|Died||2 February 1995 86) (aged|
Sarisbury, Hampshire, England
|Education||M.A., doctoral studies (cut short by leaving Germany)|
|Known for||research on the infectious agent in Scrapie, made notable during the Mad cow disease outbreak in Britain in the 1990s|
|Spouse||Max Sterne (1906–1994)|
|Doctoral advisor||Lise Meitner|
Tikvah Alper (22 January 1909 – 2 February 1995) trained as a physicist and became a distinguished radiobiologist.Among many other initiatives and discoveries, she was among the first to find evidence indicating that the infectious agent in Scrapie does not contain nucleic acid: a finding that was instrumental in understanding the development of the Prion theory. She was director of the MRC Experimental Radiopathology Unit, Hammersmith Hospital, London, UK, 1962–1974.
She married Max Sterne but never adopted his name.
Tikvah Alper was born in South Africa, the youngest of four daughters in a family of Jewish refugees from Russia.As a schoolgirl at Durban Girls' High School, she was described as "the most intellectually distinguished girl ever to attend the school", and matriculated with distinction a year early. She graduated with distinction in physics from University of Cape Town in 1929, and then studied in Berlin with the nuclear physicist Lise Meitner in 1930–32, publishing a prize-winning paper on delta rays produced by alpha particles in 1933. In 1932, she returned to South Africa to marry the (later) renowned bacteriologist Max Sterne, the inventor of the most effective livestock vaccine for anthrax. Because married women were not then permitted to work at University, Tikvah and Max established a home laboratory where they worked together. Their sons, Jonathan and Michael, were born in 1935 and 1936. From then on, Tikvah Alper combined demands of motherhood (Jonathan was born profoundly deaf), marriage and career. These included pre- and post-war spells in England, where she worked with the pioneer radiobiologist, Douglas Lea. Over ten years from 1937, Tikvah retrained and then also worked as a teacher of the deaf. Her physics training and technical skills were evident in her published research on making speech articulation visible, for use in speech training for deaf children She became head of the Biophysics section of the South African National Physics Laboratory in 1948.
Despite their growing scientific renown, in 1951, Max Sterne and Tikvah Alper were forced to leave South Africa because of their outspoken opposition to apartheid. Tikvah found an (unpaid) research post at the MRC Radiobiology Laboratories at the Hammersmith Hospital, London, directed by Hal Gray, whom she had met on earlier visits. Here, work focussed on the mechanisms of the effects of radiation on cell biology. The complexities of the effects of radiation on different cell types, and their interaction with other physiological and chemical processes began to be mapped out at this time, and continued through the 1950s and 60s. She was Director of the Radiobiology Unit from 1962 until her retirement in 1974. Her classic text Cellular Radiobiologywas published in 1979. Tikvah Alper continued an active professional life in retirement, culminating in a "brilliant lecture to the Radiation Research Society in Dallas, USA at the age of 83..". She died in Sarisbury, Hampshire, England, in 1995, and was survived by her husband Max, sons Jonathan and Michael, six grandchildren, and three great-grandchildren.
Scrapie is a fatal infectious disease of the neural system of sheep; one of a class of brain diseases that can affect cattle (BSE) and humans (Kuru, nCJD). Scrapie had been thought to be caused by a 'slow virus' – one that could take years to show as a change in behaviour or movement. By the mid-1960s, it was established that cells could only replicate via DNA. Radioactivity stops cell replication by 'killing' DNA. Alper found that radiation did not kill the infective agent in scrapie, suggesting that a virus was unlikely to be the infective agent. The infective agent had to be smaller and simpler than (viral) DNA. Alper also found that the agent remained active under ultraviolet light. DNA is inactive under UV light. Instead, the agent was killed by light at 237 nm, a wavelength specific to polysaccharide inactivation. Alper and colleagues reported these properties of the scrapie agent – a finding that was greeted with astonishment in many quarters, for it appeared to contravene the central dogma that holds that replication (and hence the growth of the disease and its infectious properties) can only proceed via DNA. However, once these empirical findings were accepted, several theories developed to accommodate the peculiar properties of the scrapie agent. The most widely accepted theory today is the prion theory, which posits a 'rogue' protein as the infectious source. However, Alper could not accept that a protein 'mutation' was the agent. Firstly, her UV radiation studies did not indicate a protein agent and, secondly, isolated prions did not induce scrapie. Her own theories concerning the agent were developed in the last years of her life and suggested a more dynamic and complex story.
Creutzfeldt–Jakob disease (CJD), also known as subacute spongiform encephalopathy or neurocognitive disorder due to prion disease, is an invariably fatal degenerative brain disorder. 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 transmit its misfolded shape onto normal variants of the same protein. Prions are the causative agent of several transmissible and fatal neurodegenerative diseases in humans and other animals. It remains unknown what causes a normal protein to misfold into a prion, however, its consequent abnormal three-dimensional structure confers infectious properties by collapsing nearby protein molecules into the same shape in a chain reaction.
A human pathogen is a pathogen that causes disease in humans.
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, new studies suggest a link between scrapie and sporadic CJD.
Transmissible spongiform encephalopathies (TSEs) are a group of progressive 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, including memory changes, personality changes and problems with movement that worsen chronically.
Structural inheritance or cortical inheritance is the transmission of an epigenetic trait in a living organism by a self-perpetuating spatial structures. This is in contrast to the transmission of digital information such as is found in DNA sequences, which accounts for the vast majority of known genetic variation.
The virino is a hypothetical infectious particle that was once theorized to be the cause of scrapie and other degenerative diseases of the central nervous system; it was thought to consist of nucleic acids in a protective coat of host cell proteins. The hypothesis was never widely accepted, and the causative agents responsible for these diseases are now widely accepted to be prions.
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 CWD or BSE.
Major prion protein(PrP), is encoded in the human by the PRNP gene also known as CD230 (cluster of differentiation 230). Expression of the protein is most predominant in the nervous system but occurs in many other tissues throughout the body.
Laura Manuelidis is a physician and neuropathologist at Yale University.
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.
Kuru is a rare, incurable, and fatal neurodegenerative disorder that was formerly common among the Fore people of Papua New Guinea. Kuru is a form of transmissible spongiform encephalopathy (TSE) caused by the transmission of abnormally folded proteins (prions), which leads to symptoms such as tremors and loss of coordination from neurodegeneration.
Bovine spongiform encephalopathy (BSE), 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 around the time between infection and onset of symptoms. In 2002, the 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.
Surround optical-fiber immunoassay (SOFIA) is an ultrasensitive, in vitro diagnostic platform incorporating a surround optical-fiber assembly that captures fluorescence emissions from an entire sample. The technology's defining characteristics are its extremely high limit of detection, sensitivity, and dynamic range. SOFIA's sensitivity is measured at the attogram level (10−18 g), making it about one billion times more sensitive than conventional diagnostic techniques. Based on its enhanced dynamic range, SOFIA is able to discriminate levels of analyte in a sample over 10 orders of magnitude, facilitating accurate titering.
In biology, a pathogen in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ.
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 medical doctor 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.
John Stanley Griffith (1928–1972) was a British chemist, mathematician and biophysicist. He was the nephew of the distinguished British bacteriologist Frederick Griffith.
Alma Clavering Howard Rolleston Ebert was a Canadian-born English radiobiologist. She was joint editor for many years of the International Journal of Radiation Biology and deputy director of Paterson Laboratories in Manchester. She made a "fundamental contribution to cell biology" in collaboration with physicist Stephen Pelc when they "were the first to ascribe a timeframe to cellular life," creating the concept of the cell cycle. Their nomenclature for the stages of cell replication is used universally and appears in every textbook of biology and pathology.
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.