Steven Dealler Comments on recent scientific articles concerning BSE
Adapted from Stephen Dealler's site in UK -- repeated here because that server is often down
Bovine spongiform encephalopathy and public health.
Concerning the article in the J. Public Health Medicine. Volume 17 number 3, 1995, pages
W. J. Patterson (Consultant in Public Health Medicine)
S. Dealler (formerly Senior Registrar at York District Hospital. now: 01282
Symptomatic cases of BSE in British cattle now total more than 146,000. As BSE is one of a
group of transmissible and fatal spongiform encephalopathies (TSEs) affecting both animals
and humans this has raised concern regarding possible risks to human health. The infective
agent in TSEs, thought to be a prion has not been clearly described. There are no early
diagnostic tests, incubation periods are prolonged (possibly up to 30 years in humans) and
the pathological process which leads to a rapidly progressive and fatal encephalopathy has yet
to be explained.
It is not yet known if the BSE agent can cross the human species barrier to infect humans. It
has now been transmitted to 18 species and to 16 of these (possibly 17 if pigs are included)
Given the importance of beef in the human diet, it is essential that control measures to protect
health are rigorous, comprehensive and objective. In this respect there are four factors which
are important in assessing risks. These are the likely magnitude of the species barrier
between cattle and humans, the dose (single or cumulative) that are needed to transmit the
disease, the method of exposure (oral or subcutaneous) and the likely period before
symptomatic disease appears.
To assist knowledge and understanding in these areas we recommend the wider involvement of
public health professionals in the existing nationally co-ordinated multi-agency research
programme. We also recommend further studies into the oral transmissibility of the BSE
agent to primates, an acceleration of the search for diagnostic tools and treatments for
established prion infection and enhanced surveillance of neurological disease in humans.
It is now clear that probably a large percentage of the population will have been exposed to
BSE in the UK.
Humans will have eaten 1,800,000 infected cattle by 2001 and will have eaten tissues that
have been shown to be infective in other species, but inadequately tested in cattle. Humans
have already taken risks in eating bovine products that have now been banned. The recurrent
banning of foods or procedures by MAFF will not help the people that have been exposed before
the ban. It is possible that further action such as this by MAFF will seriously damage the
public's respect for its action.
The article's most important part is to show that the World Health Organisation's publicised
opinions on how to decide whether or not the exposure of a human to a specific amount of an
infective agent could not have been carried out as inadequate information was available with
which to decide the action. As a result of this it was important that Government action should
assume a tolerable level for human exposure to BSE to be very low indeed, possibly 10,000
times less then the amount felt acceptable by MAFF. Concerning the article in the British Food
Journal 1995, volume 97, 3-18.
The most important aspect of the article seems to be the WHO directives as to how to decide
what levels of an agent should be considered non-toxic to humans. Clearly a wide error margin
is given by the WHO but still this would suggest the risk that is being taken with BSE as being
unacceptable in public health terms.
BSE: an update on the statistical evidence.
British Food Journal 1995, volume 97, p3-18
S. Dealler Medical Microbiologist, Burnley General Hospital, Burnley, UK BB10
2PQ. 01282 474292
John Kent Professor of Statistics, University of Leeds, Leeds, UK. LS2 9JT. 0113
The article explains that, as a fatal disease, with no method of treatment, inadequate methods
of diagnosis and no method of prevention in any animal afer infection has taken place, this
subject should be studied closely. Infectivity is presumed, if like in other TSEs, to be present
in many tissues and to not be destroyed by cooking. One of the major problems is in trying to
calculate the number of infected animals that are being eaten and at what point in their
incubation period this takes place. It seems that there is adequate data now available from
MAFF for this to found. The major findings of the article are:
Cases of BSE are becoming severely under-reported. For instance only 40% of clinical cases
of BSE reached UK Government statistics in 1993.
BSE may continue in the UK for many years, with cases born each year, showing symptoms 3
to 8 years later.
BSE may not be derived from the disease of sheep, scrapie and if it is, we cannot rely on it to
carry the same properties as that disease. The UK Government used the idea that BSE was
scrapie originally to suggest that BSE would not infect humans although this was invalid at the
1,800,000 cattle incubating BSE will have been eaten before 2001 even if no cases are born
after 1991. This figure assumes that all cattle with BSE were always reported by farmers to
veterinary officers, that the VOs always accepted them, and that histological diagnosis was
always correct (up to 1991). It is therefore likely to be an underestimate of the true BSE
incidence. Many of the younger cattle incubating BSE would have been exported to Europe.
The epidemiology of BSE in the UK is that of an infection passed down from the mother to the
offspring but where the mother would show symptoms later in life. It may be that BSE cases
that we see are derived from infections in their mother and it was the mother that ate infected
food. If this is true then the total number of infeced cattle eaten in the UK will be around
8,000,000 by 2001.
UK Government advisors have suggested that there is little risk from eating liver, kidneys,
nerves and muscle from infected cattle. The article shows that this cannot be true if these
tissues contain the same amount of infectivity as is found in other species with a similar
The acceptable levels (UK Government) of infectivity to found in food may be 10,000 times
the amount that could be seen as acceptable under WHO directives used for other potentially
UK Governernment Advisory Committee on Dangerous Pathogens reported in October 1994
showing that cattle that may be infected should be treated as if they are infective. They say that
some tissues should not be even touched (e.g. liver) that the UK Government continues to tell
its population as being acceptable to eat.
The risk to humans in Europe from BSE is unacceptably high but cannot be stated precisely at
this time. The article states again that the cumulative amounts of BSE in our diet in the UK is
expected to be between 10,000 times and 100,000 times the amounts of scrapie that we
would be eating.
No directions are given as to whether bovine tissue in the UK should be considered toxic.
In situ hybridization and immunohistochemistry for
prion protein (PrP) in BSE
Graber, HU, Meyer, RK, Fatzer, r, Vandevelde, M, Zurbriggen, A.
In about 5% of the cows showing clinical signs of BSE the histopathological examination is not
conclusive (it is closer to 15% in the UK - Ed). In order to rule out BSE in these cases,
additional methods are necessary. For that reason, non-radioactive in situ hybridization
(ISH) was performed. In addition, for immunological testing a polyclonal antibody was raised
against a synthetic peptide derived from bovine PrP. These two techniques were used on 4
cows with clinically suspect but histologically negative cattle. It is not completely clear what
they found but it seems that the four cases were also shown to be negative by these new
techniques, allowing BSE to be ruled out. The immunological technique can also be used with
EM to look for SAF.
Western blot mapping of disease-specific amyloid in
various animal species and humans with TSEs using a
high yeield purification method
Beekes, M, Baldauf, E, Cassens, S, Diringer, H, Keyes, P, Scott, AC, wells,
GA, Brown, P, Gibbs, CJ, Gajdusek, DC.
J. Gen. Virol. 1995;76:2567-76.
A complex study in which a 20-100mg sample of tissue could be used to extract TSE-specific
amyloid, this would be concentrated and the material detected by Western blotting. It was
discussed as a potential method of diagnosis.
Proposed link between transmissible spongiform
encephalopathies of man and animals.
Lancet November 4 1995, 1208-1209
Heino Diringer Robert-Koch Institute, Nordufer 20, D-13353, Berlin, Gemany
030 4547 2214
It is suggested that scrapie is the source of all TSEs in animals and man but that, by passing
from one species to another the agent is either selected or changed in such a way as to alter the
range or type of disease that it might produce in a further animal species.
For instance it is suggested that scrapie does indeed cause the endemic types of CJD that seem
to be present in some parts of the world (e.g. Slovakia) and partly associated with PrP gene
aberrations. However, when scrapie is transmitted to cattle, it then becomes more infective to
humans and is involved in the production of sporadic CJD in many parts of the world.
The cases of GSS that are not fully penetrant may be because the genes are correct but the
agent (scrapie) is still required. In cases of fully penetrant GSS perhaps the agent also
remains with the infected person.
The argument is fairly reasonable in that it will be very difficult to find groups that have not
been exposed to meat at all, even though they think they have not. It will also take a long time
to be able to carry out statistical research to say if beef is involved in sporadic CJD or not
(because the controls will also eat a lot of beef and the difference between the groups will be
small). Diringer recommends research as the way to find out what is going on but the current
PrP research avalanche may only be of some use if animal inoculation studies are carried out
Royal College of Pathologists Symposia.
CJD and health and safety in the autopsy
25th Jan 1996 JW Ironside, Univeristy of Edinburgh. He goes through the necessary
practices to avoid a risk to people following the death of someone with possible CJD.
(avoidance of penetrating injuries, minimal contamination of the mortuary environment,
traning and education fo staff, adequate decontamination of instruments and rooms. The major
thing that is not incluced is that we do know currently know which patients are infected and
which are not. While the number of humans currently incubating BSE is unknown, the
regulations in the mortuary suite must apply to all patients.
Will BSE transmit to humans
BMJ 25th November 1995 p1415-6
Jeffrey Almond. School of animal and Microbial Sciences, University of Reading.
He says that although TSEs do transmit, we still do not have proof that BSE will transmit to
humans. He reviews the molecular biology of the PrP gene that may help us decide.
The Jury is still out
. BMJ 25th November 1995 p1416
Paul Brown. Lab of Central Nervous Studies NIH, Bethesda, MD
"In fact no one can say yet with any confidence whether the recent cases of CJD in adolescents
and farmers are the results of infection with BSE.". he states that really young cases have been
seen before and we should not assume that the new cases are anything to do with BSE. F
"Finally there does not seeem to be any need for new governmental hearings, committee
meetings or parliamentary debates about what more might be done because the precaustions
taken some yars ago to eleiminate potentiallly inecvtious products from commercial
distribution were both logical and thorough" (I hope he was right, but I doubt it-Ed)
More than happenstance: CJD in farmers and young
BMJ 25th November 1995 1416-8
Sheila Gore. MRC Biostatistics Unit, Inst of Public Health, Cambridge
She demonstrates that the chance of getting two teenagers 'back to back' and four farmers with
CJD in 4 years is so low that they could not have happened by chance. He work sparked off a lot
of debate and it was felt from this that something was happening that theydid not know about.
Who gets CJD?
BMJ 25th November 1995 1419
Ros Ridley, Harry Baker. MRC Comparative Cognition Team, Department of Experimental
Psychology, Cambridge Univ
. They put forward the argument that the figures are simply not big enough for there to be any
great risk. Four cases of apparently idiopathic CJD have been reported in teenagers in Europe
and the USA. Obviously these were nothing to do with BSE. They felt that the CJD Surveillance
Unit led to a higher level of reporting of cases and that these cases were of little significance.
Furrowed brow over mad cow
BMJ 25th November 1995 1419
GW Roberts. Molecular Neuropathology, Smith Kline Beecham, prk North, Harlow.
He explains that we simply cannot know. The data islong and hard and at the end of going
through it we still dit not end up being sure if BSE infected humans. He quoted the work of
Dealler and Kent showing that the number of people that would have eaten various doses of BSE
could be actually so variable as to be unhelpful but a worst case scenario would suggest a
dreadful result. He discusses the problems that changes in environmental factors, changes in
reporting levels, changes in many other factors may mislead us.
Risk of human exposure to BSE
. BMJ 25th November 1995 1420
Kenneth Tyler. University of colorado, Health Sciences Center, Denver VA medical Center,
He looks at the inoculum size, the routes of inoculation the host factors (e.g. can humans be
infected at all), the genetics and the implications for disease prevention. In the end he does not
say if humans have caught CJD but says that really to avoid any risks we should avoid contact
with nervous and lymphoreticular tissue. He does not even make the same pretece that MAFF
does continually i.e. that there is no infectivity in any bovine tissue except brain and spinal
cord. He says that meat is not expected to harbour major amounts of infectivity.
If BSE infects humans, when will we start to see
Federation of Infection Societies, Manchester Symposium, November 29th 1995
S. Dealler, Burnley General Hospital
By looking at other species and the incubation period that is produced by the transfer of
infectivity it is possible to estimate when a rise in BSE cases in humans as CJD2 cases would
be expectd to take place. This shows that we might be lucky to see any cases at all before the
year 2000 and that the peak may be 15 years later. The reason for this is that humans have a
very long life expectancy, BSE has been transmitted by mouth, and it has had to cross a species
barrier. If cases of CJD2 were to appear earlier than 2000 that might be an indication of the
size of the peak to come.
Research paper 95/132 Produced by the Science and Environment Section of the House of
Commons Library. Christopher Barclay and Jane Cushion.Dec 1995
A rather poor review but attempts to go through all the possibilities of CJD and risks from
Diagnosis and incidence of prion (CJD) disease: a
tetrospective archival survey with implications for
Neurodegeneration vol 4 1995;357-368.
CJ Bruton, RK Bruton, SM Gentleman, GW Roberts. Corsellis Collection Brain Bank,
Dept of neuropathy, Runwell Hosp, Wickford, Essex. etc.
Reliable identification of CJD in the UX has become essential following the suggestion that
prion disease in cattle might transmit accidentally to humans who eat contaminated beef.
recent data suggest that some cases f CJD may be conically unrecognized; in order to examine
this proposal we reviewed all cases of dementia (n-1000+) collected between 1964 and
1990. We identified 19 cases of CJD of which only 11 were diagnosed before death. These 11
had a characteristic clinical history of CJD. Their brains showed little or no external
abnormality. In contrast only 2 of the 8 clinically unrecognized cases had characteristic
symptoms. The remaining six presented atypically; their illness lasted 3 years or more,
motor signs were much less evidnt and simple dementia was the most promminent feature. the
brains showed moderate or severe cereral atrophy. Our data indicate that only about 60% of
prion disease cases with pathologically typical SE were identified clinically during life. This
suggests that human prion disease may bemore common than previously supposed and that a
further review of the epidemiology is required.
Inactivation of the BSE agent by rendering precedures
Veterinary Record. Dec 9. 1995. p605-8
DM Taylor, SL Woodgate, MJ Atkinson, Neuropathogenesis Unit, Edinburgh University
Bovine brain infected with the BSE was used to spike material processed in pilot scale
facsimilies of 12 rendering processes which are used within the EU and 3 which are not. the
raw material for experimental rendering represented those used inpractice, and consisted of
appropriateproportions of BSE infected brain tissue, bovine or porcine intestine and bovine
bone. Meat and bone meal and tallow were produced from the rendered tissue. Suspension sof
all the meat and bone meal samples were assayed in mice for BSE. Four of the 15 processes
produced MBM with detectable BSE infectivity. Neither of the tallow samples did. The problem
with the results was that they did not show any great effect for themethods of talow extraction
using solvents. This was the method that was blamed for rendering the MBM safe until the
process was stopped at the beginning of the 1980s in the UK. Presumably the change in
manufacturing cannot be now assumed to have had a specific effect.
CJD and BSE
BMJ 20 Jan 1996 p 180
Terence Featherstone of the Department of Radiology, Darlington Memorial Hosp suggests
that magnetic resonance imaging may be of value in diagnosis of CJD.
Aetiology of scrapie in cetain circumstances is not
evidence against another aetiology in different
BMJ 20 Jan 1996 p 180
Ros Ridley and Harry Baker, Dept of Exp Psychology University of Cambridge. This is the
continued argument that the findings of various groups that suggest vertical transmission of
scrapie can be explained in a genetic manner.
BSE is being maintained by vertical and horizontal
BMJ 20 Jan 1996 p 180
Professor Lacey, University of Leeds He explains that the epidemiological models used
by MAFF had one by one been shown not be be adequate to explain the huge number of cattle
that have developed BSE after being born after the feed ban. He says that the recycling of
remains would cause the rapid rise of the disease but could not be the only cause for the
number of cases remaining so high.
Scrapie can be transmitted to mice by the instillation
of inoculum intothe conjunctiva
BMJ 20 Jan 1996 p 181
Janet Fraser, James Foster, Hugh Fraser, Institute for animal Health, Neuropathogenesis
this was shown in mice.
Secret Government: the Scott report
BMJ 24 February 1996 p455-6.
Martin McKee (Health Secvices Research Unit, London School of Hygience and Tropical
Medicine. Tim Lang
Links with industry cast doubt on the government's role in public health. The report said that
everyone that mislead the House of Commons, misled the media, mislead the people, lied to the
judges, and were determined to send arms to a country that had been banned from receiving
them for political reasons throughout the world, were in fact doing it with a clear heart. They
thought they were doing it for the best even when it came to allowing a group of men to go to
jail even though they carried out the exports with the OK of the Government. The report
suggests that the associaton between industry and Government may be too close to allow. The
meaning of this for BSE is important.
Message from Sir Kenneth Calman, chief medical
A statement indicating to medical practitioners in the UK that in the last two weeks the CJD
Surveillance Unit has described a distinct variant of CJD in 10 cases, in people aged under 42
with dates of onset of illness in the last two years. He states that still the risk of CJD in the UK
is the same as in europe and hat it remains a rare disease. Patients presentig with the
non-specific symptoms are no more likely to be suffering from CJD than previously. There is
no reason for a change in referral patterns to neurologists or other specialist services.
Neurologtists are aware that they can obtain advice from the CJD Unit. 20 march 1995
Mr Dorrell followed by Mr. Hogg speaking on the subject of BSE risk to humans. this was
following the weekend discussion by SEAC concerning risks to children and various others.
Hansard. 25th March 1996 3.31 pm.
Mr. Dorrell states that research into the subject would have to increase and that he had asked
Professor Swales (now at Richmond House, Whitehall, DofH) formerly Prof of Gen Med at
Leicester University, to produce a list of the research that would be required to be carried
Mr. John evans (St. Helens North) asks how Mr. Dorrell could accept advice from the same
group that had been telling him for years that nobody would die of CJD (p722)
Mr. Hogg (p724) gives out the data concerning the number of cattle that would be expected to
be slaughtered and what would be the sort of regulations that would be reqired.
Message frm Sir Kenneth Calman, Chief Medical Officer
25th March 1996
This is the report on the statement as to the risk to children concerning BSE in food products.
It concluded that there was no increases sceptibility to infection for pregnant women, hospital
patients, the immunosuppressed, or children. there is nothing to lead the committee to change
its advice on the sonsumption of milk andmilk products. SEAC also concluded that gelatin was
safe. Children are no morelikely to become infected than adults. He states that further
research isneeded and the WHO will organise an international seminar on the latest results
from the CJD unit as soon as possible.
Lessons from BSE for public confidence
Nature 28 March 1996. 380;271
The scare in Britain over infections across species by rions was badly handled. whether the
research community can do more to prevent future public crises of confidence needs to be
examined in the light of the past influenceof interested parties.
The article makes it plain that the population has difficulty believing what is told to it by
MAFF, which has too many vested interests in selling foods, no matter what the potential risk
to them. Prion research must now be strengthened, denial of information from the people must
be stopped, and external review will be essential.
Mad cow scare threatens political link between food
Nature 28 March 1996. 380;273
A short article on what had gone on during the previous week. It pointed out that the
Government's position to avoid specific research or to take severe action had been that there
was no proof of BSE causing CJD...but there still was no proof.
BSE: the questions that need answers
Nature 28 March 1996. 380;273
A short review of the research that has not been done but requires to be done
Sheila Gore. Senior Statistician, MRC Biostatistics Unit, Cambridge
British Medical Journal. 30 March 1996. 312 p 791-3
Failures of opidemiology must be remedied. The article makes it plain that the action so far
taken in epidemiology was inadequate in order to work out the risk that has been taken in the
UK. She calculates the chance of 10 cases developing CJD betwen the ages of 17 and 41 yrs and
whether that should have been thought of earlier as abnormal. she goes back on her own work
showing that there was excess risk to farmers and teenagers. With the amount of data
currently available she says that it is not possible to assess the risks being taken by people in
the UK by carrying out certain procedures (working on farms, eating beef, dringking milk)
purely because the data was not adequate at the time. Mistakes were made with other
epidemiological attempts e.g. with HIV and false reassurances were given (e.g. HIV and breast
milk). The main aim of the article is to put forward the data that would be required in order to
find out much more about the epidemiology of CJD2. One of the factors that is suggested is that
the disease be made 'notifiable'. This means that doctors seeing a case must report it to
officials and the data would be built up centrally. "Practically we do not have in vitro or in
vivo tests for infected cattle and so have continnued to play Russian roulette with no
information on the odds. Age specific prevalence of infected cattle has not even been monitored
by random pathology after slaughter for which there is now the stronges case".
This is in the editorial section and is very aggressive in its demands
Bovine spongiform encephalopathy and CJD
The risk is unproved but no better explanation is presently forthcoming.
Paul Brown. Medical director, US PHS. Lab of central Nervaous System
British Medical Journal. 30 March 1996. vol 312. p790-1.
He admits that the cases that have been seen have been different clinically from the sporadic
type of CJD and that the finding of neuropathology that is also different (but similar to each
other) would make BSE the most likely explanation. Ill defined early emotional behavioural
dymptoms of the new variant will obviously openthefloodgates to hundreds if not thousands of
suspected cases of CJD over the next few years and it will be a matter o enormous practical
importance that a screening test is produced. He says that a new test is soon to be reported
with a sensitivity of 97% and s specificityof 98%. "A good deal of work remains to be done i
order to esztablish the link between BSE and CJD, much of which has already been initiated.
None of it will be ofany help to htose who may have been exposed to the agent in the 1980s....
Nor will it remedy the possible failure of the scientific pudits (including me) to forsee a
potential medical catastrophe" (Ed-it was good of him to admit that he was wrong, as he had
been denying any risk to humans from BSE for many years)
CJD and BSE
BMJ Vol 312 30 March 1996. p 843
Ridley, RM and Baker H. MRC Comparative Cognition Team, Dept of Experimental
Psychology, Univ of Cambridge. Study so far shows no evidence for maternal and horizontal
transmission. This is an argument with the previous article from Lacey suggesting that there
was evidence. They quote the work of Hoinville and Wilesmith in which they compared the
likelihood of a cow developing BSE as to whether their mother did so. '94.4% of animals with
SE and 95.7% of controls were born to dams that did not subsequently develop BSE'. The
difference was not significant. (Ed-The problem with this is that it would be needed to work
out what percent were actually the offspring of infected mothers and in one of the major
epidemiological models including vertical transmission, there would not be expected to be any
difference between the groups, because such a high percentage of the dams in any herd were in
Cohort study of cows is in progress
BMJ Vol 312, 30 March 1996. p 843
John Wilesmith, Cenral Veterinary Lab
He says that the study will show if vertical transmission is taking place by comparing the
offsppring of cattle known to have BSE with those that are the offspring of other cattle from
the same herd. The results should be ready by the end of 1997. At the moment he denies any
evidence of vertical transmission.
(Ed-this has come under considerable discussion. It is not clear why it is a blind study, as this
should make no difference as to the diagnosis of the vet at the time. After all it is a fatal disease
and the cow cannot be making it up. Similarly the histopathologists looking at the slides in
diagnosis need not be told if they are looking at the slide of the dead cow or a control. A lot of
demands have been made to un-blind the study. Also many people have made it cleat that the
study cannot actually show if there is any vertical transmission or not as the control dam
would also be infected i.e. both the case and the control will have come from infected mothers)
Incidence of BSE is higher in cows born
after the feed ban
BMJ Vol 312. p 843
M. Bennett. Environmental Technology Centre, Depf of Chemical engineering,
UMIST. Box 88, Manchester M60 1QD
He shows that the epidemiology actually shows that the number of cases of BSE born after the
feed ban actually increased and it is not surprising that Lacey makes claims that the disease is
not going away.
Magnetic resonance imaging is not a
sensitive test for CJD
BMJ Vol 312. p 844
Martin Zeidler, RG, Will, J, Ironside, CJD Surveillance Unit Western General Hosp,
Edinburgh and R. Sellar, J. Wardlaw Dept of clinical neuroscience, Western Gen Hosp
Replying to a previous letter sugesting that MRI would be useful.
Meltdown: the media and mad cows
BMJ, 312, 30 March 1996, p854-5
This goes through the days in which BSE was admitted to be a likely risk and the effect it had
on the media.
Slow release of data adds to BSE confusion
Nature 4 April 1996. 380;370
Various European research groups say that the hiding of information by the UK groups does not
help when trying to work out what is going on.
Less beef, more brain
Editorial Lancet April 6 1996, 347; p915
Editorial. It explains the risks that have been taken and how the unfolding story of scrapie,
BSE and CJD underscores the weakness of separating agricultural and medical science and of
allowig one Government department to protect the intersts of both thefood consumers and the
farming industry. Morover the advice of independenet scientists and the creation of political
policy should not come from the same stable. this latest drama points to the need for a
separate, independent agency that reports to the public not to the policy makers. Such an
agency would be a forum for open scientific debate. the iformation andopinions proffered would
be pubicly subjected to critical evaluation. we would all then have the opportunity to
understand how expert opinion and recommendations are formed and politicians could begin at
last to build foresight into their policy responses rather than simply react in confusion and
haste to the latest scientific alarm." Excellent-ed.
A new variety of prion disease
Lancet April 6 1996, 347; p916
John Collinge (Prion disese Group, Dept of Biochemistry, St. Mrys Hosp, London
Martin Rossor Dept of Neurology, St. Mary'sHospital Trust.
They explain how the new cases with CJD2 have different behavioural, clinical, and
histopathological factors that will separate them from CJD1. They make it clear that it would
be better to remain open minded about whether infection has been passed also to other species.
They describe the new condition and how to go about diagnosing it. A good article.
A dreadful challenge.
Lancet April 6 1996, 347; p917
JG Collee. Department of Med Micro, Univ of Edinburgh
Considering Collee wrote a major article in the Lancet in around 1990 indicating that the
risks from BSE to humans, although possible should not be considered to any great degree, this
article is absolutely excellent. It describes the way in shcih infection could take place, how it
may pass into a pathogenic phase, how it could spread around the body, how it could develop
into a clinical disease. A list of essential factors and key questions is put forward and he
explains that we simply know quite inadequate amounts at present to know what isgoing on
with the new CJD2.
A new variant of CJD in the UK
Lancet April 6 1996, 347; p921-25
RG Will, JW Ironside et al . CJD Surveillance Unit, Edinburgh.
Summary: Background. Epidemiological surveillance of CJD was reinstituted in the UK in
1990 to identify any changes in the occurrence of the disease after the epidemic of BSE in
cattle. Methods. Case ascertainment of CJD was mostly by direct referral. Death certificates
onwhich CJD wa menthioned were also obtained. Clinical details were obtained for all referred
cases and information on potential risk factors for CJD was obtained by a standard
questionnaire administered to patients relatives. Neuropathological exam was done on 70% of
cases. Findings. Ten cases of CJD have beenidentified in the UK in recent months with a new
neuropathological profile. Other consistent fewtures that are unusual include the yong age of
the cases, clinical findings and the absense of the EEC features typical of CJD. Similar cases
have not been identified in other countries in the Eurlpean Surveillance system.
Interpretation. These cases appear to represent a new variant of CJD, which may be unique to
the UK. this raises the possibility that they are causally linked to BSE.
Creutzfeldt-Jakob disase in a young woman
Lancet April 6 1996, 347; p945
Tabrizi. SJ. St. Thomas' Hospital, London
A 28 year old woman who had had various neurological problems since the age of 14.
Scrapie theory fed BSE complacency
New Scientist. 13 April 1996 p4.
A journalistic news item. investigating why MAFF in the UK failed to carry out the
experiments to find out if BSE was derived from scrapie and yet continued to claim that 'as
BSE came from scrapie, therefore we wont catch BSE either'. Robert Rohwer who studies
spongiform encephalopathies at the veterans affairs Medical Centre in Baltiore Md said that
the xperiment should have been simple. You just feed scrapie to cows. Iain Pattison suggested
that happen in the UK but Wilesmith simply dismissed this and said it would only tell us what
we knew already. In 1994 18 calves were injected with scrapie. The cows became sick after
14-18nmonths and died within 5 months. But the cattle did not die of BSE, as could be seen by
post mortem study. Mark Robinson of the Animal Disease Research Unit in Pulman,
Washington said "The pathology in the brain did not resemble BSE at all" No strain of scrapie
to date produces a disease incows that resembles BSE. MAFF continue to say that it could jsut
be from a strian that they have not tried. Rohwer agrees that the MAFF scientists explanation
for the origin of BSE is plausible 2but it doesnt excuse the fac thay they have not doen the
experiment2 He suggests that BSE is in fact a new disease that first arose in a few British
cows. because cattle carcasses were also rendered into animal feed, the agent would get to
further cattle. Other influential scientists share Rohwer's criticism that the Brit Govt were
too eager to accept the vfiew based on limited scientific understanding"
Potential transmission of BSE via
...now fears grow for unborn babies
New Scientist. 13 April 1996 p5.
Young women with CJD2 might pass ont the deadly cnodition to their children before showing
symptoms themselves warnds Sheila Gore of the MRC
Messsage from the deputy Chief Medical
This was sent to allthe GPs and most other doctors in the UK. It refers to the following article
in the BMJ. showing that the Mdicines Control Agency who have revisited the subject this
month. Their expert advice remains that medicines licensed for tuse in the Uk are safe.
Non-bovine material or bovine material outside the UK is used. Tallow derivatives have gone
through rigorous extraction procedures to eliminate the causative agent of BSE
Ed-It is not clear just how tallow can be rendered safe from scientific literature
Potential transmisisonof BSE via
BMJ 312, 20 April 1996 p988-9
E Anne Wickham. Hox 246, Canterbury CT4 5YY
Editorial saying that patients can be reassured that measures are in place to reduce risk.
Measures aimed at minimising exposure to TSEs via medicinal products were intoduced soon
after the report of the Southwood committee in 1988 in guidelines for manufacturers issued
by Britain's Comjittee on Safety of Medicines in 1989 and essentially adopted by the European
Committee for Propriatary Medcinal Products in 1992. Materials were to be sourced from
cattle under the age of 6 months, from countries fee of BSE or where low number of cases had
been reported. The guidelines included a classification of various tissues and body fluids
according to potential risk of infectivity based on expoerimental data from scrapie in sheep
and goats. Notably they did not use information from other species e.g. mice, hamster, mink.
She talks about specific products that had been derived from cattle. Notably heparins derived
from lung (lung was found to be highly infective in mice), insulin from the pancreas, and
various sources for gelatins, and serum and lactose. The guidelines recommended purification
procedures known to remove or inactivate agents causing TSEs: autoclaving or treatment with
sodium hydroxide, these being more effective than other methods. The Assn of British
Pharmacutical Industry declare their products to be safe.
She admits that people may well have been at risk from products from before the regulations,
that there may be a risk in the produts still at a low level but stopping the product may be a
greater risk, and the SEAC were happy that the guidelines were satisfactory to protect ..human
She does ot seem to be able to show that any methods of assay of infectivity in the produts has
been carried out, she suggests that assays in mice would be adequate when this is very
unlikely (only a very small amount can be inoculated into a mouse), and does not provide any
calculations as to the number of infected cattle that would have been used for manufacture (or
the point in their incubation period at which this would have taken place), even though this
data could now be calculated from MAFF data. This editorial is calming but does not put
forwards risk analyses, which are what is required.
France wakes up to mad cow risk
New Scientist 20th April 1996
France ignored a warning 4 years ago abou tht erisks of BSE passing to humans the minister
Francois d'Aubert said last week. The previous government dragged its feet apparently. In
1992 the Govt commissioned Dominique Dormont of the Atomic Energy Commissionto write a
report on human and animal forms of TSE. The report was never made public but according to
the research ministry it warned of the "existence of risks from BSE". Marc Cesbron who
studied TSE at Pasteur Inst in Lille says he wrote to the Government in 1991 warning them of
the possibility that BSE could pass to humans. the letter was forwarded to the European
Commission but little happened. D'Aubert said that an extra 5 million franks (650,000
pounds) would bee earmarked for research in 1996 and that next year spending would
increase to 69 million francs (more than in the UK). D'Auberts said he was also launching an
action plan to improve surveillance.
USA takes a close look at deaths from brain disease.
New Scientist 20th April 1996
Four sites: Coneticut, Minnesota, Oregon and California were chosen by CDC to check that their
CJD patients were not really CJD2 that had been exported from the UK!
A role at last for mad cow protein
New Scientist 20th April 1996 p18
Shigeru Katamine a virologist at Nagasaki University and geneticist Tetsuo Noda showed that
when the entire PrP gene was removed specific damage appeared to happen to the mice after a
year. Purkinje cells were damaged and destroyed in the cerebellum. (Nature 380, p528.)
This was one up on the Zurich team that removed on ly part of the gene and the animal
Irene Tobler of the University of Zureich looked a little harder at the PrP mutant mice
(nulls) she showed that they did not sleep normally and repeatedly stayed awake for periods of
up to 16 seconds. Perhaps this explained the fatal familial insomnia syndrome Nature 380
Lancet 20.4.96 Evidence from America and Iceland
that infection of scrapie can remain in 'infected' hay
The Lancet 347, April 20th 1996 p1114.
Wisniewski H. Sigurdarson S Rubenstein R Kascsak R Carp R All from the Inst for
basic res in development and disabil, Staten Island, NY 10314, USA except for Siguardson,
who is from Inst of Experimental Pathology, Univ of Iceland, Reykjavik, Iceland
This is a very important in that it shows the agent for scrapie (or at least a strain of TSE) is
present inside the hay mites that are present on the land. It showed that a relateively high
proportion of the mites were infested, that mice could be infected from them, that hte amount
of prion protein was high enough that the western blotting looking for it in the mite could find
it after dilution of the agent by 200 fold. This may actually suggest that the agent can not just
remain in the mites but perhaps multiplies in them as well. This was required to somehow
explain why scrapie remained associated with the land but gradually died out over many years
(i.e. that sheep put on such land gradually became less and less likely to develop the disease).
What was not made clear in the article is that the hay mite does not live on blood as a source of
food and is not specifically found in parts of the country or with specific groups of sheep etc.
Also the hay mite is very small and it would have been very difficult to carry out the
experiments. This major finding may need a complex investigation.- Ed
Phylogenesis of prion protein
Nature 380 25th April 1996 p675.
Krakauer DC, Pagel, M, Southwood TRE Dept of Zoology Oxford. Zanotto PM Inst
Virology Mannfield Rd Oxford.
Phylogenic analysis for the prion protein. It appears that the PrP structure may actually be
an indication on the ability of the disease to transmit between animals. This may actually
explain why BSE infects humans and scrapie does not. This clearly cannot be the whole story,
however, as although it shows specific parts of the DNA for the PrP in cattle and humans being
the same, they are actually different at around 23 other sites. The chances of the specific
similarity that was found having arisen by accident was 1.2 in 10,000 and so the researchers
believe that the evolutionary pressures that drove the human PrP to change in a specific way
was similar to the pressure on the bovine PrP. The researchers note that the two amino acid
substitutions occur within a region of protein that is known to be involved in prion disease.
Moving the British cattle herd
Pete smith, JU Smith, David Powlson Soil science, ICR Rthamsted, Harpenden, Herts
Nature 2 May 1996;381:15 They calculated the affect that ploughing in the soil on which the
cattle had been grazing and decided that it was too detrimental. They calculated the carbon
content effect on the UK soil pool and felt that, without a strong scientific reason this would be
Two years ago we warned of the danger from BSE and
were criticised, now officialdom has changed its
Safety management. vol 12 May 1996.
This discusses why the British Government was determined not to take into account the advice
from safety groups earlier in the BSE epidemic in the UK.
Prediction of future BSE spread
Stekel DJ, Nowak, MA, Southwood, TREDep tof Zoology, Univ of Oxford, Oxford, UK,
This is a statistical attempt, using the same method as Dealler in 1993 (Br. Food J.) to
calculate the number of cases of BSE that are currently being incubated and will appear as
clinical cases .The data is derived from MAFF, is assumed to be fully correct and is assessed
using standard techniques. No attept is made to show or calculate underreporting but they also
show that the age distribution of BSE appears to become younger in cattle born after the feed
ban, although this does not make a lot of sense. A further 15,000-24,000 cases were
predicted of BSE between 1996 and 1999 assuming no cattle born after 1992 would develop
BSE. About 75% of future cases will occur in cattl eborn in 1989 or later (at least 5 monhts
after the feed ban). No attempt was made to correalate the pattern with that expected for
specific epidemiological models e.g. vertical transmision or to calculate when the initial cases
of BSE were infected.
Lancet. May 11, 1996, vol 347 p 1332/3
Jean-Francois Foncin Laboratoir de Neurohisologie, Ecole Pratique des hautes Etudes et
Unite 106, 75651, Paris Cedex 13, France
He is worried that the article by Will et al, claiming that CJD2 could be a result of the
epidemic of BSE. He is extemely critical of the methods used in stating that there was no
specific genetic link found in the patients with the disease. He claaims that in the late 1970s
he showed around the French neuropatholigal circles an apparently sporadic erly onset case
with initial ataxia, terminal dementia and abundant plaques as "le Kuru de Gonesse". It was
published as GSS only after protracted inquires had showen that four relatives had died with
similar symptoms in psychiatric hospitals..
Lancet. May 11, 1996, vol 347 p 1332/3
Jean-Phillipe Deslys, corrinne Ida lasmezas, Thierry Billette de Villemeur,
Alexandre Jaegly, Dominique Dormont Various sources.
They explain that the reasons given by Will et al for the cases of CJD2 appearing in younger
groups were possibly not the only possible story. Will et al felt it was because younger people
were more exposed to infective material (this has been shown by other groups as well - Ed).
This groups, however feel that there may be another factor, a genetic one also, that made these
people more open to infection. Also, as almost all the population would have been exposed to
some degree, it may even be that a factor is protecting the other members of the community
but missing in these people. They suggest that people already carying non-virulent strians of
disease may actually be non-susceptible to BSE. Only young, gnetically susceptible people who
had not been previously exposed to this agent would beinected with BSE. As a result the
exposure of the whole population to BSE would be apparent in an unusual form of CJD ina
small group under the age of 40 years. (this is actually very similar to what was said by
Harash Narang to the House of Comons Select Committee on 17th of April 1996- Ed).
Lancet. May 11, 1996, vol 347 p 1332/3
Diringer H robert Koch-Institut, Nordufer 20, D 13353, Berlin, Germany.
He puts over the fact that the population going down with CJD2.
Polymorphism at position 129 of the prion protein.
% of investigated cases No investigated
Met/met Met/val Val/val
Normal population 48 42 10 1397
Sporadic CJD 78 12 10 73
CJD2 100 0 0 8
He suggests that the reason for sporadic CJD having such a high proportion of met/met may be
because they did not really appear out of the blue but caught the condition from animals in the
same way as the CJD2 patients may have done.
Lancet. May 11, 1996, vol 347 p 1332/3
Taylor DM Neuropathogenesis Unit, Inst for Animal health, West Mains Rd, Edinburgh, EH9
This is following the article suggesting that sterilisation of medical devices contaminated with
CJD need not be a problem. He says that there is simply not enough known to make that sort of
statemet. He explains that in different TSEs the time needed to sterilise products was not
relaible for instance BSE in cow brain dropped 3.5 logs whereas scrapie infected hamster
brain dropped 7.5 logs under the same action of heat. One of the ideas was that there was
always a small percentage of the agent that was completely resistant to heat and hence he did
not agree with the original author.
Chemotherapeutic trials with a new plyene antibiotic
derivative, MS-8209, in experimental prion diease
European Congress of Chemotherapy, Glasgow, 14-17 May, 1996
Adjou, KT, Demaimay, R, Deslys, JP, Lasmezlas C, Seman M, Dormont D. All are
from Service de Nerovirologie, CEA, Fontenay aux Roses, France (except Seman)
This is an attempt at testing the use of an amphoteracin derivative, supposedly less toxic on
the incubation period of scrapie in mice. They looked for the accumlation of glial fibrillary
acidic progein (GFAP) and the accumulation of PrPres. What they found was that the treatment
during the incuabtion period delayed all factors. The continuous treatment with the drug in
this experiment may make it impossible in humans, however.
Half of physicians are unaware of surveillance system
Franks, A, Schweiger M
British Medical Journal. 25 May 1996 312:1358
It showed that many of the doctors that would be likely to see patients with CJD were not aware
of the surveillance system for the disease. This was not true for neurologists, however.
Britain caught out by 'unscientific' reactions to
Europe's beef crisis
Nature 30 May 1996 p353
A discussion of the various committees and groups including the WHO that were going over the
problem of BSE and how they, for shortage of information could not make fully scientific
statements. As a result they did not feel that a wider ban on the UK beef exports could be lifted
BSE a specific bovine disease?
Claude E Chastel Lab de Virologie, Faculte de Medcine, Univ de Bretagne Occidentale,
29285, Brest, France
Nature 30 May 1996 p353
States that it surely should be postulated that BSE was not derived from sheep but from other
cattle. A French vet in southern france, M. Sarradet described as early as 1883 a "case of
scrapie n an ox". Re. Veterinaire 3, 310-312; 1883.
BSE. What have we learned?
Health Which, June 1996;89-91.
Puts over the problems of being sure that the food we handle and eat are actually safe. It shows
that there is still too much uncertainty for people that do not wish to take risks to continue
eating potentially risky meals. It is also quite aggressively scathing about the way in which
the controls the MAFF said it was taking to avoid BSE infected tissue getting into the human
diet were inadequately enforced and indeed the MAFF admits this.
CJD researchers seek greater access to data on
Nature 6 June 1996 p453
The worry that information concerning CJD cases is not being released for investigation by
other scientists by the UK Government groups has been found unacceptable, particularly in
France, where a number of cases may well have appeared. French workers were complaining
that htey had been left completely in the dark over what was happening and the results from
the new cases that seem to have appeared in 1996 of CJD2.
BSE: Does it transmit to humans
Almond, J School of Animal and Microbial Sciences, Reading, RG6 2AJ
Society of General Microbiology Quarterly May 1996;23 part 2;48-9
Goes over the reasons why we should assume BSE to be a cause of the CJD2 form of disease
until further evidence appears. A good short review.