Ethical considerations in toxicology

Fd Chem. To'~i~. Vol. 23, No. 2, pp. 137--138. 1985

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ETHICAL CONSIDERATIONS IN TOXICOLOGY G . ZBIN DEN

Institute of Toxicology, Swiss Federal Institute of Technology and University of Zurich, CH-8603 Schwerzenbach. Switzerland Abstract--Since most of the research necessary for the safety evaluation of chemicals requires the killing of laboratory animals, toxicologists are faced with an ethical conflict between their professional duties and the interests of the animals. In the past, the protection of consumers against chemical injury was considered to be of the greatest importance, and society approved of all efforts to detect even the slightest hazards from man-made and environmental chemicals. In recent years, toxicologists have become aware of their ethical responsibilities not only for the safety of the human population but also for the welfare of the animals. They have begun to review the classical toxicological procedures critically and now require that the maximum amount of relevant information is obtained from the smallest number of laboratory animals. Toxicologists have also become aware of the alternative methods that permit the investigation of toxicological responses in unicellular organisms and cell cultures. The problem of testing chemicals for irritant properties on skin and mucous membranes is an excellent example of how concern for animals has generated a range of original and imaginative research leading not only to a reduction in the use of animals but also to a more efficient and scientific approach to an important health problem.

Ethics in everyday life The rules that govern the orderly course of business, regulate the smooth flow of traffic and, in general, ensure the peaceful coexistence of people are established by laws, But even in 1984 people are left with considerable space in which to act of their own volition. It is within the large area of these behavioural patterns permitted by law that moral concepts and ethical standards provide the important guiding principles without which a civilized society could not function. This divison of responsibility between the powers of the state and the moral force of the people is, on the whole, a.good thing. It would, for example, be impossible if the precept "you shall not steal" were to be interpreted by every member of society according to his own ethical beliefs. On the other hand, it is difficult to imagine a country where one of the two principal commandments of the Christian ethic "you shall love your neighbour as yourself" would be part of the code of civil law, or even enforced by penal legislation. Not many citizens would walk around with a record clear of convictions! In this paper no attempt will be made to distinguish between the various schools of ethics, as they were created by the great philosophers of mankind and the founders and apostles of world religions. For the sake of simplicity, I shall observe the moral views currently held in most parts of the Western world. These mor~il concepts provide us with a serviceable ethic for everyday life based on standards of the Christian and Hebraic religions and also containing sundry remnants of the Hellenic philosophies and the teachings of Kan.t. The implications of these moral concepts for biomedical scientists are quite straightforward. They require that scientists make every effort to further the well-being and prosperity of people and to contribute to a healthy and happy life for all creatures. Causes of ethical conflicts As biomedical scientists we have always con-

sidered our profession as a service for society. In fulfilling this mission, and convinced of the moral sincerity of our dealings, we have concentrated on our noble goals and have not given much thought to whether our work was truly appreciated by those outside the biomedical field. Consequently it has been a great surprise to many biomedical scientists to be confronted recently with violent criticism. Many on whose behalf we have struggled faithfully have suddenly begun to question our moral standards, doubt the adequacy of our methods and declare our motives dubious. Quite clearly, biomedical science has come down from the platform of infallibility and is now forced to defend itself against its accusers. For some time this critical attitude was attributed to a passing lack of information and an understandable weariness with an ever more visible technocracy steadily intruding into everyday life. Because of this, little thought was given to determining how to change popular attitudes to science and technology in general. However, even the most erudite scientists have now become aware that their endeavours are at variance with the thoughts and ambitions of a considerable section of the population and that a state of conflict and potential confrontation has developed. Let us look at one of the important ethical issues of great concern to people who are not part of the biomedical research establishment. It emerges from what might be called a moral dilemma. It is the fact that the scientist is often forced to make a decision that violates the interests of some people, although it is usually made with good intentions and is ultimately in the best interests of the human race. In many instances the biomedical scientist simply cannot choose between a good and a bad solution. To reach his goal he is often forced to select one of two evils. For example, if I wish to use in small children a new drug that has proven to be beneficial in adults, I am forced to make a choice: either I give the drug to a sick child before I know about the dosage schedule and special risks in this patient 137

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population, or I must test the compound first in healthy children. And if I decide to do the latter, it is unavoidable that the research subjects will be exposed to a certain risk. The same dilemma is encountered in many other research projects with human subjects. Although such studies may be of great.importance for science or to mankind as a whole, they do nothing for the subjects who act as human guinea-pigs. In fact, such studies may even put the health and well-being of the subjects at risk. I have used the expression 'human guinea-pig' on purpose in order to make a transition to the current controversy over the use of laboratory animals in biomedical research. As scientists we regard not only the use of healthy volunteers but also the use of laboratory animals as ethically justified, as long as the results gained by our investigations benefit the sick Or help to expand our knowledge about the mysteries of life. These views are now opposed by critics whose standards of value are different from ours. Instead of considering the battle against human disease as pre-eminent, they propose that the supreme ethical objective be respect for life; Instead of looking at the human race as the lords of creation, they introduce the concept of a partnership of animals with man, and they stress the very special protection to which those creatures whose livelihood depends on the omnipotence of man are entitled. What many moral philosophers and, with them, a large group of non-scientists demand is a reexamination of our traditional views on the hierarchy of values and of the possessions that are deserving of protection. They also want a reassessment of man's claim to the unconditional liberty of having authority over nature and all her creatures. They insist that scientists, in planning and executing their research projects, respect the well-being of all the parties concerned, including humans, animals and all other living organisms. In other words, they require that biomedical scientists consider not only the technical and economic aspects of their research but hold it to be their duty to give equal consideration to the ethical, or--to use the current term--the bioethical concepts. The practical consequences of these demands are considerable. If we follow these views, it will no longer suffice to consider the benefit of a research project to human society and to calculate the costs on materials and personnel. What must now be added is the 'moral cost', that is, the risks for the subjects involved in a research project and the sacrifice of laboratory animals. If these concepts are endorsed and applied unconditionally, it will mean that research projects must not be undertaken if the expected gain in knowledge does not justify the moral cost inherent in the planned experiments. It also means that we would have to establish standards by which this moral cost could be assessed.

The special responsibility of the toxicologist In the discussions about moral issues in biomedical research, toxicology is, in general, considered to be o n e of the least objectionable among all the sciences requiring data from experiments with laboratory animals. This is understandable, since even the most ardent defender of animal rights knows about

the dangers of chemicals in our environment, be they man-made and sold as drugs and consumer products, or be they pollutants or substances occurring naturally in the biosphere. In fact, extensive toxicological testing of such substances in live animals was not only proposed by scientists and made mandatory by health authorities, but was, and still is. aggressively demanded by consumer advocates. These three influential parties, the concerned scientists, the conscientious public health authorities and the organizations formed to protect the health of the consumers have joined in promoting toxicological testi-ng and in establishing the highest standards for the safety evaluation of consumer products and environmental chemicals. Over the last 30-40 years enormous sums have been spent on building test facilities and on investigating the safety of many chemicals. Experimental methods have been improved and amended so that even the slightest undesirable effect can be detected. This has meant two things: the application of very high doses to some of the animals, and the use of large numbers of laboratory animals. Moreover, whenever a toxicological experiment failed to predict a toxic reaction that was later found to occur in man, the toxicological procedures were revised and the regulatory requirements were toughened--and very often this meant larger numbers of experimental animals, more laboratory tests and longer treatments with even higher doses. In the light of this escalation, the enormous use of animals, the high costs and the demands on highly skilled manpower, toxicologists should, from time to time, pause to contemplate their activities critically and to review their past achievements. They must realize that their important mission--the protection of mankind against chemical injury---does not give them an unconditional licence to kill as many laboratory animals as they wish and to hide behind regulatory requirements, testing guidelines and bureaucratic prescriptions for good laboratory practice. As scientists they must take time to learn what is happening outside their own sphere of interest. If they do this, they will realize that the biomedical sciences have made fantastic progress in many areas, and they will, inevitably, question whether the methods and concepts that currently form the basis of experimental toxicology are still valid. Having done this they must consider carefully the routine experimental procedure and ask themselves, whether they really get the best, the most comprehensive and the most relevant information from each animal they kill in the name of human safety. If they are not convinced that their current approaches are indeed the best to protect human health against chemical injury, they have an obligation to make their doubts known, to initiate well directed research programmes and to press for revision of regulatory requirements should their investigations demonstrate that new methodological approaches provide more relevant results. A perfect area for such a critical review of past performance, of the adequacy of current techniques and of the possibility of better scientific approaches forms the subject of this symposium--the experimental testing of chemicals for their irritant properties on the skin and mucous membranes,