Childhood Lead Exposure: A Tribute to Dr. Herbert Needleman

Well, I'm a little bit on a high horse here, so please bear with me because this topic is very close to my heart and also close to my head. So I do have some passion about what I'm going to say. It has to do with a very good article, research article that was just published in the Journal of the American Medical association in the March 28, 2017 issue that I believe has a lot of interesting implications as it pertains to this association between lead exposure and cognition. But it also has another message that's below the surface that you might miss that I wanted to bring to your attention. And this message actually goes back in my life to an interview on Functional Medicine Update in June of 2006. So over a decade ago. So the title of the article in the JAMA March 28 issue is association of Childhood Blood Levels with Cognitive Function and Socioeconomic status at age 38 years and with IQ change in socioeconomic Mobility between Childhood and Adulthood. So here they're looking at what effect would infant exposure to lead have on later stage cognitive function after the age of 38. And it's a very powerful study that comes to a conclusion that I think is probably not too surprising to most of us who have been in this field for a while. It says in this cohort, this was a study from in 1972 and 73 in New Zealand, that childhood lead exposure was associated with lower cognitive function. I want to emphasize function because we're not talking about pathology here and socioeconomic status at age of 38 years with declines in IQ and a downward social mobility. And they go on to conclude that childhood lead exposure may have long term ramifications. The editorial that is associated with this is entitled Childhood Lead Exposure and Adult Outcomes. And once again it revisits probably in the wake of what we've all seen in Flint, Michigan recently with the water supply system being contaminated with heavy metals, this association between lead IQ and neurocognitive behavioral problems. In the reading of these articles, however, I was immediately struck when I read the references that they did not give attribution to where this all started and the extraordinary valiant efforts by a single person ultimately to mobilize the scientific and medical community to this question. Does lead exposure impair intellectual performance? And it was not an easy path nor journey that this individual was on. And some of you know who I'm talking about. And it takes us back to June of 2006 to Herbert Needleman, who probably most of you recall was credited as being one of the principal people to make this discovery between low levels of lead exposure producing functional disturbances, not acute plumbism, that is associated with hemolytic anemias and problems related to gamma levinic acid synthetase inhibition that you see with producing red cell hemoglobin deficiencies with acute lead toxicity. We're talking about low level alterations in a very sensitive organ system called the central nervous system in lead exposed children. And prior to Needleman's work, this was a topic that had really been kind of laid dormant in the literature in the late 60s. There were some concerns about tetraethyl lead, which was an additive put into gasoline, and the effects that it would have on spewing lead into the environment and the effect that it could have on sensitive children that lived close to freeways and roadbeds where they could be lead exposed. But it was not really until Needleman put this to the hard test in some extraordinary studies that it started to really gain some traction. So I'm talking about the early 1970s and in fact in the New England Journal of Medicine he published a paper in March 1 issue of 1973 entitled Getting the Lead out, in which he talks about the fact that there are 200,000 tons of lead that were inserted into the atmosphere in that year, 90% of which coming from the contribution that was from from leaded gasoline. And that most of this is in very small particle size, of which he goes on to point out that most of it is readily absorbed across the lungs and gets into the bloodstream. And so in this period of time, the late 60s and early 70s, there was this extraordinary revelation that low level lead exposure from the ambient environment could have a significant adverse effect potentially on sensitive function of the nervous system. This was followed up with a paper that I recall so vividly when it was published in the New England Journal of Medicine. This is the March 29th issue of 1979. And the reason I remember this so vividly is that I gave numerous seminars during that period of time in the late 70s and early 80s where I cited this article and the procedures and protocols and outcomes from the study because I thought it was so significant. Again, this is Herbert Needleman and his co investigators at Harvard at the time at Mass General Hospital where he was on faculty there in neuropsychiatric department. And the title of this article is Deficits in Psychological and Classroom Performance of Children with Elevated Dentin Lead Levels. And he actually pioneered this whole concept of measuring in the deciduous teeth of children the level of lead in the dentin of their teeth, which was found to correlate very closely with the integrated level of exposure that the child had and actually was more accurate over kind of a weighted sample of exposure than just taking a single blood lead analytical value. And in this particular study, if I could go on and on about it, let me just summarize it. However, it was found that children that had higher deciduous levels of lead in their teeth were children that had poor school performance, poor IQ tests, had inability to stay at task, so they had behavioral dysfunction in terms of their ability to concentrate. And it was for the first time really raising the spectrum that children in metropolitan areas that were across multiple socioeconomic categories were at risk to significant intellectual impairment as a consequence of ambient lead, of which I've said over 90% of the time came from tetraethyl lead additives in motor fuel. This was followed up by a whole series of subsequent papers that Needleman and his colleagues were involved with in very high tier journals. For instance, in jama, a paper that was published again by Needleman et al. In 1984, entitled the Relationship between Prenatal Exposure to Lead and Congenital Abnormalities, showing that Low level exposure in vitro, excuse me, in vivo in pregnant women could have an adverse effect on the development of the fetus and produce congenital abnormalities with increasing risk in the offspring. And then in 1987, another New England Journal of Medicine paper, Longitudinal Analysis of Prenatal and Postnatal Late Exposure and, and Early Cognitive Development, again showing retardation of cognitive development. So the story increasingly was showing against tremendous opposition from the lead industry that ambient exposure was having a functional impairment in children in terms of their intellectual development and cognitive function. Now, to make this story a little bit more dramatic, I think you have to recall that this was not well received by the lead industry, to say the least. And there were tremendous amounts of pushback from all sorts of interesting quarters that had kind of connections into this, sometimes circuitous connections to the lead industry, the lead battery industry, the storage batteries were one of them, obviously those that produced the additives for, for automobile fuel, for gasoline, and the whole petrochemical industry that were related to gasoline were pushing back even real estate developers and commercial developers, because it would suggest that when you had a commercial facility next to a roadbed, that those individuals would be more at risk to lead exposure regardless of their socioeconomic status. And it may end up impairing children development, which could be a whole liability issue. So there was pushback from the development and real estate industry as well. As, as a consequence of that, Needleman became extraordinarily scrutinized and this work was looked at upside down from every perspective. And he had. Criticism was brought to bear on his work by individuals that were representing as academic psychologists, as consultant representatives to the lead industry who found fault with his data. And they suggested that he had misappropriated his data, that he had falsified certain information, he had done inappropriate statistical analysis, and that his facts were not right, and that in fact he had an axe to grind and it was not factually correct. A huge, huge debate pursued, as you probably know, that went on for two decades. Yes, two decades, 20 years. There were four investigative panels that were put together to evaluate Needleman's work in his papers, particularly this 1979 paper. And as a consequence, he lost his academic appointment, ended up eventually at Case Western Reserve, and then even from there on to University of Pittsburgh, where his life was troubled continuously by people criticizing, saying that this was not good science. Well, all I can say is that all four panels that were designed to evaluate his data and see if it was correct came to the conclusion on all four cases of exonerating him. And in fact, his evidence was, if anything, conservative, because he suggested that there was no safe blood level for children for lead, that any level was not good, but that if you were talking about where the risk started to go up significantly was at levels above 20 micrograms per deciliter of blood, of lead content. It turned out that on further analysis by other investigators and other studies, that that was probably even too high, that really it shouldn't be higher than 5 micrograms per deciliter of blood. So, if anything, he was overly conservative and not overly ambitious in his associations. And in fact, there's a meta analysis study that he published, this was in Jamaica in 1990, volume 263, entitled Low Level Lead Exposure and the IQ of Children. This is a meta analysis of all the modern studies, again, confirming without any question that there is a very strong association of a functional impairment of the neurological system of children and that that could translate into later age than changes in cognitive function. I find it very interesting because if you study through the Needleman work, you're ultimately led into a kind of a philosophical paper that he wrote and published in the Environmental Health Perspectives, entitled what can the Study of Lead Teach Us About Other Intoxicants or Other Toxicants? And this particular paper goes on to say, we should learn something from this lead story because there was a heightened interest. Eventually lead was removed from gasoline as a consequence of this work. It reduced the level of lead in the blood of children significantly, but it didn't completely remove the problem. And then it kind of went away. Once the heat was off, people kind of forgot about lead. And he said, you know, this is what happens often with the area of toxicology that we get very excited about something, very concerned as citizens, something is done, and then we lose our vigilance. And then later it comes back to be a rejoining problem later. So that led into a very interesting public health now and then paper that he authored in in the American Journal of Public Health, entitled Childhood Lead the Promise and Abandonment of Primary Prevention. He says, here is a place where everyone was very concerned about primary prevention of lead intoxication in children or lead impairment in children. And then, as we thought, we kind of got the problem solved. We kind of abandoned the primary prevention. Only now to come back to revisit that it can come from many other sources, including our water supply, AKA the Flint, Michigan study. So what I want to leave you with is kind of a twofold story. Number one is I want to celebrate Herbert Needleman. Secondly, I also want to acknowledge that these issues of functional impairment at low levels are much more complicated to understand than acute toxicity, where people are really so acutely ill that you can make a cause effect relationship much more clearly. It's in these gray areas where you're getting impairment of certain cohorts of the population, in this case children, in which the symptoms are chronic and diffuse and not associated with overt toxicity, where you have a lot of controversy and debate and you have those individuals who have axe to grinds and certain economic and political motivations for holding onto an old model and being the kind of the voice of saying, oh, that really isn't a problem, when really the data, when you look at it in the totality and particularly the superb work done by needleman, with over 100 publications in this area over the 25 to 30 years of his engagement proves a very strong association. So there's lessons to learn for all of us. But in this moment, I just want to say I was somewhat disappointed and somewhat is probably an understatement that in the paper in JAMA in this 2017 issue acknowledging the association of childhood blood lead levels and later age decrements of intellectual function, that there was not a single mention of Herbert Needleman's incredible pioneering work. So, Dr. Needleman, just to let you know, we're still remembering the extraordinary contributions you made and thank you for your warm and actually gracious interview that we did with you in 2006 in which you had no anger. You were just pleased to see that the system has accommodated reduction of lead in our environment.