Philosophy of AR > Animal Testing - Index > Anti-Vivisection Index

Financial Times (London, England)
September 23, 2005

A small dose of our own medicine
ALTERNATIVES TO ANIMAL TESTING: 'Human microdosing'
 offers a way to produce more accurate data about
 new drugs without experiments on animals
By ROBERT MATTHEWS

In the bitter debate over animal experiments, science often loses out to stunts. Anti-vivisection campaigners seized the headlines last month after the owners of a farm breeding guinea pigs for research abandoned the business after the remains of one of their relatives were stolen from a graveyard.

That same week, pro-vivisectionists went on the media offensive with a petition backing animal research signed by more than 500 UK scientists and doctors - including three Nobel prizewinners.

This month the US listing of Huntingdon Life Sciences, the animal testing company, was postponed by the New York Stock Exchange. The company has been the target of a long-standing, often violent, campaign against its activities in the UK; and extremists had threatened US institutions involved in the listing.

Such events create an impression of a straight fight between cool-headed seekers-after-truth and activists convinced that guinea pigs have souls. In reality, many campaigners concede that animal research has led to important breakthroughs such as transplant surgery and therapies for premature babies.

At the same time, many scientists admit to being concerned about the lack of systematic evidence for the reliability of insights based on animal testing. And many, if not most, would prefer to use alternatives - if they were available.

The view that there is no alternative to using animals is becoming harder to sustain. For while it attracts little media attention, research into alternatives is soaring, with impressive results. In the very week that the guinea pig farm and pro-vivisection petition were making headlines, hundreds of scientists gathered in Berlin for the 5th World Congress on the use of alternatives to animals in the life sciences.

The focus was on the so-called "3Rs": refinement, reduction and replacement of animals in research. Researchers described progress towards these goals, using techniques ranging from computer modelling of how compounds behave in living organisms to "in vitro" studies of the response of cell cultures to compounds. The predictive value of such techniques can be high. A review by researchers in the Netherlands published in the current issue of the journal Regulatory Toxicology and Pharmacology reports hit rates of 70-90 per cent for some forms of harmful Âreaction.

Although the reliability of animal testing has never been assessed systematically, regulatory bodies remain chary about accepting alternatives. One exception is a technique now attracting huge interest among researchers, pharmaceutical companies and anti-vivisectionists: human microdosing.

Advocates for replacing animals insist that tests on animals can never be as reliable as those on humans. Yet a key problem facing alternatives such as cell cultures is that while they may use human tissue, they do not detect "whole body" effects, which can be crucial.

Tests on animals have long been seen as the only way of gauging these whole-body effects. But there is a middle way: exposing humans to the compound, but at levels too low to cause health effects. This is the basic idea behind human microdosing, now being investigated by a number of companies. The current front-runner is Xceleron, a company spun out from the University of York in 1997 to turn human microdosing into a commercial service.

The core technology is long-established. A proposed new drug is first "labelled" using an isotope of carbon, and then injected into volunteers at levels typically about 100 times lower than the proposed medical dosage.

How the body responds to the drug - for example, its conversion of the original drug into other molecules, and how long they stay in the body - is then studied by measuring the level of radioactivity in blood and waste products. As only microdose levels of the drug are used, the radiation dose is so low that sophisticated equipment is required to detect it.

The result is a technique that - in principle - produces a host of whole-body data about a new drug safely, reliably and without using animals.

As with any proposed alternative to animal testing, however, human microdosing has faced questions about its predictive value. For example, do results obtained at very low doses reflect reality at much higher therapeutic dosages?

To answer these, Xceleron has recently taken part in an independent trial to test the ability of microdosing to predict the behaviour of five drugs, each with idiosyncrasies that had tripped up animal tests. Despite the difficulty of the test, the results from the microdosing studies showed a 70 per cent correspondence with those from full-dose studies. The technique has received a further boost from regulatory bodies, including the US Food and Drug Administration, which have signalled their willingness to accept human microdosing data.

Several pharmaceutical companies have now begun their own studies of microdosing. Speedel, a Basel-based company specialising in therapies for cardiovascular disease, has used microdosing to identify promising candidate compounds and plans to move into clinical trials later this year. Radiant Research of Seattle, which conducts clinical trials for many big pharmaceutical companies, has just completed its first study of the technique, and expects clients to start requesting microdosing tests within the next 12 months.

The big pharmaceutical companies will be watching the outcome of such studies very closely. They are spending 10 times more in real terms on research and development than in the early 1980s, yet the number of new drugs winning approval has remained essentially static.

The failure of much-vaunted genetic medicine to convert into effective drugs has prompted the FDA to warn drugs companies to focus less on blue-sky ideas and more on hard practicalities. With its potential to speed up drug development and cut the risk of nasty shocks during clinical trials, microdosing may be just the tonic that big pharma needs.

Its impact on the use of animals in testing remains to be seen. Toxic effects often reveal themselves only at relatively high dose levels, and animal testing may still be needed to find these - at least for the time being. Even so, the signs are that microdosing may bring about reductions in the use of animals that no amount of sick stunts by activists could ever achieve.

The writer is visiting reader in science at Aston University, Birmingham