New variant Creutzfeldt-Jakob disease: the epidemic that never was

BSE epidemic: Caused by three poisons

Researchers: Anthony & Benjamin Parish

BSE is scientifically categorized as a transmissible disease. In 1996
we were able to prove it was not. The discovery had far reaching
implications as it condemned all previous research interpretations as
faulty. On the basis of this new knowledge (rejected by SEAC) we were able
to discover what we believe to be the real cause of the epidemic.

The cows were poisoned from eating recycled waste meat and bone meal
(MBM) The MBM content within the feed was doubled in the early 1980s to
help boost milk yields.(1) Prior to this around the 1970s a new solvent
free MBM feed process was introduced (2) this had already allowed bio-
accumulated dioxins and other free radicals to survive within the fat
component of the MBM (3). Previously the full solvent cleaning method
had efficiently removed them.

The double portion of the inherently unnatural MBM together with the
double dose of free radicals within, produced the main poisoning.The third
toxicant was the governments compulsory prophylactic warble fly
eradication campaigns 1978 and 1982, England and Wales (4) (5). These
three toxic events when combined synergistically produced the "trigger
factor" that caused the epidemic. The illusive infectious agent was not
an infection or any other living organism it was a poisoing. The MBM when
combined with the synthetic chemical poisoning was embryo toxic, producing
BSE in the calf but not sufficient to cause the disease in the dam.This
explain the period between the consumption of the toxically enhanced MBM
and the manifestation of the disease.
The discovery facts:

(a) The neurotoxic free radicals still exist in cows today

(b): The animal feed solvent process is still being used around the
world today.The solvents are the same as those used in dry-cleaning
establishments. These chlorinated hydrocarbon solvents would remove
synthetic chemicals as they are solvent soluble.

(c) The organophosphate toxic payload was increased by the warble
fly eradication campaign 1978-82 England and Wales. (Very low incidence
of BSE in Scotland)

(d)The calculated date of origin (2) including the period of
incubation, coincide with the actual date of the epidemic (2) (3)

Alzheimer's link

Alzheimer's disease and free radical damage (7) (8) (9)

The fat laced milk in the suckling feed is implicated as it came from
the same source:

http://www.alz.org/media/news/current/071200highfatdiet.htm

Note:BSE is not spreading from Britain to around the world. The rare
disease is just being found.

Summary and conclusions

The epidemic was caused by the double helping of MBM introduced in
the early 80s prior to this the solvent free process allowed dioxin free
radicals to survive in the fat component of the MBM, The double helping
of recycled cannibalistic MBM also provided a double helping of free
radicals.This together with the known neurotoxic damage caused by
organophosphates enhanced the protein poisoning disease process. A very
rare disease of old age began affect the young.

The trigger factor responsible for the British BSE epidemic has been
scientifically determined as "unknown" we propose that we have clearly
identified that "unknown" factor.

References

(1) BSE inquiry looks at animal feed

(2) Wilesmith J.W., RYAN J.B.M, & Atkinson M.J. (1991) Bovine
Spongiform Encephalopathy: Epidemiological Studies on the Origin, The
Veterinary Record, 2 March 1991, 128, pp 199 -203.

Extract from (2)

"the results of further epidemiological studies of bovine spongiform
encephalopathy (BSE) support the previous findings that the onset of
exposure of the cattle population to a scrapie like agent, sufficient to
result in clinical disease occurred in 1981/82. The onset of this exposure
to the cessation. in all but two rendering plants, of the hydrocarbon
solvent extraction of fat from meat and bone meal. A further possible
explanation, related to the graphical variation in the processing of
greaves to produce meat and bone meal, was identified for the geographical
variation in the incidences of BSE".

(3) Eradication campaigns

(4) Free radicals defined

(5) Purdy, M. (1994) Are organophosphate pesticides involved in the
causation of Bovine Spongiform Encephalopathy? Journal of Nutritional
Medicine 4, 43-82.

(6) Current hypotheses

(7) BSE and Alzheimer's disease

(8) Harman Denham. Alzheimer's Disease. A hypothesis on pathogenesis.
Annals of the New Academy of Sciences. Vol 854, p515, 1998.

(9) An interview with Denham Harman

The above is presented as discovery, we also present as
hypothesis: that the same poisoning damaged the bovine immune system and
as a consequence it may have promoted two more disease epidemics. (1)
Foot and mouth disease and (2) bovine tuberculosis

This discovery proves the free radical theory of ageing (9)
Spongiform disease is probably an accelerated rapid onset form of
Alzheimer's disease.
More proof on our site

”All truth goes through three stages. First it is ridiculed. Then it
is violently opposed. Finally, it is accepted as self-evident.”
(Schoepenhouer)

The purpose of the paper was to stimulate debate. It has and I am
grateful to all who wrote.

The main counter arguments lie in speculative explanations of
epidemiological findings, differing opinions on clinical features and the
characteristics of transmissible spongiform encephalopathies. None
overturns the basic epidemiological points in my paper nor provides
irrefutable evidence in favour of B S E infectivity to humans or the
novelty of variant Creutzfeldt-Jakob disease. They are dealt with in more
detail as an annex to this letter.

Given the failure to refute the epidemiological case, the possibility
of recycled B S E prion having caused an epidemic in any other species
than cattle, is highly unlikely and becoming ever less. That being so the
question whether variant C J D is an entirely new disease remains very
much open.

From the outset B S E prion infectivity to humans was unlikely and
this was the position that SEAC supported prior to 1996. While detection
of a putatively new condition may have been a legitimate cause for
concern, this did not invalidate previous evidence and demanded proper
scientific investigation. What would have been appropriate would have been
the articulation and testing of hypotheses including the null hypotheses.
However it seems that a possibility was seized on as probable and work
developed to confirm it. As a consequence the general public, farmers and
"non-conformist" scientists and science itself have suffered. The general
public have been unnecessarily alarmed about the food they eat and
internationally stigmatised as potentially infectious. Farmers have lost
livelihoods, scientists have lost support for research and areas of
potentially productive work have been ignored.

Why SEAC became locked into this position, is an interesting question
which, should be explored with a view to preventing it happening again or
elsewhere.

This correspondence has revealed a range of work in other areas which
should help us improve our knowledge of spongiform encephalopathy 1,2,3 I
would hope that scientists working in them could escape from the funding
blight in which they have languished because of the challenge they present
to current flawed orthodoxy. Their contribution is essential if we are to
develop a comprehensive understanding of causes of spongiform
encephalopathies and how to treat them.

There is historical evidence in variation of processing of cases
within and between specialist centres. This, along with inter-observer
variation and recognised difficulties in the precision of neurological
diagnosis of rare conditions, may be sufficient to explain differences in
detection of that particular manifestation of spongiform encephalopathy
currently called variant C.J.D.

I am fortunate in that I am not involved in prion research and
therefore have no axe to grind other than that of science and the public
interest. In publishing my paper, the BMJ has done both a service.

For those who have the interest and stamina, I append my more
detailed observations which I have grouped into those relating to the two
null hypotheses, that recycled BSE prion is not infectious to humans and
that variant CJD is not new.

ANNEX:

THAT EATING BSE PRION CAUSES SPONGIFORM ENCEPHALOPATHY IN HUMANS.

No one has refuted the epidemiological point that rate of growth of
cases should parallel rate of growth in population exposure.

Professor Will was given an earlier version of this paper in January
1999, pointing out that there was no epidemic. His efforts to reconcile
the facts with his hypothesis are unconvincing, requiring the invocation
of an age-related susceptibility based upon a presumption of B S E
infectivity to humans.4

The information on transmissible encephalopathies is of interest but
irrelevant, as such issues as doses, susceptibilities and incubation
periods are allowed for by the comparison made in the paper.

Biological similarities between B S E and v C J D have been developed
as supporting circumstantial evidence. Given that prions cannot replicate
themselves and are species-specific, the concept of "strain" typing
overstates the level of similarity between different species’ prions.
Their primary structure remains species-specific.

Ingestion of foreign prion by susceptible species under laboratory
conditions may cause spongiform encephalopathy but preparation of
infective material and doses consumed are very different between the
laboratory and the real world. We have no evidence that humans are a
susceptible species and, given historical levels of exposure to scrapie
prion, some that we are not.

Even analogies with species believed susceptible are open to
question. There is no sign of an epidemic of feline spongiform
encephalopathy (F S E) in cats in the UK, despite the likelihood of their
substantial exposure to low grade animal protein over the same period as
humans. Cats born after the specified offal ban are now developing the
disease. (www.defra.gov.uk/animalh/bse-statistics/level-3-tsestat.html).
Also the weight of strain typing similarities as evidence for a causal
link is undermined if FSE prion is to be included amongst those having
similar characteristics to BSE and vCJD prions.

The issue of failure to detect the disease in equal numbers in
countries without BSE is an argument which can be developed in a number of
ways. It may be seen as a weighty argument in favour of BSE infectivity
but, given the different levels of population exposure between Britain and
the rest of Europe, that it occurs at all raises problems. Nevertheless it
is an issue, which merits further consideration and this follows later.

THAT VARIANT CREUTZFELDT-JAKOB DISEASE IS NOT NEW.

The disease was considered as new, i.e. having never occurred
previously because contemporary neurologists and neuropathologists had not
seen examples of it before. To establish it as an entirely new disease
requires scrutiny of possible other conditions and reasons why it might
have been missed.

That neither Kuru or Professor Dr Creutzfeldt’s original case was
mentioned in the original paper reflects a limited view of possible
contender conditions. Kuru clearly shares clinical similarities with the
putatively new variant, yet thus far has been omitted from the strain
typing studies.

The last two years of Bertha E’s life were entirely consistent with
those observed in cases of vCJD. While the neuropathological detail
differs from that of vCJD, we have the advantage of 80 years hindsight
over Creutzfeldt.

The validity of retrospective neuropathological comparison is
problematic. Management of patients and processing of corpses and brains
has changed substantially over the years. In Master’s review of Jakob’s
series, slides for one case had to be re-stained to reveal the vacuolation
pathognomonic of CJD.5

Creutzfeldt’s failure to record neuropathological features we would
look for could have been because he never looked for them, failed to find
them, saw but considered them unimportant, or they were absent. Without
access to the original specimens and Creutzfeldt himself, we will never
know which of these possibilities is correct.

Failure to find cases prior to the current series is legitimately
cited as an argument for the novelty of the disease. But not finding a
needle in a haystack, does not mean it is not there. It is also difficult
to guarantee appropriate objectivity when the proponents of hypotheses are
the arbiters of criteria by which to rate the weight of evidence relevant
to these hypotheses.

Ascertainment of cases raises many problems in determining frequency
of occurrence of disease. At the outset, it appears to have been rejected
as an explanation for the appearance of an apparently new disease. Since
then the rate and pattern of occurrence of cases, is consistent with
better ascertainment of cases and this is the likeliest explanation of the
appearance and recognition of vCJD.

For a disease to be detected it must be suspected and relevant
diagnostic procedures consistently applied. Referral processes to CJD
surveillance units will be moderated by the index of suspicion among the
general and medical public of the possibility of disease. Belief in BSE
infectivity as a necessary cause is likely to bias the referral process –
for it in the UK, against it elsewhere.

Consistency of processing and interpreting specimens is likely to be
higher in the UK CJD surveillance unit than elsewhere given the
differences between centres of numbers of cases processed. Such technical
variation may contribute to observed variations (deficits) in numbers
reported.

The apparent deficit in numbers elsewhere is interesting because
there is an a priori argument, which could be made to justify the
existence of at least two types of CJD other than familial or iatrogenic
if abnormal prion is considered causal.

If neurological and lymphoid tissue produce prion, the inference is
that either independently can be a source of pathogenic prion. It is only
when infectious prion reaches the CNS that spongiform encephalopathies
occur. When its source is intrinsically the nervous system one
manifestation would be expected, i.e. sporadic CJD. If the pathogenic
prion arises in the lymphoid tissue, only if and when it reaches the CNS -
where nerve endings meet lymph nodes - do you have another manifestation
of CJD, for example vCJD.

If other possible causes are considered such as auto-immune
reactions2 or nutritional1 or toxic3 causes then the range of possible
variants may be considerable but whether these might be distinguishable
neuropathologically is questionable.

CONCLUSION

Evidence regarding the case for infectivity of BSE prion in food to
humans is piecemeal and insubstantial. Laboratory studies may have helped
illuminate biological processes and reveal what might be possible but the
most searching test of hypotheses is what happens in real life.
Epidemiology is focused on what does happen and shows that there is no
food borne epidemic of variant CJD in the United Kingdom.
Given that this is so, the novelty of the variant is unlikely and other
explanations for its detection should be sought.

REFERENCES

1. Crawford, M.A., Budowski, P., Drury, P.,Ghebremeskel, K., Harbige,
M., et al (1991) The nutritional contribution to Bovine Spongiform
Encephalopathy. Nutr. and Health 7: 61-68

2. Tiwana, H., Wilson, C., Pirt, J., Cartmell, W., Ebringer, A. (1999)
Auotoantibodies to Brain Components and Antibodies to Acinetobacter
calcoaceticus Are Present in Bovine Spongiform Encephalopathy. Infect.
Immun. 67: 6591-6595

3. Brown, D.R.,(2001) BSE did not cause variant CJD: an alternative cause
related to post-industrial environmental contamination. Med
Hypotheses.57:555-560

4. Valleron, A-J., Boelle, P-Y., Will, R., Cesbron, J-Y. (2001) Estimation
of Epidemic Size and Incubation Time Based on Age Characteristics of vCJD
in the United Kingdom. Science. 294: 1726-1728

5. Masters, C. L., Carleton Gajdusek, D. (1982) The Spectrum of
Creutzfeldt-Jakob Disease and the Virus-induced Sub-acute Spongiform
Encephalopathies. Pp139-163, In Smith, W.T., Cavanagh, J.B., (eds.)"Recent
Advances in Neuropathology, Number Two." Churchill Livingstone, Edinburgh.

The above article is a no-response to what Venters argues in his
paper.

And the stats of the CJD unit in Glacow do not seem to confirm what
Ironside et al have said in the 2000 annual report of the Glagow Unit
last year. They promised a new increase of deaths due to vCJD somewhere
around 36 deaths for 2001 ( up to 53 !).

The last stats issued last monday 3 december ( 18 deaths only for the
last 11 months ) do not seem to confirm the trend predicted and it is not
the unfortunate death of Rachel Forbes that will change my opinion on the
subject. Probably in ten years from now, vCJD will not deserve more than a
footnote in papers devoted to CJD.

It should be the right time to try a real etiological treatment of
the condition based on what other hypothesis than "official" one might
suggest : even if mepacrine is able to melt amyloid plaques, the toxicity
of the molecule prevents lengthy use. It should be possible to prevent
possible oxidation effect of modified prion at the synapses ( glutathion ?
, vitamin C , other molecules fighting free-radicals) , and perhaps try
to fight the possible involvement of a metal imbalance in the brain (
chelates or chelating agents ? ).

Maurice LEGOY

New variant Creutzfeldt-Jakob disease: the critique that never was

List of authors: Will RG, Knight RSG, Ward HJT, Ironside JW

National Creutzfeldt-Jakob Disease Surveillance Unit
Western General Hospital
Edinburgh EH4 2XU

Dr Venter's article on new variant Creutzfeldt-Jakob disease (vCJD)
is intended to stimulate debate, which we hope will be better informed
than the article itself. The possibility that the identification of vCJD
might reflect improved case ascertainment rather than a new disease was
considered to be unlikely when vCJD was first described and subsequent
evidence provides strong support to the original hypothesis that vCJD is a
new disease, caused by bovine spongiform encephalopathy (BSE).

Is vCJD a new disease? Dr Venters places great emphasis on
Creutzfeldt's case, acknowledging the need for help in translating the
original 1920 paper, although a full English translation was published in
19891. Creutzfeldt's case had a neurological illness lasting at least 6
years, characterised by initial gait disturbance, a relapsing and
remitting course, 'distinct' nystagmus and terminal status epilepticus.
These are not the clinical features of vCJD. Crucially, the neuropathology
did not show spongiform change or plaque deposition and the appearances
were 'not characteristic of CJD as now understood' and 'Creutzfeldt's
patient apparently did not have CJD'2, an opinion in accordance with
Creutzfeldt's own views. The clinical and pathological features of vCJD
are not, as suggested, similar to kuru and there is no published
information on lymphoreticular involvement in kuru. Furthermore kuru was
caused by ritual cannibalism, a risk factor excluded very early in the
investigation of vCJD.

In 1996 confidence in the novelty of vCJD was based largely on the
identification of a distinctive neuropathological phenotype in comparison
to experience in the UK extending back to 1970. Since then archival
tissues have been reviewed in many countries and no past cases with a
similar neuropathological pattern have been found. vCJD is indeed a new
disease.

Was vCJD identified solely because of improved surveillance? There
was a doubling in the annual mortality rates for sporadic CJD in the UK
between the 1980s and the 1990s, presumed to be due to increased
efficiency of case identification. However the mortality rates stabilised
in the early 1990s, well before the identification of vCJD, and,
crucially, similar increases in the apparent incidence of sporadic CJD had
occurred in other European countries involved with the UK in a harmonised
system for CJD surveillance3. These countries have been subject to similar
potential improvements in case identification, but vCJD remains a disease
occurring predominantly in the UK. The clinical and pathological features
of vCJD are now well known and, if vCJD is an old disease only recently
recognised, significant numbers of vCJD cases are being missed. If vCJD
were occurring worldwide with the same incidence as the UK there should be
at least 25 cases a year in France, 35 a year in Germany and over a 100 a
year in the USA. Since 1996, 4 cases of vCJD have been identified in
France, none in Germany and none in the USA. It is of note that a case of
vCJD was recently identified in Hong Kong, without the formal CJD
surveillance system in place in many countries such as France and Germany.

The hypothesis that vCJD is a new disease is supported by a
retrospective study, not referred to by Dr Venters, which aimed at
identifying missed cases of vCJD in England from 1979-19964. No missed
cases were found and the paper concluded 'the surveillance system is
unlikely to have missed a significant number of cases among people aged 15
-44 years'. A further study from Wales, which reaches similar conclusions,
is to be published shortly. Furthermore a national retrospective review of
the neuropathology of CJD and atypical dementias extending back to 1970
has not yet led to the identification of any missed cases of vCJD.

If vCJD is linked causally to BSE there must be a temporal
relationship between the numbers of vCJD cases and the BSE epidemic. Dr
Venters argues correctly that the vCJD epidemic curve does not parallel
the number of BSE infected cattle between 1983 and 1988, but human
exposure to the BSE agent depends on a range of variables that are not
addressed by this simple model, for example the numbers of cattle in the
final year of the incubation period, the load of bovine CNS tissues
entering the human food chain, the efficiency of legislative measures and
temporal changes in food production. Modelling of human exposure to BSE is
complex, with risk extending well beyond 1988 and probably up to 1996.
Extrapolation from conventional foodborne epidemics to vCJD and BSE
epidemics is likely to be too simplistic. On the other hand the estimated
minimum incubation period of vCJD, if there is a link with BSE, is
entirely compatible with data from kuru and iatrogenic CJD.

Apart from these neurological or epidemiological issues, Dr Venters
appears to be confused about the basic science. Prions are well known to
be remarkably resistant to disinfection and would be expected to survive
'cooking, digestion and the human immune system'. The BSE epidemic was
caused by oral exposure to contaminated meat and bone meal, and both
domestic cats and zoo animals developed BSE after oral exposure. In prion
diseases the oral route can effect transmission even across a species
barrier. Dr Venters refers to a transmission study by Bruce et al in
'human prion protein transgenic mice' whereas these experiments were
actually carried out in wild type mice. There is a wealth of laboratory
evidence supporting the hypothesis that BSE is the cause of vCJD5.

Dr Venters states correctly that there is no direct evidence that the
BSE prion is infectious to humans, but obtaining such evidence would be
difficult to justify ethically as this would involve inoculating humans
with BSE. A judgement on the link between BSE and vCJD inevitably depends
on an assessment of a range of clinical, pathological, epidemiological and
laboratory based evidence. There is now overwhelming evidence that BSE is
the cause of vCJD, although there remain uncertainties about the future
numbers of cases and the mechanism of transmission of BSE to humans.

1. Richardson EP. On a particular focal disease of the central
nervous system (preliminary communication) H.G. Creutzfeldt. Alzheimer's
Disease and Related Disorders 1989;3:15-25.

2. Richardson EP,.Masters CL. The nosology of Creutzfeldt-Jakob
disease and conditions related to the accumulation of PrPCJD in the
nervous system. Brain Pathology 1995;5:33-41.

3. Will RG, Alperovitch A, Poser S, Pocchiari M, Hofman A, Mitrova E
et al. Descriptive epidemiology of Creutzfeldt-Jakob disease in six
European countries, 1993-1995. Ann Neurol 1998;43:763-7.

4. Majeed A, Lehmann P, Kirby L, Knight R, Coleman M. Extent of
misclassification of death from Creutzfeldt-Jakob disease in England 1979-
96: retrospective examination of clinical records. BMJ 2000;320:145-7.

5. Zeidler M,.Ironside JW. The new variant of Creutzfeldt-Jakob
disease. Rev Sci Tech Off Int Epiz 2000;19:98-120.