POSTED 14 FEB 2002
As those highly bred dogs prance and strut at the Westminster Kennel Club, The Why Files got to thinking about the downside of inbreeding: genetic defects. Inbreeding reduces genetic diversity, and concentrates defective genes in the offspring, leading to genetic disease.
Many dog breeds are known for hip problems, largely due to the continual inbreeding required by kennel-club regulations. But blindness may be even worse: Irish setters, Norwegian elkhounds and collies, among others, suffer congenital blindness.
Even a little-known sheepdog called a Briard suffers inbred blindness, in the form of LCA, or Leber congenital amaurosis. LCA in patients -- whether canine or human -- may lack a gene for a protein that transports a chemical called a retinoid in the retina. This vitamin A-like compound plays an essential role in the first stage of vision -- the transformation of photons of light into chemical energy in the eye's retina.
It's as simple as this: No transformation, no vision.
Can genes be fixed?
"This study takes a great stride forward in demonstrating that gene therapy does not just slow down a retinal degenerative disease, but can actually provide recovery of vision to an animal that was previously blind," Bennett said.
The success could set the stage for a similar experiment in humans, but since that's several years down the pike, let's see how the dog's sight was restored.
The researchers genetically engineered a virus that frequently infects people but does not cause disease to carry the RPE65 gene, which was lacking in the dogs (and in the 2,000 Americans born each year with LCA, who go blind soon after birth). Then they injected the virus beneath the retina in the dogs, waited a few months, and performed electrical tests to see whether the dogs could see.
And they could -- but only in the eye that had gotten the virus carrying the gene. In fact, the eyes not only responded on electrophysiological tests of retinal function. The dogs could also navigate mazes and dodge obstacles -- unless they were on the left side (only the right eye had been fixed). Even 18 months after the dogs got their new genes, they continue to see, Bennett told The Why Files, and one has even made two Congressional appearances -- without pleading the Fifth Amendment, by the way...
"We have worked hard for many, many years to develop a treatment for retinal degeneration, and this is the biggest leap forward yet," states Bennett. "However, we are nowhere near the introduction of the missing protein in humans to restore sight."
The first human tests are about years away, she says,
and will start by testing the safety, not the effectiveness, of gene therapy.
University of Pennsylvania press release.
The Truth About Dogs, Stephen Budiansky, The Atlantic Monthly, July, 1999.