How Now Mad Cow

Can BSE Infect Humans?

Dr S. Heaphy.

"The spontaneous occurrence of a novel prion strain that is the same in 14 individuals in the UK over the last two years seems extraordinarily unlikely as an explanation for NV-CJD. The alternative conclusion is that these cases have arisen from a common source of exposure to a new prion strain, the lack of any history of common iatrogenic exposure indicates that this is a new animal strain." Collinge et al, Nature 383: 685-690,1996.

In this paper they described the first direct evidence that BSE is the cause of NV-CJD. They found that PrPsc isolated from 10 cases of NV-CJD all had an identical 'fingerprint' on SDS polyacrylamide gels. This fingerprint was quite distinct from that seen in cases of familial, sporadic and iatrogenic CJD. However it was identical to the fingerprint found in BSE strains isolated from several animal species. Strain typing experiments currently in progress will be necessary to confirm this result but I think we can now answer the above question with a Yes.

Towards a Risk Assessment for the UK Population:

The figures used in this very simplistic assessment are taken from a variety of sources, some unpublished. Therefore there accuracy is more than unusually certain. If anyone wishes to comment on them please do so.

1. How much infected beef did we eat, 1983-1995 ?

Pre-1989 (before any offal controls), 446,000 BSE-infected animals were eaten
Between 1989 and 1995 when there was only a 50% compliance with the specified offals ban, a further 283,000 BSE-infected animals were eaten.
It has been estimated that this represents 3-5% of the animals entering the human food chain.

2. What meat was infected?

In the main: brain, spinal cord, eye and parts of the gut. Infectivity has not been detected in lymphoid tissues, other organs, or milk. However that does not mean that these tissues are safe. Brain and nervous tissue represents 0.1% by wt. of edible cow, 1% of offal.

Conservative(?) assumption 1 beef meal per week for 12 years with a 3% chance of the beef being infected = 500 x 0.03 = 18 independent exposures.

Whatever the risk of infection, it is additive.

3. Infectious dose:

1 LD₅₀ unit by definition is the amount of agent required to kill 50% of the population exposed to it. This dosage varies depending on the route of exposure e.g intracerebral inoculation (i.c.) or via the diet.

Some claim 10¹⁰ LD₅₀/g wet tissue by the intracerebral (i.c.) route. Most agree 10⁷ by the i.c. route in scrapie. Unpublished reports suggest 10⁷ in BSE. Most of the infected animals will have been incubating the disease and have had a titre lower than 10⁷. But some will have had full blown BSE and titres approaching 10⁷.

Assuming that of the 18 exposures 1 was major, (beefburger, pate, your favourite meat pie, pastrami, cows brain!) cooking will have done little to reduce the titre. 10g@ 10⁷ = 10⁸ ic LD₅₀ eaten.

1 gastric LD₅₀ = 100,000 i.c. LD₅₀ (measured by comparing BSE titres in mice) i.e. 10³ or 1,000 gastric LD₅₀.

Unless these assumptions are badly flawed, it seems reasonable to assume that most of us have been exposed to an enormous infectious BSE prion dose. In which case we have to thank the powers that be for the species barrier

4. The species barrier is impossible to predict a priori.

It reflects the fact that interspecies transmission is less efficient than within the species. BSE titres in cows of 10⁷ are reported to be about 10⁴ in mice, i.e. there is a species barrier of about 1,000. A similar value has been reported for sheep scrapie in mice. CJD has not been transmitted to mice, there is a very large species barrier. A species barrier of 10⁷ is considered large. It seems reasonable but not necessarily correct to assume the species barrier between cow and human is greater than 1,000 (Collinge transgenic mouse experiments.)
The table below gives some idea of the fatalities that might be expected depending upon the size of the species barrier assuming an exposure of 1000 gastric LD₅₀ to a population of 50 million:

Species Barrier:	Effective LD₅₀:	Deaths:
10⁴	10^-1	2.5 million
10⁵	10^-2	250,000
10⁶	10^-3	25,000
10⁷	10^-4	2,500
10⁸	10^-5	250

Other risk factors include the PrP 129 polymorphism. For the Caucasian population:

12%V/V
37% M/M
51%M/V

The relative Sporadic CJD Risk for these genotypes is 11 : 4 : 1.
For growth hormone iatrogenic CJD it is 50% V/V, 31%M/M and 19% M/V.
So far 100% of NV-CJD patients have had a M/M genotype.

Final words:

BSE is almost certainly the cause of 15 confirmed NV-CJD cases.
Is beef safe ? As the chief medical officer states, it depends on what you mean by safe.
The major risk of infection from beef was pre-1995 .
The nature of the epidemic is not yet fully predictable but is now completely beyond our control.
The size of any epidemic will depend on the magnitude of the species barrier. Experimentation may yet give us an idea of what this is.
Kuru had a 5-30 years incubation period (10 years is a reasonable guess for the average incubation). Likely that BSE would take longer than 10 years to manifest in humans because of the species barrier.

Worst case scenario:

Current infections are fast responders to early 1980s infections when even retrospectively we can't see BSE in the national heard. By 1992, cattle infections were increased by more than 1000 fold. This would imply that we will see at least tens of thousands of human cases.

Best case scenario:

Current cases are the sensitive responders to the peak of the BSE epidemic in 1989-93. This would imply only a few hundred deaths.

For an alternative view, read: Cousens SN. et al.
Predicting the CJD epidemic in humans. Nature 385: 197-8 (1997).