What am I on about? The Blue Brain Project has published details of its most ambitious simulation yet; a computer model of a tiny sliver of rat brain. That may not sound exciting on the face of it, but the level of detail is unprecedented…
The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.29 ± 0.01 mm3 containing ~31,000 neurons, and patch-clamp studies identify 55 layer-specific morphological and 207 morpho-electrical neuron subtypes. When digitally reconstructed neurons are positioned in the volume and synapse formation is restricted to biological bouton densities and numbers of synapses per connection, their overlapping arbors form ~8 million connections with ~37 million synapses.
The results are good. Without parameter tuning – that is, without artificial adjustments to make it work the way it should work – the digital simulation produces patterns of electrical activity that resemble those of real slivers of rat brain. The paper is accessible here. It seems a significant achievement and certainly attracted a lot of generally positive attention – but there are some significant problems. The first is that the methodological issues which were always evident remain unresolved. The second is certain major weaknesses in the simulation itself. The third is that as a result of these weaknesses the simulation implicitly commits Markram to some odd claims, ones he probably doesn’t want to make.
First, the methodology. The simulation is claimed as a success, but how do we know? If we’re simulating a heart, then it’s fairly clear it needs to pump blood. If we’re simulating a gland, it needs to secrete certain substances. The brain? It’s a little more complicated. Markram seems implicitly to take the view that the role of brain tissue is to generate certain kinds of electrical activity; not particular functional outputs, just generic activity of certain kinds.
One danger with that is a kind of circularity. Markram decides the brain works a certain way, he builds a simulation that works like that, and triumphantly shows us that his simulation does indeed work that way. Vindication! It could be that he is simply ignoring the most important things about neural tissue, things that he ought to be discovering. Instead he might just be cycling round in confirmation of his own initial expectations. One of the big dangers of the Blue Brain project is that it might entrench existing prejudices about how the brain works and stop a whole generation from thinking more imaginatively about new ideas.
The Blue simulation produces certain patterns of electrical activity that look like those of real rat brain tissue – but only in general terms. Are the actual details important? After all, a string of random characters with certain formal constraints looks just like meaningful text, or valid code, or useful stretches of DNA, but is in fact useless gibberish. Putting in constraints which structure the random text a little and provide a degree of realism is a relatively minor task; getting output that’s meaningful is the challenge. It looks awfully likely that the Blue simulation has done the former rather than the latter, and to be brutal that’s not very interesting. At worst it could be like simulating an automobile whose engine noise is beautifully realistic but never moves. We might well think that the project is falling into the trap I mentioned last time: mistaking information about the brain for the information in the brain.
Now it could be that actually the simulation is working better than that; perhaps it isn’t as generic as it seems, perhaps this particular bit of rat brain works somewhat generically anyway; or perhaps somehow in situ the tissue trains or conditions itself, saving the project most of the really difficult work. The final answer to the objections above might be if the simulation could be plugged back into a living rat brain and the rat behaviour shown to continue properly. If we could do that it would sidestep the difficult questions about how the brain operates; if the rat behaves normally, then even though we still don’t know why, we know we’re doing it right. In practice it doesn’t seem very likely that that would work, however: the brain is surely about producing specific control outputs, not about glandularly secreting generic electrical activity.
A second set of issues relates to the limitations of the simulation. Several of the significant factors I mentioned above have been left out; notably there are no astrocytes and no neurotransmitters. The latter is a particularly surprising omission because Markram himself has in the past done significant work on trying to clarify this area in the past. The fact that the project has chosen to showcase a simulation without them must give rise to a suspicion that its ambitions are being curtailed by the daunting reality; that there might even be a dawning realisation internally that what has been bitten off here really is far beyond chewing and the need to deliver has to trump realism. That would be a worrying straw in the wond so far as the project’s future is concerned.
In addition, while the simulation reproduces a large number of different types of neuron, the actual wiring has been determined by an algorithm. A lot depends on this: if the algorithm generates useful and meaningful connections then it is itself a master-work beside which the actual simulation is trivial. If not, then we’re back with the question of whether generic kinds of connection are really good enough. They may produce convincing generic activity, and maybe that’s even good enough for certain areas of rat brain, but we can be pretty sure it isn’t good enough for brain activity generally.
Harking back for a moment to methodology, there’s still something odd in any case about trying to simulate a process you don’t understand. Any simulation reproduces certain features of the original and leaves others out. The choice is normally determined by a thesis about how and why the thing works: that thesis allows you to say which features are functionally necessary and which are irrelevant. Your simulation only models the essential features and its success therefore confirms your view about what really matters and how it all operates. Markram, though, is not starting with an explicit thesis. One consequence is that it is hard to tell whether his simulation is a success or not, because he didn’t tell us clearly enough in advance what it was he was trying to make happen. What we can do is read off the implicit assumptions that the project cannot help embodying in its simulation. To hold up the simulation as a success is to make the implicit claim that the brain is basically an electrical network machine whose essential function is to generate certain general types of neural activity. It implicitly affirms that the features left out of the simulation – notably the vast array and complex role of neural transmitters and receptors – are essentially irrelevant. That is a remarkable claim, quite unlikely, and I don’t think it’s one Markram really wants to make. But if he doesn’t, consistency obliges him to downplay the current simulation rather than foreground it.
To be fair, the simulation is not exactly being held up as a success in those terms. Markram describes it as a first draft. That’s fair enough up to a point (except that you don’t publish first drafts), but if our first step towards a machine that wrote novels was one that generated the Library of Babel (every possible combination of alphabetic characters plus spaces) we might doubt whether we were going in the right direction. The Blue Brain project in some ways embodies technological impatience; let’s get on and build it and worry about the theory later. The charge is that as a result the project is spending its time simulating the wrong features and distracting attention from the more difficult task of getting a real theoretical understanding; that it is making an electric gland instead of a brain.