NIDA’s Volkow Defends New Medications for Addiction

On Big Data, Big Vaccines, and a Big New Agency.

In her Director’s Report to the 2011 meeting of the College on Problems of Drug Dependence in San Diego last week, Dr. Nora Volkow, director of the National Institute on Drug Abuse, sought to refute allegations that NIDA lately has been too focused on pharmacological approaches to treating addiction—“magic bullets” in the form of pills or vaccines. Dr. Volkow presented figures showing, as the CPDD Community Website reported, that “NIDA funding allocation for new medication development has remained stable at about 12% for some time, despite concerns expressed by some researchers that funding in other areas is being sacrificed to support the medication development portfolio.” Basic and clinical neuroscience research accounts for 45% of expenditures, she said.

In other news, Volkow expressed her avid interest in the possibilities presented by so-called “big dataset science”—the act of pooling together huge amounts of data in order to generate greater statistical power. She traced a set of disciplines—genetics, epigenetics, proteomics, brain imaging, clinical data, and systems biology—and said that the NIH’s Working Group on Data and Informatics  was seeking systematic ways of integrating and analyzing large biomedical datasets in these crucial areas.

As for treatment, the current emphasis is on stimulants. Volkow said that work continues on finding reliable antagonist drugs to combat the dopamine disruptions promoted by active drug abuse. She suggested that work on buspirone, the D3 receptor antagonist and partial serotonin 5HT agonist used to treat generalized anxiety disorder, has shown that it may reduce cocaine self-administration in rhesus monkeys. This would be of considerable clinical interest, since addiction medicine presently has no effective drug treatments to offer for stimulants like cocaine and methamphetamine. A large clinical study now underway is showing that buspirone blocked D3 receptors in monkey brains in a way that reduced their interest in cocaine.

And she referred to the failed promise of NicVax, the short-lived vaccine for cigarette addiction. The treatment “failed to meet the primary endpoint in Phase II trials.” In other words, it flunked out. Only 30% of addicted smokers developed sufficient antibodies from NicVax to do them any good. But she cited new research on an alternative approach to vaccines, including a new cocaine vaccine (dAd5GNE) shown to be effective in reducing cocaine addiction-related behaviors in rats through the long-term blockade of dopamine transporters.

In a related approach to producing a reliable anti-cocaine antibody, researchers in the Department of Genetic Medicine at Weill Cornell Medical College went to work on “an adeno-associated virus (AAV) gene transfer vector as the delivery vehicle to persistently express an anti-cocaine monoclonal antibody in vivo, which would sequester cocaine in the blood, preventing access to cognate receptors in the brain.” An AAV is a small virus that is infectious but not pathogenic in humans. You might have it right now, but wouldn’t know it, since AAV doesn’t cause disease. So, the researchers used an AAV to build a transporter mechanism for their monoclonal antibody, GNC92H2. In mice, the result was “persistent serum levels of high-affinity, cocaine-specific antibodies that sequestered intravenously administered cocaine in the blood.”

And finally, while the name is still up in the air, a new national institute combining the study of alcohol and the study of all other addictive drugs will follow after final recommendations submitted to NIH Director by year’s end. Volkow briefly laid out the timeline of the merger for the assembled scientists. Call it the Institute for Substance Use Disorders, or the Institute for Addiction Disorders, or the National Institute of Substance Abuse, but whatever the eventual name, it will be fully operational by late 2013, or at least that’s the plan—and Nora Volkow, the current director of the NIDA, which will merge with, or rather absorb, the National Institute on Alcohol Abuse and Alcoholism (NIAAA), won’t be its director (See "NIH Turf Wars"). Whether that’s good or bad is the subject of much debate, but the project marches on, and seems sensible in the end.

Random Notes from the College on Problems of Drug Dependence

Opening day addresses at the annual meeting.

(These are notes on research in progress, not findings written in stone).

--NIDA director Nora Volkow talked up buspirone (Buspar) as a treatment for cocaine addiction, and referred to favorable results on buspirone for cocaine self-administration in monkeys in a large clinical trial. Also, different vaccine strategies are in the works, including different pharmacological approaches to blocking specific dopamine transporter molecules.

--Edward Sellers of DL Global Partners, a drug research consulting firm, emphasized the importance of enzyme variations in smoking. Variants of the CYP2A6 enzyme of metabolization allow us to identify “slow metabolizers” who respond well to placebo or nicotine patch therapy, and other smokers who don’t.

--Sherry McKee of the Yale University School of Medicine reminded everyone that cigarette smokers—even very light smoking “chippers”— are far more likely to have concurrent drinking problems than non-smokers. Smoking helps drinkers drink more and longer. To demonstrate such “potentiated reinforcement,” she showed a delightful video of her child eating cookies, then craving a glass of milk, then succumbing to another round of cookie consumption…

--Jack Henningfield of Pinney Associates, and former NIDA research chief, said that the reason the National Institute on Alcohol Abuse and Alcoholism (NIAAA) became an agency focused on “one molecule” is because Senator Harold Hughes, recovering alcoholic from Iowa, and Bill W., co-founder of Alcoholics Anonymous, wanted it that way.

--David Penetar of Harvard Medical School and McLean Hospital added more evidence of the link between alcohol and cigarettes, noting that “90 per cent of smokers drink,” and that smokers are three times as likely to be alcoholics than non-smokers. He pointed to research documenting a disturbing “increased desire to drink” when wearing a nicotine patch. With a patch, subjects reported feeling the effects of alcohol sooner and longer.

Photo Credit: http://www.thejournalshop.com/

Bath Salts and the College on Problems of Drug Dependence

CPDD holds annual meeting.

I’ll be out of the office for a few days, attending the annual meeting of the College on Problems of Drug Dependence (CPDD), the oldest group in the United States dedicated to addressing problems of drug addiction. The organization functions as an independent body, and is affiliated with other scientific and professional societies involved in the study of drug dependence and abuse. The meeting dovetails with the 2012 NIDA International Forum. A broad selection of the nation’s top drug and addiction researchers will be there, along with Nora Volkow, Director of the National Institute of Drug Abuse (NIDA), and Drug Czar Gil Kerlikowske, director of the Office of National Drug Control Policy.

 I’m pleased to be the recipient of the organization’s 2012 CPDD/NIDA Media Award, which is given each year for “contributions through the media that have enhanced the public understanding of scientific issues concerning drug use disorders.” That’s pretty nice of them, and you can find an interview I did for their CPDD blog HERE.

While in attendance, your faithful correspondent will be attending what looks to be a massively interesting panel discussion called “A Stimulating Soak in “Bath Salts”: Investigating Cathinone Derivative Drugs.” Look for a blog post on that one.

I’m also planning to attend a symposium on “Exercise as a Treatment for Drug Dependence in Humans,” and plan to report back on that topic as well.

High-Risk Haplotypes in Smokers

It’s getting harder to interpret genetics studies, and that’s a good thing.

Reporting the results of published studies concerned with genetic risk factors has always been a tricky proposition. Beyond the inevitable, and too often ideological nature/nurture split, there has been an unfortunate history of false positives in the rush to make news with a “gene for” alcoholism or schizophrenia or belief in God.

But single gene theories are mostly a thing of the past, and results tend to be broader and more tentative, as befits the state of our knowledge about genes and risk in a post-epigenetic landscape. Nonetheless, there’s no denying that genes play a strong role in all kinds of behaviors and processes. A large group of U.S. tobacco researchers went looking for associations between genetic risk factors and the ability to stop smoking successfully, and published their results in the American Journal of Psychiatry. The group came down strongly in favor of the proposition that genetic variations in the chromosome 15q25 region help dictate who manages to quit smoking and who does not.

The genetic variants in question are for nicotine receptors, and are called CHRNA5-CHRNA3-CHRNB4. They compose a “high-risk haplotype” that Li-Shiun Chen and coworkers believe to be involved in the ability to quit. (A haplotype is a combination of DNA sequences on a chromosome that are transmitted as a unit). People with these genetic variants “quit later than those at low genetic risk; this difference was manifested as a 2-year delay in median quit age.” However, this association tended to wash out at very high levels of smoking. Nonetheless, “pharmacological cessation treatment significantly increased the likelihood of abstinence in individuals with the high-risk haplotype,” compared to the low-risk group.

The suspicious haplotypes did not reliably predict tobacco abstinence across all groups that were studied. And any pharmacological treatment at all vastly increases abstinence rates, compared to placebo, while those who smoke the fewest cigarettes per day have the best shot at abstinence no matter what. In one sense, all the study is saying is that anti-craving drugs are more likely to be effective in smokers “who are biologically predisposed to have difficulty quitting.” Other smokers may not need them at all as a quitting aid—which is very much as common sense would have it. But further research in this area may allow medical workers to genetically identify smokers who will definitely require a pharmacological booster shot to overcome their crippling addiction.

In brief, the study says that success in quitting may be directly modulated by certain types of genetic variation among smokers. And genetic variations influencing quitting success may be different from gene variants controlling for “severity of nicotine dependence” (how many cigarettes you smoke), and whether you get addicted in the first place. It is all very complicated. But it’s the sort of thing that gives researchers hope when they contemplate deploying forms of personalized medicine in addiction treatment.

Study limitations abound. The work looked at only one genetic locus, while the success of smoking cessation might depend on multiple gene sites. The placebo arm was relatively small, and the smoking reports were obtained through a combination of biochemical confirmation and self-reporting.

Baker, T. (2012). Interplay of Genetic Risk Factors (CHRNA5-CHRNA3-CHRNB4) and Cessation Treatments in Smoking Cessation Success American Journal of Psychiatry DOI: 10.1176/appi.ajp.2012.11101545

Graphics Credit: (Li-Shiun Chen)

Science, Academia, and Tobacco

A review of The Golden Holocaust: Origins of the Cigarette Catastrophe and the Case for Abolition

Part III

Academic collaborations come in many flavors. Just because the money is corporate doesn’t mean the studies that are funded are flawed by definition. But the cigarette industry’s academic philanthropy set new records for hubris, writes Robert Proctor, professor of history at Stanford University, in his new book, The Golden Holocaust. Duke University and Bowman Gray School of Medicine, both in North Carolina, are named for tobacco magnates.

Harvard has a long and dubious history of tobacco largesse.  Harvard’s Tobacco and Health Research Program kicked off in 1972 with a generous tobacco grant from the Tobacco Institute, who dreamed up the program in the first place. “The Harvard project made the industry look good and so was handsomely endowed, absorbing $7 million over an eight-year period.” Also in 1972, Harvard anthropologist Carl Seltzer testified for the industry in numerous public hearings, stating: “We do not know whether or not there is a causal relationship between smoking and heart disease.” In 2002, Harvard’s School of Public Health declared it would no longer undertake research sponsored by the cigarette industry. Many universities had already gone cold turkey, and after Harvard, bans were put in place by the Karolinska Institute, Johns Hopkins University, Emory University, and many others.

Proctor informs us that “Washington University in St. Louis has been another big sponge for tobacco money." In 1971, the university set a new world record for an industry grant to a single institution, and “millions more were eventually funneled into the School of Medicine, turning it into a hotbed of cigarette-friendly activism.” The irony of taking money from Big Tobacco to fund research on lung cancer is not lost on Proctor. A good deal of the research was aimed away from tobacco and toward possible causes like viruses. “The goal was clearly more than cancer cures,” he writes. “The industry also hoped to generate good PR and academic allies.” The industry was able to garner  sympathetic headlines, like “Helping in Fight against Cancer,” in the St. Louis Globe-Democrat.

The other academic hotbed thoroughly penetrated by Big Tobacco was UCLA, according to Proctor. “Tobacco collaborators at UCLA have attracted their fair share of criticism from public health advocates, and for understandable reasons.” The university picked up its own multimillion-dollar grant from cigarette makers for the Program on Tobacco and Health in 1974, and that wasn’t the first tobacco money the university had taken. “As with all such projects,” Proctor writes, “industry lawyers… played a key role in the decision to fund—with the companies also conceding that the decision ‘should be based more on public relations than on purely scientific grounds.’” The end came in 2007, when “UCLA’s dance with the devil” garnered a ton of unwanted press. Reports showed that UCLA had taken more than $6 million from Philip Morris for research “to compare how children’s brains and monkey brains react to nicotine.”

Proctor admits that singling out Harvard, Washington University and UCLA is somewhat misleading, “given that scholars throughout the world have gorged themselves on tobacco money. Indeed it may well be the rare institution that has NOT at one time or another dipped into this pot.”

Including Stanford, where Proctor teaches. Plenty of Stanford researchers have undertaken contract work and served as expert witnesses for the industry right in Proctor’s own backyard, where “at least eighteen faculty members have received monies (in the form of sponsored research) from the Council for Tobacco Research, with at least two of these—Judith Swain and Hugh McDevitt from the medical school—serving on its Scientific Advisory Board. Stanford pharmacologists were assisting the industry with its diethylene glycol studies as early as the 1930s…”

In the conclusion to his densely researched but surprisingly readable work, Proctor returns to the controlling irony of the book: “Our bizarre starting point is the well-stocked shelf of cigarettes, to which we respond by begging people not to purchase them.” He presents the dream of a world in which cigarettes have been abolished. To do so, he admits, would require a leap. “If phasing out tobacco seems out of reach, this is only because our imaginations are impoverished.” And he has scant patience for the “Prohibition failed” argument. It failed, he says, because people like to drink. “Tobacco presents us with a very different situation. Nicotine is not a recreational drug. Most people who smoke wish they didn’t, and most smokers (90 percent) regret ever having started.”

Graphics Credit: http://www.prwatch.org/node/7004

The Tobacco Industry as Disease Vector

A review of The Golden Holocaust: Origins of the Cigarette Catastrophe and the Case for Abolition

Part II

The famous Surgeon General’s Report of 1964, officially warning Americans about the dangers of smoking, and publicizing the cancer connection, is typically seen as a triumphal moment in American medical history. But according to Stanford history professor Robert Proctor in his book, The Golden Holocaust: Origins of the Cigarette Catastrophe and the Case for Abolition, the report was “flawed in a number of interesting respects.” [The author, above, with paraphernalia] For one thing, members of the advisory committee consulting on the report, many of them congressman friendly to the tobacco cause, succeeded in their attempts to have smoking referred to as a “habit” rather than as addiction—a shameful Orwellian turn that went uncorrected for 25 years.

Meanwhile, the industry continued to fund new institutes, and continued to give out research grants for “red herring” research. As an example, the highest-ranking officer of the American Heart Association received money from one of the industry’s fraudulent research arms.

As late as the early 80s, most smokers believed they suffered from a bad habit, rather than an addiction—even though a majority of them wished they didn’t smoke. That is an odd kind of consumer “choice.” Cigarette makers have spent millions to perpetuate this myth. Proctor views tobacco industry executives and lawyers as a unique form of disease vector, spreading the pernicious health consequences of smoking across the globe.

The 2008 World Health Organization (WHO) Report on the Global Tobacco Epidemic fleshes out this metaphor, suggesting that all epidemics have a means of contagion, “a vector that spreads disease and death. For the tobacco epidemic, the vector is not a virus, bacterium or other microorganisms—it is an industry and its business strategy.”

In an email exchange, I asked Professor Proctor to expand on this notion of a disease vector:

“We tend to divide "communicable" from "non-communicable" diseases,” Proctor told me, “when the reality is that many "non-communicable" diseases are in fact spread by communications.”

Examples? “Through ignorance and propaganda, for example, which can spread like a virus,” Proctor wrote. “We don't count the anthropogenic communications, oddly enough, even though these can be just as dangerous, and just as deadly. And just as preventable--by changing our exposure environments.”

In a recent article for Tobacco Control, Proctor laid out how the calculus of the disease vector plays out. We know, for example, that smoking will cause roughly 6 million deaths in 2015. And about a third of those will be from lung cancer. We know that 25 acres of tobacco plants will result in about 10 lung cancer deaths per year, starting 20 or 30 years down the road. Here’s a sick equivalence: “A 40 ft container of the sort shipped overseas or trucked by highway houses 10 million cigarettes, which means that each container will cause about 10 deaths.” Proctor works out the numbers for the value of a human life:

“Cigarette companies make about a penny in profit for every cigarette sold, or about $10,000 for every million cigarettes purchased. Since there is one death for every million cigarettes sold (or smoked), a tobacco manufacturer will make about $10,000 for every death caused by their products…. The value of a human life to a cigarette manufacturer is therefore about $10,000.” 

Proctor has even produced a “factories of death” chart, illustrating that arguably the world’s most lethal production plant is Philip Morris’s Richmond cigarette facility, which churned out 146 billion cigarettes in 2010, which adds up to about 146,000 deaths per year.

By 1964, researchers at Harvard had already identified the presence of radioactivity in the form of polonium 210 in cigarette smoke, and the cry went up for safety. As for the notion of safer cigarettes, Proctor says all cigarette filters function the same way—“basically like drinking through a somewhat thinner straw.” He goes even further, arguing that “filters have reduced smoke particle size, producing cancers deeper in the lungs, making them harder to identify and harder to treat.” (Scientists determined that the radiation source was the newer “superphosphate” fertilizers being used heavily on tobacco plants.)

 Next came mandated “tar and nicotine numbers,” which turned out to be misleading measures obtained from smoking robots. Then, “an opportunity presented itself to game the system, as we find in the brilliant trick of ventilation.” Manufacturers pricked tiny holes in the paper near the mouthpiece of cigarettes brands like Carlton and True, which consumers got around by covering the holes with fingers or with “lipping” behavior. “Low tars were a fraud, just as “lights” would be,” Proctor writes. Smokers just smoked harder, or differently, or more frequently. In 1983, pharmacologist Neal Benowitz at UCSF broke the official news in the New England Journal of Medicine: Smokers got just as much nicotine, whether they smoked high-, low-, filtered, unfiltered, regular, light, or ultra-light.  The industry itself had known this for more than 20 years. “Nicotine in the actual rod was rarely allowed to drop below about 10 milligrams per cigarette,” Proctor asserts, “and no cigarette was ever commercially successful with much less than this amount.” (A Philip Morris psychologist compared nicotine-free cigarettes to “sex without orgasm.”)

Indeed, almost every design modification put in place by tobacco companies over the past century, from flue-curing to filters, has served to make cigarettes deadlier than before. “Talk of ‘safer cigarettes’ is rather like talking about safer terrorism, or safer smallpox, or safer forms of drowning,” Proctor concludes.

And the industry testing continues. The point of tobacco-sponsored research is not simply to discredit an individual researcher’s work, but to create an aggregate bias in the pattern of research—a lot of “noise” in the signal. In other words, “you basically fund lots of research to dispute a hazard, then cite this same research to say that lots of scholars dispute it.” We are told about “mucociliary escalators,” which dredge the tar up and out of smokers’ lungs. We learn that “a rabbit will scream if nicotine is introduced into the eye.” We read excerpts from anguished letters to tobacco companies: “Do you suppose if I continue to smoke Camel Ultra Light Cigarettes and I should develop cancer it will be ‘Ultra Light Cancer?’”

Proctor brings us up to date: Harm reduction, he writes, has become the industry’s new mantra. “The companies now want us to believe that less hazardous products can be and are being made and marketed.” Proctor thinks harm reduction “may end up causing even greater harm” if products touted as “safer” make smokers less likely to quit. As for public health campaigns, “consumers are encouraged to stop consuming,” Proctor writes, “but producers are never discouraged from producing.” Or, as Louis Pasteur once wrote: “When meditating over a disease, I never think of finding a remedy for it, but, instead, a means of preventing it.”

So, what comes next? A glimpse of the future may already be here, in the form of cinnamon- and mint-flavored Camel Orbs, “which look like Tic Tac candy and contain about a milligram of nicotine in a highly freebased form.”

As for the industry’s success in corrupting scientists and academics through various means, the story is just as bad as you think it is: “It would take many thousands of pages to chronicle the full extent of Big Tobacco’s penetration of academia; the scale of such collaborations is simply too vast. From 1995 to 2007 alone, University of California researchers received at least 108 awards totaling $37 million from tobacco manufacturers….”

Part II of III.

Photo Credit: http://theloungeisback.wordpress.com/

The Hidden Story of How Big Tobacco Invented Freebasing

Review of The Golden Holocaust: Origins of the Cigarette Catastrophe and the Case for Abolition.

Part I

It’s easy to think of cigarettes, and the machinations of the tobacco industry, as “old news.” But in his revealing 737-page book, The Golden Holocaust, based on 70 million pages of documents from the tobacco industry, Stanford professor Robert N. Proctor demonstrates otherwise. He demonstrates how Big Tobacco invented freebasing. He shows how they colluded in misleading the public about “safe” alternatives like filters, “low-tar,” and “ultra-lights.” We discover in Lorillard’s archives an explanation of menthol’s appeal to African Americans: It is all part of a desire by “negroes” to mask a “genetic body odor.” Radioactive isotopes were isolated in cigarette smoke, and evidence of the find was published, as early as 1953. He reveals that the secret ingredient in Kent’s “micronite filter” was asbestos. And he charges that the “corruption of science” lies behind the industry’s drive to continue its deadly trade. “Collaboration with the tobacco industry,” writes Proctor, “is one of the most deadly abuses of scholarly integrity in modern history.”

Half of all cigarette smokers will die from smoking—about a billion people this century, if present trends continue. In the U.S., this translates into roughly two jumbo jets crashing, killing everyone onboard, once daily. Cigarettes kill more people than bullets. The world smokes 6 trillion of them each year. (The Chinese alone account for about 2 trillion). Some people believe that tobacco represents a problem (more or less) solved, at least in the developed West.

All of this represents a continuing triumph for the tobacco industry. The aiders and abettors of tobacco love to portray the tobacco story as “old news.” But as Stanford Professor Robert M. Proctor writes in The Golden Holocaust, his exhaustive history of tobacco science and industry: “Global warming denialists cut their teeth on tobacco tactics, fighting science with science, creating doubt, fostering ignorance.”

Checking in at 737 pages, The Golden Holocaust is nobody’s idea of a light read, and at times its organization seems clear only to the author. But what a treasure trove of buried facts and misleading science Proctor has uncovered, thanks to more than 70 million pages of industry documents now online (http://legacy.library.ucsf.edu) as part of the Master Settlement Agreement of 1998. Once the material was finally digitized and available online, scholars like Proctor could employ full-text optical character recognition for detailed searchability. Ironically, this surreal blizzard of documentation was meant to obscure meaningful facts, not make them readily available, but tobacco executives seem not to have factored in digital technology when they turned over the material.

The single most important technological breakthrough in the history of the modern cigarette was flue-curing, which lowers the pH of tobacco smoke enough to make it inhalable. The reason few people inhale cigars, and very few used to inhale cigarettes, is that without some help, burning tobacco has a pH too high for comfortable inhalation. It makes you cough. But flue-curing lowered pH levels, allowing for a “milder,” less alkaline smoke that even women and children could tolerate.

World War I legitimized cigarettes in a major way. Per capita consumption in the U.S. almost tripled from 1914 to 1919, which Proctor considers “one of the most rapid increases in smoking ever recorded.” After World War II, the Marshall Plan shipped a staggering $1 billion worth of tobacco and other “food-related items.” (The U.S. Senator who blustered the loudest for big postwar tobacco shipments to Europe was A. Willis Robertson of Virginia, the father of televangelist Pat Robertson.)

The military, as we know, has historically been gung-ho on cigarettes. And Proctor claims that “the front shirt pocket that now adorns the dress of virtually every American male, for example, was born from an effort to make a place to park your cigarette pack.” In addition, cigarette makers spent a great deal of time and effort convincing automakers and airline manufacturers to put ashtrays into the cars and planes they sold. Ashtrays were built into seats in movie theaters, barbershops, and lecture halls. There was even an ashtray built into the U.S. military’s anti-Soviet SAGE computer in the 50s.

In the early 50s, research by Ernest Wynder in the U.S. and Angel Roffo in Argentina produced the first strong evidence that tobacco tars caused cancer in mice. Roffo in particular seemed convinced that tobacco caused lung cancer, that it was the tar rather than the nicotine, and that the main culprits were the aromatic hydrocarbons such as benzpyrene. Curiously enough, it was influential members of Germany’s Third Reich in the 40s who first took the possibility of a link seriously. Hans Reiter, a powerful figure in public health in Germany, said in a 1941 speech that smoking had been linked to human lung cancers through “painstaking observations of individual cases.”

In the December 1953 issue of Cancer Research, Wynder, et al. published a paper demonstrating that “tars extracted from tobacco smoke could induce cancers when painted on the skins of mice.” As it turns out, the tobacco industry already knew it. Executives had funded their own research, while keeping a close eye on outside academic studies, and had been doing so since at least the 30s. In fact, French doctors had been referring to cancers des fumeurs, or smokers’ cancers, since the mid-1800s. All of which knocks the first leg out from under the tobacco industry’s classic position: We didn’t know any stuff about cancer hazards until well into the 1950s.

Only weeks after the Wynder paper was published, tobacco execs went into full conspiracy mode during a series of meetings at the Plaza Hotel in New York, “where the denialist campaign was set in motion.” American Tobacco Company President Paul Hahn issued a press release that came to be known as the “Frank Statement” of 1954. Proctor calls it the “magna carta of the American’s industry’s conspiracy to deny any evidence of tobacco harms.” How, Proctor asks, did science get shackled to the odious enterprise of exonerating cigarettes? The secret was not so much in outright suppression of science, though there was plenty of that: In one memorable action known as the “Mouse House Massacre,” R.J. Reynolds abruptly shut down their internal animal research lab and laid off 26 scientists overnight, after the researchers began obtaining unwelcome results about tobacco smoke. But the true genius of the industry “was rather in using even ‘good’ science, narrowly defined, as a distraction, something to hold up to say, in effect: See how responsible we are?”

Entities like the Council for Tobacco Research engaged in decoy research of this kind. As one tobacco company admitted, “Research must go on and on.”

A good deal of the industry’s research in the 50s and 60s was in fact geared toward reverse engineering competitors’ successes. Consider Marlboro. Every cigarette manufacturer want to know: How did they do it? What was the secret to Marlboro’s success?

As it turns out, they did it by increasing nicotine’s kick. And they accomplished that, in essence, by means of freebasing, a process invented by the cigarette industry. Adding ammonia or some other alkaline compound transforms a molecule of nicotine from its bound salt version to its “free” base, which volatilizes much more easily, providing low-pH smoke easily absorbed by body tissue. And there you have the secret: “The freebasing of cocaine hydrochloride into ‘crack’ is based on a similar chemistry: the cocaine alkaloid is far more potent in its free base form than as a salt, so bicarbonate is used to transform cocaine hydrochloride into chemically pure crack cocaine.” Once other cigarette makers figured out the formula, they too began experimenting with the advantages of an “enhanced alkaline environment.”
  
(End of Part I)

Photo Credit: http://theloungeisback.wordpress.com/