Considered to be the world’s foremost expert on the neurotoxicity of fluoride compounds, Phyllis Mullenix, Ph.D., formerly of Harvard University, to her surprise found that fluoride crossed the blood brain barrier, accumulated in the brain, and impacted the behavior of rats in a manner consistent with a neurotoxic agent. She experienced the wrath of the dental industry when she tried to publish her research titled ‘The Neurotoxicity of Sodium Fluoride in Rats‘ in the ‘Journal of Neurotoxicology and Teratology’ that fluoride was neurotoxic. Three days after being approved for publication, Mullenix was dismissed from her position (and her employer, the Forsythe Institute, received a $250,000 grant immediately afterwards), all funding and grants for her research were taken away claiming her fluoride research was not “dentally related”, and her science equipment and computer destroyed or damaged by water leakage. Forsythe, where Dr. Mullenix was the Chairman of Toxicology, is one of the most prestigious dental research institutes in the US, if not the world. Mullenix was hired by Forsythe to study the neurotoxic effects of chemicals commonly used in dentistry.
Abstract
Fluoride (F) is known to affect mineralizing tissues, but effects upon the developing brain have not been previously considered. This study in Sprague-Dawley rats compares behavior, body weight, plasma and brain F levels after sodium fluoride (NaF) exposures during late gestation, at weaning or in adults. For prenatal exposures, dams received injections (SC) of 0.13 mg/kg NaF or saline on gestational days 14–18 or 17–19. Weanlings received drinking water containing 0, 75, 100, or 125 ppm F for 6 or 20 weeks, and 3 month-old adults received water containing 100 ppm F for 6 weeks. Behavior was tested in a computer pattern recognition system that classified acts in a novel environment and quantified act initiations, total times and time structures. Fluoride exposures caused sex- and dose-specific behavioral deficits with a common pattern. Males were most sensitive to prenatal day 17–19 exposure, whereas females were more sensitive to weanling and adult exposures. After fluoride ingestion, the severity of the effect on behavior increased directly with plasma F levels and F concentrations in specific brain regions. Such association is important considering that plasma levels in this rat model (0.059 to 0.640 ppm F) are similar to those reported in humans exposed to high levels of Fluoride.
Here’s her Story
The following interview with Phyllis Mullenix took place on October 18, 1997. The interviewer is Paul Connett.
I. ACADEMIC BACKGROUND
Connett: We’re talking with Dr. Phyllis Mullenix, who in 1995, published a very important work on the neurotoxic effects of fluoride in rat studies. And Phyllis would you begin by telling us your background? What are your qualifications?
Mullenix: Well, I got my PhD in pharmacology from the University of Kansas back in 1975. From University of Kansas Medical Center I went to John Hopkins School of Public Health in Baltimore between 1975 and 1977. And then in 1977 I was hired to come to Boston and work at Harvard with Dr. Herbert Needleman on the lead project. And so, I started then in 1977 and I’ve been in the Boston area for the past 20 years.
I was at the Childrens Hospital in Harvard Medical School in the Psychiatry Departments and Department of Neuropathology at the Harvard Med School between 1977 and 1982. Then [in] 1982 I left and went to the Forsyth Dental Center in Boston. I went first into the Department of Pharmacology and then in 1983 we established the first toxicology department in any dental research institution in the world, in 1983.
Connett: And, if I may interrupt, your task at that point, your brief as you understood it, was to examine the toxicological effects of the kind of materials that we’re using in dentistry?
Mullenix: Yes, Dr. Hein, who was the director of the institute at the time, wrote a nice newspaper article that was in the Forsyth Dental Center news in the spring of 1984 which described who I was and why I was brought in to the department and that I was brought in to head up this department to look at the environmental impact and the toxicity of products that are used by dentists and the dental community. And in particular they specifically mentioned fluoride, mercury, nitrous oxide, and some of those things.
II. NEUROTOXICITY OF FLUORIDE
Connett: Ok. Could you briefly summarize your paper, and where was it published first of all?
Mullenix: My paper concerning the neurotoxicity of sodium fluoride in rats was published in the Neurotoxicology and Teratology journal. That’s a peer reviewed journal… And that was published in 1995. It was submitted in 1994, but it was published, it appeared on the shelf, in ’95.
Connett: After extensive peer review?
Mullenix: That’s right. As a matter of fact, it went through extra reviewers because the editor at the time recognized that this was a controversial subject and that to be on the safe side he suggested that they send it to an extra reviewer… and they took a good deal of time with it, and did it right.
Connett: And what did you find?
Mullenix: The study basically found three things. First of all, that if you put sodium fluoride in the drinking water of young animals, that with time – meaning a period of weeks in a rat’s lifetime – they would develop changes in their behavioral patterns. And that pattern change was a hypoactivity pattern. They became slower, ‘couch potatoes’ if you like. But it was definitely a hypoactivity pattern. And it had a specific pattern to it which was very, very strikingly similar to the pattern that I had seen in substances or drugs that they used to treat acute lymphocytic leukemia in children, which clinically cause IQ deficits. And when I saw that specific pattern… that I was getting when I exposed animals to radiation or chemotherapy and steroids… that was very striking.
So, that was one thing – in young animals that were exposed, they became hypoactive.
I also found that if I started the exposure at a little later age, I would get the same pattern, but I would get it at a blood level of fluoride that was lower, even, than the young animals. So it suggested that, in particular females, that the older animal was more susceptible to this fluoride in the drinking water.
And a part of this whole common theme – what’s happening at different ages – we also did a prenatal study. Because I wanted to see if I could do one specific exposure in the prenatal situation giving a subcu[taneous] shot of sodium fluoride at a specific age where a certain part of the brain is developing, if the fetuses of this mother, when they grew up, if they had any type of permanent behavioral damage.
And we gave the subcu[taneous] injections to the mother, we gave no other fluoride exposure, and when those pups were born and when they grew up and we tested them, they had a permanent change. And their pattern was this very distinct changes that are compatible with hyperactivity.
Connett: Hyperactive.
Mullenix: Right.
Connett: So this is above, more active than usual?
Mullenix: That’s right. And some people would say, well, doesn’t it seem a little odd that if you gave the prenatal exposure you get a hyperactivity, and if you give a postnatal exposure you get a hypoactivity? And I say not at all. That’s not unusual at all because the stage of brain development in the prenatal situation is extremely different from that in the postnatal situation. So there are different regions of the brain that are developing, therefore you’ve got different regions of the brain that are going to be susceptible. So it is not at all uncommon to have the long term outcome be strikingly different.
Connett: And you also found that the fluoride accumulated in the brain tissue?
Mullenix: Yes. Besides the prenatal exposures and the postnatal, the third thing that we wanted to look at was – what were the levels of fluoride in the brain? We had gone back in the literature, and it was said, I think it was Gary Whitford’s studies that had said… that fluoride did not get across the blood-brain barrier and get into the brain to any extent. But I had a problem with that study, because what they did was they took fluoride and they gave an IV injection and then 1 hour later they looked at the levels in the brain.
But that’s a far different cry from how people really get fluoride, they get it, you know, orally and day-to-day. And so, looking at fluoride levels in brain tissue 1 hour after injecting an IV does not mimic the real world situation at all…
So we went in with our drinking-water exposure, took out the brains – we dissected the brains in these animals into seven different regions – and then analyzed each region for the fluoride content. Now what we found was that, absolutely no question, there was major accumulations of fluoride in all the regions of the brain, and that some areas looked like there were greater accumulations than others, that were sex-determinant. That was a very interesting piece of information.
Just the fact that we could any level of fluoride at all, when we weren’t expecting the brain to accumulate any fluoride, was a very big surprise and very, very disturbing to some people, of all things, that fluoride was accumulating in the brain.
[Note: At this point in the interview, Connett asked Mullenix questions concerning her relationship with Jack Hein, the Director of Forsyth, & Harold Hodge, a prominent expert on fluoride toxicology who oversaw Mullenix’s work. To read this portion of the interview, scroll down to Section V (“The Manhattan Project Connection”).
III. REACTION TO MULLENIX’S FINDINGS
Connett: Now, when you got these results, when it became apparent that fluoride, both prenatally and postnatally, effected rat behavior, what kind of responses did you get from your institution and elsewhere?
Mullenix: Well, there was two separate types of responses.
First of all, when I went to Jack Hein [the Director of Forsyth], and I said, look I think there’s a problem with this stuff and I explained the data and everything, Dr. Hein got very excited. He thought this was extremely important. And he said, I want you to fly down to the National Institute of Dental Research and tell them your results. Forsyth paid for my trip down there.
I went there. It was in September of 1990. I’ll never forget it.
Jack Hein also went with me, and he presented this to Harold Loe, who was then the Director of the National Institute of Dental Research, and I was to give this seminar.
Well, just prior to my seminar, I walked over to the main corridor of the National Institutes of Health, and I walked in and all on the walls of this main corridor was this story called “The Miracle of Fluoride”, all over the walls. And it had newspaper articles and artifacts, everything, from back in the 1940s and ’50s, which described and made fun of the anti-fluoridation movement at that time. It called the people crackpots and it made jokes, it had stories about little old ladies in tennis shoes, you know, screaming about communist plots and everything else. And I’m very upset at this point because I knew how they made fun of people, about anti-fluoridationists, and I’m getting ready to walk into the National Institute of Dental Research and tell them that I thought that fluoride was lowering the IQ of children.
And so, I was really very shocked by that. I had no idea that there was that much political controversy.
So when I went in and I gave the seminar, I was amazed. The room was full. It was a small, private room. There were a lot of people from public relations there. There were a lot people from the public health service because they had, what looked like to me, a military uniform on. There was an individual from the Food & Drug Administration. And I proceeded to give my seminar, and I even made a joke about the little old ladies, and I said I’m a little old lady, but I don’t have tennis shoes on. And nobody laughed. I mean there wasn’t a single smile in the entire room. And they proceeded to really grill me on the technique and the technology, and basically, I had to be wrong.
Then, Jack Hein got a letter from the Director, Harold Loe, from the National Institute of Dental Research about two or three weeks later. And basically it was thanking him for the seminar, and he described me as being very enthusiastic, that the technology was extremely innovative, that it was very important that they get in and they look at this. And then he made suggestions of how the National Institute of Dental Research should follow up on this and provide money to do this research in the future.
And then that proceeded to start several tactics on how to get money; and they led me in circles for months, and then into years, of first following this procedure for getting the money through a contract and then I went down that road and then I found out that wasn’t plausible. And…
Connett: And your paper hasn’t been published at this point?
Mullenix: Oh, absolutely not. It was all preliminary data. And, then, at that time, I mean I wasn’t real sure, I only had done a few experiments and so I said, yea, I really need to do more experiments, I need help to go forward. Because the only money to do this is whatever I came up with.
So, we felt obligated. I had this information. I was on the fence. I either had to go forward or I had to bury it. And I wasn’t about to bury it.
I was academically into this because I’d been given a grant from the National Cancer Institute to look at the effects of neurotoxicity on the treatments for childhood leukemia. So, I was being praised on one side of the fence and how great the technique was, how sensitive it was. I’d been given a big grant to do that. And yet when I found the very same problem with this fluoride in drinking water, there all of a sudden they were questioning the technique, they were questioning me, and you know it was a completely different acceptance; that something had to be wrong with me. So here I was being applauded on one side and defamed on the other.
So at that time then at [Forsyth], the first time I really came out of the closet, so to speak, at the institution, other than Jack Hein – and I got the impression that Dr. Hein really didn’t talk to very many faculty members about my work and fluoride research and what the results were, he kept that somewhat quiet – and I didn’t talk about it until February of 1992.
And then when I stood up in the institution and I gave a seminar which told my results, the looks on the faces I’ll never forget. It was almost complete horror. And I told them the dilemma I was in. I thought I was studying a control group and I wasn’t expecting the answers I was getting [that fluoride was affecting the behavior of rats], and I was basically asking help.
What happened though was… 24 hours after that seminar, the Director of Research came up and talked to the second author on the paper that I was working with, Dr. Pam Den Besten, and basically said that, what would you think if we were not going to, as an institution, not going to allow you to publish this information?
Well, Dr. Den Besten got very upset that, you know, they started talking about ways of keeping us from publishing this information. That all of a sudden they were going to make these papers go through an approval system before they could be going into print.
Well, she came and told me and I got very upset about this because we’d never done this kind of thing. You write the paper, you send it out for peer review. You don’t go through the institution. We’re not like a government agency or something like that where you have to have approval by your institution before you can publish this information.
So I got very upset. This was on Friday. And, the Director of Research then started working on Dr. Den Besten, and finally she got very exasperated with the whole situation and said you go talk with Dr. Mullenix yourself.
So the seminar was on a Thursday, this on Friday – they were talking about not allowing me to publish it – and then on Monday, finally, the Director of Research came to me personally and sat down in my office. And said to me things, such as, first of all he said you have to do more studies because this can’t be correct.
I said, I would love to do more studies. Help me do more studies. You know, maybe there was something we’ve done wrong. We need to do further studies. So help me.
The institution, he says, well, we don’t have, we can’t give you support for doing this. He also said that you are jeopardizing the funds to our institution from the National Institute of Dental Research if you go forward and come out with this.
He said that I was going to cause hysteria on the part of the public and that they just didn’t want me to go into this controversial area.
And there were some other remarks that these types of results and the way I was presenting it was an ‘hysterical response.’
So I got very upset with this because I didn’t exactly like being portrayed as an hysterical female all of a sudden when for ten years I’d been the Head of the Department and encouraged by the Director to even do these studies in the first place.
But unfortunately, at that time what happened was, my supporter and the reason that I did these studies – Dr. Hodge had died – and then Jack Hein went into retirement in 1991. And then what happened was the successors, the people, the Assistant Directors and Director of Research, then they became the Director. And at that time they had some consortium money from groups like Colgate, and whatever, and they were not in favor of the fluoride research at all.
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