JUST a trace of ricin on the sharpened tip of an umbrella was enough to kill the Bulgarian dissident Georgi Markov, after an infamous attack on London鈥檚 Waterloo Bridge in 1978. Now a vaccine against this lethal toxin could soon be available 鈥� and it may be needed.
鈥淎 big stash of ricin was found in the caves of Afghanistan,鈥� says Ellen Vitetta of the University of Texas Southwestern Medical Center in Dallas, whose team developed the vaccine. 鈥淭hey weren鈥檛 collecting it to make stew.鈥�
Ricin, a natural toxin found in castor beans, is cheap and relatively easy to produce. And as it鈥檚 a powder, it is easily turned into an aerosol that can be inhaled.
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Nor does it take much to kill someone: just 1 to 10 micrograms of ricin per kilogram of body weight. A pellet recovered from Markov鈥檚 umbrella wound probably delivered about this dose. He died in five days. 鈥淵ou get flu-like symptoms, then suddenly you鈥檙e dead,鈥� says Vitetta. 鈥淭his stuff really frightens me.鈥�
The toxin has two components. Its 鈥淏 chain鈥� binds to cells, allowing the second component, the 鈥淎 chain鈥�, to enter the cell and disable the protein factories. Just a single A chain can kill a cell.
The team鈥檚 vaccine, which is a stripped-down version of the A chain, arose as a spin-off from Vitetta鈥檚 work on ricin-based anti-cancer drugs. The idea, which many groups are working on, is to attach the A chain to antibodies that target tumour cells. In trials, however, Vitetta found that while the ricin-based drugs do kill cancer cells, patients given high doses can develop a side effect called vascular leakage. 鈥淭hey retain fluid, gain weight and can have organ failure,鈥� Vitetta says.
To improve the anti-cancer drugs, Vitetta and her colleagues stripped out the part of the toxin that was causing vascular leakage. 鈥淭hen we thought: why don鈥檛 we make a vaccine by stripping out the active site, too.鈥�
Of the three versions of the A chain they genetically engineered, two turned out to have the desired effect on mice. The animals survived exposure to 10 times the dose of ricin that killed unvaccinated mice, Vitetta reports in Vaccine (vol 20, p 3422).
鈥淚t鈥檚 cheap, simple and protects wonderfully without side effects because it鈥檚 a totally inactive protein,鈥� Vitetta says. She has now applied to the National Institutes of Health for further funding to test the vaccine against aerosolised ricin and hopes eventually to test the vaccine in people.
The US Army is also interested because no approved vaccine exists. Previous attempts to make one by chemically inactivating the toxin failed.