Are these researchers really making progress? The full text of Markram's letter was too long to print here, so I'll just summarize the science behind his vitriol. In short, Blue Brain is composed of model neurons that are highly sophisticated in their handling of electrical and chemical signals. They are more faithful to real neurons than are the model neurons of Modha's simulation, which in turn are more realistic than the weighted voting model discussed in this book.
There is plenty of empirical evidence that the weighted voting model approximates many neurons well. But we also know that the model is not perfect, and can even fail badly for some neurons. Markram is correct that real neurons have many complexities that are not captured by simple models. A single neuron is an entire world in itself. Like any cell, it's a highly complex assembly of many molecules, a machine built from molecular parts. And each of these molecules in turn is a minuscule machine made of atoms.
As I mentioned earlier, ion channels are an important class of molecule, because they are responsible for the electrical signals in neurons. Axons, dendrites, and synapses contain different types of ion channels, or at least have them in differing numbers, which is why these parts of neurons have distinct electrical properties. In principle, every neuron is unique in its behavior, owing to the unique configuration of its ion channels. This is a far cry from the weighted voting model, according to which all neurons are essentially the same. But it sounds like bad news for brain simulation. If neurons were infinitely diverse, how could we ever succeed at modeling them? Measuring the properties of one neuron would tell you nothing about another.
There is one hope for escaping the morass of infinite variation: neuron types. You may recall that Cajal [neuroscientist pioneer Ramón y Cajal] classified neurons into types based on location and shape. You can think of these properties as being like an animals’ habitat and appearance. When a neuroscientist speaks of the double bouquet cell of the neocortex, it reminds me of the way that a naturalist speaks of the polar bear of the Arctic. The naturalist might also point out that polar bears, unlike brown bears, hunt for seals. Likewise, neurons of the same type generally exhibit the same electrical behaviors. This is presumably because their ion channels are distributed in the same way.
If this is the case, then neural diversity is actually finite. We should compile a catalog of all the neuron types, a “parts list” for the brain, and then construct a model for each type. We’ll assume that each model is valid for all neurons of that type in all normal brain, much as we assume that all resistors behave the same way in any electronic device. Once all neuron types have been modeled, we’ll be ready to simulate brains.
Markram's laboratory has characterized the electrical properties of many neocortical neuron types through experiments in vitro, and constructed a model for each. Each neuron type is modeled as hundreds of interacting electrical "compartments;” which is an approximation to simulating the millions of ion channels in a neuron. Markram deserves credit for the realism of the multicompartmental model neurons used in Blue Brain.
But Blue Brain [which has now morphed into the Human Brain Project] is severely lacking in one respect. Since no cortical connectome is known yet, it's not clear how to connect the model neurons with each other. Markram follows Peters' Rule, a theoretical principle stating that connectivity is random. The accidental collisions of axons and dendrites in the tangled "spaghetti" of the brain lead to contact points. At everyone of these, a synapse occurs with some probability, as if it were the outcome of tossing a biased coin.
Peters' Rule is conceptually related to an idea introduced earlier, the random synapse creation of neural Darwinism. The ideas are not equivalent, however. Neural Darwinism includes activity-dependent synapse elimination, which makes the surviving connections end up nonrandom. Violations of Peters' Rule have already been discovered. I suspect that many more will be found, and that the rule has managed to survive only because of our ignorance of connectomes.