CHAPTER ONE It used cameras to record changes in the pattern of behavior of laboratory animals that had been given tiny amounts of toxic chemicals. Computers then rapidly analyzed the data. By detecting how the animals behavior differed from that of similar control animals — that were not given the toxic agent — scientists were able to measure or quantify the extent to which a chemical affected the animals central nervous system. Previous such efforts had relied on subjective guesswork as to the severity of the chemical s toxic effect or on laborious and time-consuming efforts to quantify the changes the chemical made in behavior. The speed of the computers and the accuracy of the camera measurements in the Mullenix system, however, could potentially revolutionize the study of toxic chemicals. As her car flew along the Charles River that summer morning in 1982, Mullenix knew that her new job and the support of the prestigious Forsyth Dental Center would finally allow her to complete the work on her new system. Mullenix had caught the eye of Forsyth s director, John Jack Hein, some years earlier. He had attended one of her seminars at the Harvard Medical School, where she was a faculty member in the Department of Psychiatry. He had sat in the audience, dazzled, his mind racing. Hein remembers a very bright woman describing a revolutionary new technology, which he believed had the potential for transforming the science of neurotoxicology. She had the world by the tail, said Hein. There is nothing more exciting than a new methodology. ' Jack Hein wanted Mullenix to bring her new technology to For-syth and to set up a modern toxicology laboratory. It would be the first such dental toxicology center in the country. Many powerful chemicals are routinely employed in a dentists office, such as mercury, high-tensile plastics, anesthetics, and filling amalgams. Hein knew that an investigation of the toxicity of some of these materials was overdue. The Forsyth director's boyish enthusiasm helped to sell Mul-lenix on the move. I was very impressed with Dr. Hein, she said. He was like a kid in a candy store. He couldnt wait for us to use the new methodology and apply it to some of the materials dentists work with. THROUGH THE LOOKING GLASS 3 Phyllis Mullenixs transfer to Forsyth was a move to one of Bos- tons most prestigious medical centers. The Forsyth Dental Infirmary for Children was established in 1910 to provide free dental care to Bostons poor children. By 1982, when Dr. Mullenix accepted Jack Heins invitation, the renamed Forsyth Dental Center was affiliated with Harvard Medical School and had become one of the best-known centers for dental research in the world. At the helm was Forsyth s director, Jack Hein, a well-known figure in American dental research. Hein had attended the University of Rochester in the 1950s, and there he had helped to develop the fluoride compound sodium monofluorophosphate (MFP). Colgate soon added MFP to its toothpaste, and Jack Hein became the company's dental director in 1995. When he came to Forsyth in 1962, Hein was part of the new order in reshaping American dentistry — a changing of the guard then taking place in many dental schools and research centers.' Like Jack Hein, the new generation of leaders was uniform in its support of fluorides use in dentistry.' Forsyth had read the tea leaves well. While a previous Forsyth director, Veikko O. Hurme, had been an outspoken opponent of adding fluoride to public water supplies, Jack Heins support came at the same time that Colgate poured cash into new facilities and fluoride research at Forsyth.' Additional funds came from research grants from other private corporations and from the federal National Institutes of Health (NIH). A sparkling new research annex, built in 1970, doubled the size of the Forsyth Center, with funds from the NIH and major donors, such as Warner Lambert, Colgate Palmolive, and Lever Brothers.' Jack Hein s track record as a fund-raiser for the Forsyth Center and his support for fluoride's use in dentistry owed much to his membership in an informal old boy's club of scientists who had also once done research at the University of Rochester. The University had been a leading center for fluoride research in the 1950s and 1960s, with many of its graduate students taking leading roles in dental schools and research centers around the United States. In 1983, a year after Phyllis Mullenix arrived at Forsyth, director Hein introduced her to an elderly gentleman who had been Hein's professor and scientist mentor some thirty years earlier at the Uni v ersity of Rochester. The old man was a researcher with a distin- 4 CHAPTER ONE guished national reputation — the first president of the Society of Toxicology, Mullenix learned, and the author of scores of academic papers and books. His name was Harold Carpenter Hodge, and his impeccable manners and formal dress left an indelible impression on Mullenix. I was impressed with Harold, she said. He was very gentlemanly. He would never say an inappropriate word, and he always wore a white lab coat. Hodge had recently retired from the University of San Francisco. Jack Hein had brought him to Forsyth for the prestige he would bring to Mullenix s new toxicology department, he said, and out of admiration for his former professor, who was then in his mid-seventies. "I thought it would be fun," Hein added. Mullenix grew fond of Hodge. He seemed almost grandfatherly, ambling into her laboratory, chatting as her young children frolicked alongside. Hodge was especially fascinated by the new computer system for testing chemical toxicity. He would fire endless questions at Mullenix and her colleague, Bill Kernan from Iowa State University, Mullenix remembered. He would quietly come up to my lab. And Harold would ask Why are you doing this? and What are you doing? and Bill [Kernan] would take great pains to explain every little scientific detail, showing him the rat pictures. By the early 1980s Jack Heins vision for the Forsyth Center included more than just dentistry. The canny fund-raiser believed that the new Mullenix technology could become another big money spinner for Forsyth — a winning weapon in the high-stakes field of toxic tort litigation, in which workers and communities allege they have been poisoned by chemicals. "It was an exciting new way of studying neurotoxicity, said Jack Hein, who would eventually assign Mullenix to spacious new offices and laboratories on the fourth floor of the Forsyth research annex. Neurotoxicology was still a young science. If someone claimed to have been hurt by a chemical in the workplace or had been exposed in a pollution incident, finding the scientific truth was extraordinarily difficult. Big courtroom awards against industry often hinged on the subjective opinion of a paid expert witness and the unpredictable emotions of a jury, said Mullenix. Industries did not like that. They felt that the answers were biased, and so the thought of THROUGH THE LOOKING GLASS 5 taking investigator bias out of the system was very exciting to them. They thought this would help [industry] in court, she added. The Computer Pattern Recognition System quickly attracted attention from other scientists, industry, and the media. The Wall Street Journal called the Mullenix technology precise and "objec- tive. Some of Americas biggest corporations opened their wallets. The medical director of the American Petroleum Institute personally gave $70,000 to Mullenix. Monsanto gave $25,000. Amoco and Mobil chipped in thousands more, while Digital Equipment Cor- poration donated most of the powerful computer equipment. Several oil and chemical companies such as Monsanto Co. are supporting research on the system, the Wall Street Journal reported. " Questions are being raised more frequently about whether there are behavioral effects attributable to chemicals, a Monsanto toxi-cologist, George Levinskas, told the newspaper. The Forsyth system has potential to give a better idea of the effects our chemicals might have," he added.' In a letter of recommendation, Myron A. Mehlman, the former head of toxicology for the Mobil Oil Corporation, who was then working for the federal Agency for Toxic Substances and Disease Registry (ATSDR), called the Mullenix technology a milestone for testing low levels of exposure of chemicals for neurotoxicity for the 21st Century.... The benefits of Professor Mullenix discovery to Forsyth are enormous and immeasurable. 9 Industry trusted Phyllis Mullenix. Since the 1970s the toxicologist had earned large fees consulting on pollution issues and the legal requirements of the Clean Air Act. Hired by the American Petroleum Institute, for example, she'd acted as scientific coordinator for that lobby group, advising it on proposed and restrictive new EPA standards for ozone. "Whenever it got technical they would dance me out, she said. Every time EPA came out with another criteria document I would look for the errors." Mullenix is not apologetic for waltzing with industry. Anybody could take her to the ball, she said, explaining, "I did not look at myself as a public health individual. I was amazed that the EPA did such shoddy work writing a criteria document. I thought that at the very least those documents should be factual. At Harvard, Mullenix had been criticized by some academics 6 CHAPTER ONE for her industry connections, a charge she calls ridiculous. Said Mullenix, No one group, be it government, academia or industry, can be right one hundred percent of the time. I dont see science as aligning yourself with one group. Industry can be right in one respect and they can be very wrong in another. And Mullenix had other consulting work — for companies such as Exxon, Mobil, 3M, and Boise Cascade. Companies including DuPont, Procter and Gamble, NutraSweet, Chevron, Colgate-Palmolive, and Eastman Kodak all wrote checks supporting a 1987 conference she held titled "Screening Programs for Behavioral Toxicity." Like many revolutionary ideas, the concept behind the Mul-lenix technology for studying central-nervous-system problems was simple. The spark of inspiration had come from Dr. Mullenix s graduate advisor at the University of Kansas Medical Center, Dr. Stata Norton. A slender and soft-spoken woman, Dr. Norton was one of the first prominent female toxicologists in the United States. She had won national recognition by demonstrating that there were "threshold" levels for the toxic effects of alcohol and low-level radia tion on the fetus. Now retired to her summer cottage, surrounded by lush Kansas farmland, Dr. Norton's face opened in a smile as she remembered her former student. Normally, she said, graduate students rotated through the various laboratories at the Medical Center. But there was something different about Phyllis Mullenix. "Phyllis came into my lab to do a short study — and she never left, " Norton recalled, laughing. Mullenix had a special willingness to grapple with complex new information, Norton said. When Norton was studying the effects of radiation on rats, Mullenix wanted to learn how the radiation had physically altered the rats' brains. She had never done that work before, Norton recalled, but her student stayed late at the lab, poring over medical journals, dissecting the rat's brains, and looking for tiny changes caused by the radiation. "I don't think she thought it was difficult, said Norton. She was happy to jump on the project and get with it." There was something else. Norton noticed her student had a fear -less quality and a willingness to challenge conventional wisdom. The professor found it refreshing. "It takes a certain personality to stand up and do something different. Science is full of that, all the way from THROUGH THE LOOKING GLASS 7 Galileo, Norton said. That doesn t mean you are right or you are wrong, but I can appreciate that in Phyllis because I am like that." In the mid-1970s Stata Norton was a pioneer in the new field of behavioral toxicology, inventing new ways for measuring the ways chemicals affected behavior. At first Norton studied mice that had been trained or conditioned to behave in certain ways by receiving food rewards. Some scientists believed that by studying disruptions in this "conditioned" behavior, they could most accurately measure the toxic effects of different chemicals. Norton was not so sure. One day, working with mice that had been trained to press a lever for food at precisely timed intervals, she suddenly wondered how the animals knew when to press the lever. "I looked in the box," she said. Inside she saw that each mouse seemed to measure the time between feeding by employing a sequence or pattern of simple activities such as sitting, scratching, or sniffing. "There was a rhythm," she explained. "They timed it by doing things." Norton began her own experiments. She wondered if, by study- ing changes in this rhythm of "patterned" behavior during the time between feeding — as opposed to studying disruptions in the condi- tioned behavior exhibited for food rewards — she could get a more sensitive measurement of the toxicity of chemicals. Norton and Mullenix took thousands of photographs of rats that had been given a chemical poison and compared them with similar photographs of healthy "control" rats. They were able to detect changes in the sequences of the rats' behavior, even at very low levels of chemical poisoning. "We were all very excited," said Norton. The spirit of independence and free inquiry in Stata Norton's laboratory inspired Phyllis Mullenix. It was the kind of environ- ment she had grown up in. Her mother, Olive Mullenix, was a Missouri schoolteacher who'd ridden sixteen miles on horseback to her one-room schoolhouse each day and made her "own" money selling fireworks from a roadside stand. Her father, "Shockey" Mullenix (he had a shock of white hair), had left the farm with a dream to become a doctor. He settled for the workaholic life of a gas-station entrepreneur and trader in the small town of Kirksville, Missouri and the hope that his three children would realize his dreams. The son became a nuclear physicist for the Department of Energy; another 8 CHAPTER ONE daughter was a corporate Washington lawyer; and the youngest, Phyllis, the Harvard toxicologist. In the late 1970s the Environmental Protection Agency grew interested in the Kansas research. The federal agency wanted a new way of measuring the human effects of low-level chemical contamination. The head of the EPAs neurotoxicology division, Lawrence Reiter, visited Stata Norton s laboratory. Phyllis Mullenix told him that the key to the success of the new technique was to speed up the time-consuming process of analyzing each frame of film. Mullenix thought that computers could do the job faster. The EPA agreed, and Mullenix became a consultant on a $4 million government grant awarded to Iowa State computer experts Bill Kernan and Dave Hopper. Kernan had worked previously for the Defense Department, writing some of its most elegant and sophisticated software. I was to train the physicist, said Mullenix. The physicist would train the computer. Developing the Computer Pattern Recognition System, as Mulle-nix s technology became known, took almost thirty years. Dr. Norton had begun studying her rats in the 1960s. When she passed the baton to Phyllis Mullenix in the 1970s, computers were barely powerful enough to handle the vast data-processing requirements for detecting subtle behavior changes and measuring chemical poisoning. In Boston in the mid-1980s Mullenix grew incredibly busy. She now had two young daughters. She was consulting for industry. Her husband, Rick, was completing training as an air-traffic controller. And her father was seriously ill with emphysema 1500 miles away in Kirksville, Missouri. Her Forsyth laboratory buzzed with activity. The new computers were hooked up by telephone to big data-processing units at Iowa State. By late 1987 the Computer Pattern Recognition System was almost ready. Forsyth printed brochures, touting a system that promised to "prevent needless exposure of the general public to the dangers of neurotoxicity, and industry to exaggerated litigation claims." Mullenix soon became a national pitchwoman for Forsyth, proclaiming a new day for corporations that feared lawsuits from workers and communities for chemical exposures. "I was hopped all over the country giving seminars on how this computerization was going to help the industrial situation, she said. THROUGH THE LOOKING GLASS 9 Director Jack Hein was anxious to illustrate the sensitivity of the new machine. He suggested that Mullenix start with fluoride, giving small doses to rats and testing them in the equipment. The longtime fluoride supporter wanted to test fluoride first, he said, in order to bolster the chemicals public image. I was really interested in proving there were no negative effects," Hein said. "It seemed like a good way of negating the antifluoridationist arguments." Mullenix shrugged. She didn't much care about fluoride. Secretly she thought that fluoride was a waste of her time and that Jack Hein was overreacting. "At Harvard the rule is publish or perish. And I didn't think that I would come up with anything that would be worth publishing," she said. "I'm used to studying hard-core neu-rotoxic substances, drugs like anticonvulsants, radiation, where it can totally distort the brain. I never heard anything about fluoride, except TV commercials that it is good for your teeth." Hein introduced her to another young dental researcher, Pamela DenBesten, who had recently arrived at Forsyth. DenBesten was studying the white and yellow blotches, or mottling, on tooth enamel caused by fluoride known as dental fluorosis. Although Mullenix was lukewarm to the idea of using fluoride to test for central-ner- vous-system effects, DenBesten was more curious. She had noticed that when she gave fluoride to rats for her tooth-enamel studies, they did not behave "normally." While it was usually easy to pick up laboratory rats, the animals that had been fed fluoride would " practically jump out of the cage," DenBesten said. The two women worked well together. Phyllis would often bring her two young daughters to work, and the Mullenix laboratory on the fourth floor became a sanctuary from the predominantly male atmosphere at Forsyth. DenBesten knew that Phyllis Mullenix had few friends at Forsyth. Many of the other researchers were hostile to the plainspoken toxicologist. DenBesten describes it as "gender-discrimination type stuff." 10 Another Forsyth scientist, Dr. Karen Snapp, quickly made friends with Phyllis Mullenix. "I was always told that Phyllis was the batty woman up in the tower on the fourth floor, said Snapp. I ran into her at lunch one day in the cafeteria. We started chatting, then we went out and had a coke together. Snapp found Mullenix refreshing, both for the quality of her science and her plainspoken 10 CHAPTER ONE manner. She didnt bow down to the powers that be at Forsyth. A lot of people put up fronts and are very pious, and Phyllis was not that way at all — that is what I liked about her. She was very honest, very straightforward, you knew exactly where you stood, Snapp explained. Snapp was also impressed with the rigor Mullenix brought to her scientific experiments. She was very, very thorough. She at times had no idea what the outcome of an experiment was going to be. If she did an experiment and didn't get the result she thought she should get, she'd repeat it to make sure it was right, and [if the unexpected data held up] it s like, well — we change the hypothesis. If Phyllis Mullenix was at first nonchalant about testing fluoride for central-nervous-system effects, that was not the attitude of perhaps the oldest boy at the Forsyth Center. She found that Dr. Harold Hodge, the affable old man in the freshly pressed lab coat, took what then seemed an almost obsessive interest in her fluoride work, firing endless questions about her methodology. He wanted to push me to do certain fluoride studies, and do this and do that, and how can I help? said Mullenix. 2 Fireworks at Forsyth The two white-coated scientists stared at each other, startled. High above Boston, surrounded by computer terminals and data printouts and the bright lights of a modern toxicology laboratory, Phyllis Mullenix and Pamela DenBesten fell suddenly silent. Only the white rats in their cages scuttered and sniffed. The information slowly sank in. The scientists had repeated their experiment and, once again, the results were the same. They laughed, nervously. "Oh shit," Dr. Phyllis Mullenix finally blurted out. "We are going to piss off every dentist in the country." BY 1989 th Mullenix team was getting its first results from the fluoride experiments. They had been gathering data for two years, giving the rats moderate amounts of fluoride, monitoring them in their cages, and then analyzing the data in the RAPID computer system, as her new technology was known. But something was wrong. The results seemed strange. "Data was coming back that made me shake my head," said Mul-lenix. It wasnt at all what we expected. Mullenix had expected that giving fluoride in drinking water would show no effect on the rats' behavior and central nervous system. Mullenix wondered if the problem was a bug in the new machinery. The team launched an exhaustive series of control experiments, which showed that the RAPID computers were working fine. All the results were "amazingly consistent," said Mullenix. Fluoride added to their drinking water produced a variety of effects in the Forsyth rats. Pregnant rats gave birth to hyperactive
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