Monday, April 26, 2010

My friend Edward is on the front page of nytimes.com today!


My friend Edward Marcotte is on the front page of Nytimes.com today! It's a good article about his lab's incredible "phenolog" work. Way to go Edward, John, Kris and everyone else involved!

Sunday, April 25, 2010

Biological comparative advantage simulations 1

I gave myself a few days break from Traitwise coding this week which was enough time to think about some science once again. As a result of a talk with Andy I got around to coding up a simple kinetic simulation of a hypothetical trading system between two cellular "agents". It is far from a completely justifiable molecular system but it does now capture the heart of the matter. It was a little trickier to write than I had imagined -- as usual there was some divide between the hand-wavy description and the accounting of each important detail.

Background
From economics arises a lovely little non-obvious theory called "comparative advantage" that demonstrates how trading pressure arises. I have a stock illustration of this which involves an old man and young man living on an island. (Yesterday I went and looked at the Wikipedia article and saw a very similar description and it took me a while before I remembered that I was the one who had written that part of the Wiki article!).

Imagine an old man and a young man are on an island. Suppose the following:
  • there's only two products needed by both: fish and water
  • neither man is close to satiated: i.e they want as much of both products as they can get
  • they both consume with a 1:1 ratio of fish and water
  • neither has or will ever meet the other
Each man makes a choice: he could only gather water and thus catch no fish or he could only fish thus gather no water or -- realistically -- he could find some combination of the two activities that maximizes his consumption. The area of "production possibility" can be visualized as in the following graph. The young man can allocate his efforts anywhere under the blue line and the old man anywhere under the red line. Under the assumption that neither man is satiated then the optimal production for each is at the intersection of the consumption line and the edge of their production possibility area. (Click to enlarge figures.)



One day the young man is hauling water back from a spring and stops for a break at a big rock. He accidentally forgets one of his buckets and continues on his way. The next day, the old man who knows nothing of the presence of the young man, stumbles upon the lost bucket of water while returning from a fishing hole. The old man values water more than fish because for him to gather one unit of water costs him two units of fish. Seeing the precious water just sitting there he decides to abandon two of his fish and picks up the water and heads on his way. A little while later the young man returns along the path and sees that fish sitting there on the big rock. The young man values fish more than water because if he wants a fish it costs him two units of water so he decides to leave two units of water behind and pick up that fish.

You can imagine this pattern of leaving-behind one thing and taking-the-other could repeat itself day after day. Both men are better off engaged in this trading game -- they both increase their consumption. Note that the men do not need to know about the others existence -- as far as they are concerned each are simply abandoning a less valuable product and picking up a more valuable one. The pressure to trade does not require understanding the mechanism nor personally engaging with the trading partner. Rather, the pressure to trade is a mathematical consequence of the comparative cost of production each agent. Given the simplicity, I imagine that such a "leave and take" trading system could easily exist between species (say micro-organisms trading metabolites) or between agents of the same species (such as members of the same microbial colony) given differences in micro-environments.

Consider the long-term consequence of our two-man island "economy". The old man finds that he can consume more of both fish and water by specializing in fish production and dropping the fish off at what he thinks of as the "magical" fish-to-water conversion rock. Likewise the young man finds he can consume more of both fish and water by specializing more in water and dropping off some water at what he thinks of as the water-to-fish conversion rock. Each would begin to push his production towards his personal comparative advantage as illustrated below.



The amazing thing about trade is that both parties end up consuming outside of the limits of their own production. Furthermore, the trade benefit is mutual despite the fact that the young man is better at both activities! This result may be counter-intuitive but perhaps is more obvious when stated as "a group is best off when everyone in the group is working in a way that maximizes the time spent on their best abilities." Note that this is not the same thing as saying: "everyone should work on nothing but what' they're best at" as that statement does not account for the fact that the consumption may not be maximal in that situation. There is *some optimal mixture* that is prejudiced towards each agent working on their best ability but is unlikely to be at the extreme for everyone.

Consider the limiting case of the two-man island economy: as specialization occurs, the old man will hit a vertex first; that is, he will end up doing nothing but fishing. In contrast, the young man will end up fishing *and* gathering water albeit more water and less fishing than would have been the case if there was no trade.

The long term consequences of this hyper-specialization can be profound.

If the old man completely abandons gathering water then he may lose his ability to do so. For example, his buckets may go un-mended, he might lose track of where the good springs are, etc. In the short-term the trading is mutually beneficial but in the long-term the old man's situation may become brittle. That is to say, if the trading were to suddenly stop for some reason (for example, the young man might be injured) then the old man might suffer a severe short-term inability to gather water. In the worst case, he might die before he could re-establish his water gathering skills.

Thus the short term benefits of trade may also lead to longer-term danger. It is this conundrum that should be at the heart of free-trade vs. protectionist debates. Both extremes are correct: free traders are correct that trade benefits everyone but protectionists can be correct to argue that free trade may create dangerous, brittle, dependencies. It is reasonable social policy to find a balance that reaps some fraction of trade benefits while also avoiding over-specialization as insurance against future catastrophe.

That said, one almost never hears the above reasonable trading arguments. Instead one hears a much more simplistic and selfish argument regarding "taking away jobs" vs "cheaper products". As the island economy story demonstrates, engaging in trade does not reduce total labor (both men are still working full-time in the island economy) yet it does increase total consumption. That said, in a macro-scale re-telling of the same story the specialization by the two sides would imply that one sector of the economy (say, the fishing industry) would either have to switch its investments and labor to water production or the labor and capital would need to be allowed (and be willing) to move from one area or country to the other. In reality, neither option is in the short-term best interests of the most effected minority -- the owners of the capital and and labor employed in the existing industry. Therefore one (quite reasonably) hears the loudest anti-trade voices coming from those few who are greatest effected. They're best rational argument against trade would be to demonstrate that the proposed trade was not in the long-term interest of their society by an over-specialization argument. Alas, the best rational argument is too rarely the best emotional argument and so instead one usually hears anti-trade rhetoric as status-quo preserving, supposedly job maintaining, often nationalistic, calls against some particular free-trade agreement.


Back to biology
The contrived island economy story is of course an over-simplification of any real human economy; however, it isn't that far at all from a plausible biological story.

Imagine two humble cells who find themselves in some micro-environment where metabolites might be exchanged in an unconscious "market" akin to the magical trading rock on the island economy. Instead of fish and water, imagine the cells exchange two kinds of molecules, let's say two kinds of amino acids.

Suppose that each of these cells can make make either amino acid on their own or their can import or export either of these. With no trade, each would homoeostaticlly regulate their production so as to match their consumption at the limit of their production as demonstrated in the following figure (a copy from above).

Using some hypothetical trading mechanism one imagines that they would be better off to export their lessor valuable products into the inter-cellular space when the are able to import their more valuable product. That said, they would have to defend themselves against parasites that took from the environment without returning any benefit (we'll return to this.) I suggest that a molecular implementation of such a trading mechanism is fairly easy to imagine and it is this that I've been simulating.

Suppose there's a molecular importer that, as a result of importation, has a side reaction. Suppose this side reaction regulates an exporter of a different product. The ratio of the import quantity to the export quantity is the "price function". Let's imagine that the price is established by some other mechanism, for example it might be hard-coded as a result of evolutionary pressure or perhaps it might be determined by dynamic measurement by cellular hardware . Further suppose that the exporter leaks a little bit to "advertise" the existence of the exported product. If two cellular agents implemented this same mechanism yet had complementary price functions, the system should spontaneously engage in unconscious and mutually beneficial trade as described above.





Simulation
I wrote a first approximation of this machinery in Matlab using the following differential equations.

kn = arbitrary rate constants

M0 = slope of the production possibility line of the "old" cell (the one with the worse production abilities)
B0 = y-intercept of "old" cell
My = slope of the production possibility line of the "young" cell (the one with the better production abilities)
By = y-intercept of "young" cell

So1 = storage of reagent 1 by the "old" cell
So2 = storage of reagent 2 by the "old" cell
Sy1 = storage of reagent 1 by the "young" cell
Sy2 = storage of reagent 2 by the "young" cell

Po1 = production of reagent 1 by the "old" cell
Po2 = production of reagent 2 by the "old" cell
Py1 = production of reagent 1 by the "young" cell
Py2 = production of reagent 2 by the "young" cell

E1 = environmental concentration of reagent 1
E1 = environmental concentration of reagent 2

Ro = "old" production ratio = Po2 / Po1
Ry = "young" production ratio = Py2 / Py1

With rules as follows...

"import in proportion to the concentration gradient between inside and outside of cell, never exporting more than you have"...
importO2 = max( 0, k1 * ( E2 - So2 ) )
importY1 = max( 0, k1 * ( E1 - Sy1 ) )

"leak a little bit to 'advertise' the availability of less valuable product"....
leakO1 = k2 * S01
leakY2 = k2 * Sy2

"export in price proportion to what's imported but never more than you have"...
exportO1 = max( 0, min( S01-leakO1, 2 * importO2 ) ) * (e ^ -k5 * E1)
exportY2 = max( 0, min( Sy2-leaky2, 2 * importY1 ) ) * (e ^ -k5 * E2)

"Slow exporting if the external concentration grows too high"....
exportO1 = exportO1 * (e ^ -k5 * E1)
exportY2 = exportY2 * (e ^ -k5 * E2)

"Consume in a 1:1 ratio. Consumption this limited by the least available product"...
consumeO = min( S01, S02 )
consumeY = min( Sy1, Sy2 )

"Regulate the production, moving along the production limit line so as to move the storage ratio towards a 1:1 ratio. (Bound production so that it doesn't go negative)"...
targetPo1 = max( 0, min( -Bo/Mo, Ro * Bo / ( 1 - Ro * Mo ) ) )
targetPo2 = Mo * targetPo1 + Bo
targetPy1 = max( 0, min( -By/My, Ry * By / ( 1 - Ry * My ) ) )
targetPy2 = Mo * targetPo1 + Bo


Integrate with the following 10 differential equations...

d/dt So1 = Po1 - exportO1 - leakO1 - consumeO1
d/dt So2 = Po2 + importO2 + consumeO2
d/dt Sy1 = Py1 + importY1 + consumeY1
d/dt Sy2 = Py2 - exportY2 - leakY2 - consumeY2

d/dt Po1 = k3 * ( targetP01 - Po1 )
d/dt Po2 = k3 * ( targetP02 - Po2 )
d/dt Py1 = k3 * ( targetPy1 - Py1 )
d/dt Py2 = k3 * ( targetPy2 - Py2 )

d/dt E1 = exportO1 - importY1 + leakO1
d/dt E2 = exportY2 - importO2 + leakY2


Results
The result is more or less as expected. If you remove exporting, importing, or leaking, the cells will move to their respective maximum production/consumption points. If you permit the trading, they will adapt to each others exports and regulate their production. Each ends up consuming outside of their personal production hulls as predicted. The "leak" rate can be very small -- it changes only the time it takes before they find each other. Once the symmetry is broken by the leak, the trading regime can emerge rapidly.



One part of this system that I initially omitted turned out to be very important (and obvious in retrospect!) -- the cells must monitor the external concentration of the exported product. If they export based solely as a function of their imports then as the system reaches saturation the "young" one will continue to export when there is no ability for the "old" one to consume any more. As a result, the external concentration of the "young" cell's export product will rise indefinitely thus preventing that cell from increasing it's consumption further due to wastefully dumping product into the environment. At saturation, the exporter must recognize that the exported product is not being used (for example, my measuring high external concentration) and respond by attenuating its export rates.

Returning to parasites. Imagine that one of these agents or some third party tries to "cheat" the system by consuming the export products found in the environment but not exporting anything of its own. In that case, the exporters would reduce their own exports because they're would not be receiving sufficient inputs. In other words, the system is robust against cheaters -- it simply returns to the state as if the trading paradigm didn't exist. Thanks to the small leak, if the cheaters disappear the trading will resume. In this regard, the simple proposed system is an analog computer version of "tit-for-tat".

Next I'm going to try to build a more "molecularly" realisitic simulation and then run many of these systems in parallel. In particular I want to simulate the group behavior in plausible experimental setups such as in a petri dish or chemostat. Especially on a surface, I suspect that spatial constructs will spontaneously emerge as waves of cooperation and defection propagate around the environment as has been shown in similar digital simulations by Axelrod.

Thursday, April 15, 2010

Tree sculpture in bedroom



I've barely had a chance to do any house projects because of work on Traitwise, but recently I did finish up the tree sculpture in my bedroom/bathroom. This is one of the first ideas I had for my house and one of the last to actually get implemented! This view is looking up from my bathroom toward the shared ceiling with my bedroom on the other side of the green wall.

Thursday, March 18, 2010

Traitwise alpha general release


We've made a lot of progress on Traitwise our engine for permitting people to ask and answer seemingly random health-related questions. From this public Q&A we find correlations among all the participants and permit you to understand yourself in a larger context. We also hope that in the long term this gigantic dirty database of answers will reveal interesting things about human health. And, even through we've only barely begun to populate the database, already the correlation engine is turning up intriguing things. For example, some I've looked at today...
  • Reporting that you "have trouble regulating your emotions" is strongly correlated to experiencing significant forgetfulness.
  • Experiencing dry mouth is correlated to napping
  • Being irritable is correlated to being clumsy
While some of these might be statistical flukes (we are, after all, already testing about half a million hypothesis!!) the engine will soon be able to crank up the sampling of those high-interest correlations so that we can asertain if these are statistical flukes or not. Of course, this all depends on participantion, so I beg all of my friends to go to traitwise.com and participate as well as forward the link to whomever they can.

http://www.traitwise.com

Sunday, March 7, 2010

Traitwise alpha -- Call for participation

As many of my friends know, I've been working on a project for sometime that aims to develop a user-friendly interface for answering and creating health-related questions. We are excited to release the alpha version of http://www.traitwise.com and hope you'll help us by participating.

Traitwise is about giving us all a voice in our own health care. Not only can you answer questions, but you may develop questions of your own about any health related subject. We would very much appreciate it if you would create an account and then create questions,
especially about specific diseases or conditions based on your own experience -- after all, no one knows better about a condition than those who suffer from it.

The question creation process is very easy, and don't worry about making mistakes -- all questions go through a review process.

If you are interested in creating questions, you may review the question creation guidelines here, which may make the process easier for us:
http://communities.traitwise.com/mediawiki/index.php/Question_Creation_Guidelines

For those super-technical friends of mine, be sure to check out the "Analytics" page and see a prototype of how it is that our system finds interesting patterns. (Try "sleep" as an example).

Please note that as this is an alpha release and thus there are plenty of bugs to find (please report them on the "Feedback" page) and many features missing. The most important of the missing features is "results" -- that is returning back to you the interesting findings about your health. As it is now, the system mostly takes from you (your answers and questions) but gives back very little (the results). By answering questions, you are helping us to gather a sufficient amount of data that we may fully develop the results pages.

Thank you for all your help!
http://www.traitwise.com

Wednesday, February 24, 2010

Closet, bathroom, and bedroom





Bruce delivered the major pieces of my closet drawers and shelves today! Hooray, storage! We use the same CNC web-based box builder as before -- "Top Drawer Components" -- just love the results from them. Every box is dove-tailed, perfectly square, and already polyed at very reasonable prices. For the drawers I'll eventually put on drawer plates that will hide the slider hardware.



For some bathroom storage we ordered two different sizes of box and screwed them together for this nice effect. (There's several more bathroom fixtures yet to be installed.)


Meanwhile, last week we started on the "tree" element that spans out between then bathroom and the the bedroom. There's a lot more pieces to add to this, but all the heavy stuff is done.

Tuesday, February 9, 2010

Fountain pumps






It's taken years to get around to, but the fountain by my back door finally pumps water. Still lots of details to clean up -- hiding the plumbing and finishing the brickwork, but progress nevertheless!

Meanwhile, I've commissioned a bas-relief sculpture of the nerd-martyrdom of Hypatia from my friend Holly Melear that will go on the top back along the wall.