Wednesday, March 25, 2015

The asinine reason why the name JCD was converted to CJD

Originally referred to as Jakob-Creutzfeldt disease (and believed by many to rightfully be called simply Jakob's disease), we now refer to this prion disease as Creutzfeldt-Jakob disease. Why? It all stems from a Dr. C. Joseph Gibbs, a colleague of D. Carleton Gajdusek at the National Institutes of Health, who worked on this disease back in the 1960's. Here's the explanation, lifted from Nobel laureate Stanley Prusiner's Madness and Memory: The Discovery of Prions - A New Biological Principle of Disease:

"Alfons Jakob wrote a paper in 1921 describing several cases of progressive dementia with widespread neuronal loss in the brain. A year earlier, Hans Creutzfeldt had described the brain of a woman who died after a prolonged series of seizures. He found widespread vacuolation, but some medical scientists believe that his patient died of a seizure disorder complicated by hypoxic brain damage and doubt that she had what became known as CJD. So why did the named Jakob and Creutzfeldt become flipped in an important report on the disease, regarding the transmission to a chimpanzee? Twenty years passed before I found the answer, in conversation with Gibbs. 'When I was writing my first paper on the transmission of Jakob-Creutzfeldt disease to an ape,' he told me, 'I wanted to rename the disease Gibbs disease. I didn't think this would be acceptable to the scientific and medical communities, so I decided to reverse the names, because my first name is Clarence and my middle name is Joseph and my initials are C.J.' Thus did the diease become known as Creutzfeldt-Jakob disease, or CJD for short - a case of mind-boggling scientific mischief." 

Gibbs (left) and Gajdusek with a New Guinea kuru patient in 1972.
A remarkable case of hubris, although from what I hear about Prusiner, he is not one to point fingers at those who grasp credit for the work of others. Gajdusek, also a Nobel prize winner, once wrote in his diary the following about Prusiner:

""I never heard a word of original thought from you nor read such ideas in anything you authored for which I did not recognize immediately its source, which you always went out of your way to obscure. You a heretic? You a martyr? You a defender of unacceptable ideas? Bullshit! You shrewdly jumped onto a bandwagon of creative ideas and experimental work and shrewdly got on to the winning cart, proclaiming outrageously in press and media it was yours! I respect you less and less as your despicable game succeeds and you bask in your coveted fame."

But then again, Gajdusek himself, who died in 2008 at age 85, was no paragon of virtue.In the course of his research trips in the South Pacific to study kuru , Gajdusek had brought 56 mostly male children back to live with him in the United States, and provided them with the opportunity to receive high school and college education. He was later accused by one of these, now an adult man, of molesting him as a child. In fact, seven men testified in confidentiality about Gajdusek having had sex with them when they were boys.  Gajdusek was charged with child molestation in April 1996, based on incriminating entries in his personal diary and statements from a victim. He pleaded guilty in 1997 and, under a plea bargain, was sentenced to 12 months in jail. After his release in 1998, he was permitted to serve his five-year unsupervised probation in Europe. He never returned to the United States and ultimately died in Norway.

Monday, March 9, 2015

Peto's Paradox: why elephants don't get brain cancer

I was recently informed by a second-year medical student that elephants rarely, if ever, get brain cancer -- or other malignancies for that matter. This statement seemed illogical. If every living cell has a chance of becoming cancerous, massive animals like elephants and whales - by virtue of the fact that they have so many more cells -- should have a greater risk of developing cancer than do humans or mice. But, when I looked into it, it turns out that the student was right! A January 2013 article in Nature points out that across species, the occurrence of cancer does not show a correlation with body mass.

The lack of correlation between body mass and cancer risk is known as Peto's Paradox, after epidemiologist Richard Peto of Oxford University in the UK, who noted it in the 1970s. Evolutionary biologists think that it results from larger animals using protective mechanisms that many smaller animals do not.

Evolutionary biologists say that evolution does not always favor tumor-suppressor genes. Although these mechanisms could reduce cancer mortality in any animal, they may come at a cost — reduced fertility, in the case of one research group's model. The result is that for intermediate-sized animals, the evolutionary cost of having many tumor suppressor genes is greater than the benefits of cancer protection they offered. In other words, it is better for the population, evolutionarily, to tolerate more deaths from cancer rather than investing in more costly mechanisms to avoid cancer development. But for massive animals, the cancer avoidance cost of having many tumor suppressor genes is worth it since giant beasts tend to produce few offspring per animal.

Another theory to explain Peto's Paradox is that large animals generate fewer reactive oxygen species resulting from a lower basal metabolic rate and therefore have a lower chance of a suffering a genetic mishap.

Researchers around the world are trying to find the mechanism of Peto's Paradox with hope that it can shed light on cancer prevention and treatment in humans.

Neuropathology Blog is Signing Off

Neuropathology Blog has run its course. It's been a fantastic experience authoring this blog over many years. The blog has been a source...