OK, I'll field this one. I'll ignore any of the tell-tale signs of hokum such as writing in ALL CAPS.
Nevertheless, it's a lot of hokum. It's true that he goes into a lot of detail and I'm sure his math looks nice but the fact is that it's not grounded in reality. I would consider myself to be something of an expert (in training) in the field of phototransduction, so I'll focus on claims related to it. However, if he's as sloppy with the rest of the visual process as he is with phototransduction, then his claims are entirely bogus. I'll just be working from the Synopsis section.
Where to start...How about the first sentence of the "Background" section:
This work originated in the 1960's with the realization that rhodopsin, as then defined, did not meet the requirements for being a chromophore. It was particularly deficient in the structural characteristics required of a good chromophore.
FALSE. Rhodopsin is not a chromophore and, to my knowledge no one has ever claimed it to be a chromophore. Rhodopsin is a protein. It is coupled with a chromophore, retinal, a form of vitamin A. OK, so if this is the foundation of his research, he is off to a bad start.
The basic assumption had been that the residues of a destructive process could be easily returned to their original state and that state was a simple chemical bond involving only two components in a single molecule...It was assumed that one of the residues was the alcohol or aldehyde of Vitamin A. The other residue was assumed to be a protein and was given the name opsin. Valiant, but unsuccessful, efforts were made to define the nature of the molecule and achieve the formation of rhodopsin in the laboratory.
It absolutely is possible to reconstitute rhodopsin with the chromophore in the lab. This has been going on since at least 1983. Also, the crystal structure of rhodopsin, including the chromophore, was resolved in 2000.
A new class of retinoids was defined by the author at that time, the Rhodonines. This class met the requirements of physical chemistry and photochemistry for a high performance chromophore. However, it was difficult to obtain acceptance of the Rhodonines as a replacement for Rhodopsin within the vision research community.
I have never heard of Rhodonines and web searches only result in his page. Due to his confusion of terminology, I don't know if he is proposing them to be proteins ("replacement for Rhodopsin") or simple chemical molecules ("a high performance chromophore"). If it were the former, one would wonder why Rhodonines were not identified in a comprehensive proteomics assay of the rod outer segment. One would also wonder why rhodopsin is so highly expressed in the outer segment (on the order of 1e8 molecules in mammals and 1e9 molecules in amphibians, more than any other protein in that compartment). If it were the former, one would wonder why there is an entire biochemical cycle dedicated to recycling retinal that takes place just outside the outer segment.
I'll ignore whatever physical state these Rhodonines are supposedly in since they don't exist. I'll also ignore this "Activa" thing. He owns a patent on it, which doesn't bode well for its existence in nature.
The visual system is a very sophisticated system. It uses many of the most sophisticated methodologies known to man at the start of the 21st Century. Failure to recognize these mechanisms and methodologies leads to an inadequate understanding of the overall process.
I'll agree there, with the exception of the use of the word "methodologies"! This isn't engineering, this is biology.
The visual system employs a number of time related processes that have not previously been addressed in the literature. To understand these processes, it is necessary to employ "complex algebra" in the differential equations arena. Employing these techniques provides the complete solution to the overall photoexcitation/de-excitation process within the Outer Segment of the photoreceptor
Phototransduction has a rich history of mathematical modeling. And yes, they involve "complex algebra in the differential equations arena." An excellent review of the first few decades of it can be found in the bible: Phototransduction in vertebrate rods and cones: molecular mechanisms of amplification, recovery and light adaptation. Since that publication, there have been two very nice lineages of models: one comprehensive one that focuses on the proteins (1, 2, 3) and one that focuses on spatial accuracy and stochastic interactions and gives more attention to second messengers (1, 2, 3).
It has also been compounded by the historically poor preparation of the researchers in the field of mathematics.
I challenge him to read one of DiBenedetto's modeling papers and not glow in admiration of his mathematical prowess.
The goal has been to present an overall view of the visual system in a defendable mathematical context and a global scientific framework. This goal has required the introduction of techniques and mechanisms not normally found in the literature of vision. This has been particularly true in two areas, the definition and detailing of the initial photodetection process and a similar detailing of the mechanisms of neural signal transmission. In both cases, the dominance of chemically based concepts is shown to have impeded progress. The description of the visual system, including the neural system, as an entirely electronic, more precisely electrolytic, based system leads to much greater insight into the operation of the visual system than any chemically based theory can offer.
I had to quote in full here. This is entirely bogus. The "initial photodetection process" (phototransduction) is entirely chemical in nature. All of the main players in the process are known and their interactions are largely well understood. Viewing the system as entirely "electronic" ignores the mountains of evidence of all of the proteins participating in it.
Probably the most venerable is that of a dichotomy between types of photoreceptors, the rods and cones. The theory demonstrates in excruciating detail that there is only one functional type of photoreceptor cell and that it is associated with one of four types of chromophore. These chromophores are sensitive in the ultraviolet, the short, the medium and the long wavelength portions of the visual spectrum of light.
The problem with this is that if you look at a retina, you can see rods and cones. You can generate knock-out animals that have only one or the other. Those with only rods cannot handle bright visual stimulii, those with only cones cannot see in the dark. More damning is that you have two distinct phototransduction cascades, separated by evolution dating back to the origins of vertebrates. They share only a few proteins in common and otherwise have unique paralogs performing similar duties. You can isolate individual rod cells and, if you're clever and you have the right species, individual cone cells (they're much smaller and harder to harvest in animals like mice or cows). You can measure their electrophysiological characteristics and find that they are extremely different: cone responses are fast while rods can respond to a single photon of light. Their morphologies are completely different: the rod outer segment is filled with lipid bilayer disks, while that of the cone has a series of in-folds.
As for the whole tetrachromat thing, well, again I have to assume that he's referring to opsins when he talks about chromophores. Thanks to genomics, we can be confident that there are only three cone opsin varieties in old world apes (and one rod opsin). The rest of mammals only have two. If you get into other vertebrates, you'll find more...if you get into invertebrates, you'll find ridiculous numbers. There's not much to say here. A fourth cone opsin protein simply does not exist in the human genome.
So, that's just a quick overview. Do not worry about this guy's research. It is unsubstantiated and exists in a vacuum outside of the rest of the vision research world. I do wish that there were a way for him to work with others. I do wish there were a way for him to integrate current knowledge into his work. But the problem is that his work as it stands simply seems to ignore the wealth of data generated on the visual system and instead treats it as some theoretical circuit.
