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|Posted on June 8, 2014 at 9:17 AM||comments (91)|
Steve Cole, Phd one of the pioneer researchers in the new field of psycho-immunology, delivers the Meng Wu Lecture at CCARE Stamford University. Watch it here.
My transcript of Steve Cole's lecture:
How we interact, how we connect has a tremendous influence on how our genes are expressed. Traditionally we saw ethics, morality and the world of tangible, molecular biology of cells as very different worlds/domains. We are starting to see the shadow of each domain playing out in the other.
Gene expression and social factors
The genome isn’t expressing all its 20.000 genes at the same time. There is a lot of decision about which genes get expressed. The change of the activity of genes within our white blood cell is linked to
protracted, extended situations:
The stress-response and the genome
From a study by Irwin and Comle, Nature Reviews, Immunology, 2011
One of the major ways in which these experiences play on the genome is through the fight-flight stress response activated by the sympathetic nervous system, with the release of adrenaline (epinephrine) and noradrenaline (norepinephrine). Noradrenaline is released in the vicinity of a cell. Through its nteraction with receptors (ADRB2) on the surface of the cell the result is a pumped-up activity of genes involved in the expression of pro-inflamatory immune response genes and a stomping down of the activity of other genes (antiviral immune response genes).
Through exposure to really overwhelming stress a second response kicks in – a defeat/withdrawal response, where your system shuts down, you are overwhelmed and your body hunkers down and just tries to survive. That response is mediated by a second hormonal pathway - the HPA (Hypothalamus - Pituitary - Adrenal). The hypothalamus tells your adrenal glands to produce more cortisol, which has a different impact on gene expression – it lowers the expression of antiviral immune response genes and lowers the expression of pro-inflammatory immune response genes.
Different experiences of the same event – either as a challenge that can be overcome or as something profoundly overwhelming is going to have different effects on my genome, it will evoke different kinds of biological response.
Studies by Cole et al. Proc Nat Acad of Sci USA, 2011 and Powell et al. Proc Nat Acad of Sci, USA, 2013
Our bodies are extremely dynamic at a cellular or molecular level. The average protein in the human body has a half-life of eighty days so that every single day we have to replace 1 – 2% of the proteins in our body and that process is open to ‘advice’ from the world outside the body, including the world that psychology creates in my mind.
Gene expression can also catalyse the production of new cells (monocytes and dendritic cells which don’t live very long). This process is also orchestrated by changes in gene expression that are susceptible to regulation by the nervous system. In people who are confronting uncertain environments, the brain interprets those environments as threatening and activates these fight-and-fight responses.
Norepinephrine signalling is delivered into the bone marrow in a form of a ‘piece of advice’ to the stem cell which says 'produce more myeloid cells: monocytes, granulocytes, dendritic cells'. As a consequence of that we have more of these cells going out into the body and circulating. For most of our development that made good sense but if there is nothing for those cells to respond to - because there is no physical injury and hence no bacterial infections. These cells are programmed to find trouble and do something about it. Some of the trouble they find might be the early stages of proliferation of cancer or damage to the wall of our blood vessels or minor damage in brain cells, all of which attracts these charged, primed immune cells. As these cells attempt to repair tissue damage but can inadvertently contribute to the sort of disease that nowadays are the true architects of our longevity . We no longer die of infectious disease, we now die of heart disease, cancer and neuro-degenerative diseases.
(Sloan et al. 2010 Cancer Research – done on a mouse injected with cancer cells and then confined to a small space – a stress inducing situation)
When animals have too many of these charged up monocytes in their body during the early stages of tumour-development they get many more cancer cells escaping from the initial tumour site and spreading out (metastasising). This is mediated by those immune cells, which having gone into the tumour to kill the microbes and repair damaged tissue. They liquify tissue so that the cancer cells can grow out, they help grow blood vessels into the tumour thus feeding it and suppress the rest of the immune system’s response to the growing cancer.
Psycho-social events alter our biology
We used to think of the brain and the immune system as separate it turns out that what is going on in the world has some association with what goes on in our body at a microbial level. Over millions of years our immune system has learned to listen to the chatter from the brain and if it hears indications that you are feeling substantially threatened it gets ready to deal wit tissue damage, whether tissue damage is happening or not and inadvertently it fertilisers diseases and becomes the architect of a host of problems.
- Central nervous system: inflammation and neuro-degenerative disease
- Vasculature: artherosclerosis
- Lungs: URI, asthma
- Lymphoid tissue: neoinnervation, HIV/SIV
- Solid tumor in the breast, ovaries: metastasis
That is why so many different types of adversity (isolation, low SES, social threat, bereavement) seem to draw out disease. There are many different ways that humans have learned to feel threatened and stressed.
Attachment and isolation and how the body responds to stress
There are two different ways to run our bodies which correspond to two social genomic programs in immune cells. One operates in a world in which we are attached and safe, connected. In this the big threats that we confront are the diseases that travel from one to another (viruses). A separate modus operandi takes place in the context in which we are separated from our community or feel threatened within our community, which up-regulates these inflammatory genes which produce monocytes, geared to fight bacteria (in anticipation of tissue damage). It doesn’t help us as well because it fertilises chronic diseases.
Hedonic versus eudaimonic happiness
What is the secret to making people feel genuinely safe? (Frederickson et al., PNAS, 2013) How should we live? What is the best way to thrive in human life? What is the nature of true happiness. Hedonic happiness: consuming happy experiences (Epicur). Eudaimonic happiness: satisfaction that derives from a deeper sense of making a contribution to a purpose or a group outside ourselves, a community, a cause, creation, discovery. It turns out that either eudaimonic or hedonic pursuits are correlated to low levels of depression, but when researchers asked the genome, eudaimonic happiness is correlated with healthy immune profiles whereas hedonic happiness is not.