MIT Reports to the President 1994-95

Center or Environmental Health Sciences

Faculty, students and research staff are focused on discovery of the agents in our environment responsible for genetic changes in humans. Our focus is based on our perception of public health needs. Genetic disease causing severe physical or mental impairment of our newborns approaches 2%, and fills nearly half of the beds in our pediatric hospitals. Human cancers require several genetic changes (mutations) inherited or occurring within the organ from which the tumor arises. We hope to make substantial contributions to understanding basic mutational mechanisms, finding the causes of human mutations and defining the quantitative relationships that govern the lifetime occurrence of diseases which require multiple mutations in humans.

We have developed technology which allows us to measure chemical reaction products with proteins and DNA in human tissue (NIEHS Biomarkers Program). We have developed means to measure the point mutational spectra arising in the human mitochondrial genome (NIEHS Superfund Program, DOE Human Cell Mutagenesis Grant). We have studied chemicals entering humans from the environment: food in the Biomarkers Program, air in the Mutagenic Effects of Air-borne Toxicants Program and water in the Superfund Program have all received our attention.

Yet we have never assumed that environmental chemicals are the primary causes of human genetic change. Two major programs, Endogenous Nitrite Carcinogens in Man (NCI) and Genetics and Toxicology (NIEHS) have focused specifically on either one powerful endogenous mutagen, NO, or the endogenous process of DNA replication are responsible for our genetic change rate. We have cast a net to discover if the patterns of spontaneous mutations in bacterial or human cell studies are recapitulated in human tissues. Recent data suggests that for human mitrochondrial DNA, errors in DNA replication, not exogenous chemicals, are the primary causes of point mutation.

CEHS research is Organized as three Programs:


The Air Quality Program has two components. The first is directed at identifying airborne chemicals which are mutagens for human lung cells and to relate these to their sources and atmospheric transformation processes. The second is to assess the potential human damage associated with the emissions from a variety of thermal processes proposed for remediation of Superfund sites.


The Water Quality Program focuses on the behavior of toxic chemicals in the natural environment with particular emphasis on processes that lead to human exposure. The studies also work to determine the effectiveness of remediation technologies to attain high waste destruction efficiencies without the formation of mutagenic by-products.


Our Toxicology and Epidemiology Program focuses on discovering the causes of genetic change leading to human disease. We have developed technology which allows us to measure chemical reaction products with proteins and DNA in human tissue and have also developed means to measure the point mutational spectra arising in the human mitochondrial genome. These twin technologies are now being used in parallel to try to discover the causes of mutations in people.


Air Quality Program

Our study of air samples from major US cities has confirmed that they contain chemicals which are potent mutagens in human cell assays. We have identified the specific chemicals accounting for 1/3 of this activity in the form of 4 polycyclic aromatic hydrocarbons. We should soon know the identities of most of the remaining mutagenic compounds which appear to be semipolar derivatives of the polycyclic aromatic hydrocarbons.

These mutagenic air pollutants are among the larger, less volatile air pollutants. We find that these are disproportionately represented on the smallest air-borne particles which are most likely to reach and reside in the human lung.

Our effort to use electron microscopy to characterize particles from various sources has brought gratifying results. It appears that the approach should allow accurate identification of environmental sources of the particles found in human lungs.

Water Quality Program

In attempting to find a cause for the 1970-1986 Woburn, Mass childhood leukemia cluster, we used hydrogeologic methods to show that municipal wells would have drawn some 60% of their volume from the nearby Aberjona River. Sediment core analysis showed that at or about the time of the wells' use, substantial quantities of arsenic and chromium were suspended or dissolved in the river. To discover if these or other metals reached the users of the municipal water supply, we collected 109 hair samples cut from children from 1938 to 1994. Testing for metals in hair allowed us to demonstrate that the suspected municipal wells could not be associated with metals in children's hair.

Another may help clean up arsenic Professor Hemond has announced the discovery of two forms of bacteria; one which takes up arsenic and oxidize it to an insoluable form, while another turns arsenic into an insoluble glop called "orpiment." Having identified the kinds and sources of chemicals now moving down the Aberjona River, we are working to devise means of preventing this continuing process. We will investigate how these new bugs can be used to clean up arsenic as it seeps from groundwater into surface waters.

One key observation arising from the use of neutron activation analysis of hair and sediments was the discovery of a recent increase in the lanthanide elements. These highly reactive elements are being used in a wide and growing number of manufacturing processes and automobile catalytic converters. Their properties as strong redox catalysts would seem to make them potent persistent irritants. We will follow this lead in 1995 both in the Air and Water Quality Programs.

Toxicology And Epidemiology Program

We have at long last observed point mutations as they occur in human tissues and compared them to those arising in human cells in culture. Curiously, the mutations observed, some dozen hotspots in a 100bp mitochondrial sequence, appear to be the same in human cell culture, human colon, human lung and human muscle samples. This may mean that such mutations in humans arise from endogenous chemical reactions or DNA replication error. It may also be that the first sequence studied is not representative of other mitochondrial or nuclear sequences. Reconstruction experiments seem to exclude the possibility of analytical artifact, but at the mutation fractions of about 2 X 10-5 and 2 X 10-6 respectively, caution in interpretation of these observations is justified.

Our ability to measure DNA adducts with the methionine 35S post labeling approach coupled to HPLC has given increased sensitivity as well as a separation and isolation procedure which integrates with mass spectrometry. This, with continuing advances in the technology to measure certain polycyclic aromatic hydrocarbons adducted to proteins, has greatly advanced our ability to measure the actual amounts of many environmental chemicals which react with the chromatin (DNA and histones) of all human organs. The combination of analytical chemistry and analytical genetics in studying human populations opens new vistas for students and faculty alike.

We may now imagine studies of humans in which both exogenous and endogenous causes of genetic change are considered and analyzed. For instance, the finding that mismatch DNA repair defects were important in the early appearance of colon cancer in certain families followed our earlier discovery that human cell mutants existed with high spontaneous mutation rates which were deficient in this repair pathway. These "mutator" human cells mutate on their own so fast that the low levels of environmental chemicals in the human body are unlikely to contribute to mutations arising in such individuals.


MIT Education

CEHS faculty recognized that there was no formal way for these students to gain a working understanding of environmental chemical problems. Thus, we created a series of four courses collectively called Chemicals in the Environment. CEHS faculty teach the first three: Sources and Controls (Sarofim), Fate and Transport (Hemond), and Toxicology (Thilly). Professor L. Susskind in the Department of Urban Planning teaches the fourth: Policy and Regulation. These courses have been a hit with students and we find both undergraduates and graduates enrolled. In 1991 we received the Sizer Award for Outstanding Contribution to Graduate Teaching at MIT for the series.

TOX 104J required of Civil Engineering IE students is being revised to account for the greater understanding of molecular biology resulting from the Institute biology requirement.

Community Outreach

Public Meetings on Local Superfund Site

We have been studying the chemical sources, fate and transport, and human exposure in the Aberjona River Watershed here in Massachusetts for seven years. When we began this work we knew we had a special obligation to the people in the several towns included in our work to communicate our aims, our findings and our limitations in interpreting these findings in terms of public health. To do this we hold two annual public meetings to discuss our progress and try to answer questions. Faculty and students present their work and hear what the public thinks soon thereafter.

Of course, since we have found that a local Superfund Site is "leaking" fair quantities of chemicals like arsenic into the Aberjona, our presence is regarded as a problem to those who wish to inexpensively develop the site for municipal and commercial use. In order that our observations are available to all in a timely manner, we have agreed with Congressman Edward Markey's staff to meet some weeks before our public presentations to discuss technical progress with representations of the U.S. EPA, Massachusetts Department of Public Health, Massachusetts Department of Environmental Protection, the custodial and remedial trusts responsible for the particular Superfund Site as well as elected public officials or their representatives. In our first meeting of this group an assertion was made that the public could not understand our work as we present it and it was causing undue stress when it was discussed in newspaper articles. My answer was, and is, that our interactions with the public have impressed all of us with their basic understanding, interest and support for a policy of openness as expressed through our public meetings. Let any one attend one of these open forums and hear the intelligent and informed questions from the audience before positing that the public cannot comprehend the essential elements of our research tasks or fail to differentiate between the testing of hypotheses and findings of fact.

Tangible assistance from the community has taken many forms, including site access, contribution of sample material (including human hair), recollections of historical events not otherwise recorded in the literature, and the identification of potential sources of contamination (repositories of tannery waste, etc.). In the long run, we believe such outreach is both a responsibility of scientists who work in a community, and a policy that is in the long-term best interests of the research itself.

Teaching in the Environmental Technician Program at Aquinas College

Each spring graduate students from the Center teach a toxicology course for nearby Aquinas College's program to train area adults to enter the environmental technology field. The program, designed last year, to allow motivated, older students with little or no technical skills to take positions as environmental technicians after one year of class work and internships, was the initiative of three graduate students, Hilary Coller, Paula Lee and Aoy Tomita. This spring Rony Gal taught the course entitled Applied Toxicology and Environmental Health. The course covers fate and transport of chemicals in the environment and within the body, metabolism, DNA structure and function, mutagenesis and case studies on the toxicity of several different chemicals. Laboratory work includes bacterial mutagenesis and molecular biology experiments. Several of the students in the class have secured internships and even permanent positions in the environmental field as a result of their experience. Next year, students from the Center are expected to teach not only toxicology but also related classes including biochemistry and microbiology.

Legislative Educational Effort

As we look into the future we see a real need to provide our elected representatives with knowledge about public health and hazardous waste issues as well as our need for basic research support. We know that in a real sense "all pollution is local" but who among us has the means to go into a community and discover the primary causes of mutations leading to cancer, birth defects or other diseases requiring genetic change? To this end, we have coordinated an endeavor involving 23 Superfund Research Centers and 24 NIEHS centers nation-wide. Faculty from these research centers made presentations to members of Congress or their appropriate aides both in their home districts and in Washington, D.C.


In fiscal year 1995 our research volume exceeded 8 million dollars, a first in our history. This has been due to our successful renewal of the grants that have become the base of the CEHS support. These grants include a NIEHS Center Grant (funded to 1999) as well as the NIEHS Superfund Basic Research Program (funded to 2000), our program studying mutation induced in human lungs by air pollutants, NIEHS Mutagenic Effects of Air-Borne Toxicants in Human Lungs (funded to 1997), and our program studying the role of nitric oxide as an internal toxicant, NCI Endogenous Nitrite Carcinogenesis in Man (funded to 1999). Additionally two renewal proposals are currently under review; our program in genetics and toxicology (NIEHS Genetics and Toxicology and our program using mutational spectra to measure point mutations in humans (DOE Comparative Mutagenesis of Human Cells In Vivo and In Vitro). Unfortunately, one of our Programs: NIEHS Molecular Biomarkers did not fare well as reviewers reacted negatively to the news that our new technology raised doubts about the role of environmental chemicals in causing human mutations.


The CEHS supports the affirmative action goals of the Massachusetts Institute of Technology while maintaining our commitment to hiring solely on qualification of the candidate for the position. This year we were pleased to fund four feasibility studies submitted by female junior faculty members. The majority of all members of our staff, including research specialists, students and support staff are women.

The Center has continued to actively recruit graduate students from minority institutions. We, with NIEHS, support undergraduates in summer research internships which have yielded multiple top-notch recruits. This past year we hosted more than a dozen potential applicants from Cheyney College near Philadelphia; one of their number then served a summer internship and has recently entered our graduate program in toxicology. Our Director, Bill Thilly along with Dean Ike Colbert coauthored a grant request to the Sloan Foundation which now provides funds for entering minority graduate students to take the time to fill in their backgrounds if necessary before beginning the graduate curriculum.

William G. Thilly

MIT Reports to the President 1994-95