Human Genes in Other Organisms:
Ethical, Spiritual and Cultural Dimensions

New Zealand Organisation for Rare Disorders

John Forman, Executive Director

The New Zealand Organisation of Rare Disorders (NZORD) exists to provide information, support and advocacy to people affected by rare disorders and assist their support groups to operate effectively. We support ethical research into human health solutions through the use of transgenic technology, and we believe approvals given for these experiments do comply with ethical standards and properly consider spiritual and cultural views. But to do this discussion justice we need to discuss the meaning of ethics. Ethics concerns what is morally right or morally wrong. People often say, That's unethical when they might mean something quite different, such as I don't like that, It makes me queasy or That offends my spiritual beliefs or cultural view. Further analysis is needed.

A quick overview

There are key traditional philosophical frameworks like utilitarianism and deontology which help determine if actions in many parts of life are ethical or not. But for most people with health or disability issues and their support groups, those frameworks can seem complex and remote. It can be difficult to apply them to the questions we are interested in are: What is ethical in this particular situation? How do we tell the difference? How are ethics applied in medicine and research? Getting there takes some explanation. Fortunately there are additional measuring tools to help the process.

My brief interpretation of ethics in medicine and research is this. Out of the broad philosophical concepts of ethics flow a number of specific concepts like justice, benefit, minimising harm, and promoting personal choice for others. When courses of action are considered in medicine and research, the proposal is measured against these ethical principles, to decide if the action should be taken or not. Benefits and harms are balanced, and the decision takes into account other factors including the circumstances in which the action is considered.

Balancing competing interests

In recent decades bioethics has become increasingly important in ensuring that medicine and research respect the people and animals that are being treated, or are the subjects of research. Ethical codes, and the ethics committees to oversee them, have been put in place for many reasons. These include our wish to have more control over matters of importance to us, social movements like human rights and animal welfare that influence social thinking, and the wish to prevent abuse. Changing knowledge and technology also reinforce the need for ethical controls. The ethical standards set the rules so that expectations are clear, treatment and research can be measured against them, and enforcement can be carried out, protecting us all in a neat, tidy and logical way - we hope.

One way of describing bioethics is to think of it as the point at which the technical capacity of science is influenced by the values of society. Guided by discussion and analysis, ethical controls manage the new possibilities. This has been described by some writers in phrases like keeping values connected to science, or the crossroads where the possibilities of science meet the values of the community. There is a connection taking place.

In a nutshell, ethics in medicine and research determines what should be done, as opposed to what could be done. That sounds simple enough. But if only it were that simple.

For many people ethics is viewed as what is acceptable versus what is not, but that is not the same as what should or should not be done. Acceptable to the majority? Or acceptable to those directly involved? The presumption of majority interests may give one view, but the results may be different when considering benefits, harm minimisation and acceptability to the affected people.

The rights of individuals or groups to receive a benefit may prevail over community concerns where the benefit can meet the principles derived from ethical philosophy. In one sense this is a classic conflict of minority rights versus the power of a majority. This may get more complex to manage the more we analyse it - especially when support groups have a particular interest in controversial research. For example, there are situations where the benefit to an individual or group must be denied to them because there are risks, and the benefits would not outweigh that possible harm.

In the early 19th century there was community anxiety at the use of a vaccine derived from cow-pox virus, to vaccinate people against smallpox. An anti-vaccine society was formed. There were riots in the streets of London. The vaccine worked, millions of lives were saved, and smallpox was eliminated from human health concerns. The benefits to the whole population over-rode the vocal concerns of many in the community.

At the end of the 20th century experimental xenotransplantation placed genetically modified pig cells into six patients with diabetes. The experiments seemed successful as the patients were able to produce their own insulin, and therefore end drug treatment. However, the research was stopped when a risk of transmission of pig diseases to humans, was identified. The interests of a group were outweighed by the risks to the wider community.

These examples relate to the situation of placing animal material into humans. Although the smallpox example was well before the formal discipline of bioethics was established, no doubt the debate was similar to the current debate about inserting human genes into animals. What these examples show is that putting ethics into practice is not simply a matter of looking up a list of approved or prohibited actions. It takes on the complexity of balancing competing interests, benefits and harms, in the context of the society we live in and the circumstances of the matter under consideration.

Adding spiritual and cultural issues

Will the addition of spiritual and cultural issues to the mix make it even more difficult to work through the ethical decision-making, even before we take these complicated principles and interactions and contemplate inserting a human gene into a cow? Perhaps - but not necessarily. Ethical codes may not have explicitly taken spiritual and cultural issues into account, but it can be argued they have done so implicitly by taking society's values into account when balancing the benefits and the harms. Our values are strongly influenced by our spiritual beliefs and cultural norms.

Mentioning spiritual and cultural factors as separate areas requiring consideration is probably not adding new matters to the list, but rather gives explicit acknowledgement to them as important factors in the ethical consideration. In the New Zealand context this may reflect social evolution, as in the Treaty of Waitangi increasingly being acknowledged in public policy and in case law.

The specific issue of human genes in other organisms

Let's now look specifically at the central issue of inserting human genes into other organisms. For this discussion I will focus exclusively on the insertion of human genes into cows, the very procedure that AgResearch has already carried out at Ruakura for its myelin basic protein project, and which it plans again in its next round of experiments. The specifics of these real projects probably provide a more useful discussion than a more general theoretical discussion. The consent application referred to here is the most recent application, GMD 02028.

Two main ethical issues were raised for consideration in the applications by AgResearch. The first concerned animal ethics. Not surprisingly, AgResearch as an experienced animal research institution was easily able to identify these issues and their management requirements. These potential problems were seen as manageable and not outweighing the potential advantages of the research. The Environmental Risk Management Authority (ERMA) noted that animal welfare risks were low, and also noted the animal welfare controls and oversight that were in place, when it granted its approval.

The second ethical issue raised by AgResearch was the risk of affront to spiritual beliefs and values of Ngāti Wairere, the local hapū. This matter had been the subject of previous hearings and a High Court review. Notably, there was support as well as opposition from Māori to the research proposal, as there has been divided opinion among Māori generally over uses of modern biotechnology. The discussion of these matters in the application, at the hearings and in the ERMA decision clearly shows how the spiritual and cultural aspects of ethics were thoroughly dealt with. ERMA's decision noted that spiritual issues were relevant considerations, that processes were in place to manage those concerns, and concluded that "the risks attributable to spiritual concerns is low".

Discussion in the ERMA decision about the principles of the Treaty of Waitangi demonstrates how important the spiritual and cultural aspects are considered to be, but of interest is ERMA's conclusion that taking those issues into account "does not extend to accepting those beliefs as the determinant of whether the research proposed by the applicant should be approved". In other words, there is no power of veto.

It was in the submissions of opponents to the research, and in public media comment by these submitters, that the claim of "unethical" research was frequently made. The opponents' submissions focused on:

• the ethics of animal use (as noted above)
• concern about the animals getting into the food chain (controls were established to prevent this)
• contravention of Biblical teachings (ERMA did not regard the research as necessarily unethical from a Christian point of view).

The ERMA decisions from a health and disability support group perspective

ERMA's decision on the AgResearch application took account of many spiritual, cultural and ethical issues and addressed them all, while still granting approval because of the potential benefits of the research. ERMA's position relating to Māori concerns could perhaps be compared to earlier discussion about the 'acceptability' of practices or research to the community, and the influence such views might have, whichever social group they are held by and whether they constitute a majority or not. The outcome seems well balanced from a support group perspective. There was a very careful analysis of all the ethical, spiritual and cultural issues by AgResearch as the applicant, and by ERMA in its hearings and decision.

There is not one single view among support groups, or among those in a particular support group. We can be as diverse as the rest of society, but we usually have a close interest in the development of new treatments for our health and disability problems. As citizens and as members of communities we want those developments to be managed in a safe and ethical way. We would be most upset at a medicine or treatment option that was of benefit to us, but caused serious harm to others or to society. Remaining objective can come under some pressure when the issue gets close to home for a particular group, but I have yet to see any individual or group argue that risks or ethics should be ignored for their sake.

I feel sure that the thorough consideration of these issues - and the outcomes - would be welcomed by people affected by health and disability issues. A close scrutiny of the process shows that the right thing has been done, and has been seen to be done.

Public comment on the research application

Perhaps the greatest volume of commentary on the ethical aspects of this research occurred in media reporting of opponents' views, outside of the hearing process. The Green Party, GE-Free NZ, Greenpeace, MadGE and others often made the bald claim that this research is unethical. At times they have received support from a small number of scientists who have made the same claim, including members of the Sustainability Council. This often-made claim needs examining.

Almost without exception such claims give little or no reasoning for why the research would be unethical. The statement is made and left hanging, unsupported. The implication is they are simply expressing personal or political views. If these claims are to be taken seriously in any decision-making process or in policy, there needs to be more rigorous analysis, which is why I began this article with a brief discussion on understanding ethics.

To give credit to the co-leader of the Greens, Jeanette Fitzsimons, she often stated why she thought it would be unethical, so an analysis of her statements may help in assessing the ethics of this research. To the Royal Commission on Genetic Modification, in oral evidence to support the official Green Party submission, Ms Fitzsimons stated, "It's ethically irresponsible to use sheep and cows as bio-reactors to [produce therapeutic proteins]... particularly when that manufacturing can be done with micro-organisms in a laboratory" [Transcript page 3231, lines 54 to 59.]. However, the Royal Commission noted the rebuttal evidence of Lysosomal Diseases New Zealand that "micro-organisms [are] not effective producers of the complex enzymes found in mammals", and concluded that it was "satisfied that it will not always be possible to use vats to produce the pharmaceuticals required" [Royal Commission of Genetic Modification, Report, Chapter 7, page 161 (PDF 141KB).]. Of course an alternative source that is safe and effective may be preferable, but would that necessarily make a transgenic source unethical? What if the alternative had environmental impacts or limited effectiveness?

A press statement from the Greens stated: "In response to claims by the website of Professor Dick Wilkins that 'the medical claims made by AgResearch were largely a nonsense', Ms Fitzsimons said she was pleased the spin employed by AgResearch to try and make an ethically disturbing experiment acceptable to the public had been exposed." [Greens press statement, 6 May 2001.] The quoted page on the website was permanently removed more than a year ago. Subsequent pages from Professor Wilkins support the basic science, but note that medical applications may be some years away. No comments on the ethics of the experiment are included. In this context it needs to be remembered that the theoretical merits of a project have weight in deciding if an experiment meets ethical criteria; contrary opinion about the outcome of the experiment does not in itself make the experiment unethical.

Another Greens press statement reads: "Ms Fitzsimons said putting human genes into large mammals has raised more ethical concerns than any other genetic engineering experiments done in New Zealand so far"[Greens press statement, 13 August 2002.]. Although this type of assertion has been frequently made, we have yet to see any instance where such ethical issues have been discussed in a systematic, open and authentic fashion to support such statements. Here the phrase "ethical concerns" seems to be used loosely to support a political position rather than as a serious contribution to ethical debate.

Finally, in commenting on transgenic research in sheep, Ms Fitzsimmons is quoted as saying: "Sheep and cattle are put through intrusive and unethical procedures to cause them to produce a human protein in their milk before that protein has been tested to see if it has any medical use... The correct process would have been to first test the protein, which is already available from human sources." [New Zealand Herald, 23 June 2003.] However, there are serious safety issues with the use of post-mortem or placental tissue. The risk of transmitting diseases like Hepatitis, HIV and Creutzfeldt-Jakob disease is high. Human sources of medicine have been steadily replaced with genetically engineered proteins over recent years, for safety. The transgenic medicine projects proceed because of the potential value of reliable, standardised sources of these proteins, successful experimental treatments in animals, and the need for alternative production methods.

Safety issues and the development of cost-effective proteins are vital aspects of ethical considerations, justifying research into genetically modified proteins in animal cell lines, transgenic animals, transgenic plants and other sources. Experimental success with the protein in question seems a strong counter to Ms Fitzsimons's claim. Her claims about correct procedures seem to confuse research purposes with research results.

Regrettably, these examples contribute little to the ethical debate. If we carefully analyse Jeanette Fitzsimons's statements we find they amount to little more than I don't like it, mixed with unsupported allegations of safety issues, confusion over research methodologies, and a barely disguised political agenda.

So are we any wiser for all this public comment? I believe the answer has to be, unfortunately, no. We see the words 'ethics' and 'unethical' used and abused in many ways to reinforce the various social and political agendas of opponents. There is little or no constructive dialogue about the objective ethical issues involved.

The consultation process: the ethics of it all

Because public policy now includes detailed consultation processes, it is worth taking a moment to consider how well this process contributes to decision-making. Unfortunately, groups wanting to oppose innovations in science, especially in modern biotechnology, often act in ways that do little more than frustrate and impede the process, score political points and cause delays. Listening to opponents at hearings and reading their submissions exposes a serious absence of well-reasoned arguments that identify real or even potential problems with the science, risks to the environment, or matters of serious ethical concern. Many opponents are very poorly informed on the issues. A well-reasoned and challenging debate would be welcome.

The behaviour of these groups also raises a different question of ethics: in what sense do they embrace a community ethic of integrity, truth and fairness in terms of how they engage in the consultation process, and in the standards of behaviour they apply when they promote their concern or their political agenda?

Conclusions

In examining the nature of ethical decision-making and applying this framework to a specific example of inserting human genes into other organisms, there seems very clear evidence that all of the ethical, spiritual and cultural issues were thoroughly canvassed and given serious and meaningful consideration. The analysis was thorough, and the approval that was given signals to health and disability support groups that:

• innovation to find treatments for health and disability problems is supported
• the potential risks and benefits of research are thoroughly assessed
• the decisions carefully weigh the ethical, spiritual and cultural issues
• matters of potential risk are suitably dealt with, and potential harms do not outweigh the benefits of proceeding
• the approval to insert human genes into animals has been found to meet ethical criteria.

Some challenges will arise for the Bioethics Council out of these experiences, including finding ways to:

• encourage an environment in which the public become better informed about what ethics actually is, and how ethical decisions are made
• separate ethical considerations from a variety of social and political agendas that are often dressed up as ethics
• help an appreciation of ethics as a process of reconciliation of various concerns, not an opportunity for any group to have a power of veto because of their 'superior' issue.

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