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 
No comments:
Post a Comment