David R. Brown | |
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![]() David R. Brown | |
Born | |
Citizenship | British/Australian |
Alma mater | University of Sydney (BSc, MSc, PhD) |
Known for | Research on prion diseases |
Scientific career | |
Fields | Neuroscience |
Doctoral advisor | Max Bennett (scientist) [1] |
Professor David Ronald Brown (born 7 September 1964, Sydney, Australia) [2] is an Australian-born research scientist notable for his work on prion diseases, which include bovine spongiform encephalopathy and vCJD. His most notable research relates to the metal binding of the protein central to these diseases, the prion protein, and its possible cellular role as an antioxidant.
Brown was a member of the Spongiform Encephalopathy Advisory Committee (SEAC), a British government advisory board on BSE and related diseases. [3] Since then he has pursued research related to other neurodegenerative diseases. [4]
Brown completed his studies at the University of Sydney at the age of 25 and gained the degrees B.Sc. M.Sc. and Ph.D. His doctoral studies were carried out in the Neurobiology Research Centre under Professor Max Bennett and involved research on nerve regeneration.
After completing his Ph.D. he worked for several more years in Australia before moving to the US in 1993 where he worked at the Albert Einstein College of Medicine. He moved to Germany and worked at the University of Göttingen where he first began work on the study of prion diseases in the Department of Neuropathology with Hans Kretzschmar. In 1997 he moved to the University of Cambridge and in 2001 to the University of Bath, where he is currently Professor of Biochemistry. [4] He consults in this capacity with the media. [5] He is the author of several textbooks and a number of research papers on prion diseases, and has served on the boards of four scientific journals, [6] [7] [8] including the Journal of Neurochemistry. [9]
Brown advanced research related to the role of metals in the cause of prion diseases such as vCJD. Media attention focused on this work when it became associated with that of the farmer Mark Purdey, who argued that human cases of vCJD might be caused by exposure to manganese rather than eating beef from BSE-infected cattle (the medical consensus). [10] [11] Both Purdey and Brown agreed that exposure to elevated levels of manganese in the environment could increase the incidence of BSE. [12]
Brown's research showed that manganese causes the protein to change conformation, similar to that seen in prion diseases such as BSE. [13] Additionally, his research also showed that animals with BSE and humans with vCJD had elevated levels of manganese in their brains, and that prion protein extracted from their brains retained some of this manganese. Brown agreed with Purdey only in as far as the potential for manganese to be a risk factor, increasing the likelihood that BSE or another prion disease would occur. Brown supported Purdey in his quest to investigate the potential role of manganese in prion disease and this led to the filming of a program for the BBC in which both Brown and Purdey appeared. [14] While Purdey pursued the notion that environmental manganese was a cause of BSE (something that arguably could never be proven), Brown suggested that a chelation therapy to remove the excess manganese from patients with vCJD could be of benefit. While Brown's more conventional research was very well funded, such chelation therapy for prion disease was never funded despite support for the idea from a number of sources including Charles, Prince of Wales. [11]
Books
Articles
Creutzfeldt–Jakob disease (CJD), also known as subacute spongiform encephalopathy or neurocognitive disorder due to prion disease, is a fatal neurodegenerative disease. Early symptoms include memory problems, behavioral changes, poor coordination, and visual disturbances. Later symptoms include dementia, involuntary movements, blindness, weakness, and coma. About 70% of people die within a year of diagnosis. The name "Creutzfeldt–Jakob disease" was introduced by Walther Spielmeyer in 1922, after the German neurologists Hans Gerhard Creutzfeldt and Alfons Maria Jakob.
A prion is a misfolded protein that can induce misfolding of normal variants of the same protein and trigger cellular death. Prions cause prion diseases known as transmissible spongiform encephalopathies (TSEs) that are fatal transmissible neurodegenerative diseases in humans and animals. The proteins may misfold sporadically, due to genetic mutations, or by exposure to an already misfolded protein. The consequent abnormal three-dimensional structure confers on them the ability to cause misfolding of other proteins.
Scrapie is a fatal, degenerative disease affecting the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies (TSEs), and as such it is thought to be caused by a prion. Scrapie has been known since at least 1732 and does not appear to be transmissible to humans. However, it has been found to be experimentally transmissible to humanised transgenic mice and non-human primates.
Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of progressive, incurable, and fatal conditions that are associated with prions and affect the brain and nervous system of many animals, including humans, cattle, and sheep. According to the most widespread hypothesis, they are transmitted by prions, though some other data suggest an involvement of a Spiroplasma infection. Mental and physical abilities deteriorate and many tiny holes appear in the cortex causing it to appear like a sponge when brain tissue obtained at autopsy is examined under a microscope. The disorders cause impairment of brain function which may result in memory loss, personality changes, and abnormal or impaired movement which worsen over time.
Feline spongiform encephalopathy (FSE) is a neurodegenerative disease that affects the brains of felines. This disease is known to affect domestic, captive, and wild species of the family Felidae. Like BSE, this disease can take several years to develop. It is currently believed that this condition is a result of felines ingesting bovine meat contaminated with BSE.
Protein misfolding cyclic amplification (PMCA) is an amplification technique to multiply misfolded prions originally developed by Soto and colleagues. It is a test for spongiform encephalopathies like chronic wasting disease (CWD) or bovine spongiform encephalopathy (BSE).
The major prion protein (PrP) is encoded in the human body by the PRNP gene also known as CD230. Expression of the protein is most predominant in the nervous system but occurs in many other tissues throughout the body.
John Mark Purdey was an English organic farmer who came to public attention in the 1980s, when he began to circulate his own theories regarding the causes of bovine spongiform encephalopathy.
Variant Creutzfeldt–Jakob disease (vCJD), commonly referred to as "mad cow disease" or "human mad cow disease" to distinguish it from its BSE counterpart, is a fatal type of brain disease within the transmissible spongiform encephalopathy family. Initial symptoms include psychiatric problems, behavioral changes, and painful sensations. In the later stages of the illness, patients may exhibit poor coordination, dementia and involuntary movements. The length of time between exposure and the development of symptoms is unclear, but is believed to be years to decades. Average life expectancy following the onset of symptoms is 13 months.
Bovine spongiform encephalopathy (BSE), commonly known as mad cow disease, is an incurable and invariably fatal neurodegenerative disease of cattle. Symptoms include abnormal behavior, trouble walking, and weight loss. Later in the course of the disease, the cow becomes unable to function normally. There is conflicting information about the time between infection and onset of symptoms. In 2002, the World Health Organization (WHO) suggested it to be approximately four to five years. Time from onset of symptoms to death is generally weeks to months. Spread to humans is believed to result in variant Creutzfeldt–Jakob disease (vCJD). As of 2018, a total of 231 cases of vCJD had been reported globally.
Meat and bone meal (MBM) is a product of the rendering industry. It is typically about 48–52% protein, 33–35% ash, 8–12% fat, and 4–7% water. It is primarily used in the formulation of animal feed to improve the amino acid profile of the feed. Feeding of MBM to cattle is thought to have been responsible for the spread of BSE ; therefore, in most parts of the world, MBM is no longer allowed in feed for ruminant animals. However, it is still used to feed monogastric animals.
The National Prion Clinic (UK) is part of the University College London Hospitals NHS Foundation Trust. Its aim is to diagnose and treat patients with any form of human prion disease (Creutzfeldt-Jakob disease, CJD). In addition, the clinic facilitates research in diagnostics and therapeutics, organises clinical trials, and counsels those with an increased genetic risk of the disease.
Dundee Cell Products (DCP) is a biotechnology company headquartered in Dundee, Scotland, United Kingdom.
Rosalind Ridley is a British psychologist and researcher who was head of the Medical Research Council Comparative Cognition Research Team in the Department of Psychology, Cambridge, UK, until 2005. She was a fellow of Newnham College, Cambridge from 1995–2010 and Vice-Principal from 2000–2005. She holds the privileges of a Fellow Emerita at Newnham College.
Frank O. Bastian is an American physician and neuropathologist, who previously worked at Louisiana State University, moved to a university in New Orleans in 2019. He specializes in the transmissible spongiform encephalopathies (TSEs), which include, but are not limited to, Bovine spongiform encephalopathy (BSE) "Mad cow disease" in cattle, scrapie in sheep and goats, and Creutzfeldt–Jakob disease (CJD) in humans.
Diseases of abnormal polymerization, or simply DAPs, are a class of disorders characterized by a novel alteration in base unit proteins that results in a structure with pathogenic potential. This functional alteration in a protein in relation to its thermodynamic and kinetic properties enacts an extended chain response among neighboring proteins until an extensive and potentially harmful polymerized structure is formed. Due to this endogenous foreign formation, these diseases are often untreatable and very severe in clinical manifestation. Although DAPs are rare infections, the poor outcome in patients and the need for further understanding makes this class of diseases a pillar for future research.
The United Kingdom was afflicted with an outbreak of Bovine spongiform encephalopathy, and its human equivalent variant Creutzfeldt–Jakob disease (vCJD), in the 1980s and 1990s. Over four million head of cattle were slaughtered in an effort to contain the outbreak, and 178 people died after contracting vCJD through eating infected beef. A political and public health crisis resulted, and British beef was banned from export to numerous countries around the world, with some bans remaining in place until as late as 2019.
Real-time quaking-induced conversion (RT-QuIC) is a highly sensitive assay for prion detection.
Michael Coulthart is a Canadian microbiologist who is employed as the head of the Canadian Creutzfeldt–Jakob Disease Surveillance System (CJDSS) within the Public Health Agency of Canada (PHAC), which terms CJD a zoonotic and infectious disease. In 2006, a working group named "classic CJD" as well as Variant Creutzfeldt–Jakob disease as two notifiable diseases. It is unknown whether PHAC tracks in an official capacity other transmissible spongiform encephalopathies (TSE), but Coulthart is on the Advisory Committee of the Center for Infectious Disease Research and Policy for Chronic Wasting Disease of cervidae.
The Creutzfeldt-Jakob Disease Surveillance System (CJDSS) is a unit of the Public Health Agency of Canada. It studies the various variants of Creutzfeldt-Jakob Disease, and at least as of 2017, assisted "with DNA sequencing, autopsy and case confirmation". As of 2014, the CJDSS conducted "prospective national surveillance for all types of human prion disease in Canada. The main purposes of the CJDSS [were then] to better understand the epidemiology of human prion diseases, to improve the options available for their rapid and accurate diagnosis, and ultimately to protect the health of Canadians by reducing risks of prion disease transmission."