James Ketchum’s Chemical Warfare is an autobiography of a lead researcher at Edgewood Arsenal during the 1960s, a presentation of some of his key findings, and an apologetic for testing incapacitating agents on military and prisoner volunteers. In addition to providing an important window into the formerly-classified world of US chemical weapons research, Chemical Warfare is a valuable source of information on a plethora of psychoactive compounds, including BZ (QNB), LSD, THC, scopolamine, and atropine. Technical information included in a long Appendix will greatly interest the specialist, particularly toxicologists and pharmacologists.

Despite the technical nature of the material and the gravity of the ethical issues involved, the book is written in a chatty prose that is easily accessible to the layperson. While inviting and amiable, the prose is loose and at times unfocused. This book is a long 360 textbook-size pages, and it could benefit from more ruthless editing.

James Ketchum enlisted in the Army in 1955. After completing his medical training in psychiatry he was assigned to the Edgewood Arsenal near Baltimore, Maryland in 1961. Edgewood was already conducting research into the use of psychoactive drugs when he arrived. Research began in 1957 as a joint operation with the Intelligence Center at Fort Holabird. At that time, researchers began administering LSD to volunteers, some of whom took LSD as many as 20 times in a two-year period.

The Army was primarily interested in LSD as a potential incapacitating agent – something that could bewilder and disable enemy troops with a minimum of bloodshed. Edgewood investigated a number of agents for this purpose, including early experiments with PCP that were apparently discontinued after one civilian research subject suffered paranoid psychosis and had to spend six weeks in the hospital.

In 1960, a year before Ketchum arrived, Edgewood Arsenal began investigating an obscure drug designated EA 2277, more commonly known as 3-quinuclidinyl benzilate, QNB, or BZ (apparently short for Benzilate). BZ was first synthesized by the pharmaceutical firm Hoffman-La Roche Inc. as a potential ulcer remedy. It came to the attention of the Army when it was found that very small doses (around 500 ug) produced stupor and delirium lasting for days.

Ketchum quickly became a lead researcher at Edgewood and was given wide latitude to design and implement experiments. He began exploring the effects of eight stereoisomers of THC administered in various combinations, and soon shifted focus to LSD and BZ. Over the next several years he would conduct extensive research on the clinical pharmacology of these compounds with his colleagues. Their work frequently involved drug trials with volunteer subjects. The sessions were closely monitored and analyzed, and many findings are described in this book.

If you are interested in BZ, this is the book for you. It is unlikely that another book will ever focus on BZ in comparable depth. The course of BZ’s effects receives detailed attention and copious description. BZ is a competitive antagonist of muscarinic acetylcholine receptors of the sympathetic and parasympathetic nervous systems. It acts as an anticholinergic deleriant, generating long-lasting effects that closely resemble those of its tropane alkaloid cousins atropine and scopolamine, the active agents in datura and belladonna. This includes highly idiosyncratic effects such as the impulse to take off one’s clothes, or the impulse to smoke imaginary cigarettes.

The average effective dose is 7-8 ug/kg (roughly 500 ug per average male adult). The onset is slow, lasting roughly 3 hours. By the fourth hour, subjects generally enter a stuporous slumber. Around hour 12, subjects become ambulatory but profoundly disoriented for another day or two, during which time subjects typically experience extreme confusion, hallucinations, and delirium closely resembling datura intoxication.

Ketchum and the other Edgewood researchers investigated the effects of BZ on reaction time, various delivery methods, possible antidotes, and so forth. In one operation called Project Dork, aerosolized BZ was delivered to eight volunteers at Dugway Proving Grounds during combat simulation. The operation was a success; most of the troops experienced the predicted course of symptoms with the predicted impact on their performance, and all recovered fully within 72 hours.

We follow Ketchum through his experiences with the military and the media, his two-year post-doc at Stanford, and into private practice as he provides off-the-cuff commentary on familiar faces and interesting places. I was particularly intrigued to hear personal anecdotes of important early researchers such as Sidney Cohen and George Aghajanian.

Ketchum argues throughout the book that the dangers and improprieties of the Edgewood experiments are exaggerated by over-zealous investigative reporters, many of whom inappropriately associate the Edgewood Arsenal experiments with the notorious CIA operation MKULTRA. In that operation, hundreds or thousands of civilians were surreptitiously dosed with psychoactive drugs without their knowledge or consent. Ketchum maintains that his work was scrupulous and that he and his colleagues were careful to obtain consent from subjects. He argues:

Unwitting guinea pigs? Naïve young men taken in by Army propaganda? Mentally marginal soldiers who could not make good decisions? Ignorant individuals who didn’t know what they were getting into because of tight security? In my view, none of the above! (p. 30) … Nevertheless, years after extensive testing with drugs such as BZ and LSD had ceased, investigative reporters continued to apply the pejorative “guinea pig” cliché to Edgewood volunteers. (p. 31)

The book meticulously documents the considerable lengths to which Ketchum and his team went to obtain voluntary consent, but difficult questions remain. Beginning in 1965, Edgewood Arsenal began recruiting prisoners from the Holmesburg Prison in Philadelphia. While the prisoner subjects were a small percentage of the volunteer population (less than 1%), it is unclear that prisoners are in a position to make a free, balanced decision, when income opportunities are tightly constrained.

Allan Lawson, a former Holmesburg inmate and experiment volunteer, testified before a Senate subcommittee investigating the use of prison inmates in 1973. He stated that prisoners were “trading [their] bodies for money,” making “any claim of voluntary participation ... in human experimentation a cruel hoax.” Following those Senate hearings, the use of prisoner volunteers in experiments became much less common.

Ketchum offers broad defenses of Edgewood research. For example:

Many think that the so-called Army volunteers we tested more than forty years ago were not really volunteers … In short, they assert that Army testing in the 1960s was unethical, incompetent, and carried out in violation of basic human rights. These erroneous beliefs could have been dispelled by authentic information long ago, but very little ever appeared in the public media. (p. 2)

However, we later read:

In the late 1950s Dr. Van Sim and his colleagues sometimes gave LSD covertly to Edgewood volunteers. Such studies could be, and eventually were, criticized as lacking in rigorous design, and particularly for their lack of sufficient regard for possible adverse psychological consequences, as well as trampling on the civil rights of the unknowing recipients. (p. 118)

While Sim’s malfeasance occurred before Ketchum’s arrival at Edgewood, this admission is hard to square with the unqualified defenses of Edgewood Arsenal that appear in this book. Some of these issues are simply not black and white, and I would have liked to have seen more shades of gray.

Ketchum rightly rejects media reports linking Edgewood to CIA experiments. Although Ketchum himself does not criticize the book, Lee and Shlain’s widely-read Acid Dreams describes Edgewood side-by-side with MKULTRA and makes little effort to distinguish between them. Those authors scarcely note that the Edgewood experiments were an Army operation investigating non-lethal incapacitants, that experiments conducted at Edgewood overwhelmingly used informed volunteers, and that the entire process was monitored by oversight. MKULTRA, on the other hand, was a CIA operation investigating mind control that circumvented oversight at every turn, and it frequently used civilian subjects without their knowledge or consent.

But again, the issue is not black and white. This book is full of mentions – sometimes laudatory – of MKULTRA personnel, including Harold Wolff, Harry Abramson, and Harry Isbell, some of whom were involved in deeply troubling research. During the 1950s and 60s, the CIA was involved in a great deal of psychoactive drug research. While MKULTRA was certainly not running the show at Edgewood, it would be going too far to say that there was no connection whatsoever.

For example, during his tenure as Director of the Addiction Research Center, and while receiving funding from the CIA through MKULTRA, Harry Isbell routinely offered morphine or heroin to patients in exchange for participating in his experiments. Most of these patients had been remanded to his facility to receive treatment for addiction. “Volunteers” for his experiments were administered experimental psychoactive chemicals including bufotenine, psilocybin, scopolamine, LSD, mescaline, and DMT. They sometimes received very high doses of a drug, as in one experiment in which Isbell’s subjects were given progressively-higher doses of LSD for 77 days in a row.

Adjacent to a photograph of the author chatting amiably with Dr. Isbell, Ketchum notes:

Some critics have cited Isbell’s seemingly cavalier experiments as an example of gross mistreatment of volunteers … The inmates, however, did not seem reluctant to take the drug every day, apparently feeling that being given generous doses of their beloved morphine after each test was sufficient compensation. Isbell found no evidence that his volunteers suffered any damage from their multiple-dose LSD experience. Of course, one might question the ethics of supporting a morphine addict’s habit in a facility established to treat addiction. (p. 123)

Ketchum’s arguments are ill-served by this characterization of Isbell’s experiments, which constitute one of the darkest chapters of the whole MKULTRA affair. Referring to these subjects as “volunteers” makes a mockery of the very idea of consent, and saying that “some critics” cite Isbell’s “seemingly cavalier experiments” strikes this reviewer as equivocation.

From the point of view of contemporary ethical standards governing human subjects experimentation, there is an intrinsic challenge posed to the idea of consent when considering volunteers over whom the experimenters have direct power, such as subordinates, prisoners, or a semi-captive group of opiate addicts. It is hard to miss that Ketchum sides with the experimenters in nearly every case – even when considering Isbell, who is frequently regarded as an icon of human subjects misconduct. In my view, this minimizes the vital importance of the opposing perspective. During those years, very serious human rights violations were occurring in the name of science and defense of country. The gravity of those abuses warrants careful scrutiny of any human subjects testing, whether conducted by the military, a hospital or another type of research context. I found this book to be too quick to disregard critics as ambulance-chasers or unscrupulous media hounds, given what we now know about what went on in those days.

Ketchum meticulously documents the informed consent procedure used at Edgewood and carefully explains follow-up studies showing little evidence of lasting harms suffered by the volunteers. But he does a poor job of conveying a nuanced awareness of the world that exists beyond his lab. “I was never aware, however,” he writes, “of the CIA’s use of LSD on unwitting civilians, and indeed this did not become widely publicized until 1999, after the death of [MKULTRA director] Sidney Gottlieb,” (p. 222 ). This surprised me to read, given the three open Senate hearings into the matter covered in the national press, as well as the publication of The Search for the Manchurian Candidate in 1979 and Acid Dreams in 1985. The fact that information regarding MKULTRA was widely available by the mid-1970s is important for understanding the context in which critical scrutiny of Edgewood was undertaken by the media. Widespread suspicion and incredulity regarding the ethics of Army testing of psychoactive drugs makes more sense given this context.

I would have liked to have seen a discussion of the joint CIA/Edgewood Arsenal Project OFTEN conducted from 1968 to 1973. That project investigated the effects of psychoactive drugs on animals and humans. Consideration of this operation might shed more light on the CIA-Edgewood connection.

While Ketchum provides compelling evidence that many of the experiments conducted at Edgewood were done appropriately, I am left with misgivings. What worries me – and I hope this worries you too – is what happens when things like BZ get out of the lab. At one point Ketchum notes that “Thirty or forty pounds of chemically-pure LSD had spent a week in my office and had now disappeared with no comment from anyone, no receipt form and no other paperwork!” In an interview following the publication of Chemical Warfare, the interviewer jokes with Ketchum about this story, but I’d like to know what the hell the US Army was doing with 40 pounds of LSD, and I’m not laughing.

I’m thinking of Harold Blauer, who died in 1953 in a civilian hospital after seeking treatment for depression. Unbeknown to him, his doctors were under Army contract to investigate the experimental psychoactive drugs MDA and MDMA. Blauer died when doctors injected him with an enormous dose of MDA as part of an experiment that had little to do with his treatment. That MDA was procured from Edgewood Arsenal.

Despite these caveats, Chemical Warfare is an interesting, often-entertaining book with a wealth of information. It provides a valuable window into a classified Army research facility and aptly refutes many misunderstandings and missuppositions about what went on there. Ketchum is quite right in asserting that Edgewood is a cut above the flywheels and sadists of MKULTRA, but I cannot conclude as he does, that when it comes to ethics, “Eventually, it seems, we got it right.”

This review is a slightly revised version of the original Chemical Warfare review published here April 2, 2007.