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Connection, Compassion and the Genome

Posted on June 8, 2014 at 9:17 AM Comments 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:
  • Low SES (social-economic status) 
  • Social Loss/ Anticipated bereavement
  • Post-traumatic stress
  • Cancer diagnosis
  • Social threat
  • Loneliness
  • Social instability
  • Chronic stress
  • Low social rank
  • Caregiving for seriously ill
  • Depression
  • Early life low SES
  • Poverty

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.

Cancer 

(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.  

The nature of communication in the talking cure.

Posted on January 12, 2014 at 6:36 PM Comments comments (106)

Mark Solms is the director of the Arnold Pfeffer Center for Neuro-Psychoanalysis at the New York Psychoanalytic Institute; a lecturer at the University College Londons Department of Psychology; a consultant in neuropsychology at the Anna Freud Center in London; and an honorary lecturer in the Academic Department of Neurosurgery at St. Bartholomews and the Royal London School of Medicine. Over the last 15 years, Dr. Solms has been the driving force in establishing the new field of neuro-psychoanalysis, which brings together the fields of neuroscience and psychoanalysis.

What is the nature of communication between the analyst and the patient 

Defining psychoanalysis as "the talking cure" is somewhat misleading, a misnomer. We have the mystical-sounding phrase from Freud about the communication from the unconscious of the patient to the unconscious of the analyst. We speak of empathic attunement and projective identification as a form of communication between patient and analyst, which is reflected in the countertransference. The nature of communication in the analytic room somehow fails to be conveyed in the words that are transcribed down from a recording of the analytic session. Something goes on inside of the patient and the analyst in parallel with the talking which cannot be readily captured. 

The building blocks of the meaning-making process. 

The most rudimentary form of a conscious thing that stands for something occurs within ourselves about ourselves, to ourselves. Communication is communication of meaning. The best theory that we are working with revolves around the notion that consciousness originates in structures within the very deep core of our brain stems. These structures which project very widely to the forebrain, are representing aspects of the state of ones self, the subjective state, the visceral bodily state. This state of self is meaningfully being represented as a feeling of consciousness which either feels good or bad. Action tendencies are intrinsically interwoven to these feeling states. Pleasurable feelings are associated with approach behaviours, they motivate approach behaviours. 

Negative/painful feelings are associated with avoidance behaviours. These raw feeling states originate in the periaqueductal gray (PAG). Even in such elementary forms of consciousness, something is conveyed but not necessarily intentionally. We see that in herd-contagion behaviour. 

The approach mechanism is essentially a seeking mechanism. It has to do with detecting needs that can only be met in the outside world. It is almost an implicit predictive mechanism: "Unless I go looking for food, I am not going to survive". The feeling that comes with it is mildly optimistic, mildly curious - "something good is going to happen and I want to be there kind of feeling". Freud defined emotions as "mnemic residues of biological situations of universal significance". The universality of significance makes us all know what it means when we see it. Basic emotion systems link our core consciousness to the outside world and those around us. Emotions are a perceptual modality, they are a medium of consciousness just as vision, smell, hearing are a medium of consciousness.  

When another animal (human) feels something and another sees it, hears it, smell it (there are all sorts of ways in which the state of an animal is conveyed) then one knows what the other animal is feeling. These are things which we can't afford to learn, they are "mnemic residues" - we just know what it means, although we may not be able to demonstrate. Empathic knowing When I see that experience it activates the same system in me. I know what it is because it is activated in me. Mirror-neurons allow a higher level elaboration of this basic system. Mirror-neurons were accidentally discovered in a research lab in Italy. When a monkey with a brain activity recording device on its brain observes another monkey eating a banana, the same areas in the brain of the observing monkey are activated. There is a mirroring of the motor-neuron activity in the acting monkey, which is activated in the brain of the perceiving monkey. 

The prefrontal cortex allows for a suppression of the basic emotional systems, inhibiting the action tendencies associated with them. They enable us to not have to act on the feeling, to create virtual scenarios, to represent the relation between things. A 'non-doing' kind of thinking evolves - a highly abstracted, symbolic thinking removed from the emotional core. It is our 'pride and joy' but the price is that it alienates us from our feelings. We develop this curious inability to know what is driving our own actions. 

In therapy the analyst is taught to listen with his "third ear", with an evenly suspended attention. The analyst does not listen to the words, because they only convey part of the story - she picks something up, she feel something, which is akin to a biological situation with universal significance. This way we recognise the patient's emotional configuration, and we use the words to convey our understanding. The talking cure is not about the talking - the talking is about feelings. 

A postmodern take on transactional analysis

Posted on July 3, 2013 at 12:43 PM Comments comments (0)
Reading the work of psychiatrist and transactional analyst James R. Allen gives me great pleasure as I discover a knowledgeable and nuanced and autonomous thinker who seamlessly incorporates science and hermeneutics. In the article "Yeastlings" Allen uses the metaphor of rising dough to signify "the quiet pockets of transformation" in transactional analysis paradigm. He is talking about a shift from Berne's modernist project to a postmodern transactional analysis.  The article is available from the USATAA website. 

Not Knowing is the Royal Road to Feeling Both a Shameful Fool and Creative Healer

Posted on July 2, 2013 at 10:26 AM Comments comments (2)
A moving article by psychiatrist and psychotherapist Robert Lewis asking:  "How does one both be the  responsible healer who maintains the frame and the wounded healer inside the frame with the wounded  patient? In some ways, one hopes to embody a presence, not unlike that of the parent who both takes responsibility for his child and yet remembers that the child (patient) knows at least as much about where  your journey together must go."

Quantum mechanics: A theory with no view of the world?

Posted on February 7, 2013 at 6:29 PM Comments comments (104)

The view of the world that fits quantum mechanics has paradoxes which are hard to accept. 

In the classical view science was considered to be a mirror of nature. This conception comes in two varieties. Western science has sought a faithful representation of reality as it is in itself (realism). Empiricists would say that a good theory is a faithful summary of observed phenomena. The idealistic view (Kant) was that our sensibility and understanding shapes phenomena into objects. 

The third possibility is that a scientific theory is neither a mirror of nature nor a projection of our minds, but the expression of a fruitful interplay between nature and us. Francisco Varela developed this view under the name of "enaction" (Embodied mind). According to him our view of the world is dependent arising on the knower and the known. Science gives us methods to relate to the world in an efficient and powerful way. It is an instrument that helps us orientate in the world and nothing more.

What is a scientific theory? 
In the history of western thought there are four major conceptions:
Aritotle (330 BC) - A statement of "first causes" and meant to find the "essential properties" of things.
Descartes (1637) - A mechanical explanation of the motion of bodies in terms of contact and collision
Newton (1687) - A mathematical description of phenomena in space and time: motion of celestial or terrestrial bodies
Bohr (1929) - A mathematical predictive tool able to predict in terms of probabilities the outcome of experiments.

We see a progressive decrease in the scope of theories coupled with a progressive increase in precision. The more efficient they become, the less they pretend to make us understand the world as it is. 

What is the difference between a theory and its interpretation?
A physical theory is a mathematical framework (Bohr and Newton) to describe or predict phenomena. It is made of laws that connect variables (e.g. position and velocity). Classical mechanics is of this type. 

Interpretations are views of what the world is made of. A physical theory can be consistent with different views of the world. The seventeenth century view was that the world is made of material bodies, which have position and velocity and attract each other (Newton). The nineteenth century view was that the world is made of pure energy and that the appearance of bodies is given by local concentrations of energy (Oswald, Duhem)

What is quantum theory?
Quantum theory is a mathematical scheme to predict the probability of a particle being found 'here' or 'there'. What view of the world fits with quantum theory? There are three different possible answers. 1. All reality is a wavelike (Schrodinger) 2. Only particles exist 3. Dual reality: part wave - part particle. Particles use waves to guide themselves through the world (Bohm)

There is a fourth possibility, which is very challenging. Quantum reveals nothing of the intrinsic nature of reality, it is just a tool that helps us orientate by probabilities through the phenomena that we meet in the world.  Quantum theory may be powerful on a statistical level but weak on a descriptive level. An insurance company uses statistics to predict how many accidents there will be in a year and deduce what to charge its customers, and yet would not be able to describe us the nature of accidents. This position is supported by Werner Heisenberg and Anton Zeilinger. According to Heisenberg one cannot say what 'happens' in the world independently of one's intervention, experimentation or observation. According to Anton Zeilinger quantum mechanics is a theory of the limits of available experimental information.

Maybe quantum theory has revealed that nature has no intrinsic nature. This is a great challenge for western thought. Most physicists believe that quantum physics has "betrayed the ideal of science" (Isabel Stengers). Rene Thom a French mathematician referred to quantum theory as "the scandal of our century".

Should we persist with the ideal of science which brings with it many paradoxes or should we drop the ideal of science and regain some clarity? The ideal was so dear to so many scientists, it cannot be easily be suspended. It may be that quantum physics is so efficient and universal precisely because it does not aim to disclose the intrinsic nature of anything. It covers many events in many domains. It can even be applied to human sciences (i.e. linguistics and semantics). The common point between microphysics and semantics is that in both we have relational phenomena.

From a buddhist stance it is enough to appreciate what is given and just describe what is given but not try to imagine what is behind the veil of appearance. Maybe there is no veil at all, nothing hidden behind phenomena (Dogen) 


A new way of thinking about the nature of reality

Posted on February 6, 2013 at 7:15 PM Comments comments (101)

The clock is an archetype of the old classical physics. What we have in the quantum mechanics is something that is not at all like that. A new way of thinking is required. 

Relativity theory
Einstein was at the crosswords between the old world and the new one. He said: "Behind the tireless efforts of the investigator there lurks a stronger, more mysterious drive: it is existence and reality that one wishes to comprehend." (Einstein, 1934) We all wish to comprehend reality, but what is our expectation about how that reality will show up?

Intrinsic properties have been defined as unique enduring properties that identify an object. Galileo made a distinction between primary and secondary qualities. He wrote" I think that tastes, odours, colours and so on are no more than mere names and they reside only in consciousness. Hence if the living creature were removed, all these qualities would be wiped away and annihilated." Secondary qualities are colour, smell, taste, sound, warmth.  Primary qualities are size, shape, location, movement, contact, mass.

The failure of classical realism
The mystery is from the point of view of quantum physics: are these primary qualities truly primary? Is there a world of intrinsic objects or is the world intrinsically subjective - is it the world of experience?

Two great theories of modern physics
Relativity, which is a revolution in our understanding of space and time and simultaneity becomes significant only at high velocity. Quantum mechanics, which has revolutionised our understanding of light and matter becomes relevant only at small scales such as atoms.

Thought experiment. A relativistic challenge. To fit a 25cm pole in a 20cm long barn. Classically it is impossible because the pole is too long to fit in the barn. However at 75% the speed of light, the pole shrinks when seen from the barn to 18cm. If the barn is observed moving at 75% the speed of light towards the pole, the barn will shrink to 14 cm. Any object that moves becomes shorter in the direction of moving. Viewed from the barn the pole fits inside. Viewed from the pole, the pole is too long. These two views are classically inconsistent, but consistent from a relativistic point of view both are true, but with respect to two different observers, two different frames of reference.  

What you are looking for is always in a context, a relationship. When you are asking what is the single true state of affairs you are presuming there can be a view from nowhere - no person just a situation with its own truth. When we forget the context we come into great difficulties. Difference reference frames create different contexts and lead to different understandings. The vantage point is absolutely important to even something like size. Every primary property is affected by relativity. From a standpoint of physics we have to keep into account the frame of reference of the observer. There is no privileged reference frame. Each observer has the same claim to truth. 

Length shortening, time slowing and the relativity of simultaneity make analysis in terms of objects inappropriate and this becomes the new framework for understanding the new physics. David Bohm: "The analysis of the world into constituent objects has been replaced by its analysis in terms of events and processes" (Special theory of relativity) We so much want the world to be made up of objects - cells, neurons, atoms but this is a wrong view. We have phenomena and processes arise in time and they give the appearance of objects of enduring nature, but what is primary is the process. 

Implications
It is a wrong view to look for a single objective state of affairs that everyone will see in a consistent way.There is a fundamental observer dependence (real or imagine). There is always a vantage point. To forget the observer is a fallacy. We find that primary atributes are relative. Properties are relational - they depend on the relationships that we experience. We are always looking for the objective reality beyond experience, we are looking for something other than experience to support experience, but this, on the basis of Einstein's theory is not a good choice. When you look ever more deeply you find context dependent relationships that give rise to phenomena that may be more and more subtle. What one has context dependent experience and there is no need for any foundation other than that. We need to not be stuck in a vantage point. If you get stuck on a vantage point you see everything from your own side and you fight from that truth. 
A reality which you circle - you actually learn to take the point of view and position of others. Engaging with something different gives a fresh view on reality.