Friend who betrayed us

profile : E Coli 0157 Once E coli helped us, now it's a killer. Bernard Dixon on the invasion of strain 0157
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Yesterday Escherichia coli 0157 claimed its 12th victim, making Scotland's outbreak of this type of food poisoning the second-worst ever recorded. This bacterium has been aptly described as a wolf in sheep's clothing. Under the microscope, it is indistinguishable from its close relatives - the many inoffensive strains of Escherichia coli that live in astronomical numbers in our colon and those of other mammals. But as the Lanarkshire outbreak shows, strain 0157 is a killer.

Escherichia coli, known as Ecoli, has shared a long and intimate history with human beings. It probably first appeared on Earth at around the same time as the mammals - between 120 and 160 million years ago. E coli then evolved together with mammals as a harmless inhabitant of the colon. When we emerged as humans a million years or so ago, it accompanied us on our journey.

Until recent years, Ecoli has been principally famed for the enormous assistance it has provided for scientific research. Growing in glassware in laboratories throughout the world, it has helped biochemists and geneticists to understand molecules and the nature of life itself. In 1956, its contributions were recognised publicly for the first time when Dutch microbiologists A J Kluyver and C B van Niel singled out E coli for praise in their book The Microbe's Contribution to Biology.

Although its name does not appear among the winners, many Nobel prizes awarded for chemistry, or physiology or medicine, have depended greatly upon the activities of E coli. In 1946, for example, in partnership with Joshua Lederberg and Edward Tatum, it revealed that bacteria have sex, and later demonstrated that their sex lives are even more varied than that of Homo sapiens. Then, in the early 1970s, Herb Boyer and Stanley Cohen worked with E coli to show that DNA from different sources can be spliced together. This was the beginning of genetic engineering, and thus of the burgeoning biotechnology industry, which is now using bacteria to make drugs such as insulin, interferon and human growth hormone.

The vast amount of knowledge provided by Ecoli is all the more remarkable in light of its apparent simplicity. Compared with the 3 billion building blocks that comprise our own genes, it possesses fewer than 5,000. Its appearance is elementary, too. Ecoli consists of stub-shaped single cells, 10 times smaller than ours, with a few wispy hairs called flagella.

But appearances are deceptive. Although Ecoli has far fewer genes than we do, they are quite sufficient for it to indulge in exactly the same activities - digesting foods, renewing its cellular materials, growing, exchanging genes and reproducing. Even the flagella have a far more sophisticated structure than observers once imagined. Ecoli rotates them to go exactly where it wishes, like a propeller driving a ship.

Ecoli first made itself known more than 100 years ago, at a time when several other inhabitants of the microbial world were receiving their initial public attention. It was the German bacteriologist Theodor Escherich, working in Munich in 1885, who identified what he called Bacterium coli commune in human intestines. In contrast to the bacteria other scientists were incriminating as agents of diseases such as diphtheria and typhoid fever, Escherich found one that lived quietly and harmlessly in association with humans. It was later renamed in honour of its discoverer.

For decades thereafter, Escherich's discovery was invariably described in terms of harmony and symbiosis. The human intestine provided shelter and nutrients for Ecoli, which in return synthesised vitamins beneficial to human health. Students of bacteriology and medicine alike came to love Ecoli as it taught them all of the key features of microbial life. It was, in short, a model bacterium.

Meanwhile, scientists were working with Ecoli to learn more not only about this bacterium, or about bacteria in general, but about the chemistry and genetics of all living things. Its cells can divide remarkably quickly - about every 20 minutes - yet its vital processes are very similar to those of animals and plants. For these reasons, Ecoli became the workhorse for many sorts of research that would otherwise have had to be conducted, less satisfactorily, on animal or plant cells. Ecoli had a hand in all of the great discoveries on DNA and the genetic code during the 1950s, 60s and 70s.

As if this versatility were not enough, Ecoli has also helped for many years to safeguard public health throughout the world. Arguably its most important contribution has been in guaranteeing the quality of water supplies. Infections such as cholera, dysentery and typhoid fever can be transmitted through contaminated water, which might therefore be screened to see whether it contains the bacteria responsible for these diseases.

This is feasible but not particularly practicable, since water may carry dangerous microbes in such sparse numbers as to make their detection difficult. However, if a water supply is contaminated with faeces or sewage (perhaps intermittently), then Ecoli will be there in far larger numbers. Routine tests thus focus on Ecoli, whose presence indicates the possibility that the water contains disease-causing bacteria too. Countless illnesses have been prevented, and lives saved, as a result of such alarm signals from Ecoli.

SIGNS that Ecoli also had a malevolent side to its nature first became apparent in the 1940s. Evidence began to accumulate that occasional outbreaks of diarrhoea among infants in nurseries - sometimes so severe that they resembled cholera - were caused by this selfsame bacterium. Textbooks began to describe the culprits as "rare enteropathogenic strains" of Ecoli. Yet laboratory tests repeatedly failed to show precisely how these differed from much more widespread harmless strains.

Ecoli 0157 announced its presence for the first time in 1982, when investigators identified it as the cause of two outbreaks of a severe form of food poisoning called haemorrhagic colitis which affected 47 people in Oregon and Michigan. Beginning suddenly, after three to four days' incubation, with watery diarrhoea (which often becomes blood-stained later) and severe abdominal cramps, haemorrhagic colitis can also lead to kidney failure. The bacterium, given its more precise label because it carries an antigen (protein) labelled 0157, was isolated from the victims and also from hamburger meat prepared by a fast-food chain, which was almost certainly the source of the outbreaks.

What distinguishes Ecoli 0157 from the many benign strains of the same bacterium is its capacity to make two toxins (poisons) which closely resemble those produced by one species of dysentery bacteria. The bacterium can now be identified through the action of the toxins on certain cells (originally obtained from African Green monkeys) cultured in the laboratory. Although the toxins were first discovered before the two US outbreaks, those incidents marked the breakthrough in indicting Ecoli 0157 as the agent of haemorrhagic colitis.

Four years after first making newspaper headlines in the US, Ecoli 0157 had caused at least 12 outbreaks in North America and three in Britain. In one of the UK incidents, it affected nearly a quarter of 93 guests who ate a buffet meal at a christening party in Birmingham in the summer of 1987. In 1993, 450 people in the Pacific north-west of the USA succumbed to the organism, 21 of them children who were sufficiently ill to require treatment on a kidney machine. At least 9,500 people were involved in the epidemic that raged in Japan in May this year, which claimed 11 lives.

These and other outbreaks have had a variety of known or suspected sources - contaminated water (including a children's paddling pool), milk, yoghurt, cheese, potatoes, cider and apple juice, and inadequately cooked or contaminated meat, especially beefburgers. It seems that the main reservoir of Ecoli 0157 is cattle, though affected individuals also shed the bacterium in their faeces. With poor personal hygiene, this poses a danger to others. However, good hygiene reduces the hazard considerably, while thorough cooking (sufficient for all parts of a piece of meat to reach 70C) destroys the organism and eliminates any risk of infection.

The need for such precautions would surprise many of the first scientists to work with Ecoli, who described it explicitly as not capable of causing disease. Writing in 1947, the Cambridge microbiologist Ernest Gale portrayed the bacterium as an excellent research partner. "This organism," he wrote, "is easily grown in large quantities, is non-pathogenic, has very wide chemical activities, and has consequently been subjected to more intense biochemical investigation than any other bacterium."

Our knowledge of Ecoli is now more extensive than ever. We have far greater understanding of its character and behaviour than was possible 50 years ago - and a map of all of the bacterium's genes is nearing completion. Nevertheless, the ferocity of strain 0157's attacks on the human intestinal tract and kidneys has come as a most unwelcome surprise over the past 15 years. Although it is likely that the bacterium developed the ability to produce lethal toxins by acquiring the relevant genes from other bacteria, this is by no means proven.

There is a sobering truth to set against the enormous contributions Ecoli has made to human welfare. From its own perspective, the new capacity gained by strain 0157 simply provides a more efficient mechanism for ensuring its further proliferation and dissemination. But for Homo sapiens, this means life-threatening disease.

The writer's `Power Unseen - How Microbes Rule the World' is published by W H Freeman-Spektrum.

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