Probably the biggest misconception about immunology is that it can be fully understood by studying it in isolation. Preventing us from fully understanding basic physiology, silos dominate our current approach and we study systems separately. Only when endocrinologists, neurologists and immunologists working together becomes the norm can we hope to fully understand how basic physiology differs between health and disease, and only then will our medicine be truly curative.
Research since the 1960s has yielded tremendous mechanistic insight into the major players of the adaptive immune system, the T and B cells, their rules of development and activation, since the 1990s, into the innate immune system and how it underpins the adaptive and so on but as to how the system works within the body, with the neuro and endocrine systems in particular, that’s still largely a mystery because of our siloed approach.
Consider nutrition advice for example. Any given day, we likely see an ad or two on TV exhorting tremendous health and immune function benefits from taking some type of supplement or eating some kind of food. These claims are hardly ever backed by rigorous, reproducible science. We know so by the repeated publication of contradictory observational, correlational studies. Does Vitamin E lower or increase prostate cancer risk? Replace intervention and condition with those from a random news headline of the past few years and same could be said for any number of interventions and conditions. Does blank lower or increase blank risk? Likely beneficial in some, apparently neutral or even harmful in others. We’re no further in our understanding. How do we figure out and predict exactly in whom an intervention is likely to be effective? We don’t have a clue and yet we’ve all heard about theeffect ( ). Placebos induce real physiological responses such as changes in blood pressure, brain activity and heart rate, and produce curative effects in conditions ranging from anxiety, depression, pain, even Parkinson’s. In other words, where brain involvement is unmistakably clear. But that’s not all, since innovators outside the mainstream can now show its effects even in conditions such as psoriasis ( ).
The placebo effect can only be understood from studying the overlap of immune function with neuro and endocrine, an overlap that’s part and parcel of nature. How do stress hormones like noradrenaline influence immune function (), how does sleeping after vaccination boost immunological memory ( ), how does meditation improve antibody response to influenza vaccine ( ), the questions are endless.
Every 10 years or so, a spectacular result from studying them together will make it to the front pages of mainstream, prestigious science, there’ll be a buzz and then it dies down unable to sustain the momentum as the silos continue on largely undisturbed. One famous example to make the point. In 2000,showed that simply stimulating the could prevent rats from going into septic shock after they’d been injected with lethal endotoxin designed to do just that ( ). Stimulate the parasympathetic pathway (vagus) this way and you can even prevent what should be irreversible trajectory to death. Isn’t that goose-bump worthy remarkable? As well, a profound insight into disease itself. More often than not, the enemy’s within, in the form of unrestrained, fulminant over-reaction. How to guide our responses so they’re more precise and better controlled? Tracey’s results hint at one of the paths ahead. >15 years later, shouldn’t we be closer to have this result be practicably useful for the thousands who die every year from septic shock? Not even close. Of course, being a big name, Tracey’s an exception in sustaining his remarkable streak of innovative, interdisciplinary discovery but the rank and file of endocrinologists, neurologists and immunologists continue mining their silos. To paraphrase Reagan, ‘Tear down those walls already!‘.
Of course, the placebo effect is ruinous for medicine and pharma. It ruins the smooth trajectory of drug development pipeline, weakens effect of promising drugs, and is perceived an overall nuisance. Only if we stick to the orthodoxy though. How about we flip the proposition on its head and instead see the placebo effect as a net opportunity? If we took the effort to scientifically decipher the placebo effect, we’d know when just a sugar pill could do the trick. Heal thyself indeed! Cost savings aside, so many of us would be saved as well from toxic side-effects that are part and parcel of so many drugs. Scientific understanding of the placebo effect could potentially revolutionize medicine, make it much more effective, less costly, safer and more precise. In fact promise of so-called precision medicine is never likely to be fulfilled unless and until we understand how placebos work. Were I a multi-billionaire looking to fund a pet project likely to leave an immeasuarble lasting legacy, I’d do what NIH and other funding agencies currently don’t do, and figure out a way to sustainably fund an interdisciplinary research ecosystem to understand the placebo effect. All of humanity, not just some group here or there, would benefit.
1. The Placebo Phenomenon. An Ingenious Researcher Finds The Real Ingredients Of ‘Fake’ Medicine. Cara Feinberg, Harvard Magazine, Jan-Feb, 2013.
2. You Can Train Your Body Into Thinking It’s Had Medicine. Jo Marchant, Mosaic Science, 9 Feb, 2016.
3. Lange, Tanja, et al. “Sleep after vaccination boosts immunological memory.” The Journal of Immunology 187.1 (2011): 283-290.
4. Davidson, Richard J., et al. “Alterations in brain and immune function produced by mindfulness meditation.” Psychosomatic medicine 65.4 (2003): 564-570.
5. Borovikova, Lyudmila V., et al. “Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin.” Nature 405.6785 (2000): 458-462.