About evolution

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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.

director-cgr

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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?

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.

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:

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:

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.

On the face of it the weirdness of quantum mechanics and biology would seem to have nothing to do with each other. Quantum mechanics deals with the subatomic world and biology with much larger things like cells. Any quantum effects in cells would be cancelled out by the multitude of noisy biological processes. But not so. Quantum biology refers to the many biological processes that involve the conversion of energy to usable chemical transformations and are quantum mechanical in nature.

Examples are photosynthesis, vision, magnetoreception in animals, DNA mutation, and the conversion of chemical energy into motion. Any process that involves the transfer of electrons and protons in chemical processes uses quantum mechanical effects. In photosynthesis it has been shown that the wave and particle conundrum occur simultaneously. The wave spreads uniformly to potential receptors, while the particle follows the path of least resistance through the field of potential created by the wave. This makes for a 95% efficiency in energy transfer.

Many important biological processes taking place in cells are driven and controlled by events that involve electronic degrees of freedom and, therefore, require a quantum mechanical description. An important example are enzymatically catalyzed, cellular biochemical reactions. Here, bond breaking and bond formation events are intimately tied to changes in the electronic degrees of freedom. For more quantum biology examples, click here.

Finally in neuroscience there is a debate as to whether the brain is a quantum computer -- that the microtubules within neurons have the capability to perform quantum computation . Stuart Hameroff  believes that the tubulin subunits which make up a microtubule are able to cooperatively interact in a quantum computational sense.

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CRISPR is causing a major upheaval in biomedical research.  It is cheap, quick and easy to use, and it has swept through labs around the world as a result.

What is CRISPR? - it is an abbreviation for ‘clustered regularly interspaced short palindromic repeats’. It was  initially found in bacteria as a resistance mechanism to foreign genetic material such as plasmids and phages.

CRISPRs are associated with cas genes that code for proteins related to CRISPRs —  Cas9 for instance  By delivering the Cas9 protein and appropriate guide RNAs into a cell, the organism's genome can be cut at any desired location. Researchers only need to order the RNA fragment; the other components can be bought off the shelf. Total cost: is as little as $30. This effectively democratises the technology so that anyone can use it.

Last year, bioengineer Daniel Anderson of the Massachusetts Institute of Technology in Cambridge and his colleagues used CRISPR in mice to correct a mutation associated with a human metabolic disease called tyrosinaemia. It was the first use of CRISPR to fix a disease-causing mutation in an adult animal — and an important step towards using the technology for gene therapy in humans.

What are the risks?

Many researchers are deeply worried that altering an entire population, or eliminating it altogether, could have drastic and unknown consequences for an ecosystem. They are also mindful that a guide RNA could mutate over time such that it targets a different part of the genome. This mutation could then race through the population, with unpredictable effects - the risk of the accidental release of an experimental gene-drive.

What is a gene-drive?

First let us look at how mutations are normally spread within  populations.

STD-1

With gene-drive the genetic change would spread rapidly throughout the population since at each mating the genetic change would occur in both parents.

GDI-1

For further information, the source article is: Nature 522, 20–24 (04 June 2015)