A dialogue about evolution

I wrote this dialogue a few years ago in the wake of reading Gödel Escher Bach by Douglas Hofstadter, but I didn't know quite what to do with it. It was originally written in Swedish and when I stumbled across it the other day I realised that I could try to translate it into English and publish it here. So here goes, a dialogue about problem solving, evolution and grass:

In a leafy clearing facing a newly plowed field the Hare and the Fox meet on a fine spring day. The Hare chews away on the light green grass while the Fox bask in the rays of the newly risen sun. He looks over the field, squints and slowly faces the Hare who continues to enjoy his herbaceous snack.

The Fox: Did you know that the grass you're eating might be one of the most intelligent life forms on earth?

The Hare: Well, that's just nonsense. It's only grass, right? Just as simple and stupid as any other plant. Or are you trying to say that all plants are intelligent?

The Fox: I think you are being a bit narrow-minded when it comes to intelligence. Just because the grass is unable to talk, and converse as we do, does not mean that it's unintelligent.

The Hare: Well, then I think you have to explain what you mean by intelligence.

The Fox: Ok. To me it's the ability to solve problems. And by that I mean unexpected and novel situations that present obstacles in ones way to achieve a certain objective.

The Hare: And how on earth do you expect the grass I'm eating to achieve anything close to that? When really all it's capable of is converting carbon dioxide and sunlight into oxygen and water. 

The Fox: Now you're being too simple-minded again. You need to widen you perspectives slightly, let some more light in. Plants have simply chosen another strategy compared to us animals when it comes to staying alive and procreating. Instead of running about looking for food, they simply stay put and let it fall down on them. And in the end it might be a clever move, considering how much energy we spend on moving, you looking for fresh grass and me chasing after you.

The Hare: You might have a point.

The Fox: Of course I have, not to talk about all the energy spent on finding the right mate. The plants instead enter the great lottery and find their mate purely through chance. Actually quite convenient when you think about it.

The Hare: This is starting to make sense. So you saying that plants have chosen a completely different strategy when it comes to surviving?

The Fox: Exactly. And therefore I find it a bit unjust to judge them by our standards.

The Hare: I agree that it's a different strategy, but still a pretty stupid one. It's not like they're fighting back, like I do when you're trying to catch me. But then again, maybe it's you being stupid for not eating the defenceless plants.

The Fox: I think you're being a bit presumptuous my dear friend. You forgot to take into account the fact that I only need to spend roughly one quarter of my time looking for food and eating compared to herbivores as yourself. But we're loosing our focus now. My point was that we need to wait longer for plants to solve their problems compared animals. The problem solving instead occurs on evolutionary time scales.

The Hare: Now you've lost me again. Or rather, I've lost myself in your complicated reasoning.

The Fox: Ok. Let me explain. What I'm saying is that if a species of grass is faced with a change in its natural environment, be it a higher temperature or an invading species that competes for light and nutrients, then those plants that can stand the heat or somehow outcompete the invader will succeed while those that don't will perish. If these plants produce offspring that resemble their parents then the beneficial trait will become more common and spread in the plant population. Without too much exaggeration one could claim that the species has adapted and learnt how to handle the change, and therefore solved the problem it was faced with. Right?

The Hare: Wow, that's mouthful, or maybe I should say mindful. But are you saying that your hypothetical species of grass is making a conscious change in response to the external environment?

The Fox: No no, not at all. The only things that are required for this to happen is that there is random variation within the grass population, plants with certain properties are better at producing offspring, and lastly that the property in question is heritable.

The Hare: Now I see.

The Fox: All the life forms on planet earth have solved a whole bunch of problems throughout their history, otherwise they would never be what they are today. Giraffes have long necks because the best food on the savannah was (and still is) high up in the trees, and sharks are streamlined because it makes swimming in water a lot more efficient.

The Hare: And I have such strong legs because of dodgy characters like yourself.

The Fox: Precisely. One could say that each species on earth constitutes the solution to one and the same problem. The problem of staying alive, and to that problem it seems like there are quite a few distinct solutions. Algae and deer are very different life forms, but they both manage to stay alive.

The Hare: But my long and strong legs have hardly solved the problem. Not that I have had any difficulties escaping myself, but I know, or rather used to know, quite a few hares who ended up in a fox's belly. 

The Fox: You're absolutely right, but that's because we foxes are trying to solve the opposite problem. That of trying to catch up with you. So it all turns into an arms race where you have to keep moving just to stay in the same place.

The Hare: That sounds an awful lot like the Red Queen in Alice in Wonderland. She says that it takes all the running you can do, to keep in the same place, and if you want to get somewhere else, you must run at least twice as fast as that!

The Fox: That might be so. I never really cared for that book.

The Hare: Why? I find them really clever and hilarious.

The Fox: Well, you actually get to play a part in the story, but nowhere to be found is a character in the shape of a fox.

The Hare: Now then, I think you are being a bit egotistic. In any case, let's return to the case of problems and solutions. Maybe it's just me, but you're making it sound like every property of every animal or plant had a purpose. The neck of the giraffe, the shape of the shark. How can you be so sure about the problems they correspond to? Is there a problem for each solution? For example take the fact that your nose is black, what problem does that solve?

The Fox: An acute observation my dear friend. Of course you're right, some things just appear by pure chance, or as a by-product of some other solution. Like the lungs that both you and me carry, they developed a long time ago from the esophagus of a poor choking fish that tried to make a living on land. If the lungs had developed from another structure they might have looked completely different today. What I mean is that the solution depends both on the problem and on the solutions that are already in place. Evolution is a tinkerer who works with whatever material is at hand.

The Hare: Finally I think I understand what you're getting at. But we started talking about the grass, let's return to that. What's so special about it?

The Fox: Well, there are several things, but for one it has managed to turn a weakness into an advantage.

The Hare: That sounds exciting. Do continue!

The Fox: Grass has the peculiar property of growing from beneath instead of, as most other plants do, with shoots from the top of the plant. This means that if the grass is chewed by characters as yourself it doesn't really hurt the grass, since it's the oldest bits that are being eaten. But that's only half the story.

The Hare: Yes…

The Fox: Now, if the grass is eaten by a herbivore, then there's an obvious chance that the neighbouring plant, that might not be a grass, is also eaten. The other plant, in contrast to the grass, might suffer from the grazing and die, which in the end means more space and nutrients for the grass. And here's the punch line: the better the grass tastes to grazing animals the more it and its neighbouring plants will be eaten. The grass doesn't mind since it's growing from beneath, while the other plants take a beating from the grazing. So in the end it pays off for the grass to be eaten! Talk about a clever solution.

The Hare: Not bad. But you said that there were even more reasons to admire the grass, right?

The Fox: Yes, you're right. There exists even more sophisticated ways of getting rid of competing plants. The smartest thing you can do is actually to get someone else to do the job for you. Most species of grass make use of grazing animals, but some have gone into partnership with a more efficient player.

The Hare: Now you've lost me again. You have to keep in mind that I'm not as clever as you are.

The Fox: Look at this field. What is usually grown here?

The Hare: I believe it's wheat. To me a pretty useless crop, doesn't really taste anything. I prefer old fashioned grass.

The Fox: That's your view, but someone else is obviously of a different opinion.

The Hare:  Ah, the humans!

The Fox: Exactly. But let's start from the beginning of the story. Not so long ago, roughly ten thousand years ago, when foxes already were foxes, and hares already hares, but humans definitely not what they are today, there was a species of grass growing in the middle east whose seeds were large, tasteful and nutritious. The humans who lived in that region really enjoyed them and realised that they could be used for cooking. At this point someone came up with a brilliant idea: let's collect the seeds, plant and grow them at one spot, instead of walking about all day looking for them.

The Hare: So the humans started to grow and harvest the grass.

The Fox: Indeed. But what does that really mean? Well, the grass was kept under strict surveillance. Weeds were removed by the humans, water was supplied regularly, and even though the seeds were eaten by the humans some were planted. The humans were given a steady supply of food, while the grass was properly cared for.

The Hare: That's an interesting view of things.

The Fox: But the history doesn't end there, it's more like the beginning. The fruitful symbiosis that humans and grass entered into on the plains of the middle east has been refined beyond recognition. The grass has been bred into oats, wheat, rye and barley, and has spread with the help of humans to almost every hospitable corner of the earth. With the aid of airplanes and pesticides the competing plants are held at a safe distance, and the grass thrives as never before.

The Hare:  But who's really benefiting from this whole scheme, the humans or the grass?

The Fox: In one way the humans are using the grass for their own purposes, but at the same time they have helped this particular species of grass to become the most common plant on earth. But let's return to my original question. It seems as if this species of grass has solved the problem of staying alive in a formidable way, so do you agree that it is intelligent?

The Hare: Well actually I think you've convinced me, and won the debate as so many times before. But at least I can still run faster than you!

The Fox: I'm not so sure about that. It must have been two weeks since I tried to chase you down the last time. I have definitely improved my running since then.

The Hare: Ok then, let's give it a go then. Just make sure you give me 10 seconds head start. My life is on the line here, but only a dinner for you.

The Fox: Alright. Don't worry, you can trust me.

The Hare: (starts running across the field)

The Fox: 10…9…8…7…6…5…4…3…2…1

Searching for synergies: matrix algebraic approaches for efficient pair screening

I have together with Sven Nelander and Rebecka Jörnsten been working on the problem of experimental design for the screening of pairs of perturbations to biological systems, be it gene knock-outs or drugs or a combination thereof. The problem that arises is that the number of possible pairs grows quadratically with the number of perturbations, and this makes it impractical to test all possible combinations. In answer to this we have developed an algorithm that searches the space of combinations in an adaptive fashion making use of information found during the screen to direct the search.

The results of this work were recently accepted for publication in PLoS ONE. Below is the abstract and here's a link to the paper (not yet available on the PLoS-site).

Abstract
Functionally interacting perturbations, such as synergistic drugs pairs or synthetic lethal gene pairs, are of key interest in both pharmacology and functional genomics. However, to find such pairs by traditional screening methods is both time consuming and costly. We present a novel computational-experimental framework for efficient identification of synergistic target pairs, applicable for screening of systems with sizes on the order of current drug, small RNA or SGA (Synthetic Genetic Array) libraries (>1000 targets). This framework exploits the fact that the response of a drug pair in a given system, or a pair of genes’ propensity to interact functionally, can be partly predicted by computational means from (i) a small set of experimentally determined target pairs, and (ii) pre-existing data (e.g. gene ontology, PPI) on the similarities between targets. Predictions are obtained by a novel matrix algebraic technique, based on cyclical projections onto convex sets. We demonstrate the efficiency of the proposed method using drug-drug interaction data from seven cancer cell lines and gene-gene interaction data from yeast SGA screens. Our protocol increases the rate of synergism discovery significantly over traditional screening, by up to 7-fold. Our method is easy to implement and could be applied to accelerate pair screening for both animal and microbial systems.