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. https://www.blogger.com/null 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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