General anesthetic research - a dangerous proposition

To start you off, here's a quote from Franks (2006) in the British Journal of Pharmacology:

"The discovery of general anaesthesia is a remarkable story rich with human tales of serendipity, impropriety, noble ambition and inflated egos...Horace Wells hit upon the idea of using nitrous oxide while watching a public demonstration of its powers of intoxication  Having satisfied himself by self-administration that it ameliorated the pain of tooth extraction, he conducted an abortive demonstration..and was publicly humiliated by this failure. A former apprentice and colleague of Wells, another dentist called William Morton subsequently took up Wells’ basic idea of a gaseous anaesthetic agent, together with the suggestion of chemist and physician Charles Jackson to use ether, a much more potent drug, and this culminated in the public demonstration of ether anaesthesia on 16 October 1846  There followed several years of unedifying wrangling between Jackson, Morton and Wells as to who deserved credit for the discovery of general anaesthesia, with Wells eventually committing suicide, Jackson dying in an insane asylum and Morton dying penniless of a heart attack at the age of 48."

Clearly, if you study anesthetics you're in for a good time!


 
 

I'm baaaack!

OK, so I've been a very delinquent blogger. But a whole year later, I'm back! I have permission to write my thesis and I need a place to vent about thesis related issues. And this will be that place - so join me as we journey into the black hole that is my thesis.

Bangs

I'm back in my experimental lab, and it's been a rough landing. I cut my hair before I left for my simulation rotation, and the new haircut has bangs. Bangs + microscopes = not seeing. Today I finally brought a hairclip. There is no way to tilt your head forward and look through a microscope without getting hair in your face!

I have three weeks to collect some much needed data for a grant, and while I had started some of this type of work before I left, I only did it for a few weeks. Now I'm trying to get set up again and it's HARD! Two nitrogen tanks had run out, someone let my cells (that they were supposed to be care-taking) get to passage 40 without thawing new ones, we didn't have the kind of glass capillaries I needed, the incubator water levels were low and I had to remake solutions. Needless to say, I did not get started on the actual work as fast as I wanted.

I'm trying to be patient about how long it's taking to ramp back up to my normal experimental output level, but given the grant deadline patience is hard to come by!

Finally legal!

Yup - it's time for Christmas music without remorse! We've been listening to 8-Bit Christmas, Mannheim Steamroller and Enya Christmas albums all day while we decorate. The dog is confused about why we put a tree in the living room. He spends a lot of time looking at it.

Units

I needed to calculate a free energy today. I knew the equation I needed to use. And it involved Faraday's constant. I looked at a table of F values (with various units) and none of them seemed to make sense. I figured out how to get free energy in units of (mv*C*kcal)/mol, which seemed fairly unreasonable. So finally, after thinking through several possible values/units of F, I gave up and e-mailed my PI. Turns out the solution to my problems is knowing that volt=joule/coulomb. Somehow I don't think I EVER knew this.

So of course, I head to Wikipedia, where I find out that not only can joules be defined as kg*m2/s2 i.e. Newton meters,  they can also be defined as the work required to move a charge of one coulomb through one volt potential difference! Obviously my physics teachers failed to prepare me for real life, because I swear I've only ever heard the Newton meter definition.

Best Poster Title Ever

The best poster I saw at SfN:


331.06 How does galactic cosmic radiation alter adult hippocampal neurogenesis? J. A. LEBLANC*; M. COLE; P. RIVERA; H. SHIH; B. P. C. CHEN; A. J. EISCH. UT Southwestern Med. Ctr., UT Southwestern Med. Ctr., UT Southwestern Med. Ctr. 


I actually laughed out loud when I walked by it, but they had a big crowd so maybe they're on to something!

SfN 2011 - Neurobiology and the Law

Went to a GREAT symposium at SfN today: The Fred Kavli Public Symposium, which was titled "The Brain on Trial: Neurobiology and the Law." This symposium had speakers addressing 4 issues

1. Memory and the courts - C.E. Stark, UC Irvine
2. The biology of violence and the law - A. Raine, U Penn
3. The adolescent brain and implications for the juvenile justice system - A Baird, Vassar
4. Addiction and the control of behavior - S. E. Hyman, Harvard

There were so many great issues and I could recap the whole entire thing from my 7 pages of handwritten notes but I'll spare you. Instead, I'd like to pose a series of questions based on the lectures with some small anecdotes...

Can eyewitnesses pick out suspects?

• Dr. Hyman points out that we best recognize people we know, and showed that people of similar ages and races can more accurately pick out someone they've seen only briefly in a line-up. 

Is eyewitness testimony reliable?

• Our memories not only fade, but we fill them in with false memories (unconsciously). 
• Some people believe that memories created in highly emotional situations are more accurate and less forgettable, such as where you were you when you heard about the World Trade Center on 9/11. But this seems unlikely, and two cases were presented
• >200 college students were interviewed  immediately after the OJ Simpson verdict and again at 15 and 32 months. At the later timepoints, elements of their stories were classified as accurate, minorly distorted, majorly distorted relative to their original sotry, or they simply said that they didn't know certain detail. At 15 months, 40% of details/stories were accurate and a similar percentage had only minor distortions and a significant percentage of students admitted to not knowing some details. However at 32 months, most details were majorly distorted and NO ONE admitted to not knowing something. Not only were they less accurate, they were more confident!
• In a simulated POW situation, soldiers were confined and subjected to harsh interrogation. Two days later, each soldier was given a packet of pictures and asked to identify their interrogator. Some packets had a picture of their interrogator, but others had no picture of that soldiers interrogator. Yet ~70% of soldiers chose a picture that they said was their interrogator in either case.

Can we predict violent behavior? Is it ethical to do so? Will it stigmatize individuals into crime? Or is early intervention necessary and responsible to avert violence?

• Psychopaths have been shown to have a reduced volume in the amygdala (which controls the "4 F's:" fight, flight, feeding and sex). Their main reduction is in areas that control the fear response/conditioning system. In a study of 1800 3-year-olds, their fear responses (a proxy for amygdala function) were measured and the children were followed for 20 years. After 20 years, 137 of them had been convicted of a crime, and (as a group) they had shown reduced fear responses at the age of 3. 

If neurobiology plays such a big role in criminal behavior, how do we define responsibility?

• A study imaged the brains of psychopaths and controls as they answered a "moral dilemma" question. 80% of people answer the question the same way, including psychopaths. But the areas of the brain used to answer the question are different between psychopaths and controls. In normal subjects, their emotional circuits and amygdala light up. In psychopaths, their cognitive areas light up. This (and other data) implies that while psychopaths know right from wrong, they don't have a feeling of right and wrong. In situations that also show that they have reduced empathy and impulse control, how much control over their behavior do they have relative to a control subject?
• A more extreme case presented was a case of acquired pedophilia. A man with no criminal or abnormal psychological history began to collect child pornography and made sexual advances to his minor stepdaughter. He was reported and sentenced to rehabilitation or prison and picked rehab. He entered treatment, where he made sexual advances to the staff and was expelled from the program and headed to prison. Right before heading to prison he had intense headaches and suicidal ideation and was hospitalized (where he made sexual advances to medical personnel). Due to his intense headaches, he receive a brain scan where they found a large tumor! After resection of the tumor, he completed rehab successfully and returned home without issue. A few years later, he had intense headaches again and his wife found pornography on his computer. He immediately had a brain scan - and the tumor had grown again! After a second surgery, his life returned to normal. How responsible was he for his actions?

Are teenagers dealt a fair hand in sentencing in the juvenile justice system? Are they judged by juries "of their peers" who can really understand their behavior patterns?

• Adolescents have immense development in the prefrontal cortex as they learn social behavior. Adult and adolescent brains were imaged as they answered whether a choice was good or bad. Adults had automatic responses (in the amygdala) very quickly. Swimming with sharks - bad. Lighting your hair on fire - bad! Adolescents mostly got the same answers, but much more slowly. And the areas of their brain involved in answering were cognitive areas, as they actually had to consider whether lighting your hair on fire is a good idea or not. As they mature, these responses become faster/more automatic.
• Additionally, juveniles are hugely influence by peer  pressure. In an imaging study where some adolescents were told that their data would be visible to peers, they make worse decisions more automatically!
• Social development during adolescence lasts for life. When teenagers are incarcerated, they are socialized as prisoners, which is evident in the correlation between re-incarceration and age.

Do drug courts and rehab programs actually help addicts reform?

• Substance addiction overloads reward circuits and is classified as "highly valuable" by the brain, making drugs the highest reward. In rat studies, electrical stimulus of reward areas is prioritized even over food and sleep and rats can kill themselves self stimulating these pathways with a lever! Imaging of addicts shows reduced prefrontal cortex action (as in psychopaths). This means that an addict is physiologically incapable of adequately prioritizing at certain stages of drug use. Their ability to prioritize fluctuates with time since last drug dose, and a decision made at one time may not carry over to the next phase of their drug experience.
• Addiction causes permanent changes in brain structure and reward systems, which makes even recovered addicts subject to relapse in response to cues and stress.

Obviously, there are no easy answers! However, neuroscience data is likely to play a role in dictating sentencing and perhaps should even prompt fundamental changes in the criminal justice system as we gain a more nuanced understanding of human capacity for responsibility and control of behavior.

BONUS EDIT: For further lay reading, check out this article from the Atlantic.