Subject: Re: IFST Position Statement on BSE: 18 July 1996.

From: [email-masked] (J Ralph Blanchfield)
Date: Sun, 21 Jul 1996 23:42:00 GMT

Hello Oz and Everyone,

On Thu, 18 Jul 1996 17:58:15 +0100, Oz <[email-masked]>
wrote:
>
>Congratulations on a cautious and wide ranging review and conclusion.

Thank you -- not just for me but for the other IFST colleagues
involved, plus the members and non-members who contibuted information,
comments and suggestions that helped.
>
>In article <[email-masked]>, J Ralph Blanchfield
><[email-masked]> writes
>
>>While scrapie is common in sheep, recorded CJD is very rare in man.
>>_The incidence of reported CJD is at a similar level throughout the
>>world (around one per million per year), regardless of the occurrence
>>of BSE
>
>or of scrapie.
>
Correct.
>======
>
>>Likewise, subsequent research into inactivation of BSE infectivity
>>indicates that the solvent extraction and steam stripping procedures
>>supposedly in operation until 1981 were not likely to have been
>>effective in destroying infectivity, and furthermore that the
>>processing change was begun by the largest renderers, not in 1981 as
>>was assumed, but in the early 1960s, and not only in the UK.
>
>I have not seen this quoted before. It is worth noting.

John Wilesmith, Head of Epidemiology at the MAFF Central Veterinary
Labs (CVL),did a rapid piece of  "detective work" on the first 200
cases of BSE, and found, by May 1988, that the only common factor was
compounded cattle feed incorporating meat and bonemeal. At the time it
was postulated that this was due to the scrapie-infected sheep
material in the feed. Doubt has subsequently been cast on this  by
experiments at Ames, Iowa and Mission, Texas, where inoculation and
feeding scrapie infection to cattle resulted in encephalopathies that
did not resemble BSE. As stated in the Position Statement, there are
increasing reservations about the sheep meat and bonemeal hypothesis,
particularly with regard to how the sheep scrapie prion changed,
during passage through cattle, to the BSE prion. There is a view that
BSE has always existed at low and previously unrecognised level in
cattle, and the inclusion of cattle meat in the animal feed resulted
in an amplification effect.  (Some older farmers and vets now say,
with hindsight, that it has always existed, but occurred so rarely
that when a cow had "the staggers" nobody recognised it as anything
but an inexplicable one-off event).

.Unlike the detective novel, where the detective ties up all the loose
ends in the last chapter, here there is a rationale that has been
accepted, in which there are many loose ends, not to mention some
mythology and incorrect history of changes in rendering.

A typical, and authoritative, outline of the supposed cause and the
rationale was given by Ray Bradley, BSE Coordinator at the MAFF
Central Veterinary Laboratory [CVL], in a seminar lecture on 29
February 1996, of which the following extracts are relevant --

"So let's look at how this epidemic started. First of all, in
scientific terms this is an extended common source epidemic. That
means that every single cow has been exposed to infection from a
common source (feed). At the end of 1987, John Wilesmith, of the
Central Veterinary Laboratory, who has kindly provided much of this
data for me, looked at the first 200 cases of BSE and did a very
careful analysis of the epidemiology He found the only common feature
was that every single case had been fed proprietary concentrates or
protein supplements and he identified that the vehicle that carried
the infection was the meat and bone meal."

"The precipitating factor causing BSE was a sudden cessation of
hydrocarbon solvent extraction of tallow in the rendering system. That
again is another story and I am sure you are probably familiar with
it. Why did this occur? Well, this process probably inactivated the
causal agent sufficiently to prevent disease and when that procedure
was stopped independently by the rendering companies for commercial
reasons, this permitted sufficient infectivity to pass into the feed
and cause disease. It was then recycled and initiated the escalation
in the epidemic from mid 1989 onwards. How had solvent extraction of
tallow prevented the disease? We think by the double heat process
which this particular kind of rendering utilised and in particular the
use of a second wet heat stage using steam in a low fat environment.
When did that happen? It happened in the late l 970s and early 1980s
especially in the period 1981/82 when cattle were first exposed to
sufficient agent to cause disease which was first recognised five
years or so later after the incubation period was complete."

There are (or were) two separate industries involved in the production
of animal feedstuffs based on meat and bonemeal. They are the
rendering industry, making and milling the meat and bonemeal, and the
feed compounding industry. The renderers do not normally sell their
product direct to farmers but to the compounders
 
The information that follows derives from discussions with Alan
Jobling,  now-retired well-known technologist who worked for one of
the major rendering companies during the period in question.

After the first heated stage of rendering, much of the fat (tallow)
was removed by pressing, leaving behind the "greaves" containing
residual fat. Why was solvent extraction ever involved? It was because
it was virtually impossible, in the small-scale batch processing
plants that existed up to the early 1960s, to mill the meat and
bonemeal without first removing the residual fat, by solvent
extraction. Up to the early 1960s, the renderers therefore carried out
solvent extraction, and sold the milled product to compounders on a
commercial specification of 50% protein, and very low fat content.

After extraction the residual solvent then was removed from the
product by "stripping" it with steam nominally at 120  deg C plus,
(though, delving further into detailed history, I am told by my
informant, that it was, in practice, not always operated above 100 deg
C). The solvent was then removed from the fat-in-solvent solution to
leave the by-product, tallow. 

By the early 1960s, there was a worldwide trend to move from a larger
number of renderers operating small-scale batch processing to fewer
large-scale continuous processing plants of modern design, on which,
moreover, it was possible to mill the product containing the residual
fat, so that there was no technical need for solvent extraction or for
the subsequent steam stripping of solvent residues. These changes were
taking place worldwide, not just in the UK.

Meanwhile, tallow was increasingly being added as an ingredient during
compounding, as an energy supplement,. Realisation  dawned that it was
ridiculous to go to all the trouble, expense, hazard and environmental
pollution involved in removing residual tallow by solvent extraction,
only for it to be added back in compounding. This led to the
increasing adoption of a commercial specification of  a 45% protein
meal with 8-10% fat, which could, of course, be achieved, and milled,
without solvent extraction. The trend started with the
largest renderers back in the early 1960s, not "in the late l 970s and
early 1980s especially in the period 1981/82" as the typical rationale
has it. Moreover, the major UK renderers doing this were not only
doing it in the UK but in their factories in continental Europe (plus
of course there was a substantial export trade from the UK). 

I have heard that two small renderers in Scotland carried on
solvent-extracting after everyone else had stopped, but that is
hearsay..

In any event, research in the last few years on the conditions
necessary to inactivate BSE infectivity demonstrates that the
steam-stripping process would be most unlikely to have inactivated it.

The economic benefit of removing the two unnecessary processes, is
interlinked with the changes in technology that made it possible, in
operating scale and in concentration of the industry into fewer larger
units. The economics were obviously significant in the 1970s after
the oil crisis of 1973 onwards (more from energy usage than from
solvent, which was recovered); and the safety aspect even more
significant in the UK in view of the general tightening up on
industrial safety after the Flixborough disaster in June 1974.

So it would seem that the changes in processing started much earlier
than is generally supposed, and were not confined to the UK. 
>
>======
>
>
>>At present, there is no significant evidence of horizontal
>>transmission in cattle. In the epidemiological study by Hoinville et
>>al (loc.cit.), there was an otherwise inexplicable statistically
>>significant occurrence of BSE in calves born of a non-infected dam on
>>the same day or within a few days after the calving of a BSE-infected
>>dam.  
>
>But note that such animals would most likely have eaten feed from the
>same bag at (almost) identical ages. 

Would that explain "the same day or within a few days after" and  "not
within a few days before"?
>
>======
>
>
>> An
>>encouraging first stage, but they are now repeating the experiments
>>with genetically-modified mice that express only human protein and no
>>mouse protein.  It was reported in the paper that these remain well at
>>264 days after inoculation (60 days longer than for CJD to develop in
>>mice of this genotype). In a later report [Collinge (1996)] he stated
>>that the mice are still doing well at 320 days post-challenge, and
>>they were later (8 July) reported to be fit and well after 440 days.
>>This study may need to go on for 600 -700 days if these mice die of
>>old age rather than succumbing to BSE. Thereafter, it is considered
>>important to repeat the studies with mice expressing human protein of
>>genotypes other than the one 
>
>
>>originally chosen (which was the one
>>considered to be most susceptible to human prion diseases). 
>
>Am I to presume that the human prion gene used is the same one that is
>responsible for familial CJD? If so then since this appears to generate
>CJD spontaneously (or if triggered, is triggered very readily) this has
>little relevence to the other 99.9999% of the population who do not
>carry it. It is not related to V-CJD either. If this is the case I am
>even more amazed that these mice have not succumbed long since.
>Unfortunately there are no controls to pick this up. Perhaps due to a
>shortage of human prion expressing mice at the time?

The Collinge et al paper on the trangenic mice experiments states
"The human PrP transgene used in the studies encodes valine at
polymorphic residue 129, known to be involved in genetic
susceptibility to human prion diseases. Human individuals homozygous
for PrP valine 129 appear to be the most susceptible genotype
following exposure to human prions. However it will be important to
repeat these studies with mice expressing human PrP methionine 129 and
with transgenic 'heterozygotes' to determine whether heterozygosity at
codon 129 protects against the transmission of BSE as it does against
the development on rate of progression of acquired, sporadic and some
types of inherited prion diseases".

Reference 

Collinge J et al (1995) "Unaltered susceptibility to BSE in transgenic
mice expressing human prion protein", Nature, 378, 21-28 December,
779.
>
>==========
>
>>There were no apparent circumstances that might suggest a common risk
>>factor. Compared with classical CJD,  the average age was younger, the
>>duration of illness longer, the clinical symptoms different, the EEG
>>brain activity different, and the brain pathology different. It was
>>subsequently reported [Collinge et al (1996)] that, although, in
>>several of  the ten cases there was a family history of dementia,
>>protein gene analysis excluded these cases as being inherited forms of
>>prion disease.
>
>Was it not also stated that under normal circumstances most of these
>cases would NOT have been diagnosed as having CJD from their clinical
>symptoms? On top of that the suggestion of familial dementia in several
>cases suggests that this might be an old disease newly identified.
>
>Shouldn't one also perhaps say "protein gene analysis excluded these
>cases as being inherited forms of *CURRENTLY KNOWN* prion disease? This
>because of evidence of familial dementia. I don't know and would be
>interested in your comments.

I have responded to this elswhere, but will give it again here for the
benefit of subscribers here.

There was no mention of family history of dementia  
re several of the V-CJD victims, in the CJDSU. research paper (Will et
al). Presumably CJDSU had not discovered that information up to then.
The information about the familial dementia was not reported until
three months later, on 6 July, by Collinge, Beck, Campbell, Estibeiro
and Will (note Will among the authors).  The paper reported prion
protein gene analysis in the first three cases of V-CJD (and
subsequently five others). This included all the cases with the
familial history of dementia, and the conclusion drawn from the
results was that they "exclude the new variant cases as being
inherited forms of prion disease with previously unrecognised coding
mutations." 

References

Collinge J et al (1996) "Prion protein gene analysis in new variant
cases of Creutzfeldt-Jakob disease", The Lancet, 348, 6 July 1996, 56.

Will R G et al (1996)  "A new variant of Creuzfeldt-Jakob Disease in
the UK", The Lancet, 347, 6 April, 921-925.
---snip---
>
>>General comment
>>
>>The whole BSE/spongiform encephalopathy scenario is extremely
>>complicated and difficult to understand.  It resembles a large jigsaw
>>puzzle in which many of the pieces are missing, and in which pieces
>>that appear to be adjacent parts of the picture sometimes do not seem
>>to fit exactly.
>
>I am not sure that I agree entirely with you here. The main problem is
>not really the scientific information, which is rather consistant
>although capable of somewhat different risk interpretation by different
>experts. The main problem that makes it SEEM complicated is the various
>wild hypotheses and press misinformation that people then try to weave
>into the fairly simple set of facts that we know of.

You are right that there is no shortage of misinformation, but the
facts that we know of are only part of the facts. We are learning a
lot, but it's the old story with science, the more we learn the more
we realise how much more we need to learn.  And not all "fairly simple
sets of facts" turn out to be simple or facts (see the rendering story
above.).  
>
>======
>
>> There can be no definitive scientific opinion until
>>all the work currently being carried out (and probably a lot that has
>>not even been started or thought of yet) has been completed and the
>>results assessed. 
>
>Definitive. Hmmmm, yes. Give it 40 years for those young people who
>might have been infected in 1985 to not go down with the disease, say
>2025. As a result it is somewhat peverse that it is probably better for
>all concerned if the level was positive at 1:10,000,000 per annum (due
>to pre 87 infection) but expressed now. The risk would thus be
>quantifiable and thus explainable and not unknown. Silly really.
>
>=======
>
>>Moreover, the public desires solutions  to ensure 100% absolute
>>safety, which is not available in any aspect of life. 
>
>I'm not so sure about this. Nobody worried about getting CJD at
>1:1000,000 per annum because they CAN quantify it.

The vast majority had never even heard of CJD until the BSE and CJD
stories hit the headlines. 

Moreover, the fact that scientists and statisticians may be able to
quantify particular risks does not mean that most people can. 

And there seems to be something special about food that makes people
adopt different criteria from those used for  other kinds of risk.

Regards

Ralph

******************************************************************
J Ralph Blanchfield
Food Science, Food Technology & Food Law Consultant
Chair, IFST Member Relations & Services Committee
Web Editor, Institute of Food Science & Technology
IFST Web address: http://www.easynet.co.uk/ifst/ 
******************************************************************

---

From: Oz <[email-masked]>
Date: Tue, 23 Jul 1996 06:56:30 +0100

In article <[email-masked]>, J Ralph Blanchfield
<[email-masked]> writes

>within a few days before"?

No. Actually I must confess to regularly misinterpreting this one. I
must have misread it the first time, and continue to do so.

Mea culpa,

------------------------------- 
'Oz     "When I knew little, all was certain. The more I learnt,
        the less sure I was. Is this the uncertainty principle?"