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France passed its first anti-doping law in November 1964.

Hans Junkermann of Germany had been ill overnight so the start was delayed by 10 minutes, but at the first hill he got off his bike and sat by the roadside, telling onlookers "I ate bad fish at the hotel last night." Eleven other riders abandoned the Tour that day, including the former leader, Willy Schroeders, the 1960 winner Gastone Nencini and a future leader, Karl-Heinz Kunde.Jacques Goddet wrote that he suspected doping but nothing was proven - other than that none of the hotels had served fish the previous night.However, the main Bordeaux–Paris race did not start until 1891, and the cyclist who supposedly died in 1886, Arthur Linton, actually finished second in 1896 and died a few weeks later, reportedly from a combination of drug-induced exhaustion and typhoid fever.Riders suffered hallucinations from the exhaustion and perhaps the drugs.The first riders to be caught were four amateurs, three Spanish (Luis Santamarina, Canet and Usamentiaga) and one Briton (Ken Hill), who were thrown out of the Milk Race when they tested positive for amphetamines after Professor Arnold Beckett first applied sensitive gas chromatographic techniques to monitor drug abuse. Raymond Poulidor was the first rider to be tested in the Tour at the end of a stage to Bordeaux.

He said "I was strolling down the corridor in ordinary clothes when I came across two guys who asked if I was a rider.

"The administration of or use by a competing athlete of any substance foreign to the body or any physiologic substance taken in abnormal quantity or taken by an abnormal route of entry into the body with the sole intention of increasing in an artificial and unfair manner his/her performance in competition.

When necessity demands medical treatment with any substance which, because of its nature, dosage, or application is able to boost the athlete's performance in competition in an artificial and unfair manner, this too is regarded as doping." In 1886, a Welsh cyclist is popularly reputed to have died after drinking a blend of cocaine, caffeine and strychnine, supposedly in the Bordeaux–Paris race.

Recombinant EPO is a bio-manufactured copy of a hormone normally produced in the kidney and was not detectable by any test at the time.

EPO stimulates the bone marrow in order to increase red blood cell production and thus the body's ability to carry oxygen.

The increased thickness of the blood (above 70% red blood cells) increases the risk of blood clotting which can block blood vessels causing a heart attack or stroke, especially in the middle of the night when the heart's rate is lowest.