Sunday, May 23, 2010

gut instinct


Video - hookworm lifecycle papermation.

Guardian | The research that so excited Lawrence was a development of the so-called "hygiene hypothesis". This theory, first developed by David P Strachan in the British Medical Journal in 1989, suggests that many of the "modern" illnesses that have grown exponentially in industrialised western countries – allergies, asthma, type 1 diabetes, Crohn's disease, irritable bowel syndrome, multiple sclerosis and possibly rheumatoid arthritis and autism, and others – are the result of inappropriate autoimmune responses. The development of chlorinated drinking water, vaccines, antibiotics, and the sterile environment of early childhood have, the argument goes, as well as preventing infection also upset the balance of the body's internal ecology. Inflammatory responses that evolved through millions of years in the certain presence of "old friends" – parasites and bacteria – have been thrown wildly out of kilter in their absence, causing autoimmune illnesses, in which the body's immune system turns on itself, and oversensitivity to harmless antigens such as pollen, or dust, or cats, or particular food groups.

The story that most interested Lawrence was the ongoing research of Professor David Pritchard, an immunologist at Nottingham University. While in the field in Papua New Guinea in the late 1980s, Pritchard noted that patients infected with the Necator americanus hookworm were rarely subject to the whole range of autoimmune-related illnesses, including hay fever and asthma. In the years since, Pritchard had developed a thesis to support this observation through painstaking clinical trials (which began after he infected himself with 50 hookworm). The thesis proved that hookworm, in small numbers, seemed able to regulate inflammatory immune responses in their hosts. (Dr Rick Maizels, at Edinburgh University, has subsequently identified the process – involving the white T-cells in the blood that regulate immunity – that allowed this to happen.)

"When I read that stuff," Lawrence recalls, "everything immediately made sense to me. In our obsession with cleansing and sterility, with the eradication of parasites, we had thrown the baby out with the bath water. The central idea is that our bodies have an internal ecosystem. One of the ironies of this, to me, is that everyone is concerned about biodiversity in the outside world, and saving the rainforest, but we've also screwed up the biodiversity inside us."

And so Jasper Lawrence set out on what became a compulsive and somewhat desperate quest. Despite the fact that perhaps one billion people in the world still live with hookworm, getting infected in the developed western world is not an easy thing. The drift of our culture has long been to eradicate parasites – or "symbions", as Lawrence prefers. To begin with, he tried to get accepted as a participant on one of the various studies investigating the phenomenon. But when that proved fruitless he determined to go to Africa and become infected.

Prior to this trip, he recalls, he contacted "all the clever people I knew who worked in medicine. I sent them all the research and asked them their opinion. They all said the same thing: 'Yes, it appears safe, but I would not advise you to do this; you need to wait 20 or 30 years for all the studies to come in. For a molecule to be identified and a drug to be tested…'"

You don't have to talk to Lawrence for long to realise he is not a man who might be prepared to wait 20 or 30 years for anything. Instead, he took a plane to Cameroon.

The life cycle of Necator americanus is not an attractive one. Hookworm infiltrate a new human host when larvae, hatched in human excrement, penetrate the soles of the feet, enter the bloodstream, travel through the heart and lungs and are swallowed when they are coughed up from the pharynx. Only in the small intestine do they mature into adults (just under 1cm long), where they can live an average of five years latching on to the intestinal wall, siphoning off tiny amounts of blood, and – this is the crucial part – "regulating the volume" of immune responses. They mate inside the host, with females laying up to 30,000 eggs per day, up to 50m eggs during a lifetime, which pass out in faeces. In the tropics, in places where there is an absence of both toilets and shoes, extreme cases of hookworm kill 70,000 people a year, and afflict many others with anaemia; they exacerbate malnutrition and stunted growth in children. There are crucial caveats to these scare stories, however. Hookworm cannot and do not replicate in the gut. They are not infectious. In small numbers they are considered harmless, and very easily eradicated. And their life cycle is fatally interrupted by the introduction of either shoes or plumbing.

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