An Article published Online First (www.thelancet.com) tracks the science behind the poisoning of Ukrainian President Victor Yushchenko in 2004, and concludes that routine analytical techniques are needed to test for metabolites of TCDD* (the poison used—a type of dioxin)—so that appropriate treatment can be given. The Article is written by Professor Jean Saurat, Swiss Centre for Human Applied Toxicology, and University Hospital, Geneva, Switzerland, and colleagues.
In late December, 2004, Victor Yushchenko presented with TCDD poisoning, indicating a concentration in his blood more than 50,000 times that of the general population. The medical team identified TCDD and its metabolites and monitored their levels for three years using various chemical techniques. Samples of blood, fatty tissue, faeces, skin, urine, and sweat were analysed.
Of the TCDD eliminated during the three years, some 60% of it was in its original form and had not been metabolised. Two metabolites of TCDD were identified in the faeces, blood, and urine. The faeces contained the highest concentration of TCDD metabolites, and were the main route of elimination. Altogether, the different routes of elimination of TCDD and its metabolites accounted for 98% of the loss of the toxin from the body. The half-life (time taken for the amount in the body to halve) of TCDD in Mr Yushchenko was 15 months.
The authors say that of 17 dioxin types analysed in Mr Yushchenko, only TCDD levels were higher than those in the general population, indicating an acute intoxication of pure TCDD. They say: "The highest levels of metabolites were detected in faeces, whereas only traces were found in the blood serum. The metabolite to TCDD ratio was 50-fold lower in the blood serum than in faeces. These findings indicate that these metabolites were unlikely to have been ingested with TCDD, and that TCDD is slowly metabolised, probably by the liver and skin." They add that high concentrations of TCDD might be needed to activate enzymes in the skin responsible for its metabolism, which might explain why the half life of TCDD varies with level of exposure.
The authors conclude: "Although not done previously, levels of TCDD and its metabolites in tissue, faeces, and body fluids should be monitored in a patient with severe dioxin poisoning because they are indicators of what the follow-up period and treatment strategy should be. The poisoning of Victor Yushchenko with TCDD has changed from a story reported in the news to a medical model. This model of TCDD poisoning indicates that methods need to be designed for the routine analysis of TCDD metabolites in human beings, and the main aims of research into TCDD poisoning in the metabolomic era should be the analysis of factors that are involved in the metabolism of this toxin."
Professor Saurat adds: "This is the first medical report in a peer-reviewed journal on the extraordinary case of Victor Yushchenko. The team was confronted in late December 2004 with a patient severely affected with what was likely to be dioxin poisoning. To cope with such a severe and painful disease, with no established specific treatment, we designed a strategy based on an aggressive monitoring of the poison, nature, distribution, and elimination—the subject of this report. We also designed a search for molecular medicine-based solutions to treat the various organs involved—likely to be the subject of future reports."
In an accompanying Comment, Professor Martin McKee, London School of Hygiene and Tropical Medicine, UK, says: "So who poisoned Victor Yushchenko? The obvious suspects are those members of the security service present at the dinner just before he fell ill, yet during the protests in December they and their colleagues gave covert support to Yushchenko, pre-empting a planned crack-down by Interior Ministry troops. Unfortunately for those seeking an answer, there were many people, within Ukraine and outside it, who had a motive. We might never know and, as Sorg and colleagues note, had Yushchenko died at the time, as he might easily have done, we would probably never even have known that he had been poisoned."
Dr Jean Saurat, Swiss Centre for Human Applied Toxicology, and University Hospital, Geneva, Switzerland T) +41 223729422 E) Jean.Saurat@unige.ch
Professor Martin McKee, London School of Hygiene and Tropical Medicine, UK T) +44 (0)7973 832576 E) martin.mckee@lshtm.ac.uk
For full Article and Comment see: http://press.thelancet.com/yushchenko.pdf
Note to editors: *full name for TCDD= 2,3,7,8-tetrachlorodibenzo-p-dioxin
Journal
The Lancet