Document DM9v4jg16MJ04Xwpy5YKZ5RMo

ENVIRONMENTAL RESEARCH, SECTION A 78, 7 9 -8 5 (1998) ARTICLE NO. ER973807 REVIEW Clair Patterson and Robert Kehoe: Two Views of Lead Toxicity H erbert L. Needleman U niversityofPittsburgh, School ofMedicine, 100 N. Belleeld Avenue, Pittsburgh, Pennsylvania 15213 Received November 4, 1997 INTRODUCTION In the early struggle to regulate airborne lead in the environm ent, two dom inant figures emerged. R obert Kehoe w as the lead in d u stry 's designated spokesman. At his antipode was Clair Patterson. These two men, the avatars of the industrial and public health outlooks, vividly define the 80-year contest to control lead in the environment. In exam ining the personalities embedded in the struggle to regulate lead we can hope to understand why it took 2 years to put lead into gasoline and 60 years to take it out. psychotic. W orkers called the product "looney gas'' and the place w here it w as fabricated ``The H ouse of Butterflies." This last sobriquet was earned by the sight of psychotic workers trying to brush phantom insects off of their arms. A m oratorium on the use of TEL was called and the Surgeon General convened a meeting of indus trialists, public health specialists, and academic physicians to determ ine if this new product was a serious enough threat to be banned or w hether it could be sold to the general public. THE INTRODUCTION OF LEAD INTO GASOLINE In 1921 General Motors lagged badly behind F ord's M odel T in sales, and GM 's flagship vehicle, the Cadillac, had an engine knock. General M otors' C. F. Kettering chafed in second place. He set his lab on an urgent search for an antiknock agent. When GM found an old G erm an patent, tetraethyl lead (TEL), th at silenced the knock in their laboratory eanlrgeiandey, ainnteerwlocinkdedu,sjtoryinwedasfobrocerns.toGpMroadnudceDtuhPeoandt, ditive and called th e ir fuel m ixture ``E thyl G asoline.'' It is clear th at the company was worried about the toxic properties of th e ir product; the w ord "lead " appeared nowhere on the label. In the Indianapolis 500 in 1923, ethyl fueled the first three winners. Production of TEL, under three separate companies, began in three plants: Standard Oil was licensed to produce TEL in northern New Jersey, DuPont in southern New Jersey, and GM in Dayton, Ohio. Shortly after production began, workers in all three plants began to go crazy and die, often in straightjackets. Som ew here betw een 13 an d 15 known deaths occurred, and over 300 men became KEHOE'S POSITION ON LEAD TOXICITY A t the Surgeon G eneral's m eeting, a young assist ant professor of pathology at the University of Cin cinnati, Robert Kehoe, emerged as the principal idnieddu sitnriathl eeDx paeyrttonanpdla nspt oiknes1m92a3n,. GWenheernalwMoroktoerrss asked Kehoe to consult and make preventive recom mendations. He made some m easurem ents of lead levels in the plant and in workers directly exposed to TwEhoL.hHadisncoodnitrreocl tgcroonutpacwt ewreithwtohrekecrosmipnotuhned.p la n t This assignm ent m arked 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 G en eral's m eeting and others th a t fol lowed his words were put forward as the final opin ion on lead by the industry representatives, and he was treated with considerable deference. Kehoe was not burdened with a hypertrophied sense of mod esty. He spoke with great confidence th at his data was the best, if not the only, guide to the truth. 79 All rights Coforpeyprriogdhut c(tio1n99in800ab1ny3yA-9fc3oa5rdm1e/m9re8isce$Pr2vr5ee.0sd0s. 80 REVIEW Virtually the only source of research support on lead for the next 50 years would come from indus trial treasuries, and m ost of it was directed to Kehoe. As a result he held an alm ost complete monopoly on lead data. To these he gave his singular and some w hat oracular interpretation. He found lead in the blood of workers in Dayton who did not handle TEL and concluded th a t lead w as a "n orm al" co n stituent ofthe hum an body. W hen challenged on the grounds that his control group was contaminated, he traveled to Mexico, found a ru ral village outside of Mexico City, and m easured lead in soil, food, tablew are, and w ater of the residents. From them he took blood, urine, and feces. He found m easurable am ounts of lead in the dishware. He found lead in the residents and reported, again with great confidence, that this proved th a t lead w as a "n orm al" p a rt of the body. That Mexican tablew are is a dangerous source of lead is a well-known fact. Kehoe offhandedly dis missed this troublesome finding. This assertion, th a t lead w as a "n a tu ra l" compon ent of hum an biochemistry, was the fundam ental s tru t in K ehoe's constructed case th a t lead poisoning is a relatively rare event, restricted to some factory workers, and th a t lead in gasoline presented no threat to hum an health. It became the fulcrum of the debate between him and Patterson. In Senate hearings on the Clean Air Act in 1966, Kehoe was one of the im portant witnesses before the M uskie Subcommittee on Air and W ater Pollution. Before Kehoe testified, the Surgeon General, W ill iam Stewart, had put on record, perhaps for the first tim e, the governm ent's concern about the effects of lead a t low doses and pointed to the vulnerability of children and pregnant women (Committee on Public W orks, 1966, p. 118): However, there is evidence suggesting th at lower levels of exposure produce more subtle but potentially serious effects on hum an health. Existing evidence suggests that certain groups in the population m ay be particularly susceptible to lead injury. Children and pregnant women constitute two of the most im portant of such groups. Some studies have sug gested an association between lead exposure and the occur rence of m ental retardation among children. Then Kehoe testified. He began by informing the chairm an th a t he knew so much of the subject th a t he was forced to leave a great deal of information out, otherw ise, ``I am afraid we would be h ere the re s t of the w eek 2 '' Kehoe said that enough was known about TEL toxicity to allow the am ount of TEL to be increased without risk: `The fact is, however, th at no other hygienic problem in the field of air pollution has been investigated so intensively, over such a pro longed period of time, and with such definitive re su lts.'' M uskie pointed out th at the Public H ealth Service and others disagreed and th at there were unan swered questions and need for more research. Kehoe: ... I would simply say th at in developing inform ation on this subject, I have had a greater responsibility than any other persons in this country ... the evidence at the present time is better than it has been at any time that this is not a present hazard. M uskie pressed on about finding a substitute for TEL: `2 would it be desirable if a substitute for lead could be found for gasoline?'' Kehoe: There is no evidence that this has introduced a danger in the field of public health ... I m ay say the work of the Kettering Laboratory in this field, that lead is an inevi table element in the surface of the earth, in its vegetation, in its animal life, and that there is no way in which m an has ever been able to escape the absorption of lead while living in this planet. (Committee on Public Works, 1966, p. 206) Kehoe asserted th a t air lead levels had decreased in Cincinnati. M uskie pointed out w hat appeared to be a paradox in Kehoe's statem ent: Over the past 30 years I assume there has been a trem en dous growth in automobiles and in the amount of traffic in Cincinnati, and yet as I understand it, you say that there has been no increase in the concentration ambient air? Kehoe: That is a fact, There has been a change downward, since the period of the Second W orld W ar... we had difficulty in C incinnati getting the kind of coal th a t w e would lik e __ During this period we had to take the coal th at could be obtained In 1945 this whole situation was changed and in the period immediately following this the lead content of the atmosphere of Cincinnati w ent significantly downward. Muskie: W hat you have just said is th at the decrease in the concentration in the atm osphere is due to better control of stationary sources of air pollution? Kehoe: That is right. Muskie: Have you drawn any conclusions as to w hether or not the concentration of lead in the atmosphere has gone up, gone down, or remained stationary? Kehoe: We conclude that there has been no increase. Kehoe neglected to m ention th a t the Cincinnati studies were biased. In the early years of air lead m easurem ent, more samples were taken from indus trial sites, and fewer industrial sites were sampled later. This may have been enough to account for the downward trend. Muskie: Is it your conclusion th at in 1937 to the present time, on the basis of that data, that there has been no increase in the amount of lead taken in from the atmosphere of REVIEW 81 by traffic policemen, by attendants at service stations or by the average motorist? Kehoe: There is not the slightest evidence th at there has been a change in this picture during this period of time. Not the slightest. Nothing could displace Kehoe from his unlim ited confidence and optimism. W hen M uskie again re tu rn ed to K ehoe's claim th a t th ere w as no h arm to be expected from atmospheric lead, he got a character istic response. Muskie: Does m edical opinion agree th at there are no harm ful effects and results from lead ingestion below the level of lead poisoning? Kehoe: I don't th in k th a t m any people would be as certain as I am at this point. Muskie: But you are certain? Kehoe: 2 It so happens th at I have m ore experience in this field than anyone else alive. Kehoe's sway in lead toxicology held u n til the late s1o9l6e0csis. mThthe adtulreaabdiliintythoef tbhoedyexwtarasonradtiunraarlyisscaietnetsitfaic m ent to the shielding power of reputation. It pays to advertise. CLAIR PATTERSON'S ROLE C lTaihrePreatwteerrseonno. sHciisenmtiefitchochdas lalenndgecorsntcoluKsieohnosecuonutlidl not have been more different. Patterson aimed his attack a t K ehoe's assertion th a t lead w as a norm al component of the hum an body, insisting that what he called "n orm al" w as in fact "typical." This was more than a semantic quarrel. Patterson fundam entally altered the vocabulary with which the debate over the health effects of lead was conduc ted. M ost people, following K ehoe's argum ents, re faeirr,remdetaoni`n`ngovrmalauleslenveealsr 'thoef laevaedraigne.blTohoedy, asossilu, manedd that because these levels were common, they were harm less. "N orm al" also carries some of the m eaning "n a tu ra l." P atterso n argued th a t "n o rm al" should be replaced by "typical." Sim ply because a certain level of lead was commonplace did not m ean it was w ith out harm . "N a tu ra l," he insisted, w as lim ited to concentrations of lead that existed in the body or environment before contamination by man. Kehoe and other workers in lead completely m is sed this distinction because their reagents, instru ments, and the very air in their laboratories were freighted with lead. As a result the baseline m easurem ents of all their samples were raised and their results blurred. In addition, the control sub jects in K ehoe's studies, the w orkers in the D ayton plant who did not directly handle TEL, were never theless exposed to it. H is second `unexposed''group, the M exican farm ers, ate food th a t had been cooked in and served from lead-containing ceramic pots and plates. Patterson was able to dem onstrate and correct this fundamental error because of the extraordinary m easures he took to avoid contamination of his speci mens. Because his lab was cleaner than others, his m easurem ents of isotopic ratios were free of the contamination that confounded the findings of Kehoe and others. W here Kehoe m easured lead in `unexposed'' w orkers in a TEL p la n t an d M exican farmers, Patterson studied pre-iron age mummies and tuna raised from pelagic waters. Patterson stum bled on the problem of global lead contam ination while m easuring the concentration of m ineral isotopes in his study of the age of the earth. Hsoeilnaontidceidcethwa tetrhee mleuacdhlehvieglsh einr hthisarneapgreendtisctaendd biny theory. It would have been understandable if he treated the contamination ofhis reagents as a severe annoyance to be overcome and then forgotten, but bthuattawcalesanrostighnisalsotyf lteh.eTcoohnitmamiitnwataisonnobyt alenaudisoafnthcee biosphere. This was an unrecognized danger, he be lieved, to everyone. In this regard, he provided facts to flesh out the warnings 40 years earlier of Yandell hHeeanldthersscoine,nDtiastvsidprEeddsiacltle,danadt tAhleicSeuHrgaemoinltoGne.nTehreasl'es 1925 m eeting th a t tetraethyl lead would lead to widespread increases in hum an lead burden. Patterson began to divert a considerable propor ptiuorneofgheoiscehxemtraisotrrdyintoartyhme isntuddayndofenleeargdycaowntaaymfrionma tion. By conducting his experiments in his ultra clean cham ber in which the air was filtered, the experimenters gowned and masked, and the re agents and water supply purified of any trace of lead, he was able to avoid contam ination and establish the true concentrations of lead in his samples. He showed that technological activity had raised mod ern hum an 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 contam ination on the way up and pre-iron age mummies buried in sandy soil, he sam pled cores of the G reenland 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. m eInn ta1l9H65eatlhthe, E K ditor athry of nB the Archives oucot, invited of Environ Patterson to 82 REVIEW write an editorial on lead pollution. He subm itted answered with a lecture in which he predicted that instead a long article en titled "C ontam inated and fu ture scientists would show th a t E th y l's activities N atu ral L ead E nvironm ents of M an '' based on his w ere poisoning the environm ent an d people and th a t findings and speculations. Kehoe was one of those this would result in the shutting down of their opera selected to review his m anuscript and decide tions. After this meeting, his long-standing contract w hether it should be published. Kehoe argued that with the Public H ealth Service was not renewed, nor the paper be accepted for publication for ironic rea was his substantial contract with the American sons: Petroleum Institute. Some members of the Board of Trustees at California Institute of Technology I should let the m an, with his obvious faults, speak in such a way as to display these fa u lts The inferences as to the natural hum an body burden of lead, are I think, remarkably naive It is an example of how wrong one can be in his biological postulated and conclusions, when he steps into this field, of which he is so woefully ignorant and so lacking visited the chairm an of his departm ent and tried to get him fired (letter from C. Patterson to H. Needlem an, A ugust 5, 1992). One week after Kehoe, Patterson testified before the M uskie subcommittee. He began by challenging in any concept of the depth of his ignorance, that he is not even cautious in drawing sweeping conclusions. This be speaks the brash young m an, or perhaps the not so young [Patterson was 43 at the time] passionate supporter of a cause. In either case hardly the m ark of the critical investi gator. the conventional wisdom that natural lead cycling and hum an activity contributed roughly the same am ount of lead to the environment. He pointed out th at 10,000 tons of lead were naturally recycled each year, while millions of tons were em itted due to We have been working with the physiological aspects of this problem carefully and step by step for more than thirty y ears... It is disappointing that viewed in this m anner by Dr. Patterson, but the issue which he has raised, in this article and by w here, cannot be `sw ept u n d er the rug .'' industrial emissions. He believed that large num our br aelr swl oooafr kdp.e oPprloheapashreetisciac nklloeytn, ed a he sebmaeerpnehsauslitz of th is ed the unnatu centra l word nceenrvto:of hues psyosimtnetomeudthaosuate lttsaheragtewt. Patter hen pu son blic was not reti health agen The virtue of the paper is its examination of the m anner in w hich m an has altered `the face of the e a rth ''in a variety of ways, and has disturbed the composition of the hum an inter nal m ilieu in so doing. It is strange th a t Dr. Patterson does not realize that this has happened to the large proportion of m ineral components of the earth, and that this is one of the outstanding physiological problems of our time. Can we adapt to these changes, individually and collectively? Are our physiological mechanisms flexible enough to cope with them? It appears, in the case of lead, th at they are ... (letter cwiehsetchoelrlapbuobralitce hweiathlthpoislluthtirnegatienndeudstbryiesthteoirdpecroidde ucts, the results are often absurd. W hen M uskie asked him if his classification of ``n a tu ra l,'' "typical," and "contam inated" concentra ptiroonaschoftoleafodlloinw,foPoadttaenrdsohnu'smreasnpsownsaes wa alsogpiocianlteadp: ``N ot if your purpose is to sell lead .'' from R.A. Kehoe to K. Boucot, April 16, 1965) Muskie: W ell, I don't th in k it is the purpose of the Public This last sentence declares his second funda H ealth Service to sell lead. m ental conflict with Patterson. Kehoe claimed that m ankind has adapted to environm ental lead. P atter Patterson: T hat is why it is difficult to understand why the Public H ealth Service cooperated with the lead industry in son's precise point w as th a t m an h ad recently in issuing this report which fails to m ake this distinction. cspreaanseodf tehxepcoosnucree,ntaratfieown othf oleuasdanadn dytehaarts,thwe assh oarnt Muskie: That is the Tri-City Study? instant in the Darwinian time scale, nowhere near Patterson: Yes. the tim e needed to develop adaptive responses. P a tterso n 's p ap er u n leashed a fusillade of angry responses from the toxicological establishm ent. The Muskie: Have you discussed this with the Public Health Service? rage was fueled by his hubris in stepping outside of Patterson: Yes. his field and talking about hum ans instead of rocks. It extended to the Editor of the journal, whose judge Muskie: W hat is their reaction? m ent was attacked for publishing the paper. Patter Patterson: I have both friends and antagonists in the Public son w asn 't bothered a t all by public criticism ; he H ealth Service. seemed to thrive on it. But there were more serious measures. He was M uskie: I think I do too. visited by a group from Ethyl Corp. who tried to (in M uskie was determ ined to throw Kehoe s industry his words) ``buy m e o u t through research support perspective into co n trast w ith the public h ealth p er th a t would yield resu lts favorable to th e ir cause.''He spective. P atterso n w as the rig h t m an for th is task. REVIEW 83 Muskie: ...those representing the industry, the American petroleum industry and others, have told us that there is no evidence of increase in the p ast since som etim e in the 1920's th a t create any cause for concern as to hazards from le a d __ Now w hat do you say on this and where is their analysis faulty? Patterson: The evidence for an increase in concentration the blood of people in American cities is clear. The difference, as I said, between the concentrations of lead in blood of people living in cities and outside of cities is that between 0.17 and 0.11 parts per million. The difference is not due to food As I say from these known things we can predict that the people in the cities will have higher concentrations of lead in their blood as a consequence of their absorbing the greater amounts of lead and the difference is due to the greater concentration of lead in the air. He attack ed Kehoe's claim th a t levels h ad dropped in Cincinnati: . there is given on the back side of the page of data from which Dr. Kehoe quoted, another figure which shows that concentrations of lead in th at very same city increased. This is data gotten from the National Air Sampling Network which is not the same organization that Dr. Kehoe repres ents. It shows an opposite trend. The point here is that those kinds of data which purport to show th at the concentrations of lead in the atm osphere of American cities is decreasing is rather invalid. After having elicited clear contradictions of Kehoe's claim s th a t lead levels h ad not changed, M uskie focused attention on the other critical issue. Iitnydbuystcryouhnatdinmg edaesauthresd, othr ea tplreeavsatlesnecveeroef dleaamdatgoexitco the brain. Muskie raised the question of a larger pool of unrecognized toxic illness: Is it conceivable that there is something different in the deleterious effects oconnhceeanlttrhatefrdomexploowsu-lreevleelaedxinpgostuorcelatshsaicnalfrloemad mpooirse o n in g ? '' Patterson: . when you expose an organism to a toxic sub stance it responds in a continuum, to continuously changing levels of exposure to this toxic substance. There is no abrupt change between a response and no response. Classical pois oning is just one extreme of a whole continuum of responses of an organism, hum an organism, to this toxic metal. There is a reason w hy this shouldn't be so. H ere is an o th er point in w hich P a tterso n 's point of view strongly d ep arts from K ehoe's, and here again Patterson is on firm scientific ground. Kehoe treated lead poisoning as a "yes-no" phenom enon: you have it or you do not. Patterson adm itted the dose-re sponse relationship to the question and treated toxicity as a dimensional trait: there are degrees of poisoning. This is of course a more sophisticated and rigorous way of examining the data. M uskie's aggressive inquiry began the govern m e n t's shift aw ay from passive complacency tow ard lead. The hearings focused awareness on increasing levels of lead in air, and tak in g P a tterso n 's point, established the idea th a t lead poisoning was not only a florid disease of workers, but also could be an insidious, silent danger. THE NSACTIEIONNCAELS RACEPAODREMT Y OF In 1970, the EPA, under pressure to regulate lead in gasoline, funded a study of airborne lead and its health effects by the N ational Research Council. Kehoe was named a consultant. From the beginning, other questions were raised about the fairness of the NAS committee. The committee and its consultants w ere chosen by an inform al ``O ld Boys' N etw ork.'' NAS staff solicited nominations for the committee from associates and people they knew and trusted. The results in this case were suspect. No member of the committee or its consultants had worked on air borne lead. Four em inent scientists with long experi ence in lead, who were obvious choices, were not selected. In addition to Patterson, the excluded scientists were John Goldsmith, head of the Califor n ia H ealth D ep artm en t's division of Epidem iology; H arry Schroeder at Dartm outh, who had conducted lsoowmedoosfet;haenodnlTy. tJr.anCshgoewn,erwahtioo nstauldsiteuddiaetsmoofslpehaderaict lead deposition as m easured in Greenland ice cores. All of these m en had done im portant work on the subject, and all were on the alarm ist side of the bp ea ol apnlec ,e . a Academy nTSdhtaeftshfeemoeAmmcibasdseieromtnoysldbwaeecrSaecmieoenbcvdeieomfuesangsitavozei.nmeOarnneye porter that Goldsmith and Schroeder were thought to be potentially disruptive to the work of the com m ittee. The committee appointed a large num ber of con sultants. Heavy industry representation was obvi ous. Kehoe and Lloyd Tepper came from the Kettering Lab. Gordon Stopps, Kam ran Habibi, and John Perrard were from EI DuPont, and Gary Ter H aar came from Ethyl Corp. Chow was appointed as a consultant. The committee gave the industry scientists major responsibility for writing sections of the draft. Stopps, whose earlier publications had for years claimed th a t TEL was harm less, was asked to write two im portant sections in the book: adult epi demiology and lead alkyls. This did not go down easily. H arriet Hardy, an em inent expert in m etal toxicity, complained about the imbalance and bias of the panel. T. J. Chow 84 REVIEW wrote about conflicts of interest encountered in ask ing industry employees to write chapters on their products. The Academy staffer responsible for this project responded ``R osters of com m ittees and panels consist of people w ith high competence in specific fields regardless or where they work and the ap pointm ent is made with the understanding that the person is thought to serve as an individual and not as a rep resen tativ e of his o rg an izatio n .''This u n derstanding did not seem to extend to Patterson, Goldsmith, or Schroeder (Boffey, 1975). T he NAS report, ``LEAD: A irborne L ead in P e r spective'' (N ational Academ y of Sciences/N ational Research Council, 1972) was a failure. It spent many pages on discussions of lead in plants and animals, but evaded a full exam ination of the questions for which it had been commissioned. It said that there were no conclusive data to show that atmospheric ltoeadbloaotd cloenacdenletrvaetliso,nsnobrelwowas 2thige/rMe 3ancyonetvriidbeuntecde to support toxicity at low levels of industry trum peted it, proclaiming that the prestig ious scientific body had given lead a health. THE SECOND NAS REPORT Eight year later, the National Academy of hSeciaelnthceismcpolincvaetnioends aonfoetnhveirrocnommemnittatleeletaod s(tNuadtyiotnhael Academy of Sciences/National Research Council, 1980). This tim e Patterson was elected to serve as taammienmabtieorn. Hofisthveiewbipoosipnhtearebobuyt ithned uusntriivaelrsaaclticvoitny received careful but respectful attention in this later publication, but he was not satisfied. He succeeded in having an entire chapter of his dissenting opinion inserted in the book. He clarified his argum ent through the use of Fig. 1: (a) rep resen ts th e lead content of a hum an body before the iron age, (b) represents the content of a 20th century American, and in (c) rep resen ts th e content of lead in th e body of a patient with classical lead poisoning. Patterson stated that between 1850 and 1923 it was believed tahmaot uthnet oafmloeuadntionf l(eaa).d Ainm(ebr)icwaanss twhoeureghtthotoubgehtthtoe have virtually no lead in their bodies. After Kehoe published his findings, it was believed that the am ount of lead in (a) was represented by (b); the h"nuamtuarnasl."Paamttoeursnotno,ftlheraoduwg hashtihs asttutydpieicsa, lelsytafobulinsdheind th a t th e "n a tu ra l" am ount of lead w as th a t in (a). P a tterso n 's personal review of th e technological history of our planet, his criticism of traditional thinking and analytic methods, and his view of the evolution of competing world views--the m anipula tilveeade.nginTeheering vleieawd and th e la te r evolving h u m anitarian world view--m ake interesting, if dicflfeicaunlt, rbeaildl ing. Hofe argued th a t m odern intracellu lar levels of lead were so high as to m ake it highly probable th at deleterious effects were occurring. This is of course of semi-scientific statem ent, as he would have been the first to state if someone else had uttered it. He pointed out the difficulties encoun tered in studying cellular interactions with lead and the need for lead-free systems in which to conduct them. He posited that biochemical systems that em ploy calcium are likely to be sensitive to lead per turbation. Eight years later, Marcovac and Goldstein would validate this prophecy by showing that intracellular protein phosphokinase-c, a cal cium-dependent part of the second m essenger sys- F IG . 1. (a) Prehistoric, un contam inated groups; (b) P resent-day Am ericans; (c) Lead-poisoned individuals. REVIEW 85 tem, is stim ulated by lead at lower concentrations than calcium (Markovac and Goldstein, 1988). The final section of Patterson s statem ent chides the com m ittee on w hich he served. ``It is intrinsically wrong to m ine and sm elt a highly toxic substance such as lead on a scale of millions of tons per year and then disperse it within hum an environments. The majority of this Committee on L ead... fails to explicitly acknow ledge th is obvious tru th . . ''H e rec om m ended the p hasing out in ``as sh ort a tim e as feasible''the m anu factu re of lead in any product th a t disperses it. He pleaded for research in the how to apply hum anitarian principles to guide future devel owphmicehnhtsas inneveenrgoicnceuerrrinedg betefcohrenoinlohgyu:m a`nsohmisettohriyn.g'' Patterson saw lead poisoning as a window through which to understand and fix our m odern dilem ma. ``The presence or absence of certain vital kinds of knowledge from these fields may very well turn out to be the factor which tips the scale for or against the survival of our hominid species in the face of chal lenges presented by impending developments in geAnegtirceaetndgeinael eorfinregs.e"arch h as been com pleted since the M uskie hearings and the NAS report. Almost all of it h as borne o u t P a t's predictions. W ith the re moval of lead from gasoline, blood lead levels in children and adults have declined by 80%. The mean blood lead level of American children, which was 15 gg/dl in 1978, is now 3.6 gg/dl. M any people re gard this as one of the most im portant public health trium phs of the past 3 decades. At the same time, better quality studies have shown effects of lead on children's psychological perform ance a t low er and lower levels. W ork rem ains to be done. M any people have felt the scorn of P a tterso n 's criticism, and been scorched by his unceasing de m ands for excellent work. Almost all have come to admire his steadfastness and prescience. To me he was a warm and simple m an, often funny, always gracious and in some ways naive about the workings of the world. It is clear that Patterson was the prim ary scient ific force in altering the narrow world view of lead toxicity. This im m ovable m a n 's insig h t enabled him to see in the troublesome contamination of his speci m ens not a technical laboratory difficulty to be sol ved, but a clue to a widely ignored public health problem of tragic dimensions. Having seen it, he was confronted with an inescapable urge to redress the 70-year-old error that perm itted the introduction of tetraethyl lead into gasoline and its products into the bodies of millions of citizens. The blood lead levels of today's children are a testim ony to his b ril liance and integrity. REFERENCES Boffey, P. (1975). ``The B rain B ank of America: An Inquiry into the Politics of Science,''p. 195, M cGraw-Hill, New York. Committee on Public W orks, Subcommittee on Air and W ater Pollution (1966). Hearings, June 8, 1996. M arkovac, J., and Goldstein, G. W. (1988). Picomolar concentra tions of lead stim ulate brain protein kinase C. Nature 334, 71-73. N ational Academy of Sciences/National Research Council (1972). ``LEAD: A irborne L ead in Perspective.'' N ational Academy Press, W ashington DC. N ational Academy of Sciences/National Research Council (1980). ``L ead in the H um an E nvironm ent.'' N ational Academ y Press, W ashington DC.