Of Prions and Panic

A couple of interesting, orthogonal news items appeared over the past few weeks, which I didn't get the chance to write up separately when they were first published, as I have been working to a deadline. Thankfully, that particular deadline has passed and I have some free time to talk a little about prions and (widespread) panic.

Prions

Perhaps it is already well-known to researchers working in the field, but it was a surprise to me when I came across a paper by Parkin et al. in PNAS describing the connection between "normal" prion proteins and the formation of beta amyloid plaques in the brain (electronic publishing date 15 June, print date 26 June 2007). This research was also picked up by the BBC.
(Edit 9 July: this has also now been picked up in New Scientist).

Basically, while misshapen versions of these prions are known to be causative agents of transmissible spongiform encephalopathies such as Creutzfeldt–Jakob disease, their function while in their normal shape is unknown. Parkin et al. hypothesize that the normal prions have a regulatory – specifically, inhibitory – role in the creation of beta amyloid plaques. Overexpression of the normal prions inhibited the cleavage of APP (amyloid precursor protein), the first step in the creation of beta amyloid. Conversely, the complete removal of the normal prion via either siRNA or the use of knockout mice resulted in significant increases in the level of beta amyloid.

This research implies that increasing the expression of the normal prion in the brain could help prevent the beta amyloid plaques forming in the first place. It is very encouraging to see so much interesting Alzheimer's research going on at the moment. While CISBAN researches other areas of ageing, including how telomere length affects the ageing process in the cell, I am always interested in research into other areas of ageing, including age-related illness.

Panic

OK, I stretched this analogy slightly in order to achieve pleasing alliteration. Go from "panic" to "Widespread Panic", a band who made one of my favorite songs, "Big Woolly Mammoth". This song leads me to another bit of science that's been in the news again recently: is it possible to re-create a woolly mammoth via 40,000-odd year old samples? The question was raised in Scientific American last week via a profile they were doing on Svante Pääbo from the Max Planck Institute for Evolutionary Anthropology in Leipzig.

This is not a new question, and Pääbo has published research in September 2006 in PNAS that described the most common errors introduced into ancient wolf mitochondrial DNA sequences via amplification and sequencing procedures. SA states that he has been doing similar work more recently on Neandertal and mammoth DNA. By determining more exactly which bits of the sequence are artefacts of either the degradation of the sequence over long stretches of time or the sequencing process, we are one step closer to being able to achieve the correct DNA sequences for very old tissue samples.

Of course, this doesn't mean that we are now able to successfully bring back extinct species. More than just the DNA itself is needed: the packaging of the DNA (notably the histones) and other assorted proteins are also necessary. One of SA's interviewees states that what is really needed is an intact cell, not just the DNA.

But this next step in the creation of a "clean" sequence does bring interesting ethical questions to the fore once again. Should we recreate an extinct species, if we could? Undoubtedly, once the techniques are available, some rich investor will try to get it done privately, even if the public research centers do not want to do it. One could argue that there is no place in today's world for Neandertals or mammoths. But what about those species that were killed in "the modern era" via ignorance or deliberate intent of Homo sapiens? The dodo was killed by humans and their associated animals such as rats and cats.Attempts had been made in the late 1800s to give the passenger pigeon, which once numbered in the billions in North America, protected status. However, it was rejected as people simply didn't believe the pigeon could be in decline. The last confirmed passenger pigeon died in captivitiy in 1914.

So, where do you draw the line? And what if we had not just DNA, but also intact cells? What if the bald eagle, recently taken off the endangered species list due to an impressive comeback over the decades, were to die off from a disease? Should all animals made extinct through methods attributable to humans be re-created? I can forsee that if a favorite pet species such as cats or dogs were made extinct through disease, there would be people clamoring for researchers to try it. Personally, I think there are good scientific reasons to seriously consider such methods in certain instances: I'm just not yet sure what those instances would be. Perhaps its just my love of sci-fi, or the sadness I feel at today's human excesses (me included, even with all our attempts to "be green") that makes me feel this way.

But I think it will happen, and within the lifetimes of people living today. The question is, how far will it go? From the passenger pigeon to Jurassic Park, anyone? 😉 Would we be doing it for the right reasons, if we did bring back the dodo or the passenger pigeon or the Quagga? Or, would it just be to make us feel better about ourselves? Perhaps "making ourselves feel better" would be a good-enough reason to bring back a species, perhaps not. How would it change endangered species legislation? Would it cause people to not worry about hunting a species to extinction, as it could just be "revived" in the same year? Indeed, would it become a goal for a certain type of hunter to make a species extinct? OK, maybe a little too much wandering into the land of sci-fi…

In any case, an exciting and fabulous time to live in, and what a fantastic area to work in.

Note from 5 July 2007: And, in an interesting addendum, National Geographic just published an article about the recent discovery of high-quality dodo bones that probably contain well-preserved DNA.

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