

They said, OK, you can just let them not list the rooms. But then we still know who they are. And we have to inspect the rooms – without knowing where they are? They also said, fine, how ‘bout you have designated reviewers for irradiation protocols and we’ll just T&R a few people. We said sorry, we all have to have protocol access and the ability to conduct full committee review. Final answer: T&R the whole committee. And check up on the T&Rs every year. Honestly.

Also in our future – isoflurane badges? Does anyone else have halogenated-ether anesthetic monitoring for animal use? These drugs have hepatoxicity, the concern is that frequent use of anesthetics may expose humans to high levels of the drug. But honestly – we use these drugs on PEOPLE! To the point of unconsciousness! Is knocking out mice a few days a week really going to stack up to actual anesthesia?

The “Age of Enforcement” is going to be the death of me – the worst part is that it seems the majority of this enforcement is not directly about animal welfare.

Loaded Topic

I have the world’s most adorable little doggie at home, and I’m totally crazy about him. I am on my university’s IACUC (Institutional Animal Care and Use Committee), which I’m sure I’ll rant more about later. I use animals in my research. If I could eliminate the use of animals in research, I would.

In all likelihood, animal research is going to come up pretty frequently here, given my involvement. It’s a complicated issue, and easier not to engage, but it is ethically important for scientists to know what they think and continually evaluate to ensure they’re following best ethical practices.

I know that some extremist animal rights groups think that animal research can and should be stopped short, right this minute. Unfortunately, their arguments are pretty flawed.

Argument 1:

One big argument is that animal research hasn’t discovered anything beneficial to humans, or that all these things could have been discovered another way. This is simply untrue. Many important breakthroughs in disease treatment have been made in animal models. Farm animals, pets and endangered animals are also beneficiaries of animal research. Just Google it.

Argument 2:

Another major argument is that animals are not good models for humans and consequently research done in animals will have little relevance to human disease. Some such groups advocate for using cell culture or computer models only, instead of animals models. There’s a reason all these things are called models: they only approximate the human situation in key respects.

I’m pretty sure there isn’t a scientist alive who wouldn’t rather use a cell or a computer instead of an animal. Animals are expensive, require constant care, enormous amounts of paperwork, and specialized training. But sometimes they’re just better than a computer or a cell. The problem with creating a cell-culture or computer model is that you can only recapitulate the aspects of your system that you completely understand. But the whole problem is that we don’t completely understand most tissues or disease processes. So if you make a computer model that tells you everything we know about liver cancer, you won’t be able to cure liver cancer. The good thing about an animal model is that it’s a real tissue, that will act like a real tissue does, even in the ways we don’t understand. Unfortunately, it is true that animal systems aren’t exactly like human ones. This can sometimes be optimized by choosing the right animal, or creating a transgenic animal to better mimic key features of the human system, but even so, it isn’t perfect. That’s why it’s a model. The best science utilizes multiple modeling systems to eventually develop hypotheses that can safely be tested in humans.

Argument 3:

The hardest argument to answer, though, is the ethical/moral argument. Is it “species-ist” to treat a living thing from another species in ways that would be unacceptable to treat humans? Research makes it clear that vertebrate animals have experiences analogous to human pain, fear, pleasure and other emotional states. Rights advocates claim that these emotional and cognitive faculties make animal eligible for membership in the moral community with equal or near-equal rights to humans. This argument can’t be answered with facts or a utilitarian argument, it is about what an individual believes about the rights of non-human species. Even among anti-species-ist advocates, you can find dissent about which animals deserve what rights from worms to mice to monkeys.

Where I am:

I fall on the utilitarian end of the spectrum. Though I strongly support alternatives to animal use and sticking to the 3Rs when animals are necessary, in the end I conclude that the potential benefits of animal research outweigh the harm to animal research subjects. I think this campaign sums it up for me:

I chose to serve on my university IACUC to learn more about federal regulations concerning animal research. I got much more than I bargained for as I hear from many sides: from researchers, from regulators and from rights activists about balancing animal welfare with human welfare. There are never easy answers.

Scientists often feel pressure to justify animal research in the face of extremists who bomb, poison and mail razorblades to researchers, but most scientists will confess that it’s not a black-and-white issue. Respect for life at all levels, from proteins to cells to organisms, is central to biomedical research, and engaging with animal rights issues is important for animal users as we work to preserve the welfare of animals as best we can.

Reality - more magical than anticipated.

Piezoelectricity - a concept that is so cool I cannot believe I hadn’t heard of it until two weeks ago! I work with electricity, and figured I knew it all, but then the universe went and surprised me.

It didn’t start well. I was trying to set up a piezoelectric translator, which apparently someone used about 10 years ago, and it’s still kicking around the lab. it’s OLD, like the manual is type-written and comb-bound old. I read the (nearly useless) manual, and tried to set it up. It did not go well. Various parameters and parts did not function as anticipated. I finally diagnosed some of my issues, but my switching time was still much too long. So I thought, “I’m not a man, I’ll just call tech support.” Well, it turns out the thing is SO old that the company that made it doesn’t exist anymore, and the company they sold the manufacturing rights to doesn’t make this device anymore, and their tech support director was in China. But, you’ll be relieved to know that this story has two happy endings: First, I fixed the switching time after looking at pictures in a book about single channel recording (good news, reading is becoming obsolete!), second, I decided to look up PZT.

Throughout the (nearly useless) manual, they kept yapping about the PZT this and PZT that. Never mind that they never spell out this abbreviation anywhere in the entire manual. So I finally looked it up on Wikipedia, and it turns out to stand for “lead zirconium titanate,” and pointed me back to a page on piezoelectricity, and I was hooked.

So, here’s the basic deal – reality is more magical than anticipated. Tension and compression causes charge accumulation (measured as voltage). Turns out, the reverse is true too, application of voltage to said crystals causes changes in length. Piezoelectricity literally means “electricity from pressure.”

Crystals are made of atoms arranged in repeating blocks called “unit cells,” where the atoms in each repeating block are arranged the same way. Piezoelectric crystals have asymmetric arrangements of atoms in each unit cell. At rest, these crystals are electrically neutral, because the charges of the atoms are arranged such that each positive charge is balanced by a negative charge (really this has to do with dipole moments, if you’re into that level of detail). But when you squeeze or stretch the crystal, you upset this delicate balance of cancelling charges as you move atoms out of place, causing the crystal to have net charge on its faces. Same deal if you apply charge: you apply electrical force that makes the atoms rearrange in an attempt to cancel the charge, causing the shape of the crystal to change. This effect can be pretty large: applying 500 foot-pounds of force to a cubic centimeter of quartz can produce 12500 volts!

Not all asymmetric crystals exhibit piezoelectricity. Some naturally occurring crystals do, like cane sugar, quartz and topaz. Later, scientists began to create manmade crystals for commercial use, like my good friend PZT, which is a manmade ceramic.

Piezoelectricity – practically magic – but what is it good for? Turns out it’s everywhere, not just in science-y sounding equipment. In cigarette lighters, pressing the button makes a little hammer hit a piezoelectric crystal, which generates a high enough voltage that current flows across a spark gap to ignite the gas. You can also find piezoelectricity used in loudspeakers, inkjet printers, clocks, MRI machines and anywhere a cool little crystal motor might come in handy.

It makes me wonder how many other things I use operate on near-miraculous science!

The origin of particular things

"Naming is the origin of particular things," said Lao Tzu, who obviously knew a thing or two, or people wouldn't quote him so much. There were many hurdles to actually starting a blog (which I have been idly contemplating for about a year). The obvious one, is of course inertia. But one of the most intractable was picking a name. I agonize over names, and like to name everything. My patch clamp rig still needs a name, but I haven't found one that encapsulates pure evil, capricious whimsy and occasional subservience.

Anyway, having finally determined the absolute best name, I would hate for it to be wasted on those who didn't grow up on gory mythology tales. (Seriously, every kid should be given mythology books! Murder, revenge, conspiracy, people with awesome powers and horrible disfigurements...) Thus, you shall be subjected to a short mythological explanation of my choices:

In Greek mythology, Mnemosyne was a Titaness, the goddess of memory, who is credited with discovering reason and language. The most well-known fact about her is that she slept with Zeus (after all, who didn’t?) and begot the nine muses. What is often forgotten is that she also presided over a river (or pool/well/spring) in Hades. The river of Mnemosyne was the opposite of the river of Lethe. Upon arriving in Hades, one would supposedly have to choose to drink either from Lethe or Mnemosyne. Choosing Lethe, the river of forgetfulness, would erase your memory of your past life and allow you to reincarnate. Choosing Mnemosyne, however, would make you omniscient.

My name, Alethea, again plays on the Mnemosyne-Lethe dichotomy. The Greek word Lethe means “oblivion” or “forgetfulness”, while Alethea is derived from the Greek word for “truth” or “un-forgetfulness.” I hope it’s obvious which Kool-Aid I drank! J

N.B. I love parenthetical statements. I know it's bad English. And I don't care.

I'm a grad student

This is what it's like. Today I peeled frog eggs with tweezers, then sat in what used to be a closet (now "renovated") full of patch clamp rigs, in the dark, with two other grad students, for most of the day. It's no wonder we lack balance.

Why hello!

Dear Internetz,

I'm a 4th year PhD student at a research university. As such, I am naturally possessed of an abundance of both angst and opinions.

Last night I had a total meltdown about my life, because let me tell you, even if you don't have kids, there is no such thing as work-life balance when you're in grad school (or probably if you're in academia at all)! Then today, as I watch my seal resistance aimlessly climb to 900 megaohms and hover there without getting a gigaseal for about the millionth time this week(I do patch clamp electrophysiology), I realized that I needed a better outlet for my rage than my poor husband.

Hence, I am officially "on the internet." Here, I will tell you what life is like as a female grad student in an all-male biophysics lab, rant about my life in general, and post the cool stuff (research, comics, videos) that helps me remember why being a scientist is worth it.

So, if you like blue-haired snarky biophysicists, you want to hear what science I think is awesome, or you just wonder why grad students are such basket cases, I hope you'll stick around!

Love,
Alethea (not my real name)