by Ana Burgos
Time was quickly running out at the chemistry lab of Arthur D. Little, Inc. There were only a couple hours until the Coca-Cola Company would call back asking for results as to whether or not their competitor’s product contained the suspected cancer-causing chemical. Coca-Cola and Canada Dry had each launched a new citrus flavored soda. There would be a press conference at noon and Coca-Cola wanted to know if their competitor used brominated vegetable oil as an emulsifier, which had been recently shown to cause breast cancer in mice (it was later known, however, that this allegation actually did not hold up). John quickly went to the local convenience store and bought a case of each soda. He went over to the x-ray facility of Arthur D. Little and ran the two drinks through a machine used to identify metals. He found that only one contained bromine. To his surprise, his client’s product, Fresca, was the one with brominated vegetable oil. Throughout his stay at Arthur D. Little, John Essigmann was able to solve several puzzles and this project was just the beginning.
At 64 years of age, Professor John Essigmann is now the associate head of MIT’s Chemistry Department, the director of the Center for Environmental Health Sciences, runs a lab, and is the housemaster of Simmons Hall, a residential dorm at MIT. He’s a tall man with a shock of white hair and an everlasting smile. Prof. Essigmann grew up in nearby Medford, Massachusetts, where his parents had also been raised. His father had been brought up in a “build everything, fix everything” culture, which also became part of Essigmann’s upbringing.
Like many young students, Essigmann did not always know what he wanted to study or what he wanted to do with his life. His father had studied electrical engineering at MIT and wanted John and his two sisters to become engineers, but John was uncertain. During high school, he had a terrific biology teacher who influenced him to major in biology at Northeastern University. Essigmann sensed that biology would somehow be involved in whatever field he went into.
To test the waters, he started volunteering at the local hospital’s kitchen, washing dishes. The personnel manager liked him so much that he offered him a job in the emergency room of the hospital. He would be shadowing doctors and assisting them in basic tasks. Essigmann loved it. He even helped deliver two babies! He was very responsible and motivated. He knew that he could have easily had a career in medicine, since he would be good at it, but he saw that there was a repetitious aspect of it that wasn’t so appealing. Doctors had to be able to pay close attention to detail. “My mind was not one that could avoid wandering. I would always be trying to do it faster or make it better,” says Essigmann. He was good at this job, but he didn’t really enjoy it.
He continued working at the hospital until his sophomore year in college, when he joined the industrial consulting company Arthur D. Little. Inc. “It was a think tank. You could take your thinking and put it into play and solve problems all day long,” says Essigmann. He worked for their chemistry division, solving any problem they threw at him. It was during this time that he worked on the brominated vegetable oil project. He also helped to create the first commercial high-performance liquid chromatography machine. “It was fun—it was like play,” recalls Essigmann. By the fall semester of his senior year in college, Essigmann had found his calling, and it wasn’t medical school. Arthur D. Little, Inc. wanted to offer him a permanent job at the company but first they sent him to graduate school at MIT, which had close ties to the company.
Those three years of solving puzzles at Arthur D. Little would be good preparation for what Essigmann encountered at MIT. As part of his master’s, which he completed in 1972, Essigmann worked in the lab of Professor Gerald Wogan, who was well known in the field of toxicology. Professor Wogan was looking for an interesting toxicity project when he came across a population of turkeys in England that had mysteriously been dying out.
Wogan investigated the turkey feed, which had been brought from Brazil, and found that it was infected. A fungus growing in the soil had contaminated the feed and was slowly killing off the turkeys. In collaboration with Professor George Büchi, a chemistry professor at MIT, they found aflatoxin, the most powerful liver carcinogen, and the toxic fungi responsible for the dying turkeys. They studied the metabolic activity of these powerful toxins and found that they were linked to the fatal effects of other natural products in developing countries. They quickly searched for a country where they could conduct further research on the relationship between these toxins and cancer deaths.
Thailand was the ideal place. Once they got there, they saw a pattern correlating the amount of toxin in food and where that food was stored. The regions where food was stored underground had higher cancer rates than those where the food was stored above ground. Essigmann was later able to analyze how the toxin works (its metabolic pathways) and how it results in cancer (it mutates normal cells into cancer cells). Based on this work, Essigmann earned his doctoral degree.
Essigmann’s work with aflatoxin led him to work with DNA adducts, particularly studying their toxicity. (At this time, he became a Junior Faculty member of MIT, continuing his research at the forefront of chemistry, biology, and biological engineering.) DNA adducts are chemicals that are covalently bonded to DNA; these products can eventually lead to the development of cancerous cells. In order to test their toxicity, he made vectors of DNA adducts and inserted them into viruses. If the virus could no longer replicate, the adduct would be labeled as toxic. Essigmann realized that if his results were fruitful, the mutations associated with the adduct could also be checked to see if they are related to those that cause cancer. If this relationship is verified for a given adduct, it will allow researchers to target cancer cells more precisely leading to the design of better anti-cancer drugs.
Essigmann is now the Associate Head of the Department of Chemistry at MIT. “I did a change in phenotype along the way,” says Essigmann about not being directly affiliated with biology. Yet, he is also a professor in Toxicology and Biological Engineering in the MIT Department of Biological Engineering.
Recently, Essigmann encountered one of the most fascinating puzzles of his career: a systems problem concerning HIV. HIV has a very high mutation rate, which creates a lot of diversity in the virus. This way, it can be sure that it will survive no matter how much its environment changes. However, its mutation rate is so high that it almost reaches the error catastrophe limit. This is the boundary between where life can exist and where it cannot. If it has too many mutations and it passes this limit, an essential gene will be knocked out and the organism will not survive.
Essigmann and his team are conducting an experiment in extinction: they have to find the limit and go over it to collapse the population of viruses, a process called “lethal mutagenesis.” Once they find this limit, they can insert mutagenic nucleotides so that when the virus replicates, it will double its mutation rate. The DNA of the cell uses repair enzymes to fix any mutation that may occur if a mutagenic nucleotide is used. However, because it replicates in the cytoplasm rather than the nucleus, HIV does not have access to these repair enzymes. Once the mutations accumulate, the population of viruses will die out.
Essigmann and his research team have taken their work out of the lab and into everyday life by incorporating these mutagenic nucleotides into a pill along with other chemicals to carry out this process in patients with HIV. These clinical trials have proven successful. Now, Essigmann is waiting to see if these tests can be conducted on patients not exposed to AZT (current drug treatment for HIV) in order to test the effectiveness of the new drug.
John Essigmann loves MIT so much that he seems to never leave campus. He even lives in one of MIT’s residential dorms, Simmons Hall. He not only lives there with his wife Ellen, but he has also been in charge of over three hundred undergraduates, since 2002. John and Ellen had been thinking about taking this important role for a while so they decided to try it and “it was addicting. We liked it!” They wanted to create an environment where everyone felt welcome everywhere. This was a puzzle that they would let the students solve. It became a more democratically run dorm where everyone is involved. They are there to provide guidance and support, but they found that they have learned from the students as well.
During the summer, when Essigmann isn’t teaching, at the lab, or running a dorm full of college students, he occasionally spends his time teaching in Thailand. After researching there for a while, he found that the least he could do was go back and share with them what he knows best: the knowledge to solve their puzzles.
For Prof. John Essigmann, MIT has been a “place that lets you reinvent yourself.” Having gone from being a molecular biologist to drug developer to synthetic chemist, he is living evidence of this statement. Volunteering at the hospital, working at Arthur D. Little, researching at MIT, Essigmann has spent his whole life solving puzzles. “Putting pieces of information together, it grabs my attention. I have a love of solving problems. What I do in my day job is play real life. It’s all puzzles.”
Sources
Essigmann, John. Personal Interview. 17 March 2012.
Ana Burgos is a member of MIT’s Class of 2015, majoring in Biological Engineering. She was born and raised in Puerto Rico; however, having Peruvian parents, she considers herself half Puerto Rican and half Peruvian. As a rising sophomore, she is exploring the different aspects of her major by participating in a UROP dealing with the more chemical and instrumental side of biological engineering. Ana aspires to be a doctor one day, always remembering the importance of communicating well in order to be heard.