The phenomenon of anesthetic awareness provides great fodder for Hollywood, but now it has also found its way onto the floor of the Supreme Court. Baze vs. Rees challenges the standard 3-drug lethal injection protocol on the basis that it may constitute cruel and unusual punishment, which is outlawed by the eighth amendment.
The current lethal injection protocol was developed in 1977 and consists of a fast-acting barbiturate (sodium thiopental) followed by a paralytic agent (pancuronium bromide) which prevents convulsions during the administration of a heart-stopping toxin (potassium chloride). Arguing on behalf of two Kentucky inmates, attorney Donald Verrilli made the argument that improper administration of the initial barbiturate could cause death row inmates to experience an “excruciating sensation of drowning or strangulation” before they pass away. Because of the paralytic agent, inmates would not be able to communicate their pain to executioners.
A glaring Catch-22 lurks behind this debate: the inmate will not experience pain if the anesthetic is administered effectively, but the American Medical Association (AMA) prohibits healthcare professionals from participating in executions. Interestingly, this hasn’t stopped many doctors from complying with government requests for supervision during executions. Atul Gawande wrote an excellent article profiling these individuals and the issues they face in the New England Journal of Medicine.
Particularly intriguing is the story of Dr. Carlo Musso, who participates in executions despite his personal belief that the death penalty is wrong:
He read about the ethics of participating. He knew about theAMA’s stance against it. Yet he also felt an obligation notto abandon inmates in their dying moments. “We, as doctors,are not the ones deciding the fate of this individual,” he said.“The way I saw it, this is an end-of-life issue, just as withany other terminal disease. It just happens that it involvesa legal process instead of a medical process. When we have apatient who can no longer survive his illness, we as physiciansmust ensure he has comfort. [A death-penalty] patient is nodifferent from a patient dying of cancer — except hiscancer is a court order.” Dr. D said he has “the cure for thiscancer” — abolition of the death penalty — but “ifthe people and the government won’t let you provide it, anda patient then dies, are you not going to comfort him?”
While the article is locked behind a subscription wall, NEJM has posted a free interview with Dr. Musso:
To be sure, these are murky ethical waters. While Dr. Musso makes a valid point about the inevitability of court-ordered executions, it seems like doctor participation sets a dangerous precedent. If doctors begin flouting the AMA’s code of conduct, then what will stop them from cooperating with torture in addition to executions? The U.S. government has already tried to make this happen.
For me, the obvious solution is to abolish the death penalty altogether, an idea that has already caught on in New Jersey. Indeed, Baze vs. Rees may be a veiled attempt to accomplish a similar goal at the national level. Writing for Slate, Dahlia Lithwick makes the point that this case is not really about pharmacology as much as it is about the constitutionality of the death penalty tout court. The Supreme Court’s decision to hear the case has imposed a de facto moratorium on executions across the country. I’m just crossing my fingers that this case doesn’t get closed anytime soon.
Not to be outdone by the New York Times,the Wall Street Journal explores the increasing usage of neuroscience tools for political ends in a recent article. They predict that companies like EmSense, a neuromarketing firm founded by MIT grads that uses EEG headsets to measure the brain activity of consumers and voters, will become increasingly prevalent in future election cycles. Though the ‘08 presidential candidates have stayed away from newfangled gizmos, both John Edwards and Mitt Romney have hopped on the neuropunditry bandwagon to some degree. Romney turned to TargetPoint, a company that offers a new twist on traditional focus groups:
TargetPoint, the Virginia-based political and business consulting firm that worked for the Bush campaign in 2004 and is now working for Mr. Romney (his campaign paid the consultancy $345,000 last quarter, according to Federal Election Commission records) is seeking ways around the problem. Alex Lundry, the company’s research director, says traditional methods of polling voters are sometimes inaccurate. “People may say one thing in a focus group and do another thing in the voting booth,” he says. To get beyond this, Mr. Lundry says, the company developed an Internet survey that asks voters questions like which candidate they support. But rather than just tallying the results, the survey tests their subconscious attitudes by recording how quickly the respondents enter their answers — the theory being that faster responses indicate stronger feelings.
In his studies, which have involved placing partisan voters in brain scanners, he found that when voters look at pictures of candidates or listen to their statements, the regions of the brain associated with emotion are more engaged than the regions governing thought. Instead of detailing a ten-point health-care plan, he says, politicians would be better off talking about health care in moral terms. An October Federal Election Commission filing shows Mr. Edwards’s campaign paid $1,951 to Westen Strategies for air fare. Mark Kornblau, Mr. Edwards’s traveling press secretary, said Mr. Westen had come to observe the candidate and give him some feedback. “He has gained notoriety and respect in the Democratic party with his book,” Mr. Kornblau says. “It was helpful to hear his ideas.” Mr. Westen declined to comment on the discussion.
Of course this news doesn’t do much to dispel the perception that John Edwards is all image and no substance.
It will be interesting to see how voters react to politicians who would rather pander to their emotions than persuade their judgments. The WSJ article argues that voters will accept the application of neuroscience tools to politics just as they have come to accept the use of focus groups. The real question is whether neuromarketing strategies will actually pay off in the primaries, and that only time can tell.
Currently I am running a study that examines the effects of chronic nicotine on sensory processing in mice. While I don’t mind coming into the lab on weekends, the prospect of visiting my animals 24/7 to inject nicotine wasn’t exactly practical. I could give daily or twice daily injections, but even that doesn’t really come close to approximating the behavior of human smokers.
That’s why we turned to a company called Alzet that manufactures miniature pumps for drug delivery in laboratory animals. These pumps can deliver small volumes of drug solution at a controlled rate over a period of up to six weeks. We opted for the 2002 model, with a reservoir volume of 0.2 mL and a flow rate of 0.5 µL/hr.
They are pretty easy to use: Just fill up the reservoir with concentrated drug solution and pop on the cap. Then, anesthetize the rodent and cut a small slit in its back using standard aseptic techniques. After opening a small cavity for the pump with a hemostat, insert the device and close the opening using medical staples.
After implanting these pumps subcutaneously, I couldn’t help but wonder if these things were actually going to work. How could a little piece of plastic control the flow of drug solution so precisely? If they worked because of osmotic pressure, then shouldn’t the flow rate depend on the concentration of the dissolved drug? I knew that osmotic pumps were popular, but I couldn’t shake the irrational fear that these $20 devices were just one big scam.
The only way I could settle my nerves was by figuring out how the devices worked. Luckily Alzet’s website is relatively transparent about the mechanism. Now I know that the osmotic pressure difference is actually between the animal’s body and the “salt sleeve” that surrounds the drug reservoir. From their website:
ALZET pumps operate because of an osmotic pressure difference between a compartment within the pump, called the salt sleeve, and the tissue environment in which the pump is implanted. The high osmolality of the salt sleeve causes water to flux into the pump through a semipermeable membrane which forms the outer surface of the pump. As the water enters the salt sleeve, it compresses the flexible reservoir, displacing the test solution from the pump at a controlled, predetermined rate. Because the compressed reservoir cannot be refilled, the pumps are designed for single-use only.
The rate of delivery by an ALZET pump is controlled by the water permeability of the pump’s outer membrane. Thus, the delivery profile of the pump is independent of the drug formulation dispensed.
Pretty nifty, huh? Even niftier is the accompanying animation:
Now I am much more confident that my mice are indeed receiving the expected dose of nicotine. In retrospect my fears were misplaced, but in science it never hurts to be skeptical/cautious.
The culture of biomedical research places enormous emphasis on high-profile publications. A few papers in Nature or Science can launch scientific careers, while failure to publish at a sufficient rate can doom other scientists. Members of admissions and tenure committees must sort through numerous applicants while simultaneously juggling their normal research commitments. This pressure leads these keepers of the gates to use PubMed listings as a proxy for individual potential.
But getting published is not really enough. Where your name falls in the byline carries a great deal of weight as well. A new paper in EMBO Reports examines the perceived contributions of authors based on their byline position. Wren et al. surveyed promotion committee members at 125 AAMC-accredited medical schools and asked them to rate the contributions of the first, middle and last authors as a function of total authors listed. Specifically, respondents could rate contributions in terms of the project’s initial conception, work performed and supervision.
As expected, survey respondents rated first authors the highest in terms of work performed while rating last authors the highest in terms of initial conception and supervision. However, increasing the number of authors from three to five decreased the perceived contributions of the first and middle authors while having no significant effect on the perceived contribution of the last author. Here’s a table with the numbers:
Clearly it is in the first author’s best interest to minimize the number of other authors on a paper. However, given the importance of authorship in the success of collaborators’ careers, it is essential that everyone is recognized for their contributions. While most of my previous supervisors have been generous with authorship (I am currently a middle author on one paper and a couple more are in the pipeline), this is not always the case. All too often, senior investigators neglect to credit junior laboratory members.
While this is problematic, an even more concerning trend is “author inflation.” Wren et al. asked survey respondents about the prevalence of honorary authorships, in which additional researchers are included in the byline merely to pad their resumes. 40% of respondents indicated that this practice was commonplace, and 50% reported that this practice made it harder to judge who deserved promotion.
In practice, science is becoming increasingly collaborative and reducing the number of authors on papers may be a lost cause. In fact, the general trend is moving in the opposite direction. Here is another figure from the Wren et al. paper that demonstrates the movement toward more authors:
One way of assisting admissions and promotions committees with the task of ranking candidates is the inclusion of author contribution statements that describe who did what for the paper. While Wren et al. indicate that such statements are helpful, ironically they do not include one on their own paper. PNAS and PLoS journals already require statements that clarify what each author contributed. Here is an example from a recent PLoS Biology paper:
Author contributions. GCF, JLV, and IM conceived and designed the experiments. GCF performed the experiments and analyzed the data. GCF, BS, and JLV contributed reagents/materials/analysis tools. GCF, BS, and IM wrote the paper.
This is certainly a step in the right direction and hopefully more journals will adopt the practice of contribution statements. To paraphrase someone with something much more important to say: I have a dream that one scientists will not be judged by their byline position but by the magnitude of their contributions.
If you haven’t seen the preview for Hollywood’s latest horror flick Awake, they are worth checking out on YouTube. The movie is about a man undergoing heart surgery who experiences “anesthetic awareness,” a phenomenon wherein the patient is paralyzed but partly or fully conscious of the surgical procedures and conversations taking place.
The condition is most likely to occur when patients are given drugs that block signaling at the body’s neuromuscular junctions, leading to paralysis. These drugs are given during delicate surgeries in which the patient cannot be allowed to move. Normally neuromuscular blockers are given in combination with an analgesic that blunts sensation, but insufficient administration of the analgesic can bring about awareness even though the patient still appears to be knocked out to the naked eye. In real-life, doctors prevent this from happening by using EEG to monitor the patients’ brain activity levels.
Anesthetic awareness makes for a great plot device, but unsurprisingly the movie inflates the risk factor. While the trailer claims that 1 in 700 patients experience this seemingly horrifying condition, this article in Slate takes a closer look at the numbers and finds the real incidence to be 1 in 14,000.
Yaawwwn. According to conventional wisdom, we get sleepy after Thanksgiving dinner because of the high tryptophan content in turkey. Tryptophan is an essential amino acid that serves as a chemical precursor for serotonin, a vital neurotransmitter involved in mood and wakefulness.
There are many studies demonstrating serotonin’s sedative effects, but I want to take a minute to highlight a paper that implicates serotonin in social cognition.
Wood et al. measured social behavior using a monetary prisoner’s dilemma game in which subjects thought they were playing against other people (in fact they were playing against a computer that utilized a standardized tit-for-tat strategy against each subject). If subjects were kept on a diet low in tryptophan, they demonstrated less cooperativity in their decision making. When subjects were given a drink with high tryptophan content before playing the prisoner’s game, they were more likely to cooperate with their automated partners.
It’s exciting to think that that something as mundane as diet can significantly modulate economic decision making. Maybe it will inspire CEOs to start dosing the the water cooler with tryptophan before attempting to broker a delicate merger. However, such scenarios are not entirely analagous to the study at hand because Wood et al. deprived subjects of tryptophan prior to behavioral testing, whereas most adults are unlikely to enter an important business meeting on an empty stomach.
The title of this post is also misleading because there’s not much evidence that eating turkey increases the concentration of tryptophan in your brain. Zack Lynch of Brain Waves does a nice job of busting this myth, so I’ll just direct you there instead of re-hashing the argument.
Today I sacrificed a laboratory mouse. Unlike most of the mice in my current study, this one lost its implanted electrode, leaving him with exposed skull and brain tissue. This is not a healthy situation, so I had to euthanize him for his own well-being. Specifically, this involved CO2 administration followed by cervical dislocation (to remove any doubt). I did not enjoy this.
Incidentally, the topic mouse pain figures prominently in this month’s Harper’s, which features an article about the mouse’s ascent within the modern biomedical research industry. Although the article is locked behind a subscription wall, I recommend picking up a hard copy. In the meantime, here’s what I learned from it:
The United States consumes 80 million rats and mice per year. Of the newborn male mice, 70% are euthanized because of their aggressive tendencies.
Neither mice nor rats are covered by the Animal Welfare Act, a law enforced by the U.S. Department of Agriculture that is meant to protect research animals.
The scientific community’s prime mouse vendor - Jackson Laboratories - was founded by Clarence Little, who developed his first mouse lines while still an undergraduate at Harvard. Some of them, such as the Dilute, Brown and non-Agouti (DBA) strain, are in continued use today.
Jackson laboratories is currently developing ways to reduce the excessive consumption of mice by preserving sperm on ice and then producing strains on request.
The article advocates the inclusion of mice in future revisions of the Animal Welfare Act, which certainly seems like a good idea to me. Nonetheless, as one of many scientists that uses mice on a daily basis, I can assure you that we use the utmost restraint in mouse experimentation. We recognize their valuable role in curing disease and respect them as fellow animals.
Regardless, I think any researcher must subscribe at some level to the premise that human life is somehow worth more than mouse life. Call it speciesism, call it whatever you want, but I’d certainly rather 100 mice died than God forbid someone in my family. I view animal sacrifices as a necessary cost in the search for cures. Far from being merely hypothetical, life-saving cures discovered with mice are already here.
That’s why we turned to a company called 
Yaawwwn. According to conventional wisdom, we get sleepy after Thanksgiving dinner because of the high tryptophan content in turkey. Tryptophan is an essential amino acid that serves as a chemical precursor for serotonin, a vital neurotransmitter involved in mood and wakefulness.