Kolokol-1

Kolokol-1 (Russian: Колокол meaning "bell") is a synthetic opioid developed for use as an aerosolizable incapacitating agent. The exact chemical structure has not yet been revealed by the Russian government. It was originally thought by some sources to be a derivative of the potent opioid fentanyl, most probably 3-methylfentanyl dissolved in an Inhalational anaesthetic as an organic solvent.^[1]

However, the only independent analysis of residues on the Barricade Theater hostage crisis hostages' clothing or in one hostage's urine performed by a team of toxicologists at the United Kingdom's center for research on chemical and biological warfare in Porton Down, Wiltshire, England found no indication that fentanyl or 3-methyl fentanyl were used. Instead, two much more potent and shorter-acting agents, carfentanil and remifentanil, were found in the samples taken from hostages' clothing and urine. They concluded the agent used in the Barricade Theater hostage rescue consisted of highly potent, very short-acting carfentanil and longer-acting but less-potent remifentanil, both fentanyl derivatives which are much stronger than fentanyl itself, in an aerosol suspension.^[2]

Development and early use

According to Lev Fyodorov, a former Soviet chemical weapons scientist who now heads the independent Council for Chemical Security in Moscow, the agent was originally developed around a secret military research facility in Leningrad (now restored to its historic name of Saint Petersburg), during the 1970s. Methods of dispersing the compound were reportedly developed and tested by releasing harmless bacteria through subway system ventilation shafts, first in Moscow and then in Novosibirsk. Fyodorov also claimed that leaders of the failed August 20, 1991 Communist coup considered using the agent in the Russian parliament building.^[3]

Use during Moscow theater hostage crisis

Kolokol-1 is thought to be the chemical agent employed by a Russian Spetsnaz team during the Moscow theater hostage crisis in October 2002. At least 129 hostages died during the ensuing raid; nearly all of these fatalities were attributed to the effects of the aerosolised incapacitating agent that was pumped into the theatre to subdue the militants. The gas was later stated by Russian Health Minister Yuri Shevchenko to be based on fentanyl.

Minister Shevchenko's statement followed speculation that the gas employed at the theater violated international prohibitions on the manufacture and use of lethal chemical weapons, and came after a request for clarification about the gas from Rogelio Pfirter, director-general of the Organisation for the Prohibition of Chemical Weapons. The minister stressed that the drug fentanyl used in the gas, which is widely used as a pain medication, "cannot in itself be called lethal".

Shevchenko attributed the hostage deaths to the use of the chemical compound on the poor physical condition of the victims after three days of captivity - dehydrated, hungry, lacking oxygen and suffering acute stress, saying "I officially declare that chemical substances of the kind banned under international conventions on chemical weapons were not used," he said, quoted by the Interfax news agency.^[4]

This comment has been disputed on two grounds. The United States Ambassador to Russia at the time complained that delays on the part of the Russian government in identifying the exact nature of the active agent in the gas led to many hostage deaths which might otherwise have been avoided.^[4]

Also, a team of researchers based at the United Kingdom's chemical and biological defense laboratories at Porton Down, Wiltshire, England subjected residues of the gas from clothing worn by two British survivors, and urine from a third survivor who survived the gas attack after hospital treatment to liquid chromatography–tandem mass spectrometry analysis. They found no fentanyl, but did find two other related - but much more potent and potentially toxic drugs, carfentanil and remifentanil, for which the specific treatment is different enough from fentanyl that had the correct antidote been given to hostages immediately, more deaths from the use of this gas might have been avoided.

The specific antidote for carfentanil is naltrexone, while doctors told that they were treating the effects of fentanyl would have used the drug naloxone, which is much less effective in treating carfentanil poisoning in humans. This report goes on to state

- carfentanil is only approved as a veterinary drug for use in sedating large animals, and not for use in humans in medical practice because of its narrow safety margin in human beings (the effective dose is unacceptably close to the dose which can cause illness or death).

- that the deaths among hostages after the Moscow theater can be explained by the use of carfentanil and remifentanil, strong anesthetic agents for which the medical literature suggests little margin of safety between the therapeutic and lethal doses in humans, and many deaths unless the people exposed get quick treatment with the drugs' antidotes.

- that it is highly improbable that a chemical agent exists for which a dose can be calibrated in a tactical environment to disable opponents reliably and without many deaths.^[2]

An article in the Annals of Emergency Medicine discusses the relative therapeutic indices (the difference between the medically effective dose and the toxic or lethal dose of a given medication) of all the possible drugs similar to fentanyl, concluding that while the biological half-life is dramatically shorter and the therapeutic index higher for carfentanil and remifentanil (accounting for the Russian claim that the gas alone could not have caused the deaths of 16% of the hostages rescued), both of those drugs are highly lipophilic (readily taken up into the body's fatty tissues) and can be released into the circulation long after the first symptoms of overdose are treated, causing severe delayed effects and even death if the correct antidote is not administered quickly when the patient shows renewed symptoms of poisoning by these drugs. This might account for the large number of deaths following use of large amounts of the agent in a closed space, where local concentrations of the gas might be unexpectedly high.

The authors of this article go on to quote an article in the Washington Post quoting one Russian physician who treated survivors of the hostage rescue who stated that toxicology testing to identify the agent used was not performed because "to conduct such tests we have to know approximately what we're looking for, and we didn't know what to look for. Besides, we didn't have the technical means to conduct such tests." This supports the United States Ambassador to Russia's allegation that information on the composition of the gas used during the hostage rescue was only given after unacceptable delay, when prompt information on the exact drugs, or the proper antidotes to those drugs used might have saved lives.

Under the heading "Lessons Learned," the authors state "It seems likely that the 800 hostages were about to be killed by Chechen rebels. To rescue them, the Russian military used a calmative agent in an attempt to subdue the rebels. The intent was likely to win control of the theater with as little loss of life as possible. Given the large number of explosives in the hands of the hostage takers, a conventional assault or the use of more toxic chemical agents might have significantly increased the number of casualties. Although it may seem excessive that 16% of the 800 hostages may have died from the gas exposure, 84% survived. We do not know that a different tactic would have provided a better outcome."

The authors concluded by saying

- The extremely high therapeutic indices of the fentanyl derivatives may have inappropriately reduced the Russian government's concern about the potential lethality of these agents.

- Factors such as the lipophilicity of the fentanyl derivatives, the health status of those exposed, great uncertainty regarding the dose each of the people present in the theater received, and the resulting potential for overdose should have been addressed more thoroughly.

- Opioid intoxication is a relatively simple poisoning to treat, and many of the deaths after the Moscow theater hostage crisis could have been avoided if trained rescuers and medical teams with the proper antidotes were made ready in advance.

- In the United States, naloxone, for a long time a critical antidote to treat heroin overdose and iatrogenic opioid toxicity, has now become a crucial chemical warfare antidote."^[5]

References