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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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December 18, 2008

When Placebos Were All There Were

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Posted by Derek

Yesterday's discussion of how to deal with various forms of pseudoscientific hoo-hah naturally brought up several mentions of the placebo effect. And that prompts me to bring in the late Lewis Thomas's The Youngest Science, his memoir of a life in medicine. We should never forget that there was a time, not all that long ago, when drug therapy was almost all placebos. Here's a description of the way Thomas's father practiced in the 1920s:

Nevertheless, despite his skepticism, he carried his prescription pad everywhere and wrote voluminous prescriptions for all his patients. TThese were fantastic formulations, containing five or six vegetable ingredients, each one requiring careful measuring and weighing by the druggist, who pounded the powder, dissolved it in alcohol, and bottled it with a label giving only the patient's name, the date, and the instructions about dosage. The contents were a deep mystery, and intended to be a mystery. The prescriptions were always written in Latin, to heighten the mystery. The purpose of this kind of therapy was essentially reassurance. . .They were placebos, and they had been the principle mainstay of medicine, the sole technology, for so long a time - millennia - that they had the incantatory power of religious ritual. My father had little faith in the effectiveness of any of them, but he used them daily in practice. They were expected by his patients; a doctor who did not provide such prescriptions would soon have no practice at all. . .

That's the world as it was. Thomas later recounts the profound shock he experienced as an intern when sulfanilamide was introduced: patients given up for dead got up out of their hospital beds and asked for something to eat. It was then, he says, that he realized that the medical profession he was entering might be turning into something different from what his father knew.

We should never forget: it's our job to make our children look back on today's medicines with the same mixture of pity and alarm. To cure disease, stop the damage, make people given up for dead stand up and walk out of the room to see their families. Things aren't going very well for us now in this business, because these are all very hard things to do, and the amount of time and money needed to do them is nearly unbearable. But not quite. We can see that such things are possible, and it's up to us to figure out how to make them real.

Comments (17) + TrackBacks (0) | Category: Drug Industry History


1. Robert Bruce Thompson on December 18, 2008 11:03 AM writes...

Well, perhaps not "almost all placebos". There were, after all, numerous powerful and useful natural and synthetic drugs available in the 1920's, including aspirin, morphine, codeine, and other opium-based drugs, not to mention quinine, atropine, cocaine, and various other useful alkaloids.

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2. Derek Lowe on December 18, 2008 11:22 AM writes...

It's true, there were a few. Thomas describes the contents of his father's medical bag:

"Morphine was the most important, and the only really indispensable drug in the whole pharmacopoeia. Digitalis was next in value. Insulin had arrived by the time he had been practicing for twenty years, and he had it. Adrenalin was there, in small glass ampules, in case he ran into a case of anaphylactic shock; he never did."

But overall, the number of useful drugs in that era could probably be counted on the fingers.

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3. milkshake on December 18, 2008 12:10 PM writes...

"if the whole materia medica, as now used, could be sunk to the bottom of the sea, it would be so much the better for mankind – and all the worse for the fishes" Oliver Wendell Holmes

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4. Hap on December 18, 2008 1:01 PM writes...

I don't know if the Wikipedia article on the placebo effect is accurate, but if it is the placebo effect would seem too limited to be useful - 30% (or less) success rate, unpredictability, dependence on disease, and temporary effect all seem to make it not a very treatment option on which to to bet your health or life.

We don't really know what can or can't be done - it's possible that some diseases can't be cured, at least not with drugs. The conviction to ask what may work and to actually listen to the answers, however, is the crucial gift of scientific research in general (and what appears to be problematic or missing in the people and companies selling various alternative drugs).

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5. on December 18, 2008 2:56 PM writes...

"We should never forget: it's our job to make our children look back on today's medicines with the same mixture of pity and alarm."

While this is fully true, I've always felt that it is even more so with mental illness. We've come a long way from Bedlam, but still have so far to go.

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6. Robert Bruce Thompson on December 18, 2008 4:00 PM writes...

How could I have forgotten marijuana, which seems to have many potentially valuable characteristics? I'm 55 years old, and I somehow made it through high school, college, and grad school in the late 60's and early 70's without ever smoking grass or doing any other illegal drugs. Maybe I missed something.

A question for Derek? Is big pharma doing anything to explore marijuana and derivatives, or does the legal status of marijuana effectively bar such research?

And I'd love to hear your thoughts on DCA. After the initial flurry of articles, there hasn't been a lot published that I'm aware of. When I read the paper in Cancer Cell, I thought we might finally have a real breakthrough. Any thoughts?

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7. Sili on December 18, 2008 4:01 PM writes...

The deep irony of this age is that people rejected the idea of the paternalistic, condescending family doctor and now we as
patients are informed of all pros and cons (well - I have been and it suit my personality).

But the selfsame people making these objections are now seeking out quacks who give them a cuppa, a pat on the head and some red sugarpills.

It works - the trouble is it works by lying to people and filling them with woo without any connection to reality. It makes people believe in magic and as such it makes for trouble in the long run.

In truth many GPs could be relieved of oodles of patients if only the NHS would finance little old ladies to serve tea an biscuits in the waiting area and allow them plenty of time to have a nice chat before seeing the doctor.

But that's not 'rational' and as such it's cut away as a waste of money.

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8. G Experiment on December 18, 2008 4:06 PM writes...

In similar manner to the placebo effect, I have heard that intention can also effect the result of an experiment. Makes me wonder if our assay results could be skewed by the operator's mood, especially when there's no control used.

Never underestimate human's powerful mind.

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9. Dlib on December 18, 2008 4:28 PM writes...


Recently they've done away with the drugs that would've stopped my munchies!!!

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10. satan on December 18, 2008 5:08 PM writes...

I have always believed that the real problems in prescribing medicines, as opposed to discovering them stem from just a few self-inflicted problems.

1] Lack of public education: Medicos are not willing to explain concepts/ drug mechanisms to people of limited technical background. Maybe, they are not sure either..

Ex- Compliance for chronically used drugs (anti-hypertensives and even anti-psychotics) is much higher if the patients understand the need and basic mechanism of the drugs they use. Shifting them to the best tolerated drug is also a good idea that is seldom practiced.

2] Lack of humanity towards the patients: The biggest reason that alternative medicine thrives is that the mainstreams medicos do not treat their patients as human beings.

Ex- Look at how we treat patients in the final stages of various terminal cancers! We do not prescribe enough opiates to control pain, refrain from prescribing amphetamines to counteract some of the less desirable effects of opiates. Often we let patients starve to death rather than have adequate legal mechanism to perform adequately documented patient-requested euthanasia.

We treat out pets with more humanity.

3] Lack of humility: Do not pretend to be god and accept your limitations. Do not blame your patients.

Ex-How many doctors blame patient lifestyle for their health problems when there is a lack of well done trials to support their opinions?

Does BMI correlate linearly with mortality or morbidity? Does fast food consumption increase mortality in humans under the vast majority of conditions? Does reduction in salt intake cause sustained reduction (> 6 months) in hypertension in most people? Why do low fat diets make people gain weight?

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11. CMC Guy on December 18, 2008 5:14 PM writes...

#6 RBT re marijuana I believe there was much research conducted (industry and academia) in the 70s-80s, particularly around THC the most active ingredient (was a Total Syn Target for a couple groups to platform novel reactions too I recall), directed toward a number of diseases with little that bore actual new drugs that I am aware of. I even think a pure chemical form of THC was/is approved for treatment of Cancer Patients (anti-nausea?) although costs/availability of street/medical growers and better tolerance/preference of smoked administration make non-profitable venture which can often be the case.

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12. milkshake on December 18, 2008 6:18 PM writes...

THC is available in US by prescription, its called Marinol but it is less active for treating nausea and appetite loss than cannabis, and seems to have more unpleasant psychoactive effects than pot.

Otsuka is developing Sativex for US market, and is in late stages of the approval process (with good phase III data). Sativex is legal in Canada and UK (by prescription). Sativex is a mouth spray pump that contains a cannabis extract with standardized concentration of THC and Cannabidiol, and so far seems just as good as medicinal pot.

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13. Anonymous BMS Researcher on December 18, 2008 9:01 PM writes...

In one of the Star Trek movies the crew time-traveled back to late-20-century San Francisco, and when an injured Chekov is in a hospital Dr. McCoy exclaims "we can't leave him in the hands of twentieth-century medicine!"

There's also a cool scene where Scotty builds and rotates 3-dimensional molecular models on an early Macintosh computer, something I can easily do on my laptop today but preposterous for a Mac of that era.

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14. DrSnowboard on December 19, 2008 5:40 AM writes...

as referred to above as the anti-munchies drugs.

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15. A Nonny Mouse on December 19, 2008 1:08 PM writes...

And the French are still at it- a great article from the BBC

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16. kieth on December 20, 2008 6:26 PM writes...

A few years ago a columnist for the Wall Street Journal (Holman Jenkins) theorized that as an investment in overall health conditions placebos were marvelously effective. As I remember it Mr. Jenkins compared the staggering investment in the sorts of drugs Derek writes about against the near zero investment a placebo requires. And compared the results.

Well, his argument was clearly not entirely serious but it is an arresting thought.

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17. Morten G on December 23, 2008 9:47 AM writes...

Well to replace the entire drugging/treating patients with placebo we would have to find out who actually responds to placebo.

Look to Science!

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