About 90 minutes’ drive from the medieval spires of Prague, doctors and 20 macaque rhesus monkeys are hard at work at seemingly the most exhaustive study into the weaponization of the rave drug ketamine. While Russian, Chinese and American scientists may have similar lines of study, the Czechs are brazen enough to go on scientific record.
“Aggressiveness and violence are spreading throughout the world. This is comparable to the epidemics of infectious diseases in the Middle Ages,” says Ladislav Hess, a scientist at the Institute of Experimental Medicine in Prague.
Hess, with researchers Jitka Schreiberova, Jiri Malek, Martin Votava and Josef Fusek, is looking for a medical solution. “Pharmacological modulation of emotions has been used for decades. An example is the benzodiazepine Valium,” he notes. “Ways for pharmacological suppression of aggressors threatening victims are sought. The drugs used for these purposes are called calmatives,” producing calm, non-violent behavior.
The group presented “Drug-Induced Loss of Aggressiveness in the Macaque Rhesus” earlier this year at an experimental weapons conference near Karlsýýruhe, Germany. But the forecast for calmatives — and the frontier for using behavior-modifying pharmacological agents as weapons in combat or law enforcement — is turbulent. The argument is over what is acceptable on the battlefield. New urgency comes with the ongoing revolution in pharmacology.
“Loss of Aggressiveness” advances experimentation into different drug cocktails involving ketamine, well known on the party circuit as an effective anesthetic and animal tranquilizer. Mixed with ketamine was the benzodiazepine midazolam, a sedative used in pulling teeth; the alpha2-adrenoreceptor agonist naphtylmedetomidine, an intensive-care sedative; and the opioid remifentanil.
The monkey subjects are 2-5 years old, weigh 2.3-7.6 kg. (5-16.7 lb.), were born and raised in breeding groups, and fed standard diets supplemented by vitamins and minerals. There were eight groups, each getting a different mix. “This species of monkey lives in despotic communities with a strict hierarchy,” said Schreiberova. “Many animals have mutilated knuckle bones or other injuries received because of fights for hierarchy.” The tranquilizers, however, calmed them. A naphtylmedetomidine-ketamine mix got the best results: loss of aggressiveness without significantly affecting circulation and breathing.
“The onset of effect was rapid and we achieved complete manipulability of the animal, with low motoric sedation,” says Schreiberova. “The results can be used to pacify aggressive people during medical treatment [e.g., mental illness], [to counter] terrorist attacks and for production of new non-lethal weapons.”
But it’s a big leap from experiments on monkeys to using an agent in the field. There are the practical issues of dosage and its effects on radically variable human physiology, and the unpredictable methods of drug deployment. There are also ethical questions, legal issues involving international treaties and a long and controversial history in the U.S. and Europe of military pharmacological experimentation involving everything from nerve agents to marijuana and LSD.
Although they’re using a new compound in the cocktail, the Czech researchers aren’t the first to consider ketamine as a way to take the starch out of a situation. A seven-year-old report from former Pennsylvania State University pharmacologist Joan Lakoski and colleagues, provided to the National Academy of Sciences’ Naval Studies Board, lays out ketamine’s potential. It’s considered, along with a dexemedetomidine mix’s alleviating effects, for use as a calmative agent within a broader rubric of “minimal force option studies.”
The Czech paper cites the potential use of paintball gun-like projectiles to hit targets with the agent, using DMSO (dimethyl sulfoxide) as a way to speed the drug through the skin. But as former University of Bradford (U.K.) Non-Lethal Weapons Research Project member Neil Davison points out in one paper, Lawrence Livermore National Laboratory was looking at DMSO-laced paintballs a decade ago. Some observers worry that advancing technology will make these dreams — or nightmares — a reality.
“The first I heard about anti-bellicosity agents was in the late 1950s, half a century ago,” says Julian Perry Robinson, a former chemist and an expert on chemical weapons law at the University of Sussex (U.K.) Science and Technology Policy Research wing. And now, “our understanding of receptors, of ligands which can interfere with receptors, how those receptors affect behavior — a vast amount of knowledge is popping up.”
The use of such agents in combat is generally prohibited. But riot control agents like tear gas, for example, are permitted during police actions. What constitutes a police action, or a chemical weapon, is becoming fuzzy. Robinson and others think the Chemical Weapons Convention (CWC) needs to be clearer about banning behavioral agents and monitoring compliance. He’s drafting such a proposal. The CWC, which includes the U.S., has its 10-year anniversary review conference next spring.
The U.S. walks a fine line in the debate. There is support among the military for research into behavioral modifiers, and more than one American researcher connected with the military thinks Schreiýýberova’s presentation is compelling. But it’s not policy. “The Defense Dept.’s Non-Lethal Weapons Program is not exploring any compound, device or system with the capabilities as described,” a U.S. military official says.
The Russian Special Forces’ hugely controversial use of an opioid agent to end the Dubrovka Theater siege in 2002, when Chechen separatists seized 725 hostages, still reverberates. Dosage and delivery (as well as organization) were a problem — the doses were uneven, and the ages and physical conditions of the hostages varied. 25 hostages died.
“You could argue with persuasiveness that these agents worked very well in Moscow. Many people were saved who almost certainly would have died,” says Mark Wheelis, a microbiologist at the University of California, Davis, and co-author of “Deadly Cultures,” a history of biological weapons. “That was because of the element of surprise. The element of surprise was lost once the first event passed.” Wheelis worries about the development of an open market for biological and chemical agents, where the CWC is eroded by de facto use and criminals and terrorists get their hands on ultra-effective calmatives. “The momentum in this field is very high and increasing, and it’s not designed to develop a weapon,” he says. “It is legitimate medical research, and it has potential for substantial benefits. If we can understand the circuits that control consciousness, the circuits that lead to schizophrenia and other kinds of mental illness, the benefits are immense. But if we can cure schizophrenia we can cause it.”
There are no known pharmacological compounds that affect human behavior on a mass scale with any kind of margin of safety. But even if the U.S. military isn’t exploring compounds, there’s always the private sector. What the Pentagon has at its disposal is extensive archives as well as robust research into airburst munitions and other delivery systems. General Dynamics has even worked on a 155-mm. non-lethal artillery projectile. When an agent comes along, its ride will be waiting.
“As we come to understand neural circuitry better, it may be possible to devise single agents that would affect cognition, but not respiration,” Wheelis says.
Meanwhile, Schreiberova’s monkeys will keep at it. For a small program, it’s focused, with a long track record. An earlier paper from the group describes research going back to 2000, and use of data from human subjects. The Czech Ministry of Health funded “Loss of Aggressiveness.” Fusek has also written about VX and phosphate poisoning; Hess and Votava have written about dexemedetomidine suppressing dominant behavior in aggressive mice.
Revolutionary advances in psychopharmacology and neurology promise wonders in treating mental ailments and nervous disorders, says Steve Wright, an ethics lecturer at Leeds University (U.K.). He’s just worried about the dark side. The goals behind artificially changing human behavior matter as much as the ability to do it.
He cites the recent tempest over the so-called “Gay Bomb,” an old U.S. Air Force program aimed at introducing pheromones among the enemy to make them lovers rather than fighters.
“We’ve laughed at it. But what if you can manipulate behavior in a way that allows one group to dominate another?” he asks. “What they should consider in decision-making circles is: Can we keep this genie in a bottle? It’s always like this. There’s nothing, there’s nothing, then there’s a resonance — the breakthroughs happen. Then, there’s a race.”
