The Placebo -Not Easy to Placate A Chemist!

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(Shankar Melkote)

Not long ago, homeopathy was practised quietly. Not many people knew about it. It was only the adventurous willing to try a system that deals with tinctures and white pills. Recently, the practitioners have become more confident in the success of their medicaments and are putting up prominent signboards and advertising in the media. Nobody seems to know why the system works and there have been some feeble attempts to give homeopathy the status of evidence based medical practice. But users aren’t interested in how it works; it is enough for them that it works. This could also be the attitude of users of other apparently “unproved” systems of medicine

From its relatively unobtrusive closet existence, homeopathy has recently been dragged into the news. A report in the Hindustan Times (January 7, 2016) quoted Venkatraman Ramakrishnan, who shared the Nobel prize for chemistry in 2009 with two others,as dismissing homeopathy as ‘’bogus’’, and saying: “No one in chemistry believes in homoeopathy. It works because of placebo effect.”

The laureates Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath showed via 3-D modelling, how ribosome looks like and functions as it translates DNA at the cellular level.

Based on DNA information, ribosomes make proteins such as haemoglobin that transports oxygen, antibodies of the immune system, hormones, keratin, the molecular substrate for skin and hair, enzymes in the digestive tract and so on.

In treatment of disease, blocking the replication of a bacterium that has colonised an organ and is causing it to malfunction – by impeding ribosomal function – might prove to be a remedial measure. Ramakrishnan and the others showed how different antibiotics bind to the ribosomal assembly line. Their important work could lead scientists to develop new antibiotics, saving lives and decreasing human suffering.

Coming back to homeopathy, if the Hindustan Times’ report is accurate, then the Nobel laureate has acknowledged that homeopathy does work, although he intended his remarks to have the opposite effect of dissuading its users. Also, by saying it works because of the placebo effect, he has inadvertently commended it. The placeboeffect is not something to be easily dismissed. I shall tell you why.

A placebo is any substance or measure that a doctor or anybody presuming to treat a patient administers to make the patient happy. Especially when the doctor is helpless. Placebo in Latin means “I please”. Powdered sugar or a pinch of pounded cereal or a few drops of plain water could be placebo. It could simply be any substance that is known not to have any pharmacological effect.

But placebo has been shown to work, even clinically.

In the words of placebo researchers Ted J Kaptchuk and Franklin G Miller, reportingtheir findings in The New England Journal of Medicine (quoted originally by Sara Adaes in her blogBrain Blogger): “[But] placebo effects are …not bogus… Of course, placebo effects are modest as compared with the impressive results achieved by lifesaving surgery and powerful, well-targeted medications. Yet we believe such effects are at the core of what makes medicine a healing profession.”

The placebo response, it appears,is mediated by the senses, perception, experience, culture, and how we understand the “ritualistic” context in which it is administered; by a sequence of psycho-neurobiological mechanisms. For instance, utterance of words that prompt anxious memory associations wouldcause the brain to trigger the production of stress hormones. Utterance of words that are soothing and reassuring could cause the body to produce relaxing chemicals such as oxytocin. The words are important; the way they are spoken in important; so too tone and body language. Indeed, the entire ritual is of great importance to placebo.

Another placebo researcher, Fabrizio Benedetti of the University of Turin, believes that therapeutic rituals move the same molecules in the patients’ brain thatare also activated by the drugs given in routine clinical practice. These rituals, and drugs,“use the very same biochemical pathways to influence the patient’s brain.”

Continuing the analogy of the ritual, researchers found that a blue pill works better than a white one; a capsule works better than a pill; and, a syringe needle better than a capsule. Also, a higher dosage works much better than a lower one.

Assuring words such as, “This is definitely going to make you better,” when uttered with conviction can go a long way. Indifferent words or words that purport to tell the patient the “truth” about his condition act as nocebo – the opposite of placebo. Especially officious words such as, “the chances of your getting better are proven across clinical studies to be 15 per cent and all I can give you is hope,” are definitely nocebo-triggering.

Evidence gathered over five or more decades has shown that the body is capable of healing itself. The Spontaneous Remission Project compiled a database of patient who had experienced remission of their symptoms when exposed to ritualistic placebo treatment in the best sense of the term. They included patients suffering terminal cancer who recovered as if by miracle. And too there were patients with blocked bronchi or severe ulcers.

Ted Kaptchuk, who has founded the world’s only multidisciplinary institute focusing on the therapeutic effects of placebo, is working with his team to see if the placebo effect can be enhancedon the same lines that drug design companies do research to see if the efficacy of the drug can be enhanced.

Kaptchuk, a practitioner of Traditional Chinese Medicine, was led to placebo study by a curious observation: that his patients got better even before he started acupuncture treatment. Over the years, working with patients suffering from Irritable Bowel Syndrome (IBS), he has found that increasing attention and caring bring the most relief, pointing to a possible quantification of placebo. Not letting go of challenges easily, Kaptchuktold his patients they were receiving a placebo and even then they got better; it was only that they were told that placebos often enhance healing.

The placebo is obviously related to the plasticity of the brain and is a byproduct of the workings of the parasympathetic nervous system – the healing counterpoint to the sympathetic nervous system that helps fight or flight or freeze, on occasion. To judge something that is so evolving and dynamic from the congealed point of view of crystallography would be limiting to say the least. It is somewhat of a conundrum that while crystallography can shed light on the dynamics of ribosomal site binding to the DNA, which indeed brought Ramakrishnan the Nobel Prize, there is an absence of suspension of disbelief about healing systems. Indeed, it is the plasticity of the brain that is responsible for much healing that happens is being, drug-induced or placebo-induced.

The human body is extremely complex. There are many things about its functioning and healing mechanisms that are counter intuitive and, hence liable to be termed and dismissed as “unscientific”.

It might just be the thing not to grudge sleeping dogs their sweet slumber!

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