Bernard Dixon

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Doubts about pasteurization—an apparently thoroughly familiar technique—are nevertheless fueling a public health controversy with potentially far-reaching implications

Bernard Dixon

A worldwide threat of serious intestinal disease could be clarified by tests on the bacterium suspected of causing that disease. The required tests are not of anything as sophisticated as toxin production genes, signal transduction mechanisms, or cytoskeletal proteins. They are tests, like those carried out by countless students throughout the world, of simple heat sensitivity.

Nevertheless, the issue remains unclarified more than 10 years after it was first raised. In an era of molecular biology and genomics, this seems bizarre. Just as peculiar is the lack of real evidence concerning the prevalence of the organism in its alleged vehicle of infection.

This too might be considered an elementary task for a few competent students.

The condition in question is Crohn’s disease, and the suspect bacterium is Mycobacterium avium subsp. paratuberculosis (MAP). Already known to cause the chronic enteritis known as Johne’s disease (paratuberculosis) in cattle, sheep, goats and other ruminants, MAP has also been implicated in Crohn’s disease in humans. This is one of the commonest forms of chronic enteritis, sometimes affecting the entire alimentary tract, with inflammation through all layers of the intestinal wall. Yet its cause remains unknown.

The similarity between the ruminant and human conditions has long suggested a common or very similar aetiology. However, the first plausible evidence came a decade ago from John Hermon Taylor and his colleagues at St. George’s Hospital Medical School in Tooting, South London, United Kingdom. They reported a DNA repetitive element, IS900, in an organism from a Crohn’s disease patient which DNA fingerprinting showed to be identical with MAP (J. D. Sanderson et a1., Gut 33:890, 1992).

This and later claims from Hermon-Taylor’s group have to be weighed against claims from other centers that MAP DNA is present not only in Crohn’s disease but also in certain non-inflammatory bowel disorders. The molecular genetics and their implications remain unclear.

Is Pasteurization Inadequate?

Nevertheless, if the St. George’s researchers are right, urgent action may be required to deal with the second plank of their argument. Hermon-Taylor and his collaborators think that the vehicle through which MAP passes from animals to humans is milk. They also believe that current high-temperature, short-time (HTST) methods of pasteurization may fail to inactivate the organism completely.

Controversy over the involvement of MAP in Crohn’s disease, and the alleged deficiency of milk pasteurization, has now spilled out from learned journals into the general media. "If there were no MAP, I believe there would be almost no Crohn’s disease," Hermon-Taylor was quoted as saying in a recent article in the The Times of London. "The problems caused by MAP in the milk supply constitute a public health disaster of tragic proportions, for which a range of remedial measures are urgently needed."

The difficulties in establishing (or disproving) the etiological role of MAP is Crohn’s disease have been similar to those encountered in implicating many other organisms in specific infections in the past. They will doubtless be overcome, as have others, by modern molecular genetics. What is baffling is that the two much simpler yet crucial allied questions concerning the presence of MAP in milk, and its (non)destruction by pasteurization, have not been answered long ago.

We know for certain that MAP causes Johne’s disease in cattle. Yet we do not even have indisputable information regarding its levels in milk from animals with this infection. There have been a few reports of isolation of the viable organism from cows with either active or asymptomatic Johne’s disease. These papers have, however, been criticized on the grounds that the milk was taken aseptically from thoroughly decontaminated udders. This precluded the fecal contamination that inevitably occurs during normal milking. Likewise, there is an alarming paucity of evidence as to whether viable MAP is present in commercially pasteurized milk. While acid-fast organisms have been reported in milk, it was not clear whether these really were MAP, nor whether they were viable. Culture results have been inconclusive.

So, despite the pressing need for reliable information, we remain in ignorance. This seems odd, given the apparent technical ease with which such information could be obtained.

Last year, Irene Grant and colleagues in the Queen’s University of Belfast and the Department of Agriculture for Northern Ireland, Belfast, tried to answer the other key question, regarding the heat tolerance of MAP. They spiked raw cow\'s milk with the organism and subjected it to various temperatures for various times.

A Methodological Disputation

Their results, published in Letters in Applied Microbiology (28:461, 1999), implied that traditional HTST pasteurization could be inadequate to protect consumers against this organism. They found that a longer duration was more effective than a higher temperature in inactivating MAP entirely, and suggested an appropriate increase in the time normally used.

The Belfast group has since become embroiled in a dispute over the true significance of this finding, and over the most basic details of the methodology used to determine thermal resistance. Observing that the Belfast results contradict those from other centers, French and

Canadian researchers (O. Cerf and M.W. Griffiths, Lett. Appl. Microbiol. 30: 341, 2000) warn of discrepancies between the results of the three principle techniques used on the laboratory bench to determine heat resistance.

In particular, the critics insist that the laboratory-scale HTST pasteurizer employed by Grant and introduced many years ago (J.G. Franklin, J. Dairy Res. 32:281, 1965) "should never be used." However, Grant points out (Lett. Appl. Microbiol. 30: 343, 2000) that the apparatus was fully immersed (apart from the inlet funnel and outlet spout) in a water bath, rather than partially immersed as Cerf and Griffiths supposed. "Once the spiked milk was introduced into the pasteurizing unit, the inlet funnel was unscrewed and replaced with a rubber bung." Is this really the stuff of 21st-century microbiology?

In fact, both Grant and her critics agree that reliable results on the heat resistance of MAP will come only from tests with an industrial scale pasteurizer, continuous-flow heating, and naturally infected milk. The Belfast workers are now testing large numbers of commercially pasteurized samples. They have also screened milk from local farms to identify a source of milk infected naturally with MAP. Thirdly, having done so, they are initiating heating trials with naturally infected milk and an industrial pasteurizer with continuous-flow heating Excellent. But could all of this not have been done long ago?