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July/August 2019

Beyond chemistry: Prions

Most people trained in the sciences have a thirst for new knowledge – call it ‘fundamental curiosity’. My own background led me in many directions, but perhaps the greatest driver, after I became a ‘specialist’, was the embarrassment when asked by a layperson ‘What do you do?’. My answer of ‘I research’ or ‘I teach’ never seemed to be acceptable, and so for years I used the words ‘I’m a nuclear magnetic resonance (NMR) spectroscopist’. Many a doubtful look led me to realise that I was not ‘communicating’, a fault that I urge most practising scientists to examine of themselves.

Over time, my group was involved in synthesising and examining a diverse range of fundamental chemical structures and conformations, first of scientifically significant hydrocarbons, then of the molecules of life, of stereochemistry in analgesic drugs and related compounds, of natural products (some noxious), selected complex carbocations, small proteins, and the chemistry of living cells that metabolise nutrients – all ultimately using NMR spectroscopy to probe structure, often correlated with theories.

Later I published a series of monographs and short reviews on subjects such as lasers, membranes, superconductivity (part of my speciality), biomaterials, electrode materials, and sensors. All had a chemical basis, but with a common theme – medical applications.

Up to a century ago, the major causes of death in the world were infectious diseases caused by bacteria, viruses and parasites. Christopher Dobson (Cambridge) notes: ‘the cause and more effective means of treatment and prevention of such diseases were dramatic following the development of vaccines and antibiotics’. However, ‘the decline in the number of infectious diseases has itself led to major changes in the human condition, not least as a result of greatly increased life spans, and a large increase in cases of non-infectious conditions, notably cancer and cardiovascular diseases’.

The discovery of prions introduced another dimension characterised by fatal neurodegenerative diseases such as scrapie (in sheep and goats), kuru in some hill tribes of Papua New Guinea, BSE (bovine spongiform encephalopathy) in cattle, chronic wasting disease (CWS) in deer, elk and moose, and Creutzfeldt–Jacob disease (CJD) in humans. In 1982, Nobel Laureate Professor Stanley B. Prusiner introduced the term ‘prion’ to describe a relatively small protein comprising about 250 amino acid residues. Subsequently, good and bad (‘rogue’) prions were identified – the former appear to perform valuable and specific biological functions, but others undergo a substantial conformational change (from a largely α-helical to a ß-sheet structure) and in so doing become the self-replicating ‘rogue’ proteins, which produce fatal consequences in their victims. In addition, many different strains of prions have been identified.

In common with scrapie, kuru, BSE, CWS and CJD, many of the maladies associated with ageing such as Alzheimer’s, Parkinson’s, and Huntington’s disease, even motor neurone disease and type-2 diabetes, result in formation of the ‘spongiform’ character of brain tissue, along with ‘proteinaceous deposits’ in the tissue of all sufferers. There appears to be growing evidence that all these diseases may be associated with a ‘rogue’ prion.

I have educated myself about prions mainly through reading and watching video lectures. I was initially fortunate enough to see the work of Dr Michael Alpers, an Australian medical officer in Papua New Guinea, and realised the history of this topic spans over 60 years (the records on scrapie go back to 1755). The most disturbing finding is that prions survive techniques to eliminate them, including disinfection and incineration; and, dangerously for some parts of the animal kingdom, they survive long term in soils where migrating herds roam. The story of the BSE outbreak in the UK also led to recognition that the production of feed pellets from various protein sources (including infected animals) might have exacerbated the BSE problem. This view was somewhat upheld when those same ‘food pellets’ inadvertently caused fatalities in animals at London Zoo.

While the structures of many prions have been determined, the mechanism by which they undergo conformation change and self-replication remains uncertain. Resolution of this mechanism may provide the avenue for effective means of treatment and prevention of prion diseases.

Many nations have established specialist research centres focused on prion research. In Australia, Professor Colin L. Masters (University of Melbourne and Florey Institute) characterised the amyloid protein that forms the cerebral plaques observed in Alzheimer’s disease (1985). (Such amyloid proteins have subsequently been identified in most prion-diseased tissue.) Masters established the Australian National Creutzfeldt–Jakob Disease Registry in October 1993. Subsequently, in 1994, the CJD Support Group Network Pty Ltd (CJDSGN) was established in Sydney. CJDSGN is a non-profit company established to receive grants and donations to fund the work of supporting all Australians affected by CJD or other prion diseases. It is funded by the Commonwealth Department of Health and offers assistance to people ‘at increased risk of developing CJD’ by promoting an environment in healthcare settings where patients feel comfortable and confident of receiving equity of care when disclosing their ‘at risk’ status. The CJDSGN provides information, support and assistance to families who are caring for or are coming to terms with the loss of a loved one to CJD.

What is the impact of this ‘new’ knowledge on my areas of interest, or in applications? I wish I were an active researcher, but alas retirement calls us all eventually. If there are others like me with an interest in prions, then I would be interested to discuss this topic on social media, as long as we aim to steer clear of sensationalism.

My intention is to keep up with the literature, notably reviewing the findings of the main players in the field, not least which is Stanley B. Prusiner (see p. 34), who currently edits some of the major international reviews on the subject.

Alan J. Jones FRACI CChem

This column features the learning of chemical professionals about a subject outside their area of expertise. Readers interested to contribute are invited to contact the Editor ( for further information.

Alan’s learning list

Alpers M. ‘The science and the sorcery’ [documentary],

Centre for Prions and Protein Folding Diseases, University of Alberta:

CJD Support Group Network,

Colby D.W., Prusiner S.B. Prions, Perspectives in Biology, Cold Spring Harbor Laboratory Press, 2011.

Creutzfeldt–Jakob disease surveillance in Australia:

Dobson C.M., Dobson J.M. Plagues and history: from the Black Death to Alzheimer’s disease, Cambridge University Press, 2017.

Dobson M. Murderous contagion: a human history of disease, Quercus, 2015.

Dorak S.J. et al. Soil characteristics may be related to chronic wasting disease persistence, Scientific Reports 2017, 7(1).

Florey Institute of Neuroscience and Mental Health ‘What causes Alzheimer’s disease?’ [lecture]:

Ingram J. Fatal flaws: how a misfolded protein baffled scientists and changed the way we look at the brain, Yale University Press, 2012.

Ironside J. ‘Prions: the serial killers that attack the brain’ [lecture],

Johnson C.J. et al. Prions adhere to soil minerals and remain infectious, PLOS Pathogens, April 2006.

Klug G.M. et al. ‘Creutzfeld–Jakob disease surveillance in Australia, update to December 2016’, Commun. Dis. Intell. 2018, 42 (PII: S2209-6051(18)00023-4)

Masters C.L. et al. ’Amyloid plaque core protein in Alzheimer disease and Down syndrome’. Proc. Natl Acad. Sci. USA 1985, 82(12), 4245–9. 

Prusiner S.B. Madness and memory: the discovery of prions – a new biological principle of disease, Yale University Press, 2016.

Prusiner S.B. (Ed.) Prion biology, Cold Spring Harbor Laboratory Press, 2017.

Prusiner S.B. (Ed.) Prion diseases, Cold Spring Harbor Laboratory Press, 2017.

Simpson D.A., Masters C.L., Ohlrich G., Purdie G., Stuart G., Tannenberg A.E.G. Iatrogenic Creutzfeldt–Jakob disease and its neurosurgical implications. J. Clin. Neurosci. 1996, 3, 118–23.

Up to a century ago, the major causes of death in the world were infectious diseases caused by bacteria, viruses and parasites.
... prions survive techniques to eliminate them, including disinfection and incineration; and ... they survive long term in soils where migrating herds roam.

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