Tag Archives: chemistry

Executions and Midazolam

It appears that the State of Arkansas plans to perpetuate its inhumane misunderstanding of pharmacology – again. It has secured a supply of Midazolam for use in executing those convicted of capital crimes.

Over the years Arkansas has shot, hanged,electrocuted, and now poisoned convicts. The last hanging was in 1914 – John Tillman was executed for killing his girlfriend and throwing her body down a well. John Swindler became the last to be electrocuted in 1990. Charles Singleton, whose appeal took 24 years due to schizophrenia, was the first to be executed by lethal injection in 2004.

The standard protocol is to use a three drug cocktail. First, Sodium Thiopental (a rapid acting barbiturate) is given to induce deep anesthesia. Second, Pancuronium Bromide is used to cause paralysis of skeletal muscles which stops breathing. This drug is similar in chemical structure and mode of action to Curare, the famous dart frog poison of the Amazon. Lastly a massive dose of Potassium Chloride stops the heart.

If one can describe any execution as humane, this is supposed to be. First you’re made completely insensate (comatose) then and only then your breathing and heart are stopped. You’re dead and it’s over. A problem in the protocol arose when drug companies decided they didn’t want to be associated with (or there was insufficient profit connected to) providing drugs for the executioner. First the European Union banned the export of Sodium Thiopental to the US, and then the only US manufacturer refused to sell it to states for execution.

Enter, arm right, Midazolam. Some states, including Oklahoma and Arkansas were unable to obtain Sodium Thiopental. They decided to stay with the three drug protocol but substitute Midazolam for the anesthetic drug. The problem is that Midazolam is not, nor was it ever intended to be an anesthetic. Midazolam is a sedative, and a mild one at that. In surgical procedures, it is use as a per-anesthetic. It can make you drowsy but not insensate. If a person is not insensate when injected with the muscle blocker trouble ensues.

There have been errors during surgeries where patients were given insufficient amounts of anesthetics, then administered Pancuronium Bromide. They report extreme pain and even terror during surgery because this drug has no effect on the central nervous system. They were awake but completely incapable of reacting physically.

In Oklahoma in 2014, an execution begun with Midazolam never finished the complete protocol. Clayton Lockett struggled, convulsed, and 14 minutes into the procedure spoke and tried to get off the executioner’s table. 43 minutes later he died of a heart attack, without ever receiving the heart stopping drug.

In April 2017 Kenneth Williams was executed with Midazolam as the initial sedative. He convulsed violently even before the administration of the muscle blocker. It is quite conceivable that he was fully aware of his circumstances but unable to react after the administration of the second drug. There are sufficient questions about the efficacy of Midazolam to induce a coma and therefore reason to question the humanity of this method of execution.

Nerve Gas and Tomahawk Missiles

In August 2012 President Obama said “a whole bunch of chemical weapons moving around …that’s a red line for us.” This was in reference to an admission by the Assad regime in Syria that they had chemical weapons but they would “never, never be used against the Syrian people or civilians during this crisis, under any circumstances.” Within a year, there was evidence that suggested that the nerve gas Sarin had been used on a civilian population.

In the U.S, polling showed that the public had tired of war and was on record as opposing more involvement by our military in the area. Obama sought a joint resolution for an “Authorization for the Use of Military Force Against the Government of Syria to Respond to Use of Chemical Weapons.” The resolution failed. With neither public nor congressional support for military action, Obama sought an agreement with Assad to remove the chemical weapons.

After the recent use of Sarin, the current administration acted without congressional approval and launched an attack with 60 Tomahawk missiles on an air base in Syria. It is thought that this was the base from which the most recent chemical attack was launched.

Sarin is a very toxic nerve agent. It actually isn’t a gas but rather a liquid designed to be aerosolized, meaning sprayed as a fine mist. Contact with bare skin or especially inhalation causes a number of symptoms ranging from heavy salivation, profuse sweating, muscle cramps, convulsions and death resulting from respiratory paralysis. Not pretty, huh?

Sarin is a member of a class of poisons known as Acetyl Choline Esterase Inhibitors. Other substances that have the same effect, but lower toxicity are a number of insecticides. Even the relatively safe house and garden type insecticides kill insects by the same mechanism. So how do they work?

Imagine you want to wiggle your big toe. A message travels from your brain via several nerves “talking” to each other to get the signal all the way to your toe. For the signal to get from one nerve to the next requires the opening and then closing of a “gate.” The gate opening allows the signal and the closing stops the signal. If the gate doesn’t close your toe would continue to wiggle. That is the way Sarin and other Acetyl Choline Esterase Inhibitors work. They keep the gate open. A small stimulation of a nerve can’t be turned off. The affected tissue is overstimulated.

Back to the deaths from Sarin in Syria and our military response. By bombing the airfield a message was sent but is seems to be a fairly ineffective one. Within days the base was back in operation and launching conventional bombing attacks on the same town that had been attacked with Sarin. Now we are left with what’s next?

A recent Galllup poll found that a scant 51% supported our missile attack on the airbase, and 54 % oppose any further strikes. Finally, 69% are not confident that the the one strike will dissuade Assad from again using chemical weapons.

Thoughts on Oxygen – Part 2

Based on genetic evidence across all life it appears that the earliest organism called LUCA, short for Last Universal Common Ancestor, contained a wealth of cellular components that handled molecular Oxygen otherwise known as O2. This in light of the fact that there was scant Oxygen present in the atmosphere, a fraction of a percent compared to the current concentration of 21 percent. Why?

Most likely is the fact that Oxygen is a very reactive gas, and it reacts by snatching electrons away from other molecules. This creates two other kinds of chemical compounds, free radicals which are electrically neutral but very reactive, and cations which are positively charged ions which also are reactive. When Oxygen or a few derivative molecules react with other components of cells or tissues they cause damage which can lead to cell death and even death of the whole organism.

One description of growing old is little more than the accumulation of cellular damage due to exposure to Oxygen. Just one example is that Oxygen reacts with a component of our skin called collagen. Over time the damage leads to reduced elasticity. This results in “brittle” skin which is more easily damaged by physical abuse. The skin also loses its tone and becomes saggy. These are oxidation reactions just like the rusting of iron and cooking oil becoming rancid. When you burn something you are oxidizing it, hence growing old is slowly burning up.

The earliest anaerobic single celled organisms had a myriad of cell components to protect themselves from oxidative damage even in an atmosphere which contained little oxygen. Today most of what we recognize as living things such as plants and animals, are aerobes. We require Oxygen to drive the processes by which we generate energy. We need the energy to do all the work of our bodies. To detoxify poisons in our liver. To move us from couch to dinner table and back. To fuel the nerve impulses to our brain that allow us to read newspaper columns.

Interestingly, our brains consume close to 25 % of all the Oxygen we use. Compare that to the heart muscle which only uses 12 % or the kidneys which need only 7 % of our Oxygen. The question now is how did we go from Oxygen being a deadly poison when life operated anaerobically (without oxygen) to our current state where it is demanded? The answer lies in a number of evolutionary advances. Those cell components that were used to protect anaerobic organisms were shifted in function by random mutations to do the job of aerobic metabolism. The advantage is that if you can control the reactivity of Oxygen, you can put it to good use to do the work of the body, but only if you control it.

Evolution does not require new constructions from whole cloth. Slight changes in a macromolecule allow it to be repurposed. Life is complex, but not so complex it requires a designer. Evolution only requires random mutations and a long time scale.

A Few Thoughts on Oxygen – Part 1

Until late in the 20th century scientists hypothesized that the earth’s early atmosphere was highly reduced, in a chemical sense. What atmospheric elements were present were bonded to hydrogen. This followed from the well-known fact that hydrogen is by far the most abundant element in the universe . Hence, other elements were more likely to be chemically attached to Hydrogen than anything else. Any carbon would be present as methane CH4, nitrogen would be present as ammonia NH3 and oxygen in the form of water OH2.

Scientists in the early 1950s (Stanley Miller-Urey) used this assumption in experiments looking for mechanisms for the beginning of life. They created an atmosphere composed of these reduced gasses and then induced chemical reactions among them using UV light (which would have been abundant ) and/ or Electric arc (simulating lightning.) They found that the could produce several “life precursor” molecules such as amino acids (to form protein), purine and pyrimidines (to form nucleic acids), and simple sugars (to form carbohydrates.)

I gave many a lecture discussing the Miller-Urey experiments, which with current understanding of what the early atmosphere was like, were wrong. Evolution of life most likely required the same simple precursors to be present but they must have come about by other mechanisms. The current wisdom as to the composition of the early atmosphere suggests in was more in line with the composition of volcanic gasses. This is based on more recent geochemical studies. Carbon would have been present in its oxidized form, CO2. Nitrogen would have been present as the diatomic gas N2, sulfur as SO3.

The only feature of the previously assumed early atmosphere and the current hypothesis is that the presence of any free oxygen (O2) was very limited, maybe a fraction of one percent of the total atmosphere. Currently it is about 21 percent.

Regardless of the competing hypotheses about the composition of the atmosphere life most likely began and then evolved in the absence of any significant amount of Oxygen for a couple of billion years. Because of the specificity of the genetic code it has always been assumed that all life is related and the earliest ancestor of all life is called LUCA – the Last Universal Common Ancestor.

What did LUCA look like? How did she make a living? Surely she was a single celled organism replicating by cell fission. Information from mother to daughter cell was transmitted by DNA replication, so the enzymes attendant to this task are shared by all her descendants. She had to have been an anaerobe as there was scant oxygen in the atmosphere at the time. What about the other cell machinery?

When certain components of cellular machinery are found across all life, it must be that LUCA had these components. Oddly, for an anaerobe, LUCA appears to have had a broad range of macromolecular structures which are for handling oxygen. What is that all about?