Chapter 1

I suppose it was because Dr. Clark had been so dismissive that what I was trying to pursue did not follow the path of his current pet theory that made me so angry. I had results that showed that something was happening, but it didn’t support his line of research so he told me to stop, and in fact chewed me out for wasting resources.

And I had to stand there and take it, while the others in the lab tried to pretend that they were too busy to hear it. They’d all been publicly embarrassed by him at one time or another, so they knew what I was going through.

Clark had had one major breakthrough about a dozen years ago and rode it all the way up to research director, and in the process convinced himself that no one else knew what they were doing. So we -- accumulated Ph.D.’s notwithstanding -- were treated like lowly grad students.

My name would be useful, I guess. I’m Sam Halloran, Ph.D. My mother was fond of using the title when talking about me to her friends. “My son, the doctor.” She would have preferred that it had been an M.D., but was willing to settle provided she could invoke the honorific to impress her acquaintances.

I had done a postdoc after finishing my degree in molecular biology and biochemistry, and through a friend-of-a-friend-of-my-postdoc-supervisor had been offered a research position here at Rayleigh-Brown Pharmaceuticals.

I’ll call them RBP just to save my fingers. They had a pretty wide range of products, some available to the consumer, some specific licensed and targeted drugs intended for use by physicians in the treatment of disease or amelioration of symptoms. The problem with patented drugs is that it takes years before all the clinical trials are over, the results submitted to the FDA, and (hopefully) approval received to manufacture and sell.

A long and expensive process before you earned the first dime back. And the fixed term of the drug patent starts when you first submit the application, not when you first start selling it. So after all is said and done, you might get ten years of exclusive rights to earn your research money back, as well as your profits.

So pharmaceutical companies were always researching new drugs, hoping they could find a lucrative new one before the competition did and before the patents on their current ones expired. And that is part of what drove Bernard Clark, Ph.D., to wield the whip to keep us focused on the one, true research path. His path.

Nothing wrong with that, I suppose. Focus is good. But science is not always linear. Some of the greatest discoveries in science have been the result of mistakes, accidents and lucky breaks. Goodyear’s discovery of vulcanizing rubber. Fleming’s accidental discovery of penicillin. August Kekulé’s concept of the benzene ring, which came to him in a dream and which opened up the huge field of organic chemistry. The list goes on. But Clark was convinced he had a similar vision, which few of us in the lab shared, but were too cowardly to call him on.

So we did as we were told, hoping that he would stumble and fall, and a more open-minded research director might take his place.

RBP’s latest focus was on the expanding field of drug addiction treatment, specifically the drugs that are used to mitigate the effects of opioid and stimulant addictions. Big bucks, if you have a treatment that doctors prescribe routinely. We were looking for something that was better than -- and if not better than, at least different from, so RBP could patent it -- the commonly available choices like methadone, buprenorphine, and naltrexone.

Clark had his pet theory which involved blocking the opiate receptors, like the commonly used treatments, but in a slightly different way. No way to say if it would be a better approach, but it would a patentable approach, and that’s what counted.

I got into science originally because I admired the purity of it. That naive concept was pretty much gone by the time I received my degree. But part of me still held on to the excitement of discovering something new, something so radical as to upend my small corner of science.

And I thought I had. I had been fascinated in grad school with the idea of how the brain learns to focus attention, and its corollary, how it suppresses stimuli that distract the brain’s focus. We’ve all had those moments, where we’re so wrapped up a ball game that we don’t hear a family member trying to call us to the phone, or so immersed in a piece of music that we can’t hear someone knocking on the door right next to us.

You can sometimes induce those states via hypnosis in people who are susceptible to hypnosis -- but not in those who aren’t. I’ve always thought that those states of hyper-focus are biochemical, as is almost every process in the body and brain. Hypnotists just find ways of stimulating them externally. I had wondered if there was a more specific biochemical approach.

The brain is an astoundingly intricate machine, and science knows about ten percent or less of how it works. There are certain areas of the brain that are localized enough so that we know what will happen if that area is damaged -- loss of vision or smell, for example, or a reduced ability to process complex ideas, or loss of short-term memory. There’s no way yet to fix those things when that area of the brain is damaged.

Less well known is how inputs are processed, categorized, and transferred to the proper part of the brain that handles that type of data. By trial and error, addiction scientists have deduced how certain drugs hook into the brain to produce that rush and feeling of well-being that addicts crave. And science has produced some drugs that inhibit the ability of addictive substances to attach to the brain’s receptors. But the treatments almost always have side effects, or they lose their effectiveness over time.

Clark’s approach, we thought, would be similar to the existing treatments, perhaps with a different set of side effects. It wouldn’t be a big leap forward, but it would make the company lots of money when it finally works. If it works.

I had been thinking for a long time about the brain’s ability to focus and to turn off stimuli under certain circumstances, much like a hypnotist could convince you that your arm was no longer subject to gravity and would float upward if you let it. The subject’s body ignores its own signals of weight and gravity and seems to rise of its own accord.

Or the hypnotist could convince us to ignore our body’s temperature sensors, and tell us that the temperature in the room had suddenly dropped to ten below zero. Our body would break out in goosebumps and begin shivering violently. The brain was told to ignore its own data concerning ambient temperature and to substitute the hypnotist’s observation.

We’ve all seen these theater and television acts, and we all marvel at the hypnotist’s ability. But underneath the entertainment there’s a scientific fact: The brain’s biochemistry is making this happen. There is a process occurring that allows the brain to block certain stimuli, and allow others to pass unaffected. That is not a hypnotist’s parlor trick; that’s science. And I thought that if the mechanism was understood at a biochemical level we could perhaps block the cravings that the body produced. And if that concept worked, it would also be applicable to most any kind of addiction -- opiates, tobacco, stimulants like methamphetamine, even caffeine!

Of course, the path between idea and application is a long and rocky one, but I thought the idea held some promise. And in fact I had synthesized some preliminary samples and had tested them in mice with promising results. I would dose them with a small amount of the sample and then do an MRI of their brains. The results were just what I had hoped. The place in the amygdala where emotions are processed became static, no activity at all. Activity returned, apparently normally, shortly thereafter.

To prove that this was what was actually happening, I did an experiment that attempted to block all emotions, albeit temporarily. I did this by training some lab mice that they could get a kind of treat that they enjoyed by going to several locations within their box and pressing a button. But one of those locations also produced a powerful but non-lethal shock while dispensing the treat. Over time all the mice learned to avoid that one location. I put the test drug into an aerosol dispenser and sprayed it into the cage.

The mice looked slightly dazed when the dose hit them, but soon recovered and went about their normal routine. Except that they now visited the previously electrified dispenser for treats, as well as the other dispensers. I had deactivated the current so they didn’t get a shock, but their learned fear should have told them to avoid that one.

After some time, the effects of the drug seemed to wear off and they did begin avoiding that dispenser again. I had interpreted that as a temporary suppression of learned behavior -- fear -- and that it was the drug that had caused it. I tried the experiment a few more times, each time with a slightly different configuration, ruling out that it wasn’t just a temporary loss of memory that caused them to revisit the hazardous dispenser, until I was pretty sure about what I was seeing.

But Dr. Clark did not share my vision and called it a waste of time and resources, reading me the riot act. He gave me the ‘cease and desist’ speech and told me to get back to real scientific work. Jerk.

So I did what most scientists would do in my position; I ignored him. I was careful about it. I hid my lab notes and working samples and did enough of “his” work to justify my position in the lab.

And by increments, after most everyone had gone, or on the weekends, I continued to work on my compound, tweaking it, refining it. I started keeping lab mice at home, building a sealed plastic pen for them, with a built-in aerosol dispenser to administer the latest drug sample.

And as I thought on what the drug was doing and how it might be used to treat addictions by blocking the pleasurable response from the alcohol, the heroin, the nicotine, and so on, I came to realize that there was an important component missing in my compound.

While the mind responds viscerally to these stimuli and cravings, a drug that simply blocks the craving will need to be taken continuously, much like methadone is used to alleviate the cravings that arise from heroin addiction. Until you go through withdrawal, you are still a slave to those cravings; the methadone simply abates it for a while.

What was missing, I mused, was something that allowed the mind to assist in the “detoxification” process, a suggestion that embeds itself strongly in the unconscious to tell the body that it no longer needs the addictive substance.

So my compound would need to be used in a doctor’s or a counselor’s office, who would implant and reinforce the command that the subject no longer needed the satisfaction that they derived from the use of the addictive substance. You could sometimes attain the same result by sitting through years of therapy with a psychiatrist. This process promised to be much cheaper and much faster.