I always find it funny to hear scientist say something is a moral imperative and that we need to do something. The problem is that scientists cannot use the scientific method to gauge the morality of something because there is no operational definition of morality.
Would you trust a medical doctor to fix your car? Certainly not! Doctors are not qualified to fix a car, unless they were once automotive mechanics. They certainly don’t have the right tools. In like manner, scientists are not qualified to judge morality.One cannot design an experiment to test if something is moral because morality does not have an objective meaning.
I can test if males are, on average, taller than females because height can be operationally defined based on a specific measurement, like meters or feet. There is some standard. For morality, there is no such standard that is defined objectively. How can I test whether it is immoral that men are taller than women on average? Well, I can’t. If a scientist ever tries to argue the morality of a situation and says they can objectively make their case, be sure to tell their boss because that scientist should be fired immediately. We don’t need more terrible scientists.That is why I find it odd that drug companies are supposedly refusing to provide their drugs for the death penalty. The media are saying that these drug companies are taking a moral stand. That is poppycock. Pharmaceutical companies are only doing this because they are either forced to by the governments of the countries of their corporate headquarters or because of money. Forget morality since it is a completely useless term. Instead, let’s discuss the pharmacology since that is actual science.
The Killer Combination
The death penalty has been successfully done using the combination of Hospira’s sodium thiopental , Mylan’s rocuronium bromide and potassium chloride from your local grocery store (I am not actually sure where they get this from). Obviously the formulations have been slightly different over the years, but in general, the idea is to make the prisoner unconscious (thiopental), make them immobile (rocuronium) and stop their heart (potassium chloride).
Thiopental belongs to the barbiturate class of pharmacological agent as it is derived from the 2,4,6-trioxohexahydropyrimidine backbone. These drugs work primarily by shutting down central nervous system function while sparing most peripheral activity. Their mechanism of action is through activation of type A gamma-aminobutyric acid receptors (GABA) receptors (Figure 1). These receptors are ionotropic, meaning they allow the passage of ions through their pores producing rapid effects on neuronal excitability. The primary ion that travels through GABAA receptors is chloride which carries a negative charge. This flow of chloride ions into the cell will prevent neurons from firing.Thiopental was created because of the slow onset and long-lasting effects of pentobarbital, a drug that is now used primarily for animal euthanasia. Donalee Tabern and Ernest Volwiler of Abbott laboratories sought to produce drugs with an unstable sulfur group (i.e. the thiol part of thiopental) in the 1930s.
The creation of thiopental led to the elimination of pentobarbital as an anesthetic and has only been rivaled by propofol, which was designed in the 1990s. This would explain why prisons have sought to get pentobarbital and propofol after losing thiopental as an agent. The mechanism of action of propofol is similar to thiopental, but it has superior pharmacokinetics in that it is cleared from the body faster than thiopental leaving less of a hangover. One interesting fact about propofol is that it is made up in an emulsion of 10% soybean oil, 2.25% glycerol and 1.2% purified egg phosphatide, leading to possible bacterial contamination of non-sterilized preparations.The lack of barbiturates led to the botched execution in Arizona because authorities chose to use midazolam and hydromorphone (which is no longer available).
Figure 1. Barbiturates, like thiopental directly activate GABA type A receptors, which prevent action potentials in neurons. By blocking communication between neurons, humans are unable to perceive the world around them and are unconscious. (A) Normal action potential firing. (B) Prevention of normal action potential firing by thiopental
Midazolam is a benzodiazepine and its mechanism of action is very different from thiopental. It was developed by Hoffman-LaRoche and serves as a sedative and not as an anesthetic. The reason is due to the fact that it enhances GABAA receptor activation but does not activate receptors independent of activity (Figure 2). Therefore, if GABA is not available to bind to the receptor, then midazolam will not do anything. It is a positive allosteric modulator (PAM). Midazolam is a superior product because it is water soluble and does not produce irritation at the site of injection. Hydromorphone is an opiate agonist and is a whole other discussion.
Figure 2. The actions of benzodiazepines, like midazolam, are dependent on the binding of GABA itself to the GABAA receptor and do not activate the receptor on their own. (A) In the presence of GABA, midazolam will prevent action potentials. (B) If GABA is not present, midazolam will not prevent action potentials.
Pancuronium bromide and rocuronium bromide are both nondepolarizing neuromuscular blocking agents. Pancuronium, historically, has been the most used drug, but clearly rocuronium has been used more recently. Pancuronium is structurally similar to tubocurarine (the curare arrow poison) that was used by South American natives. Because it has a little effect on blood pressure, it became the most used muscle relaxant for a period of time, later being replaced by atracurium and vecuronium. These drugs act by binding to nicotinic acetylcholine receptors (NACHR) and preventing the binding of endogenous acetylcholine. Since binding of acetylcholine to NACHRs is necessary for muscle contraction, these drugs therefore produce paralysis (Figure 3).
Figure 3. Nondepolarizing muscle relaxants, like pancuronium, prevent the binding of acetylcholine to nicotinic acetylcholine receptors (NACHRs) found on the neuromuscular junction. (A) Binding of acetylcholine to NACHRs causes muscle contraction. (B) By binding to NACHRs, pancuronium prevents muscle contraction.
The role of potassium chloride is to actually produce death. Without proper anesthesia, the final death by potassium chloride would be incredibly unpleasant. Essentially, by increasing the extracellular concentration of potassium in the body, you eliminate all organ function. The major organ to stop working is the heart because you’ve obliterated the ability of the heart to contract. Hence, the heart ceases to beat (Figure 4).
Figure 4. The potential difference created by high concentrations of potassium inside heart cells versus outside the heart is necessary for normal function. (A) Potassium levels are usually low outside the cardiac smooth muscle cells, which helps create a potential difference across the cell membrane of ~-90mV. (B)When potassium levels are increased in the extracellular space surrounding cardiac smooth muscle cells, the potential difference will no longer exist and eliminate normal heart contractility.
The United States prison system, from a pharmacological viewpoint, uses an elegant and sophisticated system to produce death. Pharmaceutical companies are now preventing the use of this system and therefore causing suffering for those death row prison inmates because prisons will need to use less effective methods for killing those prisoners. This is branded as a moral argument, insomuch as the controversy will cost the drug company money and possibly hurt the pay of their CEOs. Whether CEOs having their pay reduced is immoral is beyond the scope of science.
By Matthew Lazenka
June 5th 2015
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