The July issue of Nature Reviews Immunology has an intriguingly-titled opinion piece by I.R. Cohen, “Real and artificial immune systems: computing the state of the body.” 1 Maybe I’m missing something, but I find it quite disappointing. Part of that is probably that I’m not exactly the audience he’s after, but I think that’s not all of it.

The paper starts off in a humble and apologetic tone with the explanation that “I attempt to show that reframing our view of the immune system in computational terms is worth our while”. To me it’s self-evident that framing the immune system in this way could be worthwhile (so long as we don’t abandon other frames, of course). I can easily imagine that there are lots of immunologists out there who are skeptical of it, though, and presumably those are the intended audience for the introduction.

Organic computer (Woody Igou)Most of the first half of the paper seems to be a pretty basic introduction to some computational concepts — they’re concepts I’m familiar with, which means they must be basic. A couple of mildly interesting comments arise here, particularly the notion that “the immune system effectively computes the immunogenic state of the body”. I don’t think this is a deeply profound thought, just a re-framing (as Cohen says — I’m not criticizing here, that’s what he said he was doing) of an overview of the immune system. Another interesting point is Cohen’s contrast of the immune system and a Turing system, in that the former is self-organizing: “It may therefore be said that the immune system creates and modifies its own program as it goes”.

At this point I was thinking that these were some interesting turns of phrase, but was wondering whether it was just semantics. A new approach to a field is interesting as far as it generates new questions or answers that can be tested experimentally, so I was looking, in the second half of the paper, for some examples of this; at least some of the kinds of questions that could be addressed. This was where I was really disappointed. The examples he offers as powerful outcomes of “reframing immune-system behavior in computational terms” don’t seem to me to be particularly powerful, or particularly dependent on the reframing.

He talks about “Natural immune reactivity to self-antigens” as one example, and “Assessing states of stress” as another. He claims that “The computational view of the immune system sees natural autoimmunity as a physiological mechanism for detecting and responsing to the states of body cells and tissues”, and contrasts this to the “mainstream” view which has “little tolerance … for the idea that natural autoimmunity could serve some useful purpose”.

First, at least as I remember it, this notion of autoimmunity as functional is one that has repeatedly popped up throughout the history of immunology (so it’s not something that computational immunology has a unique handle on), and the reason it’s not widely accepted is not that it’s been rejected mindlessly, but that there’s never been much or good evidence put forward for it. Rephrasing an old idea in the sparkly new wrapping du jour isn’t helpful unless it offers a new way to test it — which I don’t see here.

The other problem is that this seems to come out of the blue. He claims that the computational view sees autoimmunity in this way but doesn’t really show the connections; to be honest it comes across to me as someone with a particular hobbyhorse, trying to drum up support for an old idea. In other words, I’m neither convinced that this concept is either new to computational immunology, nor that it’s particularly strongly suggested by computational immunology. To be fair, this is a short section in a short review paper, and in a longer treatment I might be more convinced by the argument.

I have the same concerns about the “states of stress” argument, though I will say that this basic concept is one I find much more plausible — though again I’m not convinced it’s particularly unique to this approach, or that it’s particularly strongly suggested by this approach.

So I’m a sympathetic audience to the basic concept that a computational approach to immunology could have some useful outcomes, but I’m not blown away by the examples in this paper. I’d like to see more explanation of the kinds of questions and answers this approach could provide, with concrete examples.

  1. Real and artificial immune systems: computing the state of the body. Cohen IR. Nat Rev Immunol. 2007 Jul;7(7):569-74. []