- Raymond Richard Neutra MD.
Division of Environmental & Occupational Disease Control
5801 Christie Avenue, Suite 600, Emeryville, CA 94608, USA
(Email: rneutra@hw1.cahwnet.gov)

Eubios Journal of Asian and International Bioethics 7 (1997), 69-70.

Ethical problems for epidemiologists arise primarily in the following kinds of relationships:
1 Researcher with Researcher
2 Researcher with Individual Study Subject
3 Researcher with those who finance a study
4 Researcher with Study Community
5 Researcher with scientific community in general
6 Researcher with societal decision makers
7. Researcher with the lay public in general

Items 1, 2 and 3 have been discussed at length. Items 4,5, 6 and 7 have been less discussed, and since they relate to issues of individual activism, they may be viewed differently by the contemplative "eastern" and the more interventionist "western" Judeo-Christian and Muslim ethical traditions. The International Society for Environmental Epidemiology has been working toward agreed upon principles of ethical conduct, but the discussion to date has been dominated by the North American and European members. In August 1997 we will be meeting in Taiwan and see this as an opportunity for learning about the perspective of those in Asian countries.

We welcome comments on the following two case histories. Each is followed by a range of options. Please comment on the ethical principles you would use in evaluating the options listed above and which ones you would ultimately advocate. Please identify the ethical tradition from which you come. Comments received by Darryl Macer will be published in EJAIB, as well as discussed at the Taiwan meeting.

Case Study 1- Raymond Richard Neutra

It is not unusual for it to take many years and many studies to clearly implicate an agent in the causation of disease and for it to take additional years and study to find a way to prevent or reverse the influence of that agent. In the early and midyears of the search, epidemiological study results will not be of much help to the study subjects, in fact the results may suggest that the subjects are at risk and that there is nothing they can do to help themselves. That situation is not only emotionally painful, but there is even some evidence that the stress induced may have adverse health consequences. Thus the very act of doing a study pits the interests of the researcher, societal decision makers and the lay general public against the interests of the study subjects.

Studies which have this property include: Studies of the environmental level of an agent suspected or proven to convey some probability of risk. Studies of a biomarker of exposure with uncertain prognosis. Studies of a biomarker of subtle physiological damage with uncertain prognosis. Studies of a susceptibility gene with uncertain prognosis or for which there is no helpful intervention. The case study presented below is of the first variety.

There is controversy as to whether power frequency magnetic fields (EMFs) from power lines and appliances could cause cancer in children and if so what level of exposure and what duration of exposure would convey a risk or how large that risk would be. To inform policy a state health department decides to carry out a survey in a sample of 90 out of 8000 schools some near electrical power lines, some far away. The goal is to establish how often magnetic fields occur, the relative importance of internal building sources and external power grid sources, and the likely cost of eliminating these exposures if they are ultimately determined to be hazardous. The hoped for benefit of this information would be to have a realistic assessment of the extent and cost of the "problem" if EMFs were determined to be hazardous so that questions of cost effectiveness could be addressed and adequate special funding provided to schools instead of expecting them to divert scarce resources from the existing educational budget.

If a particular school were to have higher than average magnetic fields there may be some parents or teachers who would be worried by these findings and demand some kind of mitigation. Yet scientific opinion does not support any costly measures for avoiding fields, since it is not clear that they are harmful. This makes for a situation of potential conflict between parents on the one hand and administrators who are responsible for the limited educational budget on the other. The press and the legal profession gravitate to these situations of controversy as a source of revenue.

Thus while the investigators and societal decision makers have an interest in gathering this information, the school officials run the risk of a no-win public relations problem, attracting the attention of creative tort lawyers hoping for a lucrative out of court settlement or being forced to divert scarce education moneys towards unnecessary mitigation, if the information is gathered and released. In that eventuality parents and teachers may be subjected to anxiety about a situation which will have no solution once brought to their attention.. Individual parents or teachers might however use information to guide their own behavior with regard to this as yet unproved hazard. Others would argue that only the threat of costly tort litigation keeps powerful industrial polluters attentive to potential side effects of their products. The legal profession therefore needs easy access to exposure information, they would argue. Aside from any arguments of usefulness, some would say that their is a fundamental "right to know" for the localized school community, the general population, the press and the legal profession. The willingness of school administrators to participate in the study will be influenced by the sensitivity of the investigator in dealing with the information generated.

Here are some options which the investigator might follow in dealing with the results of the study:

1) Gather the information with the promise of never revealing the results except as part of the anonymous statistical summaries describing the 90 schools being studied.

2) Provide a room by room summary of results with a generic interpretative guide to the administrator of each school studied, leaving it to him if he wishes to share the information with parents and teachers.

3) Same as # 2 but insist that parents and teachers at that school have access to the information and can consult with staff of the health department if they have questions.

4) Same as # 3 but insist that letters about the report are sent to all parents, teachers and staff.

5) Same as # 4 but make a press release to the local newspapers, television stations and radio stations when the material is released.

6) Same as #5 except that the identity and data of each school be made available on a state wide basis.

7) Call off the study because gathering the data may cause anxiety and cost to the schools where higher than average magnetic fields are found.

8) Find some way ( legal or through the pressure of public opinion) to force school administrators to comply with the study and implement options

8) Other solutions.

Case Study 2: Tests Among Children For A Biological Index Of Past Radiation Exposures

- John R. Goldsmith, MD, MPH. & Michael Quastel, MD, Ph.D.,
Faculty of Health Sciences, Ben Gurion University of the Negev,
Beer Sheva, ISRAEL (Email: gjohn@bgumail.bgu.ac.il),

While it is not common knowledge, there are some tests which reflect the occurrence and magnitude of past radiation exposures in otherwise healthy persons. Of these, the observation of aberrant chromosomal or chromatid changes found in spreads of circulating lymphocytes, incubated and stimulated to replicate are well known, but not attractive for use in large scale studies because each test takes about a week of technician time. Among adult populations, followed for sufficient time, some increase in leukemia occurs among subjects with chromosomal changes, but this could not be demonstrated for those with chromatid alterations.

A similar set of endpoints can be observed if serum from the exposed subjects is incubated with lymphocytes from a normal donor. The test takes about an hour and is thus realistic for population studies . Already this test, called a test for "clastogenic factor", has been shown to be elevated in otherwise normal persons with past radiation exposure even after decades. It is also elevated in some inborn conditions known to be associated with increased active oxygen species and increased risk of cancer.

Our laboratory and interview staff are engaged in studies of possible health problems among those exposed to Chernobyl radiation who later immigrated to Israel. We studied only volunteers, many of whom came for tests of the body burden of 137Cs. We asked children to return for thyroid function tests and we asked persons who were exposed as "liquidators"(the name given to workers involved in clean up and fire fighting at the destroyed reactor) to return for blood tests. We are now able to do both clastogenic tests and tests for Glycophorin mutation in the red cell series. A colleague offered to test for "clastogenic factor" on the blood samples available and on the basis of the samples being volunteered for the purpose of seeking evidence of health problems related to Chernobyl exposure, we agreed. In the liquidators, above a certain level of positive test results, there was an apparent relationship to indices of exposure. We did not expect that the 166 children tested would show many positive reactions, but about 45% (82) of them had test above the normal range, and 20% (25) had chromosomal changes as well as chromatid changes. Already we know of uncontrolled studies of liquidators with elevated levels of "clastogenic factor" in which two months treatment with oral antioxidant medication resulted in drop of the level to normal for at least several months after treatment cessation. Another colleague was giving all exposed children a different form or oral antioxidant, with no laboratory control, only the history of having been exposed at Chernobyl. Among a group of several hundred non-exposed children volunteering to give blood samples for a health study, one child had a strongly positive test. After some discussion we decided to tell the child's physicianand let her decide whether any further testing or follow-up should be done. None is being done to the best of our knowledge [Emerit I. et al. "Clastogenic Factors in the Plasma of Children Exposed at Chernobyl" Mutation Research 373 (1997), 47-54].

In summary, we are left with an unexpectedly large number of exposed, but otherwise healthy children with a laboratory test result of an experimental nature, possibly related to long term health problems and possibly treatable ( in the sense of the test being normalized) by relatively non-toxic oral medication, every few months. We have published with our colleague the results for these children. The major long-term effect of concern would be increased frequency of leukemia. However, up to now, no overall increase in leukemia in exposed children has been reported either in those who emigrated to Israel or those remaining in the former Soviet Union. We thus face the ethical issue of whether it is overall beneficial to these children and their families to identify them, and establish some follow-up procedure. This has the potential consequence of identifying the child as one with a poor prognosis, when in fact, we do not know the long-term meaning of the "positive" test. We have presented the matter to a consortium of medical scientists and representatives of the immigrants, but they took no position.

The purely scientific approach is to establish the optimal sets of possibly related tests and a careful follow-up. The purely patient-oriented approach is to maximize the physical and emotional well-being of the children and their parents. These may not be compatible objectives.

The choices from which an ethical decision may be made:

1. Take no action. The nature of the test was not explained aspart of the informed consent, and the tests, therefore, should not have been done.

2. Take no action, because there is no established meaning for the tests, as to outcome.

3. Do not inform the children or their families unless specifically requested to do so after the availability of such tests becomes known. This implies a public information effort.

4. Do not inform the children or families, but utilize "passive follow-up" until some evidence of the tests meaning has accumulated. By passive follow-up is meant monitoring for cancer occurrence through the National Cancer Registry, and the follow-up of hospitalization through the records for the region's population, available to our Department in connection with its responsibility for Health Services Evaluation.

5. Inform all of the children or families that the test was doneand results can be obtained by request through their physician. This would involve some training of such physicians.

6. Invite the children and families to participate in a controlled clinical trial of normalizing the test, using oral anti-oxidant medication, and state the uncertainties and discuss them with each patient or family in their preferred language ..

7. Call the "positive" and a sample of the "negative" children back for repeated testing, in order to estimate better the "false negative" or "false positive" test result, saying only that the initial results are not clear-cut.

8. Meet with a group of parents of "positive" children and without informing them of the results, see if they have a clear preference, suitable for the whole population.

9. Restrict one or more of the above to the subset with chromosomal changes.

10. Do not tell the subjects, but do long term monitoring of health conditions, with agreement of the personal physician.

11. Do not tell the subjects, but start investigating clinical effects of several compounds that are thought to reduce clastogenic factors, with agreement of the local physician.

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