CJD videos

UCSF's Memory and Aging Center has a nice collection of videos on CJD and prions at their website and on their YouTube channel.

"Confronting CJD & Other Prion Disorders" is a very nice overview but there are 30 videos in total, many that might answer questions you have. From First symptoms of CJD to Is beef in the U.S. safe to eat? And then there's ' Can you have a man in a tie explain prions with plasticware'?

Killing prions

How do you kill something that isn't alive? With great difficulty.

The Challenge of Prion Decontamination
Iatrogenic transmission of these diseases via contaminated medical devices is considered rare, but it has been documented. In an experimental case, transmission of the disease was observed despite cleaning and decontamination of the medical device with formaldehyde. Clinically, 2 cases of TSEs have been confirmed in which transmission of the disease was due to the use of implanted depth electrodes that had been previously used on a patient with CJD and were inadequately decontaminated by cleaning with benzene and disinfecting with 70% alcohol and formaldehyde. Other cases have been linked to the use of neurosurgical instruments. These reports highlight the need for safe and effective prion decontamination methods.

The World Health Organization and the US Centers for Disease Control and Prevention recommend that instrumentation used in cases likely to have high infectivity be immediately destroyed after use; short of destruction, it is recommended that heat and chemical decontamination be used in combination to process instruments that come in contact with high-infectivity tissues.

Stanley Prusiner

There's also an interview with Prusiner at the Nobel Prize website.

Prions and memory

As we now know Prions are really just misshapen forms of a normal protein that occurs in everyone. This raises the important question of just what these 'normal' prions do in the body. One suggestion is that they may be involved in the maintenance of memory:  Prions as adaptive conduits of memory and inheritance (in yeast) and Hippocampal synaptic plasticity in mice devoid of cellular prion protein (in mice). From the first paper:

Any molecular basis for long-term memory formation must explain its endurance (for many years) despite the continuous turnover (every few hours) of the proteins that might encode them. Information storage despite molecular turnover is traditionally explained by autophosphorylation loops, self-sustaining feedback loops in complex signalling networks, or transcription factors that stimulate their own synthesis once they cross a threshold concentration. The conformational replication of prions provides another durable form of molecular memory. Moreover, as is clear from studies in yeast, prion conformations are not usually toxic. Incredibly, prion-based mechanisms might operate in individual neuronal synapses to maintain their growth and contingent long-term facilitation.

Fungal prions are proving to be a very useful model organism for studying mammalian prions since numerous forms have now been identified, they are infectious and self-replicating like mammalian prions but they do not appear to be associated with disease in fungi. In fact there are several suggestions they may have aided fungal evolution.

The end of Kuru

A Fore woman in mourning covered with ashes, in 1957.

With the end of cannibalism in New Guinea Kuru gradually declined. In 2006 and 2007 for example there were zero cases and in 2008 the Royal Society of London held a conference to celebrate the end of Kuru. The papers are all gathered together in an issue of the Philosophical Transactions of the Royal Society and, in contrast to most conferences, include a fascinating array of personal recollections as well as scientific papers. These personal recollections are often quite moving. Check out:

‘My late husband Mr Anua was a hard-working man’
'We had to climb mountains and cross fast-flowing rivers'

‘Most people still believe that kuru is caused by sorcery’

There are also more detailed papers about the epidemiology of Kuru:

Understanding kuru: the contribution of anthropology and medicine
Early perceptions of an epidemic

Prion evolution

One of the big unanswered questions in biology is what is life? Some philosophers of science have pointed out that a science (biology) where the topic of study (life) cannot be defined is unacceptable. Drawing the boundary between life and non-life is hard because of a number of discoveries that appear to exist in the gray area - from viruses, to viroids, to satellites, to prions.

Prions are just proteins and do not show metabolism or contain any nucleic acid or genetic code but they have recently been shown to undergo Darwinian selection in the same way as living organisms. Check out the Science paper from last month, Darwinian Evolution of Prions in Cell Culture, or the BBC report on the research, 'Lifeless' prion proteins are 'capable of evolution'.

"Now we know that the abnormal prions replicate, and create variants, perhaps at a low level initially.

"But once they are transferred to a new host, natural selection will eventually choose the more virulent and aggressive variants."

Fatal Familial Insomnia

Prion diseases are all, fortunately, rare. Unless we throw some cannibalism (actual or hi-tec) into the mix - then they can increase dramatically in prevalence. It seems likely that most, if not all, prion diseases occur as rare genetic mutations. I very briefly mentioned Fatal Familial Insomnia in class. This is an extremely rare prion disease caused by an inherited genetic mutation. The mutation responsible has been found in just 50 families worldwide. Although patients frequently do not show symptoms until middle age or later the subsequent progression into complete sleeplessness is untreatable, and ultimately fatal.