John Dalton (1766-1844) was more than a chemist; he was apolymath. His name is best known for the unit of atomic mass, whichhe defined (kilodalton), and for Dalton's law on the behavior ofgases.

This British savant also studied the aurora borealis, or NorthernLights, and described their "luminous, sometimes colored displays."That was remarkable because John Dalton suffered from Daltonism_ colorblindness _ which he also studied, and which carries hiseponym.

In 1794, he treated the Manchester Literary and PhilosophicalSociety to a lecture on "Extraordinary facts relating to the vision ofcolours," which was the first detailed account of colorblindness,mainly his own. Dalton himself couldn't tell the color of red sealingwax from that of a green laurel leaf. Neither could his brother, whoalso inherited the X-linked syndrome.

Self-diagnosing this color vision defect (ophthalmologically correctterm for the color-vision-challenged), Dalton concluded that theaqueous humor in his eyeballs must be tinted blue, to filter out thelonger wavelengths of red light. He instructed that upon his death, anautopsy should examine this hypothesis. It turned out to be neat,plausible and wrong.

The day after Dalton died, in 1844, a post-mortem found the fluid inhis eyes to be "pellucid" _ crystal clear. It took another 150 years todiscover the true cause of his Daltonism.

Rediagnosis Of Preserved Eyeballs, 150 Years On

In today's Science, two British scientists, a molecular geneticist anda visual psychologist, describe how they determined "The chemistryof John Dalton's colorblindness" by analyzing the genes in hispreserved eyeballs.

"The intention of our work," said molecular geneticist David Hunt,of London University's Ophthalmological Institute, "was to go backand establish what sort of colorblindness he actually had."

The most common form of color vision defect, Hunt told BioWorldToday, is red-green colorblindness, which affects about 8 percent ofthe male Caucasian population, but only 0.4 percent of females. Thisdiscrepancy exists because the visual opsin genes cluster on the sex-linked X chromosome.

"There are in fact two extremes of this red-green colorblindness,"Hunt explained. "That is where either the red-sensitive photopigment or the green is completely absent from the visual cones inthe retina." Either way, he added, "as far as the persons' perceptionof color is concerned, of course, it's much the same; they can'tdistinguish red from green."

Hunt continued: "From Dalton's own observations, subsequentcommentators have all agreed that his colorblindness was of the kindwhere the red pigment is absent. But by looking at the molecularbasis of his Daltonism, we've been able to show that thecommentators were wrong. In fact, Dalton's retina lacks the greenpigment. He had a red pigment gene, and therefore we infer hewould have had a red photo pigment, and it lacks a green gene, andtherefore presumably lacks the green pigment."

After that 1844 autopsy, Dalton's eyeballs ended up as the propertyof the Manchester Literary and Philosophical Society, which hadheard his theories half a century earlier. They now lie locked away inthe Manchester Museum of Science and Industry.

"We approached the Society," Hunt recounted, "for permission toremove some small fragments from the eyes for DNA analysis. Theytold us: `Only small fragments; don't damage the things.'" The"things," Hunt recalled, "were wizened, dry, brown objects, whichyou would be hard-pressed, I think, to actually identify as eyes. Itwas difficult to discern anatomical landmarks on them."

With a pair of fine forceps, he took several tiny, flat slivers of tissue,"perhaps a millimeter in length by a third in width, but of course nothickness."

Record Corrected By PCR

To prepare those desiccated wisps of retina for the polymerase chainreaction (PCR), the British team immersed them in GeneReleaser, aproprietary reagent from BioVentures Inc., of Murfreesboro, Tenn.,which liberates nucleic acid from cells, while sequestering celldebris.

Hunt and his principal co-author, visual psychologist John Mollon,of Cambridge University, used the PCR to amplify fragments of thevisual pigment genes from Dalton's retinal DNA. "First of all," Huntsaid, "we started with primers specific to the genes encoding eitherthe red or green photo pigment proteins. The results gave us our firstindication that Dalton had lacked a green gene, because the red-specific primers amplified a fragment of the right size, and the green-specific ones did not."

After cloning and sequencing the gene, they compared it withpreviously sequenced red genes "from other individuals, rathernormal observers."

Having corrected Dalton's own misdiagnosis, Hunt and Mollon nowmake the point that "one must be very cautious about theinterpretation of what people with color vision defect say about theirown colorblindness."

Hunt said "that this is the first example where anyone has been ableto diagnose a hereditary defect in a specific historical figure. That'snever been done before." He added, "So we are suggesting thatperhaps it's the start of a new discipline, so to speak, which could becalled `molecular biography.'"

He pointed out that "Lots of people from the past have left bits ofthemselves behind, such as hair and so forth. One can get DNAs outof this sort of material now."

He mused that "as we find out more and more about genes of thiskind, genes particularly affecting the development and function ofthe nervous system, it may well be possible to go back to otherfamous _ and infamous _ characters, and find out what theirproblems were."

What will the newly minted molecular biographers do for an encore?Hunt replied, "We certainly are on the lookout to follow up on thissort of approach, which I think is fascinating." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.