Sunday, May 26, 2013

Whither Came We?

I apologize for not putting up a post last week. Without getting too deep into the personal space, life intervened.

Anyway: Back to Science!

At least one of my two readers may remember the series I did on Biological Revolutions. You may recall one I did on the transition of proto-life-as-we-know-it to the prokaryotes (See here.) and the rise of the eukaryotes. (See here.) From there I talked about when multicellularity occurred. (See here.) I made a leap then to neurozoans: animals who had differentiated a system of "perception" of the world that allowed integrated responses.  (See here.)

Now I left out many other Biological Revolutions in that series. One of which was the development of, well, development.

Organism development is the process by which a proto-organism, such as a zygote, develops into a larva and eventually into an adult. The core of this process is the development of an embryo, termed embryogenesis. Since an embryo is a proto-organism that is pre-directed towards developing into a larva, this is clearly the first step.

Most embryos begin as a zygote: an egg fertilized by sperm. Some embryos begin via parthenogenesis, in animals this starts asexual development from an unfertilized egg. The egg spontaneously doubles so that it resembles a zygote and development proceeds from there. This is called psuedogamy. There is a similar process in plants where pollination is required to get the ball rolling but the DNA of the pollen has no role in the developing embryo.

Regardless, once we have the moral equivalent of a zygote the process proceeds with the "goal" of a target embryo that can then continue to a larval or adult form.

When you think about it, embryogenesis is really, really strange. It starts with a single cell that looks not much different from a single celled organism. But it is programmed very differently. The zygote is packed with special proteins that are intended to shepherd the first few divisions of the cell into a multicellular collection of cells. There's a terrific experiment that one can do with frog eggs (I did this in college.) where you wait for the egg to do its first division and then carefully separate those two cells. Each of the two cells will then develop independently into a separate (and largely identical) frog.

This can occur for multiple divisions. Depending on the species and technique one can divide two, four, eight, etc., cells and get viable larval forms that grow into identical adult frogs. These cells are totipotent.. Any one of these cells can become any cell in the developed body. At some point, totipotency is lost and the cell becomes pluripotent. In animals, this means the cell can be become any cell in any of the three germ layers. Think of germ layers as the next step. They are also called primary tissue layers. At this point the embryo has formed a hollow sphere called a gastrula. (Before this it was called a blastula. I skipped that step.) The "layers" refer to the placement of the cells in the sphere. In animals, they are:
  • Endoderm: Forms the organs of the animal's internal tube such as the stomach, colon, liver, bladder, etc.
  • Mesoderm: Forms organs not associated with either the internal tube or external skin such as the circulatory system, kidneys, gonads, etc.
  • Ectoderm: Forms the organs associated with the outside skin. The skin itself, central nervous system, peripheral nervous system.
These pluripotent cells are the stem cells that everybody talks about.

This is the process for animals. Plant embryogenesis is somewhat different (See here.) but the overarching process is the same. A single cell proceeds to a larval form (i.e., a seed) which under the proper circumstances grows into an adult. (See here.) But I have to say I know animals better than plants so I'm going to stick to animals for the time being.

The critical feature here is the process by which the original single cell is programmed and the subsequent cells dance to each other's tune until the target stage is created. Remember, that there is no plan written into the genes. There are very few genes that are only used during development. Most of them are used throughout the organism's life. However, the choreography of development is exquisitely precise. I like to think of the genes as individual notes in a symphony where each note determines which other collection of notes is played.

Embryogenesis is the first step of a life cycle. Once you have an organism that can generate a life stage that can then act as a precursor to another life stage, changes can be introduced at one point that have knock on consequences down stream. The bones of the middle ear are called the auditory ossicles. There are three bones: the malleus, incus and stapes. Of the three, only one is used in the ear in reptiles. In reptiles it's called the columella. In mammals the columella is referred to as the stapes. The malleus derives from the lower jaw bone of earlier forms and is still there in reptiles and birds. The incus derives from the upper jaw bone.

In this case, "derives" means that if you take careful not of the process of jaw development in reptiles and follow the migratory path of the cells, you'll be able to identify the cells that form the articular and quadrate bones of the reptile jaw. If you follow the same cells in a mammal embryo, those same cells eventually become the incus and malleus. If you follow the cells that create the columella in reptiles you'll seem them form the stapes in mammals.

Where it can, evolutionary pressure ruthlessly forces efficiency. It is far, far cheaper to derive a structure from the embryologic development of an existing structure than create something new. Most vertebrate eyes derive from exactly the same tissue. One exception is the eyes of snakes (See here.)

The evolution of embryological development appears way back in the Cambrian (600 MYears ago.) The first clear fossil record we're familiar with is, in fact, a mark of embryogenesis. Of course, it happened earlier than the Cambrian since when we see Cambrian fossils it's already in full swing. (See here.) The article referenced talks about a bunch of circumstance that might have enabled or selected for embryogenesis but they do not address how these mechanisms might have happened in the first place.

Okay. Now I'm going to link this discussion back to the evolution of the prokaryotes and eukaryotes I mentioned in the beginning.

One of the interesting mechanisms that might have occurred to cause the creation of both groups is the creation of viruses. I mentioned in the prokaryote post that the majority of the DNA in the virus families has little similarity to the DNA the viruses target. Patrick Forterre has suggested that the viruses were instrumental in catalyzing the creation of the prokaryotes and may have been instrumental in the creation of the eukarotes. A virus happily floats around using cells to make other viruses and something breaks. It gets stuck in the cell. The virus DNA machinery becomes incorporated into the host cell and a new, hybrid, group is formed. His argument is the current viruses are those that didn't get incorporated into modern cell machinery and the modern cell machinery reflects viruses that did.

There is a type of virus that is abundant across the genome of various animals. These are endogenous retroviruses. "Endogenous" meaning part of the current genome. "Retroviruses" are those that are RNA based and then transcript into DNA. So the DNA that represents the ERV is the resulting DNA from an RNA virus. Some very interesting research has been published in the last couple of years showing that in humans, HERV (human  ERV) is a precise marker of pluripotency. (See here. And here. And here.) In fact, it is so active that there's evidence that HERV is, if not necessary, extremely important in stem cells. (See here. And here.)

HERV has been implicated in carcinogenesis, immunity and the creation of the placenta. (See here.)

This relationship to pluipotency is not limited to humans. It's been shown for other mammals as well (See here.) to the point that several scientists are wondering if the ERVs drove mammalian evolution. (See here.)

We don't have to stop at mammals. Two active endogenous retroviruses have been found in fruit flies: gypsy and tirant, though it's not clear if they're related to pluripotency. The research is still new.

But that never stops me from speculating.

What if the embryonic development derives from viral interaction with early eukaryotic cells? What if the reasons the phyla are so different from one another derives from the original root viral material that triggered their embryology?

What if we're really viruses underneath?
By the way, if anybody is interested in how we did in the solar vote last time: we won. Hard fought but we did better than the Senate with over a 2/3 majority.

Rationality triumphant.

Sunday, May 5, 2013

Rationality Bias

 (Picture from here.)

We humans have a strong bias that our decisions are based on an intelligent, rational cognitive process. It's embedded in our language-- that was a "stupid decision."

However, anybody who has lived a fairly full life must at some point slap their foreheads and say "What was I thinking?" about that boyfriend, that marriage, that job. Even when that boyfriend, marriage or job looked like the best decision at the time. We comfort ourselves thinking that we didn't have all the facts, we were young, in love, or whatever. But in the cold light of day when no one is around, we pull out that decision and look at it and realize just how dumb that decision was.

We're running into that in our little town here in Massachusetts. Here's the situation.

Massachusetts has put together over the last couple of years a set of incentives for individuals and communities to put up solar power stations. These can be on the roofs of buildings, acreage that isn't being used, etc. We put up panels on our house, for example. Several businesses and the local school has done the same.

But these incentives are coming to an end next year. A company has proposed that we lease to them a beat up old sand pit for them to build a solar farm on. In return, they would sell the electricity back to the town at a reduced rate. There's a proposed clause in the contract that whatever the price the company would sell to the town it would be unable to sell it for more than the local power company. There is no monetary investment to the town. No outlay of effort. Just give them permission to use this land-- land that has been deserted and fallow for a quarter century-- for twenty years. At the end of twenty years we can buy the installation for a dollar or tell them to haul it away. The savings can be as much as $500k/year. And if fracking suddenly made electricity as free as the rain (and probably as toxic) it wouldn't cost us a dime.

The only potential downside is that the land is out of circulation for two decades. There is some possible opportunity cost if some magic fairy came down and wanted to put up a pixie dust factory or something. Factories are sources of revenue. Homes and apartments do provide revenue but that's more than offset by the cost of services-- which has been shown by several studies.

This is like somebody handing you free money.

Now, you would think that this idea would be embraced by everyone concerned. But it's actually been quite a battle to get this approved-- we have to push it through town meeting and there is a fair amount of resistance. Why? You ask.

Good question.

I've heard a bunch of arguments that don't hold the least bit of water. At least, they hold no scientific or financial merit. That does not change the arguments' power to those who hold them in their heart. As I've read the discussion, it seems to me that there are two populations of people talking at cross purposes with one another:
  1. People who don't mind government operation and control of resources
  2. People who believe that government should never control resources or have as little control of resources as possible.
The people in group two seem to believe that any control of resources by government is tantamount to government control of all resources.

This is all very curious to me since, as Heinlein said it, "facts do not sway them in the pursuit of a higher truth."

It reminded me a lot of some rather interesting human research that also involved people who acted without regard to self-interest. Notably, the inequity aversion experiments.

These are fairly controversial experiments with diverse outcomes. There's one called the ultimatum game. Two people play in this game. One proposes a split of a pot of money and the other must approve for the money to be received. Without approval neither player gets any money. The game is only played once so no future reciprocity is involved.

The researchers found, in one iteration of the experiment, that when the proposed split was too inequitable (say $100 to $1), approval was denied. In other words, the approving player was willing to part with money in order to deny money to the proposing player. There have been variations on the game that erased this inequity aversion as well as variations that enhanced it. What's also interesting is that there is a sort of "fairness" perception in non-human primates. Capuchin monkeys will fail to cooperate when the reward discrepancy is too great.

I'm not suggesting inequity aversion is at work here in town regarding the solar array. I am pointing out that there are circumstances where an individual will sacrifice their own self-interest to deny another theirs. If altruism is defined to be when an individual sacrifices his own self-interest for another, this is its reverse.

We should not be surprised that humans are somewhat irrational in making their decisions. There's been a lot of research in this area. While we know the frontal lobes of the brain are important in human decision making and rational cognition, we also know that the amygdala, one of the seats of emotion in the brain, is equally involved. The nature of this involvement is still in the process of being understood. For a long time there was a two system model with a rational, long term thinking system corrupted by a short term emotional system.

A 2008 paper in Cell cast doubt on this two system model. Instead, they suggested that classical conditioning  plays a large role as well.Classical conditioning takes a stimulus and associates it with a response. Ring a bell every time you serve food to your dog and after a while he'll drool when the bell rings whether food is brought or not.

What's interesting about classical conditioning is it is predictive. The dog is drooling as a predictive response to the receipt of food. The amygdala has been shown to be crucial in cue-outcome associations-- and are likely involved in our hypothetical dog-drool experiment. This, in and of itself, is not necessarily an emotional response. Though many experiments have shown that the amygdala is involved in emotion-- fear, especially-- as well. Humans overly weight loss over gain in gambling scenarios. People with lesions on the amygdala lose this asymmetry. In point of fact, patients with a poorly function amygdala cannot gamble intelligently. (See here.)

The role of fear, the amygdala and decision making has also come under scientific scrutiny. It's been shown that the ability to make "rational" decisions is dependent not only on a functioning amygdala, it is also dependent on an amygdala that's not consumed with fear. The amygdala executes multiple duties: it helps associated cue and response, it manages the fear response and it aids in weighting outcomes in decision making. If the amygdala is busy processing fear would we expect it to execute its decision making function properly?

(I will leave here the exercise for the reader on why political fear techniques are so successful.)

The amygdala connection (among other neurological studies) tell us something we should already know: humans are not rational creatures. But we have bias to think we are so we fabulate arguments to explain the point of view we want to have and then defend them religiously.

Which brings me back to my irrational town, bless its pointy little head.

We get to fight it out in town meeting on Monday.