Ethical and legal principles of biomedical studies of humans and animals. Moral principles of animal

experiments.

The area of special ethical

risk

• The efficacy of modern medicine depends very largely on scientific research into the causes of disease, innovative therapies, and methods of organizing and delivering healthcare services.

• Medical research was considered to be an area of special ethical risk, exposing patients to risks of harm that could involve doctors in treating their people more as ‘‘research subjects’’ than as patients who should under no circumstances be harmed.

What is research ethics?

• Research involving human subjects can raise difficult and important ethical and legal questions.

• The field of research ethics is devoted to the systematic analysis of such questions to ensure that study participants are protected.

Why is research ethics important?• Many of the ethical issues that arise in human

experimentation – such as those surrounding informed consent, confidentiality, and the physician’s duty of care to the patient – overlap with ethical issues in clinical practice.

• Important differences exist between research activities and clinical practice. In clinical practice, the physician has a clear obligation to the patient; in research, this obligation remains but may come into conflict with other obligations – and incentives.

Law• The researcher’s duty to have informed consent from research subjects is established in almost all of the world’s legal systems.

• The legal doctrine often described as ‘‘informed consent’’ is better understood as ‘‘informed choice,’’ since a physician’s legal duty is to inform the subject so that he or she may exercise choice – which does not always result in consent.

Policy• Although the Nuremberg Code (1947) and the UN

International Covenant on Civil and Political Rights (1958) remain important early statements, the World Medical Association’s Declaration of Helsinki. The Declaration highlights an important additional requirement: subjects’ participation in research should not put them at a disadvantage with respect to medical care.

• Researchers conducting research in other countries should consult the guidelines of the Council for International Organizations of Medical Sciences (CIOMS) (CIOMS, 2002). Similarly, geneticists, for instance, should consult the guidelines developed by the Human Genome Organization (1996).

Empirical studies• Empirical studies have

much to contribute to our understanding of informed consent and the risks and benefits of participation in research.

• Empirical studies on the risks and benefits of research participation have also made an important contribution to research ethics.

How to approach research ethics in

practice?

• A critical component in assuring the protection of human subjects in research is the prior review and approval of any study by an ethics review committee.

• Clinicians should routinely consult with colleagues who have expertise in the ethics of research, particularly where relevant in developing countries, including members of research ethics boards.

Animal experimentation• Animal testing, also

known as animal experimentation, animal research, and in vivo testing, is the use of non-human animals in experiments, particularly model organisms such as nematode worms, fruit flies, zebrafish, and mice.

• Worldwide, it is estimated that 50 to 100 million vertebrate animals are used annually, along with a great many more invertebrates.

Animal-testing services to

industry

• The research is conducted inside universities, medical schools, pharmaceutical companies, farms, defense establishments, and commercial facilities that provide animal-testing services to industry.

• It includes pure research such as genetics, developmental biology, behavioural studies, as well as applied research such as biomedical research, xenotransplantation, drug testing and toxicology tests, including cosmetics testing.

• Animals are also used for education, breeding, and defense research.

Animal rights• Every medical achievement

in the 20th century relied on the use of animals in some way.

• Some scientists and animal rights organizations, such as PETA and BUAV, question the legitimacy of it, arguing that it is cruel, poor scientific practice, poorly regulated, that medical progress is being held back by misleading animal models.

• Enos the space chimp before insertion into the Mercury-Atlas 5 capsule in 1961

Types of vertebrates used in

animal testing in Europe

• The Nuffield Council on Bioethics reports that global annual estimates range from 50 to 100 million animals.

• None of the figures, including those given in this article, include invertebrates, such as shrimp and fruit flies. Animals bred for research then killed as surplus, animals used for breeding purposes, and animals not yet weaned (which most laboratories do not count) are also not included in the figures..

Invertebrates

• The most used invertebrate species are Drosophila melanogaster, a fruit fly, and Caenorhabditis elegans, a nematode worm.

• Fruit flies are commonly used. These animals offer great advantages over vertebrates, including their short life cycle and the ease with which large numbers may be studied, with thousands of flies or nematodes fitting into a single room.

Non-primate vertebrates• This rat is being deprived

of restful REM sleep by a researcher using a single platform ("flower pot") technique.

• Other rodents commonly used are guinea pigs, hamsters, and gerbils. Mice are the most commonly used vertebrate species because of their size, low cost, ease of handling, and fast reproduction rate.

A white Wistar lab rat

• Rats are also widely used for physiology, toxicology and cancer research, but genetic manipulation is much harder in rats than in mice, which limits the use of these rodents in basic science.

Non-human primates

• Non-human primates (NHPs) are used in toxicology tests, studies of AIDS and hepatitis, studies of neurology, behavior and cognition, reproduction, genetics, and xenotransplantation.

Pure research

• Basic or pure research investigates how organisms behave, develop, and function. Those opposed to animal testing object that pure research may have little or no practical purpose, but researchers argue that it may produce unforeseen benefits, rendering the distinction between pure and applied research — research that has a specific practical aim — unclear.

• Pure research uses larger numbers and a greater variety of animals than applied research.

Applied research

• Applied research aims to solve specific and practical problems. Compared to pure research, which is largely academic in origin, applied research is usually carried out in the pharmaceutical industry, or by universities in commercial partnerships.

• These may involve the use of animal models of diseases or conditions, which are often discovered or generated by pure research programmes.

Toxicology testing

• Toxicology testing, also known as safety testing, is conducted by pharmaceutical companies testing drugs, or by contract animal testing facilities, such as Huntingdon Life Sciences, on behalf of a wide variety of customers. A rabbit during a Draize test

Drug testing

Beagles used for safety testing of pharmaceuticals

• metabolic tests• toxicology tests• the effect of the drug

and the dose-response curve

• Specific tests on reproductive function, embryonic toxicity, or carcinogenic potential

Animal experimentation

• A technician assessing mice in a typical research vivarium

• Animal experiments are widely used to develop new medicines and to test the safety of other products.

• Many of these experiments cause pain to the animals involved or reduce their quality of life in other ways.

• If it is morally wrong to cause animals to suffer then experimenting on animals produces serious moral problems.

Two positions on animal experiments

In favour of animal experiments: •Experimenting on animals is acceptable if (and only if):

– suffering is minimised in all experiments

– human benefits are gained which could not be obtained by using other methods

Against animal experiments: •Experimenting on animals is always unacceptable because:

– it causes suffering to animals

– the benefits to human beings are not proven

•Any benefits to human beings that animal testing does provide could be produced in other ways

Animal experiments and animal rights

A laboratory mouse cage. Mice are either bred commercially, or raised in the laboratory.

• Those in favour of animal experiments say that the good done to human beings outweighs the harm done to animals.

• This is a consequentialist argument, because it looks at the consequences of the actions under consideration.

• It can't be used to defend all forms of experimentation since there are some forms of suffering that are probably impossible to justify even if the benefits are exceptionally valuable to humanity.

Justifying animal experiments• Those in favour of animal experiments say that

the good done to human beings outweighs the harm done to animals.

• This is a consequentialist argument, because it looks at the consequences of the actions under consideration.

• It can't be used to defend all forms of experimentation since there are some forms of suffering that are probably impossible to justify even if the benefits are exceptionally valuable to humanity.

Acts and omissions• Most ethicists think that we have a greater moral

responsibility for the things we do than for the things we fail to do; i.e. that it is morally worse to do harm by doing something than to do harm by not doing something.

• In the animal experiment context, if the experiment takes place, the experimenter will carry out actions that harm the animals involved.

• If the experiment does not take place the experimenter will not do anything. This may cause harm to human beings because they won't benefit from a cure for their disease because the cure won't be developed.

Other approaches to animal experiments

• Peter Singer, Animal Liberation, Avon, 1991• Sadly, there are a number of examples where researchers

have been prepared to experiment on human beings in ways that should not have been permitted on animals.

• And another philosopher suggests that it would anyway be more effective to research on normal human beings:

• Whatever benefits animal experimentation is thought to hold in store for us, those very same benefits could be obtained through experimenting on humans instead of animals. Indeed, given that problems exist because scientists must extrapolate from animal models to humans, one might think there are good scientific reasons for preferring human subjects.

Justifying Animal Experimentation

• In November 2008 the European Union put forward proposals to revise the directive for the protection of animals used in scientific experiments in line with the three R principle of replacing, reducing and refining the use of animals in experiments. The proposals have three aims:

• to considerably improve the welfare of animals used in scientific procedures

• to ensure fair competition for industry • to boost research activities in the European Union

The main changes proposed are• to make it compulsory to carry out ethical reviews and require that

experiments where animals are used be subject to authorisation • to widen the scope of the directive to include specific invertebrate

species and foetuses in their last trimester of development and also larvae and other animals used in basic research, education and training to set minimum housing and care requirements

• to require that only animals of second or older generations be used, subject to transitional periods, to avoid taking animals from the wild and exhausting wild populations

• to state that alternatives to testing on animals must be used when available and that the number of animals used in projects be reduced to a minimum

• to require member states to improve the breeding, accommodation and care measures and methods used in procedures so as to eliminate or reduce to a minimum any possible pain, suffering, distress or lasting harm caused to animals

The "three Rs"are guiding principles for the use of animals in research in most countries:

• Replacement refers to the preferred use of non-animal methods over animal methods whenever it is possible to achieve the same scientific aim.

• Reduction refers to methods that enable researchers to obtain comparable levels of information from fewer animals, or to obtain more information from the same number of animals.

• Refinement refers to methods that alleviate or minimize potential pain, suffering or distress, and enhance animal welfare for the animals still used.