my-genes-made-me-do-it

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us-election

Genopolitics is the study of the genetic basis of political behavior and attitudes.

The election of Donald Trump to the presidency of the United States could not pass without comment or analysis. The map above tells me that there was something more than politics going on — it is a map of fear. A threat felt by middle-America that the world is changing and that they are being left behind with no jobs and no future. This fear was fanned by Trump into the flight or fight response — a heritable conservative human trait -- hence genopolitics. Do liberals and conservatives think differently or have different brains — the answer is: YES.  (See previous posts: My Genes Made Me Do It).

There is something of a consensus regarding the genetic nature of human traits -- the so-called OCEAN classification -- Openness: (inventive/curious vs. consistent/cautious Conscientiousness: (efficient/organized vs. easy-going/careless)  Extraversion: (outgoing/energetic vs. solitary/reserved)  Agreeableness: (friendly/compassionate vs. analytical/detached)  Neuroticism: (sensitive/nervous vs. secure/confident).  For more on this, see the previous posting on  Me, Myself and Us by Brian Little. Furthermore, specific studies on the political behavior of twins has shown that political affiliations are significantly influenced by genetics. Settle et al, showed "that heritability accounts for almost half of the variance in strength of partisan attachment, suggesting [that] we should pay closer attention to the role of biology in the expression of important political behaviors". 

What are the candidate genes? A round-up of the usual suspects: monoamine oxidase A (MAO-A), the serotonin transporter (5HTT), the dopamine receptors (DRD2) and (DRD4). Using a genome-wide linkage analysis, it will be possible to identify other chromosomal regions associated with political attitudes. In particular, neuroscientific analysis has shown that in Liberal vs Conservative brains, there are differences in their amygdala, the part of the brain that makes emotional responses.  Research has shown that people’s whose basic emotional responses to threats are more pronounced,  develop ring wing opinions.

Liberal vs. Conservative: A Neuroscientific Analysis by Gail Saltz. Watch the first 4 minutes to get the gist of the analysis -- it is 15 minutes long.
 

Finally the Clinton campaign depended on genopolitics of the most fundamental kind — that women would vote for Hillary because they were women.

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Developments around CRISPR have made it possible to tackle some interesting practical problems such as making NZ pest-free by using gene drive.

What is CRISPR? Watch the TED Talk below.

What is gene drive? An explanation of CRISPR and gene drive have been previously posted. It is a natural system used by bacteria to protect themselves against viruses and is now being used routinely in genetics as a tool in research.

Recently the Department of Conservation has set a target for New Zealand to become pest free by 2050. This includes mice, rats, stoats, rabbits and possums. This is very unlikely to be achieved using the conventional methods of poisons, diseases, traps, shooting or other such methods as pointed out by Professor John Knight in the article in the ODT 10/10/2016.

Gene drive is our best hope or worst fear? Part of the fear comes from the unknown.  What is required is a very extensive public education effort to explain to people what gene drive is, how CRISPR works and what are the ethical issues. For pest control the objective would be to produce only male offsprings and thereby control the population.

Being an island  nation, we are ideally situated to use this method — we have been bold with innovation before — here is our chance again.

For an update on this issue, see: daisy-chain-gene drive for pest free nz

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Me-Myself-Us

This book by Professor Brian Little is about the new science of personality psychology.

Ever since the ancient Greeks, human traits have been described and studied in different ways. We had the Greek four bodily humours which were: air (phlegmatic - relaxed and peaceful), black bile (melancholic - analytical and quiet) blood (sanguine - optimistic and social) and yellow bile (choleric - short-tempered and irritable). In more modern times we had the theories of Sigmund Freud and Carl Jung, who focused on subconscious forces, our dreams and our primordial sex drives.

In the mid-20th century the humanistic psychology of Carl Rodgers and Abraham Maslow flourished where scientific objectivity itself was seen as a barrier to understanding human nature. This was a prominent view of the New Age understanding of self and we have the Maslow pyramid of human needs (like a food pyramid!). They believed deeply in the human capacity both individually and collectively to shape our own futures. Scientific research did not match the rhetoric of this movement.

Today we have positive psychology — it explores factors that enhance individual lives, communities or nations. It is committed to a scientific analysis of personality psychology from neurons to narratives, from biochemistry to literary biography. The study of the human triats has been revitalised and there is a consensus among psychologists, namely — OCEAN — Openness, Conscientiousness, Extraversion, Agreeableness and Neuroticism.

In previous my posts - My Genes Made Me Do It - the genetic aspects of these traits were explored and along with their associated neurotransmitters. In Brian’s book these traits are seen as flexible points around which our psychology pivots balancing different aspects within each trait: Openness: (inventive/curious vs. consistent/cautious); Conscientiousness: (efficient/organized vs. easy-going/careless); Extraversion: (outgoing/energetic vs. solitary/reserved); Agreeableness: (friendly/compassionate vs. analytical/detached); Neuroticism: (sensitive/nervous vs. secure/confident).

Brian Little, who describes himself as an extreme introvert, provides a framework for thinking about the personal implications of this new science of personality psychology. Throughout the book there are mini-questionaries that facilitate self-exploration of ourselves and other selves and examines the biogenic, sociogenic and idiogenic factors that contribute to who we are. He illustrates how we function on a day-to-day basis using our personal constructs and following our ‘core projects’. We create a confederation of ‘mini-selves’ in our interactions with our spouse, our work colleagues. our children, our parents.

In the final chapter he summarises some of the main points in his book by evoking the image of  a dance -- “Save the Last Dance for Me”. Listen to the audio below.

As an aside: The OCEAN model has been criticised for not being theory-driven. It has been argued that it is a collection of data that has been clustered together for statistical descriptions of the observations. In this regard it reminds me of the previous posting on Machine Learning. A BIG Data analysis of observations without a theoretical basis or a predictive model of their underlying mechanisms. Another criticism is that the five factors are not independent of each other — are not fully orthogonal to one another. Furthermore the factor analysis is linear and does not capture nonlinear, feedback and contingent relationships between the individual differences. Finally there is lexical issue — the use of verbal descriptors for individual differences. The use of language creates sociability bias in verbal descriptors of human behaviour. For instance, there are more words in the language to describe negative rather than positive emotions. Still OCEAN seems to be the only game in town that is worth watching.

In summary: The book is an excellent read — I bought the Audible version - it is full of illustrative and witty stories about people that you would easily recognise. I highly recommend the book.

(For further information, visit: kalmakconsultancy.com)

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The DNA genome and machine learning would seem like an unlikely partnership since one is embedded in the biological world and the other in artificial intelligence. However, in recent times the human genome has been used as ‘training data’ for machine learning and has been able to predict the phenotype (in this case facial appearance) to a remarkable degree. (Photo from Riccardo Sabatini’s TED talk)

ML-Predict

How was this done and how was machine learning used? Machine Learning (ML) is a "Field of study that gives computers the ability to learn without being explicitly programmed". My expertise in machine learning is somewhat limited and comes from a Coursera online course Machine Learning Foundations: A Case Study Approach from the University of Washington. My understanding of the process is illustrated in the diagram below (which may be only conceptually correct)

Machine Learning

The phenotypic characteristics of the subjects were codified and a random set was used along with their DNA sequences for ‘training’ the machine learning (ML) model.  A predictive model was made.  A set of ‘testing’ subjects was put through the model to evaluate the predictions. Further tweaking’ of the model was made through more iterations until some prediction endpoint was reached. This project involved the coordination of a large number of people working on different machine learning modules.

Watch the interesting TED talk by Riccardo Sabatini

At the end of Riccardo’s talk, he raised the issue that the human genome should be everyone's concern — philosophers, politicians, artists, scientists, business people and ordinary citizens. In the closing remarks of  my previous blog — I raised the concern: that since we have by and large eliminated ‘selection’ from the process of biological evolution,  we as a species shall continue to accumulate mutations in our genome — something that occurs on a daily basis. We potentially face an evolutionary dead end unless we are willing to intervene and correct these genetic mistakes. Also are we ready to grapple with the thorny problem of improving our genetic makeup?

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As a species do we face an evolutionary dead end?.

Gene&Human-Condition
This is the last blog posting about the Coursera sessions:  Genes and the Human Condition - (University of Maryland) . The first blog post dealt with some of the fundamental concepts and progressed through to the state-of-the-art technologies. This blog  highlights some of the genetic advances already made and their implications for society. Below is a  laundry list of the topics covered:

  • synthetic biology —> the concept
  • 1st transgenic example — human insulin from E. coli
  • ‘Pharming’ - using crops or animals for producing vaccines or drugs
  • aquaculture - AquaAdvantage salmon
  • golden rice - vitamin A and iron
  • BioBricks - standardised genetic components that can be linked together into new combinations
  • Craig Venter and Synthia — synthetic life
  • BioHackers - weekend workshops
  • gene therapy - replacing faulty genes with functional genes
  • CRISPR technology
  • germline therapy — benefits and the risks

A mash up of the lectures for this session --  Professor St. Leger

In the closing remarks of this course, there was a plea for the public to become more informed about biotechnology and genetics. Otherwise the fears of the new developments such as synthetic biology will block the benefits of such research for our future. We have eliminated the selection pressure on the many mutations that have accumulated in our genomes and will continue to do so. We face an evolutionary dead end if we fail to address the genetic consequences of no selection.

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If you think you are being surrounded by idiots, you are probably right. A leading Stanford University scientist, Gerald Crabtree, would confirm your view. His idea is that since individuals are no longer exposed to nature’s raw selection mechanism on a daily basis that nearly all of us are genetically compromised compared to our ancestors of 3,000 years ago.

Gene&Human-Condition
This and the previous blog are notes from the Coursera: ’Genes and the Human Condition’, University of Maryland, lectures on “My Genes Made Me Do It”. What follows is from lecture 5.

Crabtree gives the following example: "If a hunter-gatherer did not correctly conceive a solution to providing food and shelter probably died along with his or her progeny. Whereas a modern Wall Street executive that made a similar conceptual mistake would probably receive a substantial bonus and a be a more attractive mate". In other words, the consequences of being stupid were much worse in the Stone Age.

What is Self-domestication? - it is a process of transforming ourselves through self selection. What are some of the traits? We are selecting against aggression and favoring the juvenile behaviors  of trust, playfulness, and creativity. Both in brain size and physiology, we can be considered to be sexually mature baby chimps. This process is called paedomorphism, where the adult retains their infantile or juvenile features. Like most domesticated animals we have a smaller brain than our progenitors. Our brains have shrunk by about 20% in the last 10,000 years. The area that seems to have decreased in size is Area 13 which is the part of the limbic brain that establishes adult emotional reactions such as aggression.

Gerald Crabtree thinks we reached a peak in our intelligence about 7,000 years ago, but he doesn’t think our decline relates to our domesticating of ourselves. His argument is based on the idea that for more than 99% of human evolutionary history, we lived as hunter-gatherer article-crabtree-1112communities, surviving on our wits. However, since the invention of agriculture and cities and technology, natural selecting on our intellect has effectively stopped. He suggests that this has allowed mutations to accumulate in the genes involved in intelligence on average 25 - 65 per generation. He predicts the 5,000 new mutations in the last 120 generations, which is about 3,000 years, are the cause of our decline. He gives an interesting illustration: “I would wager that if an average citizen from Athens of 1000 BC were to appear suddenly among us, he or she would be among the brightest and most intellectually alive of our colleagues and companions, with a good memory, a broad range of ideas, and a clear-sighted view of important issues. Furthermore, I would guess that he or she would be among the most emotionally stable of our friends and colleagues. I would also make this wager for the ancient inhabitants of Africa, Asia, India or the Americas, of perhaps 2000–6000 years ago. The basis for my wager comes from new developments in genetics, anthropology, and neurobiology that make a clear prediction that our intellectual and emotional abilities are genetically surprisingly fragile.”

In today’s world we compensate for having a smaller brain or a more mutated one by using computers and technology. We also have an education system that provides the supportive environment to allow what brain power that remains to attain its potential. Education allows those strengths to be rapidly distributed to all members of our society. What we need to do is educate Athenians.

For a mash up of the video from Coursera; Genes and the Human Condition, University of Maryland by Professor Raymond St. Leger -- see below:

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Gene&Human-Condition

There are about 50 neurotransmitters, the most important ones studied are: serotonin, dopamine, oxytocin and vasopressin. Studies have shown that we are social creatures -- isolation and loneliness are toxic to our wellbeing.

This and the previous blog are notes from the Coursera: ’Genes and the Human Condition’, University of Maryland, lectures on “My Genes Made Me Do It”. What follows is from lecture 4.

brain-structure

One of the important neural circuits in our brain is the amygdala -- cingulate cortex neural circuit. In the diagram above, the amygdala (in red) is the threat detector and the cingulate cortex (in yellow) is connected to one of the self-awareness centers. Serotonin is used as the neurotransmitter in this circuit.

How this circuit works is illustrated in the video below. Also neurotransmitter activity during orgasm and addiction are explained as well as MAO and the 'warrior gene'. In the summary, an overall view of our genes and the environment are put into perspective.

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Gene&Human-Condition

This and the previous blog are notes from the Coursera: ’Genes and the Human Condition’, University of Maryland, lectures on “My Genes Made Me Do It”. What follows is from lecture 3.

“Psychologists don't really do consensus, but in the case of personality traits, it's hard to avoid: Openness to experience, Conscientiousness, Extroversion, Agreeableness, and Neuroticism (OCEAN for short) that constitute the sum of human personality. Each of us has our own unique coordinates depending on precisely where we fall along each of these five dimensions. Where we fall in each dimension is about 50% genetic and 50% environmental. So what do you think is the major environmental influence on personality? If you said parents then you would be wrong. Some major studies suggested that parents make only a few percent of differences in personalities and behaviors.  And the effects of family largely disappear as people get older. Criminal parents are most likely to produce criminal children. Yes, but not if they adopt the children. Likewise the children of divorced parents are more likely to get divorced. Yes, but only if they are biological children. So basically, these studies suggest that parents are overrated as shapers of values. Sandra Scarr suggests that people pick the environment to suit their characters.

You adopt the mannerisms of your peers. In the western world, at least, peers may be a lot more important than parenting. There are evolutionary reasons for this. Your peers will be your lovers, your allies, your rivals. In the long run, they're the ones who matter most. They matter more than your parents.”

Book-covers

It is interesting to compare Hillary Clinton’s politically slanted book: “It Takes a Village” with that of  Senator Rick Santorum’s conservative: “It Takes a Family”. Both books ignore the ability of children to make their own choices.

In a new field of study called genopolitics, it has become accepted that your political views may have a genetic component. Neuroscientists have shown that liberals and conservatives have different patterns of brain activity. In particular, there are differences in their amygdala, the part of the brain that makes emotional responses. Research has shown that people’s whose basic emotional responses to threats are more pronounced, develop ring wing opinions. Twin studies suggest that opinions on a long list of issues from religion, to gay marriage, to party affiliations have a substantial genetic component.

In the upcoming American presidential elections, it will be interesting to see how the idea that genes will influence the political outcome plays out.

Below is a mashup of the Coursera lecture:

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Gene&Human-Condition

This and the next blog are notes from the Coursera: ’Genes and the Human Condition’, University of Maryland, lectures on “My Genes Made Me Do It”.

The age old debate of nature vs nurture takes on new meaning in the light of modern genetics and neuroscience. Society’s misunderstanding of some of the implications genetics goes from one extreme where in 2009 a murderer in Italy got a reduced sentence because he had genes associated with criminality while in the US an argument was made for a higher sentence based on the prosecution’s evidence that people with particular genes cannot be cured. The gene in question was the SRY gene carried on the Y chromosome that determines maleness. There is NO GENE for criminality. Apart from the rare exceptions such as the gene for sickle cell anaemia which protects against malaria and Huntington's disease, a neurodegenerative disorder, all other traits involve hundreds of genes and the interaction with the environment (the nurture bit).

Most of the studies on the effect of the environment comes from the work with identical and fraternal twins. If one minimises the influence of the environment then the remaining differences become genetic. The paradox is that the more equal we make society, the more important we will make the genes.

Professor Raymond St. Leger presented such an example using IQ:

“Present studies indicate that the heritability of intelligence, judged largely by IQ scores goes up linearly across lifespan. So from 30% in very young children, to 40%, 50%, 60%, some people even say it becomes 80% heritable by the time you're middle aged. Well that's saying that 80% of the reason that we're all different in IQ is genetic and so it suggests that genes play a majority role in IQ scores. But environment is important, particularly in young people. Remember that an average IQ is 100. So potentially the 30% of variation in IQ due to environment could be fairly significant in determining if someone has an IQ of 120, or is in the sub-normal range. However, by the time an adopted child is 18, their IQs correlate with their biological parents, and not their adopted parents. This makes the point that the environment, all that mass coaching and tiger mothering can maybe have an effect on the kid's IQ when he's young, bump him up a few notches. But as he gets older, his IQ will become ever more closely correlated with that of his blood relatives.”

GWAS

The analysis of human traits has moved from using SNP’s (single nucleotide polymorphism)— a kind of barcode to the sequencing of the whole genome. This allows for genome-wide association studies (GWAS). In which tens of thousands of people are analysed for genetic variance — this also uses the non-coding parts of the DNA as well.

What are some of the highlights so far?

It turns out that some of the common conditions such as asthma and diabetes are controlled by tens or even hundreds of genes. The good news is that the pathways by which some diseases start have been identified and some entirely unexpected new pathways have been discovered. For instance a high risk version of the FTO gene has been associated with obesity and the high production of the hormone called ghrelin which makes people hungry. The study of the DNA of centenarians (people called the wellderly) have identified 5-6 biochemical pathways that are often revved up. This includes gene variants of the insulin IGF-1 pathway. As already mentioned variance of the SRY gene has been linked to violent crime.

From the twin studies a risk loci has been identified that is shared by the five major psychiatric disorders: schizophrenia, bipolar disorder, autism, major depression and ADHD. Two of these loci involve genes that are part of the calcium channels — which are used when neutrons send signals in the brain.

For a mash-up of the first set of lectures:

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Jennifer Doudna - co-inventor of the CRISPR technology talks about the need for 'ethics of CRISPR'.

Following on the issues raised in a previous post, Jennifer and numerous colleagues have called for an international meeting to discuss the safe use of CRISPR and the ethics of being able to create "engineer humans" as well as other genetically modified organisms (GMO's)

It is important that all stake holders (excuse the jargon), which includes you and me, understand the potential and risks of this technology and to have an informed discussion in accordance with the principles of a pluralist democracy. For more , click here.

For an elegant explanation of the CRISPR-Cas9 system watch the video.