Hi Everyone,

Well, the awaited reply.. and my response :)

I have a few things to throw in, but I want to go through his defense first.

Introduction
Recently a 21-year-old Pharmacology student named Bradley Speers wrote "A Rebuttal against the Dead Men Don't Pull Triggers essay written by Roger Lewis." I welcome Speers' desire to better understand the technical details. Unfortunately, several of Speers' key points are fundamentally flawed.

Why, I was saying the same thing about you... let's see what you come up with.

No Parallel To Cobain Case
Most importantly, Speers does not provide another case in which a heroin addict overdosed and suffered a self-inflicted gunshot wound. Only one case is mentioned in Speers' entire rebuttal, and the case itself is completely irrelevant to the Cobain case because instead of relating even remotely to intravenous heroin use, Speers' citation concerns morphine tolerance during a two and one-half hour period, in which the method of administration is not described.

You're right, there isn't a parallel to the Cobain Case, which makes all your research less relevant. If you really want to know how I came up with the volume of distribution idea, I'll explain it to you. Two things I notice about the Cobain case is: 1) he has a blood concentration much higher then in most overdoses of any type. 2) He has a "fatal" shotgun wound to his head. Two months later, it hit me.. the blood concentration is higher because the drug hasn't completely distributed. How in the hell could that have happened? Hang on, Kurt has died rather rapidly.. that explains it... but then.. what distribution has Roger used?? 160 Litres... the final distribution. So I think, what is the time it takes for heroin to reach Vmax... 10 minutes... therefore it CAN'T be fully distributed. He's using the wrong volume.. uh oh.. So that's why I wrote what I did.

Wrong Focus
Speers makes a big mistake when he overestimates the relevance of dose-related data compared to the data concerning the blood morphine level. Most importantly, Speers fails to recognize some fundamental differences between crucial concepts such as method of administration (eg. intravenous as opposed to "bolus"); high dose versus overdose; and even the basic differences between heroin and morphine.

All these claims and no explination. Ok, "crucial concepts": intravenous opposed to "bolus"... let's see, intravenous basically means injection directly into the veins. Bolus is when a dose of a drug is instantaneously throughly mixed into the bloom stream. They are different, in the sense that IV is administered over a second or so, while bolus is instantaneous.. bolus would help your case Roger... why discredit it? high dose versus overdose... the point with this section was to point out that overdose CAN occur in doses which were previously tolerated. It seems we both agree here (in a way). woah.. heroin vs morphine... how much detail do you want? What do you want me to clarify? heroin is converted into morphine via deacetylation... morphine is measured in the forensic tests because heroin has a low half-life compared to morphine, and morphine is indicative of the dose which was taken. That better? Where is the problem?

Substance X and Quinine Are Outdated Concepts
Some of Speers' research is based on clearly outdated concepts. Specifically, he mistakenly contends that the lethality potential of intravenous heroin is directly correlated to the toxicity associated with "Substance X" and/or "quinine." Some of the confusion about this subject stems from Milton Helpern, M.D., who wrote a very important study in the early 1970's (Fatalities from narcotic addiction in New York City - incidence, circumstances, and pathologic findings, Human Pathology, 1972; 3(1): 13-20). Several findings made by Helpern have long since been studied further and found wrong, with the relevance of quinine standing as a prime example. From my essay:

"Nakamura explains 'In more cases, it can be now shown that narcotic was taken and rapidly distributed by the body to the various organs, and it may now be unnecessary to explain narcotic deaths by blaming excipients or hypersensitivity responses.' (63). Thus, although some rare overdoses can be attributed partially to hypersensitivity, allergic, and other reactions to adulterants in street heroin, it is now widely accepted that heroin overdoses are primarily 'dose related.' " (Nakamura, G.R., "Toxicologic assessments in acute heroin fatalities," Toxicology Annual Volume 3, edited by Winek, C.L. & Shanor, S.P., Marcel Dekker Inc., New York, USA, 1979, pp. 75-87.

The advent of better testing methods, accumulating data, and increasing heroin overdoses all led to indepth research concerning the forensic pathology of intravenous heroin overdoses. One of the time consuming elements of researching the Dead Men Don't Pull Triggers essay was editing these references to include only the highest quality and most relevant work. In stark contrast, Speers describes only one case history, which is completely irrelevant, involving a man who took a large dose of morphine as a bolus over a two and one half hour period.

So you've discounted hypersensitivity reactions... that doesn't discount Substance X in my rebuttal... if you refer to my definition, substance X is any compound which either can potentiate opiates or can result in a similar type of overdose response. This point isn't the major issue, and I will just concede the 'adjuvant' issue. Let's be clear though... there are definately substances which do potentiate opiates, such as alcohol and benzodiazepines (which is one of the things Roger is using in his essay).. surely, this CAN play a factor in amounts of opiate required for overdose.

Research Is Central To Homicide Claim
For the record, I have done a lot more research than Speers on this subject. Every single reference listed at the end of my essay was read by me more than once, and many have been read several times. I have scoured seven major libraries in two cities for these references, including highly specialized facilities devoted to medical and forensic information, such as Toronto's Addiction Research Foundation, and the University of Toronto's Medical and Criminology Libraries. Although I used the computer and the Internet (eg. Medline, Toxline, et. al.) to peak capacity, and although I sought any personal communication possible, I relied solely on published, respectable references for the actual essay. I hand-searched almost every single issue of every medical and forensic journal from A to Z since 1965, making note of the finest articles and the references therein, then seeking further references based on the new information. From textbooks to poisoning manuals, I tried to make the research exhaustive so that I could honestly reach a conclusion based on all available material.

Research all you want, you haven't mentioned anything related to my claim that Kurt took a lower dose then what you have calculated.

Speers' "Conservative" Judgment Betrayed By Lack Of Research
Speers' concern to be "conservative" in his judgment is honourable, yet his conclusions and his use of outdated research both betray his conservatism. Conservative judgment in this case has been a goal of mine from the start, hence I directly compare the Cobain case only to those cases in which the blood morphine level was measured (1526 cases) instead of all cases involving a heroin-related overdose (3226 cases). Similarly, I directly compare the Cobain case only to violent suicides, not suicides in general. For the purposes of my essay, I conservatively assumed that Cobain was the world's most severe intravenous addict (if he was not an addict, then the dose of heroin he received would be approximately seventy-five times the maximum lethal dose). Speers' statement that he likes to be "more conservative about things" merely states his intention, not the reality.

I am critiquing your essay, not writing a new one... I am using your parameters. That should be fair shouldn't it?

Mechanisms Of Tolerance
Speers is basically correct when he states that there are "...two general mechanisms in which tolerance to drugs can occur," however it is important for the reader to understand this is truly a simplistic description of a complex subject. Although Speers aptly summarizes the two general mechanisms as involving "...the removal of the drug..." or "...the increase (or decrease) of receptor numbers...," he fails to understand the limits of tolerance of heroin addicts to intravenous heroin. Even Dr. Reay, the Seattle Medical Examiner, has wisely remarked that "tolerance is an amazing thing," so it is hard to criticize Speers too harshly for falling into the same faulty line of reasoning. Regardless of the "mechanisms" of tolerance, there is an established limit to the range of doses which a heroin addict can survive.

Irrelevant To Measure I.V. Heroin Toxicity Using The LD50
Speers uses the concepts related to "LD50" doses in a confusing and irrelevant manner, for example, when he says "For addicts, setting a value is impssible." Toxic substances such as chemical poisons and drugs are often measured in laboratories to better determine their exact level of safety. For example, a study conducted on a particular type of rat poison could include one hundred rats, and the test would be to measure the amount of rat poison needed to kill the average rat. The amount of rat poison needed to kill fifty of the one hundred rats is the "LD50" of rat poison, i.e. the Lethal Dose for 50% of the test group. The LD50 of intravenous heroin is not relevant to the Cobain case for two major reasons; first, the LD50 for heroin is based on data from non-addicted subjects, and second, the LD50 only tells about the lethality of the drug in 50% of subjects, not the entire 100%. The dose required to kill 100% of the test subjects is called the "LD100," and it is also largely irrelevant to the Cobain case, because it still only concerns normal subjects.

Opioids Accumulate
Speers is also wrong when he comments that "it may be possible that there was a reasonable level of morphine present before a final injection, and thus its effects are less pronounced." The level of opiates accumulates and eventually reaches a toxic level.

Not necessarily. There is a phenomenon known as steady-state kinetics, where the doses of drugs given compensates for the natural elimination of the drug.. this is often achieved after about 4 half-lives of elimination of the drug if the doses are equal and given every half-life. It is true the concentration of the drug increases for the first few doses, but soon after the drug concentration variation becomes fixed. The best example is those people who have "continual" access to opiates, terminal patients. They often have doses of drugs given periodically and they do not reach a toxic level.

For me to backup what I've said now.. One of the possible tolerance mechanisms to opiates is the release of mu-receptor antagonists and kappa-agonists (such as dynorphin). The result is there is a certain level of "natural naloxone" so to speak.. which is released upon opiate activity, and will reduce the onset and effects of the new drug, compared to a fresh (non-blocked) dose.

Heroin & Benzodiazepines A Deadly Mix
Regarding the traces of a diazepam-like substance in Cobain's blood, Speers seriously underestimates the danger of benzodiazepines mixed with heroin. He also totally neglects to consider the possibility of a fast-acting benzodiazepine as described in my essay.

I may or may not be seriously underestimating.. that's why I used the word MAY..

Roger is saying the benzodiazepine is around 3 days old, and if in particular it is a high-affinity drug (that's what he's really saying) then it still may have significant effects. Let's look at the other side of the coin, the benzodiazepine could be 4 weeks old, and just standard old diazepam. The reason why I don't think benzodiazepine is not really involved in the murder situation is... if you really wanted to be sure that the benzodiazepine has an effect, you would have a bigger dose than "trace amounts". Roger is saying low levels of benzodiazepine can significantly opiates.. that's well and good, but how many of these claims are using "trace amounts" as their evidence? Not many.. you would find that most of these reports would have a measurable amount of diazepam-like drugs, otherwise they wouldn't hold a great deal of weight.

Cobain Was Incapacitated Or Dead Before Gunshot
Note that I am not saying that Cobain died from a "drug overdose," rather I am stating that medical evidence shows he was incapacitated or dead due to the heroin before the gunshot was fired, therefore he was murdered. The information presented in the Dead Men Don't Pull Triggers essay has recently been independently and professionally validated by award-winning journalists Ian Halperin and Max Wallace in their book Who Killed Kurt Cobain?

So a journalist read your work? Point?

Overdose Reports Exist Without Any Case Parallel To Cobain's
I reviewed several dozen heroin overdose reports, and listed them all in the reference section of my essay to facilitate rebuttals. One thing rarer than overdose reports is another case remotely like Cobain's; I found none. Apparently this is because such a case does not and cannot exist. There is nothing quite as rare as something which cannot exist.

As I have said at the start, and as you like to point out.. there are two things unusual about this case.. the first is that nothing really matches the blood level.. the second is.. a gunshot wound... coincedence?

Pro-Murder-Theory Is Not "Pro-Murder"
Although I clearly state that Cobain was murdered, I strongly object to Speers' morbidly callous description of my essay as a "pro-murder" essay. My essay was written to tell the truth, not to bolster a biased preconception, and is more properly seen as "pro-fact." The phrase "pro-murder" is at best cheap jargon slang for "pro-murder-theory," and at worst an implication that I support the general concept of murder. I realize Speers is not actually saying I am "pro" murder, but it is truly evident of his lack of literary and grammatical skills that he would write such a disrespectful description.

No disrespect intended.. Sorry if it did. Your essay is factual, but you have a few mistakes, particularly the dose calculations. They aren't factual.

Dead Men Don't Wipe Prints Or Use Credit Cards Either
I was ready to accept that Cobain committed suicide until I read Tom Grant's website, then I became convinced that Cobain was probably murdered based largely on circumstantial evidence and Tom Grant's assurance that he had further, more concrete evidence. Grant has since presented a lot more evidence, and says he still has more. After about one year of researching the Dead Men Don't Pull Triggers essay, I was convinced that significant forensic evidence existed such that it was medically impossible for Cobain to have committed suicide. There are many reasons for believing Cobain was murdered, some less technical than others, and all of the evidence is important.

How much of Tom Grant's stuff is really concrete? How much is just trying to get us to call for an investigation? I personally believe he's betting that the evidence isn't conclusive that it is suicide.. Apart from your referenced essay, I wouldn't hold anything else as possible "proof" (unless he comes out with it). He's been saying for years that he is going to bring out more stuff as time goes on, but since I first read his stuff (late 95) he hasn't really brought anything new out, at least that is substantial.

Conclusion
Speers is basically a smart young man, and has done a good preliminary job drafting his rationale regarding why he personally believes Cobain was not murdered in spite of the evidence presented in the Dead Men Don't Pull Triggers essay. Although I am saddened with Speers' lackluster methodology and I disagree with all of his conclusions, he has a good grasp of some important pharmacological concepts such as tolerance and toxicity, and he asks the same questions I asked myself when writing the very essay he criticizes. It occurred to me frequently while reading his rebuttal, that he has put many hours of time and serious thought into this question, possibly a lot more than the Seattle Police Department and coroner Nicholas Hartshorne combined. Hopefully Speers will at least accept the overwhelming rarity of the Cobain case (in contrast to the Seattle Police Dept., who insist it is a "typical suicide"), and join the growing public demand for a full and independent re-investigation.

Certainly, it is a rare case, but I am not convinced that it is definately "murder" so to speak.

A couple of things... firstly, there is NO reply to my claim that the drug dose is wrong. None. It seems Roger either completely ignored that statement or he doesn't have a reply to it. Even if 80mg of heroin may kill anyone, it doesn't mean it is instantaneous... wrong, in fact for the most hard core addict (because 80mg is the lowest limit of 100% fatality), 80mg would most likely kill closer towards 10 minutes later. Granted, 240mg would make things move a lot quicker (how long before the dose reaches 80mg in the brain?).. but then my claim that the dose is only 50mg hasn't been argued... why not? Isn't this one of the essential things in your essay? Also no defence in my quotation of his essay, regarding the half-life of heroin and his seemingly misleading quotation.

Secondly, the fact that this case "is unique" means that contrary to the arguement that research holds the answers... basic pharmacology is MORE important. If you can't simulate the same situation in real life, why not go off the pharmacological models to predict the result? Let's look at a possible situation. The local street junk is only 10% pure... then all of a sudden it goes even just 30% pure, thus the junkie would have taken 3 times the dose they would be tolerant to.. as I have explained, it is all based upon a set drug/receptor (including other resistance mechanisms) ratio. Do they have blood levels similar to what Kurt had? Wouldn't they die as rapidly as Kurt possibly has? Surely the possibility that the dose is 3 times the lethal amount is there. Why haven't they got the blood concentrations that Kurt has? There has to be another factor here... the gunshot. Obviously it is significant in this issue.

Again.. drug concentrations in the blood are all dependent on the volume of distribution of the drug, as well as the dose (which is fixed). I, infact, pull myself up and realised my calculations were wrong, Roger didn't even mention that. My new values (which will still hold similar water as the current figures) are now available.