Friday, September 18, 2009

Evolutionary significance of color vision gene therapy

An aspect of the color blindness story that we didn't mention in our earlier post, but should have, is the evolutionary implication. Like humans, the monkeys in the experiment have three types of cone cells, L cells or cells that are sensitive to light of long wavelength, M, or medium wavelength sensitive cells and S, or short wavelength (blue) sensitive cells. Color blindness occurs in primates missing the L or M sensitive photopigment. In this experiment, the investigators introduced a photopigment gene that was expressed preferentially in M cone cells, into animals that were red-green color blind.

We quote here from the paper (Gene therapy for red-green colour blindness in adult primates, Mancuso et al., Nature, advance online publication 16 September 2009).

Classic experiments in which visual deprivation of one eye during development caused permanent vision loss led to the idea that inputs must be present during development for the formation of circuits to process them. From the clear change in behaviour associated with treatment, compared both between and within subjects, we conclude that adult monkeys gained new colour vision capacities because of gene therapy. These startling empirical results provide insight into the evolutionary question of what changes in the visual system are required for adding a new dimension of colour vision. Previously, it seemed possible that a transformation from dichromacy to trichromacy [from seeing 2 colors to seeing 3, which, in combination, allows us to see the full spectrum of color that we do] would require evolutionary/developmental changes, in addition to acquiring a third cone type. For example, L- and M-opsin-specific genetic regulatory elements might have been required to direct the opsins into distinct cone types9that would be recognized by L- and M-cone-specific retinal circuitry, and to account for cortical processing, multi-stage circuitry might have evolved specifically for the purpose of trichromacy. However, our results demonstrate that trichromatic colour vision behaviour requires nothing more than a third cone type. As an alternative to the idea that the new dimension of colour vision arose by acquisition of a new L versus M pathway, it is possible that it exploited the pre-existing blue-yellow circuitry. For example, if the addition of the third cone class split the formerly S versus M receptive fields into two types with differing spectral sensitivities, this would obviate the need for neural rewiring as part of the process of adopting new colour vision.

So, in these monkeys, M cone cells that were previously not sending signal to the brain began to do so after a functional photopigment gene was introduced and activated in the retina. Apparently no new brain circuitry was required for these monkeys to begin seeing color, because they began to do so at the same time that high levels of the expressed transgene were detectable. Thus, the investigators suggest this experiment is a reprise of the evolution of color vision, and that it didn't require new cortical function or circuitry but only the addition of a third cone type.

The latter conjecture is worth thinking about, but the basic color vision system is much older and many studies have been done about the gene arrangement, spectral sensitivity, and adaptive aspects of the system. It is not a simple evolution, much less a story of novel progress from simple to complex, not even in primates. But if it can help understand how eye-to-brain wiring and perception works, it will be a step forward.


John R. Vokey said...

As much as I agree with the position espoused by MT, I wish to make a different point. No question getting retinal-cells to express new proteins as a consequence of gene therapy (if that is what this was) is just way cool. It is, but there is NO EVIDENCE that it has or had anything to do with the perception of colour by these monkeys. Yes, they somehow (even the principal researchers have no idea) came to pass a test of red (and presumably green) ``colour-blindness'' that they had previously failed. But, that says NOTHING about the monkey's prior visual perceptions of colour.

The ``colour-blindness'' test is one designed such that those *with* the requisite proteins (and, normally, the corresponding receptors) pass the test and those without, don't. That does NOT mean that those without the protein (or receptor) fail to see reds or greens in natural contexts. As Land demonstrated all those years ago, one only needs some (indeed any) variant of two channels sensitive to wavelengths of light longer in one than the other to achieve full (if allegedly somewhat paler than that of those with the ``requisite'' full complement of receptors) colour vision.

So, as much as I prefer not to place anything but complete darkness in a monkey's head, to the extent that ``colour vision'' is a property of those with three receptors, I see no reason NOT to assume the same for those with only two.

What these monkeys achieved was the ability to pass a very specially-constructed test, NOT, as most reports alleged, ``colour vision''. Indeed, on has to have a very Newtonian view of colour vision to credit anything about colour vision at all to these experiments.

Don't get me wrong, getting retinal cells to express new proteins (if that is what they are doing, and that is what accounts for the results---both of which are huge unknowns at this point) is amazing, and worthy of attention. The rest, though, about colour vision, is just ignorant shite.

Ken Weiss said...

Thanks much for your thoughtful post. We totally agree. In fact, there is natural variation in the 'good' red & green opsins and there is no way to know if these colors are perceived in the same way in each of us.

I agree also about Land's work and its importance. Color blind people perceive these spectrum differences in their own way and while some have difficulty distinguishing them not all do.

I've written about this a few years ago in my Crotchets & Quiddities columns for Evol. Anthropology (titled "How the eye got its brain", available from my web page. And Anne and my earlier book Genetics and the Logic of Evolution discusses color vision at some length.

So the bottom line is not the probable hyperbole of the news story, but the possible efficacy of a method that could reverse real vision problems.

Schwoom said...

I would like to add my own layman's opinion on this subject. I am color blind, basic red-green, and in my own interests into the subject conclude me to believe that the amount of rewiring of the brain is very little. Color blindness has led me to spend more time on the mechanics of sight, and as I cannot physically see red, my brain must "add in" that color for the object that I am looking at. I find that pattern and subtle shifts in color are where I get hung up the most, as the amounts of the color I cannot see are not hit-you-over-the-head bold. I would then believe that what is lacking in the mechanics of my own sight are the original optical stimulus of red and green colors. And, if those could be added to the signals already going to the brain, the brain could stop "adding in" colors and report what it sees.

In relation to this study and others regarding color blindness there would be someone that is color blind, to give the researchers a point of reference regarding the daily practicality of not being able to see all the colors of the rainbow

John R. Vokey said...

Your brain does not ``add in'' the colours of red and green as you describe it except in so far as it could said to be doing so for all of your experiences of colour. That was my point of invoking Land's work on colour constancy. For an evocative linkage of Land's work to ``colour-blindness'', please check out Wendy Corlos' site on colour vision: .

The point is you (and no doubt, the monkeys in the original piece) already ``see'' red and green. The addition of the new proteins be expressed in the cones may assist under low-light or monochromatic (red or green) conditions to maintain the ``seeing'' of red or green, but are not necessary in that way for the experience.