The culprit was Escherichia coli O157:H7, a strain of the common intestinal bacterium that was first detected from cases of severe bloody diarrhea in the late 1970s.
E. coli is now a significant health problem worldwide. According to the U.S. Centers for Disease Control and Prevention, for example, the microbe causes some 76,000 infections a year and kills an average of 61 people in the United States alone. Yet, this is just the tip of the iceberg. In developing countries, as many as 2 million people die annually from diarrhea-related dehydration.
Canada and the United States have developed four different approaches to preventing such tragedies, both at home and abroad, but what's remarkable is that a single Canadian scientist—B. Brett Finlay, a microbiologist at the University of British Columbia (UBC) and an HHMI international research scholar—is helping to lead all four:
• Reform of water and health systems. Finlay helped establish the Canadian Research Coalition for Safe Food and Water, a $13 million effort that supports research to increase food and water safety. Finlay is also a member of the advisory board for the Institute of Infection and Immunity, a group working to establish national priorities in that field and improve communication and coordination between Canadian health, food, and water agencies.
• Vaccination of cattle that carry the bacteria. The vaccine will help banish "hamburger disease" (as infection from O157:H7 is commonly called) by keeping it out of the meat supply in the first place. In a paper published in the January 2, 2004, edition of the journal Vaccine, Finlay and colleagues reported results of a clinical trial of a cattle vaccine that successfully reduced the prevalence of O157:H7 in the feedlot. This promising finding suggests that it is indeed possible to vaccinate cattle to decrease the level of E. coli, which "could have profound benefits for human health around the globe," notes Bhagirath Singh, scientific director of Canada's Institute of Infection and Immunity.
• Understanding how O157:H7 attaches to and disrupts healthy cells. Discoveries from Finlay's lab show how the microbe works so that new strategies can be developed to defeat it.
• Boosting the body's natural immunological defenses. Finlay is a cofounder and member of the board of directors of Inimex Pharmaceuticals, a Vancouver company set up to develop and commercialize discoveries made by scientists at ubc. Inimex intends to use peptides to boost innate immunity against infections.
The past century appeared to be one of triumph over infectious disease. Antibiotic drugs such as penicillin as well as vaccines against a long list of bacterial and viral illnesses helped boost average American life expectancy by about 30 years. By 1969, the U.S. surgeon general declared, "It's time to close the book on infectious diseases."
But the optimism was premature. While human generations are about 20 years apart, bacterial generations are an hour or less apart. Bacteria trade and share genetic information, and this constant throw of the genetic dice means mutant strains rapidly arise that are resistant to our arsenal of antibiotics. In addition, new challenges—such as AIDS, Ebola, legionnaires' disease, and SARS—continue to appear.
Meanwhile, only one new class of antibiotics, the oxazolidinones, has reached the market in the past 30 years, and finding drugs to combat each form of infection is difficult to justify. It can cost upward of $500 million and take 10 years to commercialize a new drug, but bacteria mutate so swiftly in response that drug-resistant strains can appear within a year and the new drug can be obsolete in three years.
Hospitals are breeding grounds for such resistance. For his 14-year-old daughter's recent science project, Finlay helped her analyze bacterial contamination of coins collected from hospital cafeteria vendors compared to coins from an outside grocery store. Those that had passed through the hospital carried a far higher percentage of drug-resistant strains of microbes, demonstrating that these institutions' heavy use of antibiotics has helped create superbugs.
"We need to rethink this," he says. We are in a constant "arms race" with microbes and viruses that, he warns, "we will never completely win." Because the germs mutate against every defense we throw at them, we need to develop other strategies.
Bacteria evolved on the planet first, long before plants and animals, and are found in almost every environment, from boiling hot springs to shafts thousands of feet below the ground. "They live everywhere," Finlay observes, "and humans just represent another nice place for them to live." We're warm, wet, full of nutrients, and, in some ways, Finlay says, "more microbe than we are human."
The human body has 10 times more microbes than cells, or an estimated 1,000 trillion bacteria for each one of us. A square centimeter of skin can have up to a million bacteria, and a gram of feces contains approximately 2 billion. The vast majority of these microbes are benign, helping digest food in our gut and crowding out their disease-causing brethren. But some of these bacteria develop parasitical strategies that make us sick.
Until recently, the two major counterstrategies were either to kill them with antibiotic wonder drugs or trick the body into beefing up its own defenses with the aid of vaccines. But given the current wealth of information on how cells, bacteria, genes, and biochemical pathways work in a complex microscopic ecosystem of mutual dependency and attack, researchers such as Finlay seek new approaches. They don't try to kill the bacteria, thereby destroying our friends in the bacteriological ecosystem, but rather interfere with the processes that specifically cause illness.
SABOTAGING THE CELL
A key breakthrough of the Finlay lab was the discovery, in 1997, that disease-causing E. coli have a clever way of sabotaging human cells to create a place where they can anchor themselves. Each bacterium exudes a tube, like a syringe, into the cell surface and injects a protein called Tir that serves as a receptor, plus at least a dozen others that disrupt the host cell. The injections trigger rearrangement of the cytoskeleton, which underlies the cell wall like scaffolding under a tarp, and cause it to swell upward, forming a pedestal on which the bacterium can comfortably nest.
This insidious adhesion actually offers researchers an opportunity, Finlay says. If science could find a way to snip or block that syringe, bad actors such as O157:H7 would be unable to link to a cell and cause damage. Instead, they would be flushed out of the body. His lab, in fact, is working on this approach. "We tell pharmaceutical companies that you don't have to kill the bugs, you just knock out the mechanism that causes the disease," he explains.
Similarly creative thinking informs the Finlay lab's development of the cattle vaccine against E. coli O157:H7, which is sure to attract a great deal of interest. Relatively simple to prepare and economical, the vaccine shows that it may be feasible to decrease human infections by vaccinating an animal population.
The lab is also working on Salmonella, a bacterium that sickens some 1.4 million people in the United States per year. In some ways, it is even craftier than E. coli, tricking the cell into opening up and absorbing it by chemically "ringing the doorbell." Once it is inside, Finlay has discovered, it forms a protective coating to avoid being destroyed by cell defenses and starts feeding and multiplying until it explodes the cell. Is there a way to teach the cell not to open the door? If there is, Finlay is determined to find it.
Still another tactic is to improve sanitation. The town of Walkerton, Ontario, had plenty of chloride on hand but didn't use it to treat its water supply. If it had, the E. coli outbreak there might never have happened.