Communion Of Dreams


Knowing what we don’t know.

Two brief news items in the last day or so illustrate just *how much* fundamental knowledge we don’t have about our own biology.

The first is this good article from Wired about building a comprehensive model of the human brain: A First Big Step Toward Mapping the Human Brain

Relevant excerpt:

The Allen Cell Types Database, on its surface, doesn’t look like much. The first release includes information on just 240 neurons out of hundreds of thousands in the mouse visual cortex, with a focus on the electrophysiology of those individual cells: the electrical pulses that tell a neuron to fire, initiating a pattern of neural activation that results in perception and action. But understanding those single cells well enough to put them into larger categories will be crucial to understanding the brain as a whole—much like the periodic table was necessary to establish basic chemical principles.

Consider that: we’re just now really building a good map of how the different neurons interact within one small component of the brain. And not even the human brain, at that.

And this news story, which came as a shock to me when I heard it on NPR: Seasons May Tweak Genes That Trigger Some Chronic Diseases

From the story:

The seasons appear to influence when certain genes are active, with those associated with inflammation being more active in the winter, according to new research released Tuesday.

* * *

Other researchers say the findings could have far-reaching implications.

“The fact that they find so many genes that go up and down over the seasons is very interesting because we just didn’t know that our bodies go through this type of seasonal change before,” says Akhilesh Reddy, who studies circadian rhythms at the University of Cambridge but was not involved in the new research. “And if you look at the actual genetic evidence for the first time, it’s pretty profound really.”

Again, this is a really basic bit of science — akin to understanding how the sequence of gene expression leads to the development of an organism. Learning that your genetic activity changes during the year means that illnesses are much more dynamic than anyone realized previously.

Not to get too Rumsfeldian, but it really is important to know what we don’t know, as seen between the two items above. In the first case, researchers set out to build a model because they knew that they needed the basic knowledge. In the other, it was investigation of a mystery which led to an unexpected discovery.

And in both cases, it’s science at work. And very cool.

 

Jim Downey



Building a better human.

From Chapter 5 of Communion of Dreams, after the revelation that the Chinese orphan Chu Ling is a clone:

Jon looked around. He decided to tell them the rest of the bad news. “And that’s not all. There’s evidence that the original host had been genetically manipulated to radically change several characteristics related to intelligence.”

Bailey looked a little confused. “What’s that mean?”

Gish sighed. “It means that someone has created a better human, and now is producing copies.”

“Well, better in their eyes, anyway,” said Gates. Her voice contained a touch of bitterness.

 

Gee, here’s a bit of news:

Chinese scientists create first genetically modified human embryos

And so it has come to pass: Chinese scientists at the University in Guangzhou have created the first genetically modified human embryos. Although there had been rumors circulating for some time that it had already been done, until now, there has been no official scientific report.

 

Another prediction come true.

 

Jim Downey



“I prefer the term ‘Artificial Person’ myself.”

Catch this news this week?

Synthetic biology: New letters for life’s alphabet

The five bases found in nucleic acids define the ‘alphabet’ used to encode life on Earth. The construction of an organism that stably propagates an unnatural DNA base pair redefines this fundamental feature of life.

* * *

Sorry about the sparseness of posting lately. I’ve been … busy. Have had a couple of interesting things happen which could play out in some very good ways. One is still enough in an embryonic stage that I won’t mention anything about it yet, but the other is far enough along that I’ll share: there’s a literary agent who is potentially interested in representing me, something which I have been thinking about for a while.

And it seems like a good enough fit that I took all of last weekend to put together a submission package for formal consideration. That meant going through and doing fairly thorough revisions to the first few chapters of St Cybi’s Well, using the feedback I have gotten from half a dozen ‘beta readers’, as well as composing a formal synopsis of the book. Frankly, both were a lot of work, and somewhat skewed my normal work schedule such that it is just now getting back to what passes for normal in my life.

But it was also helpful, and forced me to clarify some things which I had left unfocused for the rest of the book. Because of the way I am writing this (using Scrivener), it has been fairly easy for me to block out both the overall arc of the book as well as character developments. But doing so has been based on chapter notes more than anything, meaning that it was still somewhat in flux. Creating a full synopsis meant that I had to put the whole thing into one coherent document. And even though it was something of a pain in the butt, the result is helpful.

I’ll keep you posted as to any concrete developments.

* * *

Remember this scene from Aliens?

 

Considered a classic, and rightly so. But I’ve always thought that a big part of the brilliance of it is how it sets up what happens immediately after:

Back at the groups’ table, Bishop holds up his hand and examines a tiny cut closely.

BURKE: I thought you never missed, Bishop?

To Ripley’s horror, a trickle of white synthetic blood runs down his finger. Ripley spins on Burke, her tone accusing.

RIPLEY: You never said anything about an android being on board! Why not?!

BURKE: It never occurred to me. It’s common practice. We always have a synthetic on board.

BISHOP: I prefer the term ‘artificial person’ myself.

BURKE: Right.

 

* * *

Oh, one more thing: in observation of Mother’s Day, the Kindle edition of Her Final Year is available for free download through Sunday, May 11th. If you’re new here, just a quick note: this is our care-giving memoir about the challenges and rewards of caring for someone with dementia, as well as the long recovery/reflection period which comes after. It seems to have helped a lot of people. Perhaps it can help you or someone you know.

 

Jim Downey



Looking back: Testing…testing…

While I’m on a bit of vacation, I have decided to re-post some items from the first year of this blog (2007).  This item first ran on March 18, 2007

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

There’s a very good piece in today’s New York Times titled Facing Life With a Lethal Gene about one young woman’s decision to be tested to see if she carries the gene for Huntington’s Disease.

It is a very difficult decision to be tested for a genetic disease which you may have, and for which there is no known treatment (let alone a cure). If you test positive, you know exactly the sort of future you face. And, if you test positive, it can have a significant impact on your employment and insurance possibilities, even decades before you might experience any onset of symptoms.

There is a similar disease which runs in my family called Machado-Joseph. In terms of statistics, there is about a 68% chance that I carry the gene for it, though I do not have the other familial characteristics which seem to track with the disease. So I have elected not to be tested. Besides, at nearly 50 years of age, if I did have the onset of the disease, it would be likely that it would progress so slowly that I would die of something else (the younger the age of onset, the more rapidly the disease progresses).

Anyway, I recommend you read the article. Because as the science of genetic testing develops, it is likely that at some point you will have to make a decision about whether or not you are tested for either a genetic disease or a predisposition towards some type of health problem. Better to consider the matter before being confronted with it. Trust me on this.

What does this have to do with Communion? [warning – spoilers ahead]

The book’s history is premised on a flu pandemic about 40 years prior to the story. This pandemic not only killed hundreds of millions outright (and threw the world economy into complete chaos, resulting in hundreds of millions more deaths) , it left most of the survivors sterile – and did the same to most of the resulting children born. This is a recipe for extinction.

I chose this scenario for several reasons, not the least of which is that I think we are due for a world-wide pandemic sometime in the next decade. But also my family history and personal choice came into play – long before there was a genetic test to determine whether or not I carried the MJD gene, I made the decision to be childless. I felt at the time that the risks of passing on the disease were just too great. Not having any progeny leaves one with a sense of loss, even if it was a decision made for the best of reasons. I could only surmise that the effects of imposed childlessness population-wide would be even more profound.

And, [again, spoiler alert!] the psychological impact of the transformation which comes at the end of the book, through the agency of the alien artifact, would be a very literal rebirth for the entire human race. Not only do we give birth to a subsequent species in the form of the AI/Expert Seth (who achieves true sentience, midwifed by the artifact), but the entirety of the effects of the pandemic are cleansed – meaning that humankind has a second chance, and can start afresh. The hope is, of course, that we will do better the second time around.

So, go read the article.

Jim Downey



We are the champions.*

From BoingBoing here’s an embedded video of a long (90 minutes) but *really* fascinating discussion on the topic of why homo sapiens is the sole surviving member of our genus, and what that might tell us about ourselves. What I very much enjoyed was the way the different disciplines brought their own perspective to the question, and how each different perspective tends to reinforce the science of the others.

Why did our species survive?

Today, we’re the only living member of the genus Homo and the only living member of the subtribe Hominina. Along with chimpanzees and bonobos, we’re all that remains of the tribe Hominini.

But the fossil record tells us that wasn’t always the case. There were, for instance, at least eight other species of Homo running around this planet at one time. So what happened to them? What makes us so special that we’re still here?

* * * * * * *

From Chapter 5:

Navarr turned and looked at Jon. “Any indication from the medical report what the genetic changes mean functionally?”

“No, not yet. The way that the genetic manipulation will play out is very difficult to predict, since that is a subtle and complex dance over time. They have simulations running now, and we may have an idea in a few days.”

* * * * * * *

I don’t want to give away too much, but there are other intimations in Communion of Dreams on this topic, since it is one which has long intrigued me. And while I am nowhere near knowledgeable enough to get too far into the molecular genetics, the current state of the science is such that there is room for plausible speculation.

And again, without giving too much away, I can say that this is something which will be one of the themes in St. Cybi’s Well.

* * * * * * *

Speaking of giving things away: next Saturday, June 9th, will be a Kindle promotional day for both Communion of Dreams and Her Final Year. As previously, the Kindle edition of each book will be available for free download all day, and you don’t even need to own a Kindle to get & read your free copy, as there is a free emulator app for just about every computer/tablet/mobile device out there.

In addition, I will be offering a signed paperback copy of each book as a prize — details to be announced in a couple of days!

Jim Downey

*of course.



Where the danger lies.

Last week I mentioned the genetic breakthrough accomplished by J Craig Venter and his team: the creation of functional man-made DNA. Since then, lots of very smart people have been trying to sort through the implications of this development. One of the better collections of such discussion I have seen can be found at Edge.

Here’s a bit from PZ Myers (also on his blog) that I find particularly insightful:

Nature’s constant attempts to kill us are often neglected in these kinds of discussions as a kind of omnipresent background noise. Technology sometimes seems more dangerous because it moves fast and creates novelty at an amazing pace, but again, Venter’s technology isn’t the big worry. It’s much easier and much cheaper to take an existing, ecologically successful bug and splice in a few new genes than to create a whole new creature from scratch…and unlike the de novo synthesis of life, that’s a technology that’s almost within the reach of garage-bound bio-hackers, and is definitely within the capacity of many foreign and domestic institutions. Frankenstein bacteria are harmless compared to the possibilities of hijacking E. coli or a flu virus to nefarious ends.

Let me repeat that last sentence: Frankenstein bacteria are harmless compared to the possibilities of hijacking E. coli or a flu virus to nefarious ends.

It’s almost like he’s read Communion of Dreams, eh?

Jim Downey



No surprise: it’s not that simple.

I’ve written previously about synesthesia, and most recently said this:

The implication is that there is a great deal more flexibility – or ‘plasticity’ – in the structure of the brain than had been previously understood.

Well, yeah. Just consider how someone who has been blind since birth will have heightened awareness of other senses.  Some have argued that this is simply a matter of such a person learning to make the greatest use of the senses they have.  But others have suspected that they actually learn to use those structures in the brain normally associated with visual processing to boost the ability to process other sensory data.  And that’s what the above research shows.

OK, two things.  One, this is why I have speculated in Communion of Dreams that synesthesia is more than just the confusion of sensory input – it is using our existing senses to construct not a simple linear view of the world, but a matrix in three dimensions (with the five senses on each axis of such a ‘cube’ structure).  In other words, synesthesia is more akin to a meta-cognitive function.  That is why (as I mentioned a few days ago) the use of accelerator drugs in the novel allows users to take a step-up in cognition and creativity, though at the cost of burning up the brain’s available store of neurotransmitters.

And now there is more evidence that synesthesia is a more complex matter than researchers had previously understood:

Seeing color in sounds has genetic link

Now, Asher and colleagues in the United Kingdom have done what they say is the first genetic analysis of synesthesia. Their findings are published this week in the American Journal of Human Genetics.

Researchers collected DNA from 196 people from 43 families in which there were multiple members with synesthesia. They looked exclusively at auditory-visual synesthesia, the kind where sound triggers color, which is easier to diagnose than other possible forms.

They expected to find a single gene responsible for synesthesia, but they found that the condition was linked to regions on chromosomes 2, 5, 6, and 12 — four distinct areas instead of one.

“It means that the genetics of synesthesia are much more complex than we thought,” Asher said.

No surprise there.  The article goes on to discuss what may be happening physiologically – researchers are still trying to construct a model of how synesthesia actually happens in the brain, and still tend to see it as something which “goes wrong” developmentally.  The supposition, according to the CNN article, is that there is a failure of a necessary “pruning” of cross-wiring in the young brain.

But what if it is instead a meta-cognitive function, something which is emerging as part of ongoing evolution of the human brain?  In other words, an enhancement of our current ability to think and remember, by allowing our brains a bit more complexity in the neural connections?

Hmm.

Jim Downey



“Come on baby, light my fire.”*
August 15, 2008, 12:31 pm
Filed under: Genetic Testing, Preparedness, Science, Science Fiction, Synesthesia, Titan, Writing stuff

I’ve written previously about the emergence of consciousness and the role that the biochemical stew in our heads plays in awareness and cognition. But let’s get a little more basic in our analysis. Let’s consider fire. No, not the slow fire of chemical reactions in our bodies, but actual burning of wood, and the role that it may have played in the development of human intelligence.

* * * * * * *

The Greek myth of Prometheus bringing the holy fire of Zeus to mankind, and thereby enabling civilization, has usually been understood as being an explanation of the role which technology plays in human development. After all, fire allows humans to control our environment, from living in colder climates to clearing land for farming to metallurgy. And, of course, to cook food, making a wider range of nutrients available.

But what if fire made human thought itself possible?

Cooking and Cognition: How Humans Got So Smart

After two tremendous growth spurts — one in size, followed by an even more important one in cognitive ability — the human brain is now a lot like a teenage boy.

It consumes huge amounts of calories, is rather temperamental and, when harnessed just right, exhibits incredible prowess. The brain’s roaring metabolism, possibly stimulated by early man’s invention of cooking, may be the main factor behind our most critical cognitive leap, new research suggests.

OK, that article is a little light on actual information.  So I went to check the research paper.  It’s a bit thick, but the basic idea was to study the rise of human cognition via two methods:

In this study, we attempted to identify molecular mechanisms involved in the evolution of human-specific cognitive abilities by combining biological data from two research directions: evolutionary and medical. Firstly, we identify the molecular changes that took place on the human evolutionary lineage, presumably due to positive selection. Secondly, we consider molecular changes observed in schizophrenia, a psychiatric disorder believed to affect such human cognitive functions as the capacity for complex social relations and language [612]. Combining the two datasets, we test the following prediction: if a cognitive disorder, such as schizophrenia, affects recently evolved biological processes underlying human-specific cognitive abilities, we anticipate finding a significant overlap between the recent evolutionary and the pathological changes. Furthermore, if such significant overlap is observed, the overlapping biological processes may provide insights into molecular changes important for the evolution and maintenance of human-specific cognitive abilities.

Got that?  First, you determine the differences due to evolution (specifically as seen in DNA/mRNA divergence between us and chimpanzees), then you see where the brains of people who have schizophrenia are different from ‘normal’ brains.  That can give you some indications of how cognition works, since schizophrenia is known to primarily impact cognition.

What did the researchers find?

In order to select human-specific evolutionary changes, we used the published list of 22 biological processes showing evidence of positive selection in terms of their mRNA expression levels in brain during recent human evolution [13]. Next, we tested whether expression of genes contained in these functional categories is altered in schizophrenia to a greater extent than expected by chance. To do this, we ranked 16,815 genes expressed in brain in order of probability of differential expression in schizophrenia, using data from a meta-analysis of 105 individuals profiled on 4 different microarray platforms in 6 independent studies [14]. We found that 6 of the 22 positively selected biological processes are significantly enriched in genes differentially expressed in schizophrenia (Wilcoxon rank sum test, p < 0.03, false discovery rate (FDR) = 11%), while only 0.7 would be expected to show such an enrichment by chance (Figure 1; Table S2 in Additional data file 1; Materials and methods). Strikingly, all six of these biological processes are related to energy metabolism. This is highly unexpected, given that there were only 7 biological processes containing genes involved in energy metabolism among the 22 positively selected categories (Figure 1; Table S2 in Additional data file 1). The mRNA expression changes observed in schizophrenia appear to be distributed approximately equally in respect to the direction of change, pointing towards a general dysregulation of these processes in the disease rather than a coordinated change (Table S3 in Additional data file 1).

Simply put: it’s metabolism.  The brain eats up a lot of energy, about 20% of all the energy you take in as food.  That’s a lot – for chimps the number is about 13%, and for other vertebrates it runs 2 – 8%.  The conclusion:

In this study we find a disproportionately large overlap between processes that have changed during human evolution and biological processes affected in schizophrenia. Genes relating to energy metabolism are particularly implicated for both the evolution and maintenance of human-specific cognitive abilities.

Using 1H NMR spectroscopy, we find evidence that metabolites significantly altered in schizophrenia have changed more on the human lineage than those that are unaltered. Furthermore, genes related to the significantly altered metabolites show greater sequence and mRNA expression divergence between humans and chimpanzees, as well as indications of positive selection in humans, compared to genes related to the unaltered metabolites.

Taken together, these findings indicate that changes in human brain metabolism may have been an important step in the evolution of human cognitive abilities. Our results are consistent with the theory that schizophrenia is a costly by-product of human brain evolution [11,37].

When did this take place?  From the LiveScience article first cited:

The extra calories may not have come from more food, but rather from the emergence of pre-historic “Iron Chefs;” the first hearths also arose about 200,000 years ago.

In most animals, the gut needs a lot of energy to grind out nourishment from food sources. But cooking, by breaking down fibers and making nutrients more readily available, is a way of processing food outside the body. Eating (mostly) cooked meals would have lessened the energy needs of our digestion systems, Khaitovich explained, thereby freeing up calories for our brains.

* * * * * * *

In Communion of Dreams, I posit the use of “auggies” – drugs designed to maximize the utilization of neurotransmitters in the brain.  When combined with increased sensory information thanks to technology, an artificial kind of synesthesia occures, allowing for insights (artistic, cognitive) otherwise beyond human ability.  But it is a cheat – you ‘burn up’ the available neurotransmitters quickly, accelerating brain function, but are left then less capable for a period of days after as the body replenishes.  This is by and large a metabolic function – the same way an athlete can burn up energy stored in muscles in one brief period, but then needs time to recover.

I wrote this with an instinctive understanding of the mechanism involved – we’ve all experienced something akin to this phenomenon of pushing ourselves mentally for a short period, being tired and less able to think clearly afterwards.  It’s a bit surprising to find that it may have literally been the same mechanism which lead to the rise of human intelligence to begin with.

And as for the alien artifact on Titan, which causes a similar phenomenon?  Just coincidence that Prometheus was one of the Titans in Greek mythology.

No, really – just coincidence.

Jim Downey

*and yes, I realize that this isn’t quite what The Doors meant.



Stress? What Stress?

Some years back a good friend sent me a postcard from Florida with the image of a tri-colored heron’s head (you can see the image from which the card came here). On the card, the heron is looking straight at you, top feathers standing straight up, and above it in bright blue ‘electric’ lettering are the words “Stress? What Stress?”

It’s been tacked to the wall next to my desk here since. And it has been something of a standing joke between my wife and I. When things have gotten bad from time to time, one of us will turn to the other and simply say in a squeaky, high pitched voice “Stress? What Stress?”

* * * * * * *

A month ago I wrote about slowly coming down from the prolonged adrenalin high which was being a full time care provider. Doctors have known for a while that such long term stress was hard on care providers. It’ll drive up blood pressure, screw with your sleep habits, and even compromise your immune system. Now they have started to figure out how that immune system mechanism works. Last night I caught a piece on NPR’s All Things Considered with UCLA professor Rita Effros about her research on this mechanism. What professor Effros said (no transcript yet, so this excerpt is my transcription):

So, in the short term cortisol does a lot of really good things. The problem is, if cortisol stays high in your bloodstream for long periods of time, all those things that got shut down short term stay shut down. For example, your immune system.

But let’s say you were taking care of an Alzheimer’s spouse, or a chronically ill child – those kinds of situations are known now to cause chronic, really long-term stress – let’s say years of stress.

(These care providers) were found to have a funny thing happening in their white blood cells. A certain part of the cell is called the telomere, which is a kind of a clock which keeps track of how hard the cell has been working. Their telomeres got shorter and shorter, and it has been known for many years that when cells have very short telomeres they don’t function the way they’re supposed to function.

What happens is this: cortisol inhibits the production of telomerase – a protein which helps to lengthen and buffer aging effects. Abstract on the mechanism is here, and it says it succinctly:

BACKGROUND:
Every cell contains a tiny clock called a telomere, which shortens each time the cell divides. Short telomeres are linked to a range of human diseases, including HIV, osteoporosis, heart disease and aging. Previous studies show that an enzyme within the cell, called telomerase, keeps immune cells young by preserving their telomere length and ability to continue dividing.

FINDINGS:
UCLA scientists found that the stress hormone cortisol suppresses immune cells’ ability to activate their telomerase. This may explain why the cells of persons under chronic stress have shorter telomeres.

IMPACT:
The study reveals how stress makes people more susceptible to illness. The findings also suggest a potential drug target for preventing damage to the immune systems of persons who are under long-term stress, such as caregivers to chronically ill family members, as well as astronauts, soldiers, air traffic controllers and people who drive long daily commutes.

* * * * * * *

io9 picked up on this story, and gave it a nice Science Fiction spin:

Stress runs down the body’s immune system, which is why people with high-stress jobs or events in their lives are vulnerable to illness. Now a researcher at UCLA has discovered the link between emotional stress and physical damage — and she’s going to develop a pill that will allow you to endure stress without the nasty side-effects. And there may also be one good side-effect: Extreme longevity.

It turns out that when you’re under stress, your body releases more of the hormone cortisol, which stimulates that hyper-alert “fight or flight” reflex. While cortisol is good in small doses, over time it erodes the small caps at the end of your chromosomes known as telomeres (the little yellow dots at the end of those blue chromosomes in the picture). Many researchers have long suspected that telomeres would provide a key to longevity because they are quite large in young people and gradually shrink over time as cells divide.

Rita Effros, the researcher who led the UCLA study, believes that she can synthesize a pill that combats stress by putting more telomerase — the substance that builds telomeres — into the body. This would keep those telomeres large, even in the face of large amounts of cortisol. It might also make your body live a lot longer too.

[Spoiler alert!]

Curiously, this clue about telomere length and aging is exactly the mechanism I use in Communion of Dreams to reveal that the character Chu Ling is a clone. Genetic testing reveals that the telomeres in her cells are much shorter than would be expected from a child her age, leading to the understanding that this is due to the fact that she has been cloned.

Ironic, eh? No, no one is going to think that I’m a clone. But I find it curious that the same mechanism which I chose for a major plot point pertaining to the health of the human race in my book is one which has been clearly operating on my own health.

Fascinating.

Jim Downey



Put young children on DNA list, urge police.

Primary school children should be eligible for the DNA database if they exhibit behaviour indicating they may become criminals in later life, according to Britain’s most senior police forensics expert.

Gary Pugh, director of forensic sciences at Scotland Yard and the new DNA spokesman for the Association of Chief Police Officers (Acpo), said a debate was needed on how far Britain should go in identifying potential offenders, given that some experts believe it is possible to identify future offending traits in children as young as five.

‘If we have a primary means of identifying people before they offend, then in the long-term the benefits of targeting younger people are extremely large,’ said Pugh. ‘You could argue the younger the better. Criminologists say some people will grow out of crime; others won’t. We have to find who are possibly going to be the biggest threat to society.’

“We have to find who are possibly going to be the biggest threat to society” . . . and turn them into criminals by the way we treat them from the very start.

The Minority Report, anyone? No, not the movie, which was OK, but the original short story by Philip K. Dick, which also shows the dangers of a post-war military regime/mindset to a civil society.

See, here’s the thing: people will largely react to the way you treat them (yes, I am generalizing.) If you take one set of people, and treat them like criminals from early childhood, guess what you’ll get?

I am constantly dismayed by just how much Great Britain has become a surveillance society, to the point where it is a dis-incentive to want to travel there. In almost all towns of any real size, you are constantly within sight of multiple CCTV cameras, and there is increasing use of biometrics (such as fingerprint ID) as a general practice for even routine domestic travel.

But getting DNA of all five year olds, under the excuse that it will better allow for catching criminals? Scary. To then match that up with the notion that you can predict the future behaviour of a 5 year old, based on someone’s model of personality development is just plain insane.

And you know that if they can pull this off in Britain, there will be plenty of people who think it should be instituted here.

Welcome to the future.

Jim Downey

(Via BoingBoing. Cross-posted to UTI.)