No toxic substance has been more widely distributed throughout man’s environment than the lead additive Tel in gasoline. For over seven decades, millions of autos of all descriptions have successfully dispersed this toxic substance to all corners of the world. How did such a toxic substance ever gain approval to expose hundred’s of millions of people?

In 1921, competition in the expanding American automobile market was fierce. Ford's Model T outsold all other manufacturers, and General Motor's flagship product, the Cadillac, had a motor knock. The Model T was economical, dependable, and easy to fix. Its performance, however, was unremarkable and it had as much style as an orthopedic shoe. Charles F. Kettering, director of research at General Motors, chafed in second place. He had a plan: he would displace Ford with a high-performance engine in a fashionable GM auto body. The best way to achieve high engine performance is to increase compression in the cylinder. Squeeze the air-fuel mixture in the cylinder into a smaller volume and it will detonate with much more force. But when the gas volume is severely compressed, it acts like diesel fuel and ignites prematurely. This is engine knock, and it causes loss of power and eventual damage to the engine. Kettering set Thomas Midgely, his close associate and principal chemist in GM's Dayton, Ohio, research laboratory, to find an antiknock agent.

In December of that year, after trying and discarding many compounds, Midgely tested an old German patent, tetraethyl lead (TEL), in the laboratory engine, which was knocking on ordinary gasoline. It immediately began to run smoothly and silently. A new product was born, and a new firm, General Motors Chemical Company, Kettering named the new fuel Ethyl Gas. Nowhere was the word lead mentioned on the product label. That Memorial Day the new fuel was used by some of the drivers in the Indianapolis 500. This shrewd marketing step was a spectacular success: the first, second, and third-place winners all ran on ethyl gasoline.

Shortly after production began, workers in all three plants began to go crazy and die, often in straightjackets. Somewhere between 13 and 15 known deaths occurred, and over 300 men became psychotic. Workers called the product "looney gas" and the place where it was fabricated "The House of Butterflies." This last sobriquet was earned by the sight of psychotic workers trying to brush phantom insects off of their arms.

A moratorium on the use of TEL was called and the Surgeon General convened a meeting of industrialists, public health specialists, and academic physicians to determine if this new product was a serious enough threat to be banned or whether it could be sold to the general public.

At the Surgeon General's meeting, a young assistant professor of pathology at the University of Cincinnati, Robert Kehoe, emerged as the principal industrial expert and spokesman. When workers died in the Dayton plant in 1923, General Motors asked Kehoe to consult and make preventive recommendations. He made some measurements of lead levels in the plant and in workers directly exposed to TEL. His control group was workers in the plant who had no direct contact with the compound.

This assignment marked the beginning of a major career shift for Kehoe. C. F. Kettering would, with support from the Ethyl Corp., DuPont, and others, open the Kettering Laboratory on the University of Cincinnati Medical campus and name Kehoe as its director. Kehoe would also become Medical Director of the Ethyl Corp. and a corporate officer at GM. In the Surgeon General's meeting and others that followed his words were put forward as the final opinion on lead by the industry representatives, and he was treated with considerable deference. Kehoe was not burdened with a hypertrophied sense of modesty. He spoke with great confidence that his data was the best, if not the only, guide to the truth. Kehoe's sway in lead toxicology held until the late 1960s. The durability of the extraordinary scientific solecism that lead in the body was natural is a testament to the shielding power of reputation. It pays to advertise.

There were no scientific challengers to Kehoe until Clair Patterson. His methods and conclusions could not have been more different. Patterson aimed his attack at Kehoe's assertion that lead was a normal component of the human body, insisting that what he called "normal" was in fact "typical." This was more than a semantic quarrel. Patterson fundamentally altered the vocabulary with which the debate over the health effects of lead was conducted. Most people, following Kehoe's arguments, referred to "normal levels" of lead in blood, soil, and air, meaning values near the average. They assumed that because these levels were common, they were harmless. "Normal" also carries some of the meaning "natural." Patterson argued that "normal" should be replaced by "typical." Simply because a certain level of lead was commonplace did not mean it was without harm. "Natural," he insisted, was limited to concentrations of lead that existed in the body or environment before contamination by man.

Kehoe and other workers in lead completely missed this distinction because their reagents, instruments, and the very air in their laboratories were freighted with lead. As a result the baseline measurements of all their samples were raised and their results blurred. In addition, the control subjects in Kehoe's studies, the workers in the Dayton plant who did not directly handle TEL, were nevertheless exposed to it. His second "unexposed" group, the Mexican farmers, ate food that had been cooked in and served from lead-containing ceramic pots and plates.

Patterson was able to demonstrate and correct this fundamental error because of the extraordinary measures he took to avoid contamination of his specimens. Because his lab was cleaner than others, his measurements of isotopic ratios were free of the contamination that confounded the findings of Kehoe and others. Where Kehoe measured lead in "unexposed" workers in a TEL plant and Mexican farmers, Patterson studied pre-iron age mummies and tuna raised from pelagic waters.

Patterson stumbled on the problem of global lead contamination while measuring the concentration of mineral isotopes in his study of the age of the earth. He noticed that the lead levels in his reagents and in soil and ice were much higher than predicted by theory. It would have been understandable if he treated the contamination of his reagents as a severe annoyance to be overcome and then forgotten, but that was not his style. To him it was not a nuisance but a clear signal of the contamination by lead of the biosphere. This was an unrecognized danger, he believed, to everyone. In this regard, he provided facts to flesh out the warnings 40 years earlier of Yandell Henderson, David Edsall, and Alice Hamilton. Alice Hamilton of Harvard Medical School, a pioneer in the study of occupational diseases and a recognized expert in lead poisoning, spoke briefly at the hearings to review TEL:

" I would like to emphasize one or two points that have been brought out. One is the fact that lead is a slow and cumulative poison and that it does not usually produce striking symptoms that are easily recognized. The other is that if this (as does seem to have been shown) is a probable danger, shall we not say that it is going to be an extremely widespread one"? She said that while it might be possible to educate a workforce on avoiding lead poisoning, it would be impossible to control the behavior of a whole country, and that TEL should be replaced with a less poisonous antiknock agent.

These health scientists predicted at the Surgeon General's 1925 meeting that tetraethyl lead would lead to widespread increases in human lead burden. Patterson began to divert a considerable proportion of his extraordinary mind and energy away from pure geochemistry to the study of lead contamination. By conducting his experiments in his ultra-clean chamber in which the air was filtered, the experimenters gowned and masked, and the reagents and water supply purified of any trace of lead, he was able to avoid contamination and establish the true concentrations of lead in his samples. He showed that technological activity had raised modern human body lead burdens 100 times that of our pretechnologic ancients. In addition to tuna caught in the deep strata of the Pacific Ocean and brought to the surface with great care to avoid contamination on the way up and pre-iron age mummies buried in sandy soil, he sampled cores of the Greenland ice pack. By slicing the ice cores he was able to precisely date the specimen and show the time course of lead in the atmosphere.

The removal of lead from gasoline in 1990, regarded by many as one of the major public health triumphs of the 20th century, had an immediate impact. Between 1976 and 1994, the mean blood lead concentration in children dropped from 13.7 mcg/dL to 3.2 mcg/dL, in direct proportion to the amount of tetraethyl lead produced. One could want no clearer testimony to the efficacy of a well-conceived and consistently applied public health policy.

In 1993, the National Academy of Sciences verified that lead at extremely low doses caused neurobehavioural deficits.