General principles regarding the use of adult stem cells

(1)

Cell Prolif. 2008, 41 (Suppl. 1), 78–84

Blackwell Publishing Ltd Oxford, UK CPR Cell Proliferation 0960-7722

XXX ORIGINAL ARTICLES General principles regarding the use of adult stem cells I. Carrasco de Paula

General principles regarding the use of adult stem cells

I. Carrasco de Paula

Institute of Bioethics, School of Medicine ‘A. Gemelli’, Catholic University of the Sacred Heart, Rome, Italy Received 13 September 2007; revision accepted 14 September 2007

Abstract. With only a few, almost inevitable exceptions, biomedical research has developed within the last 50 years under the tutelage of ethical standards of notable precision. In the vast world of scientific investigation, few disciplines can boast of having realized documents of such ethical rigour, and respect for the integrity and intrinsic value of the human person has been one of the cardinal principles of the researcher. Research is intrinsic to the medical profession; the reward of research is knowledge and its techniques are ordered towards maintenance of human health. Since this end concerns human beings, it demands an extremely rigorous ethical approach.

Ethical aspects are present from the first moments of the experimental project and occur on three levels: choice of the objectives, selection and use of the appropriate means for the study, and application of resultant new discoveries. Today, our moral attention cannot be reduced to a cost–benefit analysis. Biomedical sciences and medicine have overlapping areas of interest that can be sources of tension: the good of the subject versus scientific utility; profit versus complexity of research; liberty versus ethical and juridical bonds; the public versus the private; and the individual versus the community. Here, I attempt to formulate some essential principles that should guarantee humane measures for research on humans.

If the heated debate that has followed upon the heels of the Donaldson report on the use of stem cells is considered, it is striking to note a convergence of opinion among both scientists and ordinary citizens that delicate ethical problems arise only if the collection and use of embryonic stem cells is the issue.¹ In light of this fact, my presentation at the congress ‘Stem Cells: What Future for Therapy?’ might be interpreted in two ways. First, the organizers do not share this fairly common opinion that I have just alluded to; in other words, they think that the use of adult stem cells is also cause for ethical concerns. Or, secondly, we might suppose that the moral limits of research that use embryonic stem cells do not merely pertain to the destruction of human beings in the first phases of their development.

Apart from the legitimacy of these two interpretations, it seems beyond doubt that ethical considerations cannot be circumscribed to the evaluation of a specific procedure for acquiring material needed for research. Consider, for instance, the recent case of Hwang Woo Suk² whose

Correspondence: Ignacio Carrasco de Paula, Istituto di Bioetica, Facoltà di Medicina e Chirurgia ‘A. Gemelli’, Università Cattolica del Sacro Cuore, Largo F. Vito, 100168, Roma, Italy. Tel.: +39 06 30154960; Fax: +39 06 3051149;

E-mail: [email protected]

The author declares no conflicts of interest.

(2)

investigative work has turned out to be fraudulent. We could go further and cite other instances within specialized biomedical literature of serious ambiguities and a certain erosion of style. All of this demonstrates that something strange is afoot and that if this tendency is not averted – as I hope will be the case – it will become necessary to speak of an ‘ethical emergency’. As a prestigious Italian scientific journalist (Meldolesi 2006) wrote a short time ago, ‘too many results have not been replicated by independent research teams; too many scientific journals have lowered their standards for publication, overlooking weak points in their studies, since they promise to make massive headlines’.

These events do not seem to be the results of some perverse, hidden design. More than anything else, these unfortunate episodes are most likely indicative of a certain atmosphere that has developed within biomedical circles where extremely complex ethical issues are dealt with.

It seems that there is an agitated, accelerated atmosphere, and this is not a good sign. It is, of course, clear that there are many external factors and influences that are encroaching upon this important and promising field of research. Many investigators can no longer avoid unlooked for pressures and solicitations. The difficulties of research are now made up of an incomprehensible antagonism between religious beliefs, moral prejudices, and the promise of a luminous future in which degenerative diseases will be overcome. For those researchers involved, many things are at stake: the future of institutions that do not achieve a status of ‘excellence’; availability of permanent research positions; equal and fair contracts; collection and distribution of funds; the highly prized ‘impact factor’; the race for patents and innovations; and more.

Ethics must take public opinion into account, as well as the various difficulties and obstacles faced by those who live for and by scientific research. Nevertheless, the fundamental question for ethics remains the ancient and eternal question regarding the good. In the present case, this question might be formulated thus: is stem cell research that has already provided good results from a biomedical point of view, and promises much more, an unlimited good for the person or does it entail costs for our humanity that are intolerable? And if we affirm that it is a good, then common sense requires us to ask whether it is an unconditional good or if there are restraints that must be respected.

BIOMEDICAL RESEARCH AS AN ETHICAL DILEMMA

Except for a few unfortunate exceptions, in the past 50 years biomedical research was born and has developed under the vigilance of exceptionally rigorous ethical standards. In the vast world of scientific research, few disciplines can boast such internationally important documents as the Helsinki Declaration on therapeutic and non-therapeutic research, or the Belmont Report and the ethical orientations of the Council for International Organizations of Medical Sciences regarding biomedical research that involves human subjects, to cite only the most well-known texts. We must add to this list the genesis and diffusion of ethical committees for biomedical and pharmaceutical experimentation that seek to guarantee a high level of biomedical research, both in its intentions and in its procedures. The Pontifical Academy for Life, at the end of the congress held in 2003 on the subject, ‘Ethics in Biomedical Research: Towards a Christian Vision’, did not hesitate to recognize the unlimited competence of the researcher, obviously, not from a material, but from a moral point of view. It was affirmed that ‘there are no ethical limits to knowing the truth; in other words, there is no boundary beyond which man must not dare to go in his struggle to know’. It was also stated that ‘it is necessary to manifest the greatest possible gratitude to the thousands of doctors and researchers all over the world who, with great generosity and

(3)

80 I. Carrasco de Paula

professionalism, dedicate themselves daily with all their strength to the service of the suffering and to the curing of illnesses’.

Ever since medicine, like other natural sciences, adopted rational models of knowledge a century ago, it has progressively made it easier to understand the aetiological, physiopathological and therapeutic foundations of health and infirmity.

Today, the question of ethical research in any field, as well as that of stem cells, must make two things clear: (i) no one can question the legitimacy or the rigour of a methodology whose primary purpose is to acquire knowledge about ourselves and about the world that surrounds us;

(ii) no one may feel him- or herself justified in assuming an attitude of distrust towards researchers for the errors committed in the past, even if they have been many and serious. Research in the biomedical and experimental field that presupposes reasonable and controlled risks for the subjects of study is a conditio sine qua non for present advances and above all for a better future.

From an epistemological point of view, research is connatural with the medical profession, which contemporarily presents to itself as knowledge (scire per causas) and as technique (ars bene agendi). Were this not the case, then it could not truly be orientated towards the good of the person and would therefore lose all credibility.

With experimentation the ethical question presents itself on three levels: (i) the choice of goals, (ii) the selection and use of appropriate means for research, and (iii) the eventual use of that will be made of the new discoveries.

THE CHOICE OF GOALS

Here we might consider the enormous sums of human and financial resources being invested in the prevention and care of AIDS. This appears ethically justifiable by the devastating effects of this illness on individual well-being and social relations, without forgetting how this disease weighs upon public health care. In a parallel case, the therapeutic prospects looked for in research on adult stem cells have aroused and justified research in this area, even though they are prospects that in large measure have yet to materialize. Seen in this way, using a more journalistic lingo, we could say ‘yes, ethics unconditionally blesses research on adult stem cells’.

THE SELECTION AND USE OF APPROPRIATE MEANS FOR RESEARCH

If we base ourselves on what is reported in international literature, it does not seem that in this area there is much to say. Perhaps simply to underline the importance of the norms of good medical practice; for instance, in the collection and preservation of cells taken from the umbilical cord, in the necessary precaution required when passing an experimental model valid for animals to one valid for humans, in the enlistment of experimental subjects and such complexity.

There is a further question of great importance. Especially within our polemical environment, it is important to avoid creating false hopes and expectations by magnifying or instrumentalizing partial results that are achieved. We are obliged to limit ourselves scrupulously to the truth of ascertained facts and to not publish them in the public domain before they have been confirmed by other colleagues. To put it in an extreme way, this prudence should prevail even if we think ourselves at risk of losing a Nobel nomination!

(4)

THE EVENTUAL USE THAT WILL BE MADE OF THE NEW DISCOVERIES

This area requires a great degree of inflexibility, this is not merely because we must avoid deplorable abuses later on, but because passage from the laboratory to the clinic must necessarily pass through experimentation on human subjects. This point is all the more pressing if we keep in mind that the most promising area for this line of investigation is degenerative pathologies.

However, while it is true that certain ethical risks do exist, we must also recall that excellent experimental guidelines are available, that make experimentation reasonably secure. It is enough to apply them strictly.

There is a fairly unanimous consensus that since biomedicine is concerned with both knowing and acting well in relation to the overall well-being of the person, it requires an ethical approach that is more rigorous and exact than that required of disciplines that have to do with the natural world or with things.

ANTHROPOLOGICAL AND EPISTEMOLOGICAL CONCERNS

As a result of what we have said so far, we must now treat certain questions that found our ethical discourse, questions that arise from the dual nature of biomedicine. This dual nature refers simply to the fact that biomedicine bears within itself a vocation to know and to act well. This dual nature, however, presents us with two problems: the first is anthropological; the second, epistemological. This first problem derives from a possible conflict between two innate tendencies within the human person: the desire to know and the desire to dominate²; the second presents itself as a possible conflict between a logic of knowing and a logic of doing, with the possibility of one overwhelming the other.

At the origin of every investigation there is the desire to know. This is a typical characteristic of Homo sapiens. As with all innate drives, this desire can be aroused by simple experiences of curiosity, or by experiences that are much more grand and complex such as the consideration of the mystery of the cosmos or of the human being itself as he is revealed is the subtle complexity of his spirit or in the extraordinary structure and dynamism of his body. Aristotle wrote that the desire to know is one of the most potent stimuli of the human spirit. But we must be cautious to not confuse the eventual results of this desire – a structured collection of acquired information – with that of a virtue. Knowledge as an end in itself does not make a person virtuous; rather, it is the way in which that knowledge is acquired and the ends to which it is ordered that gives that knowledge a definitive ethical value. History shows that research is not born simply from the desire to know, but also from a will to control, to dominate; I do not intend to denigrate this will, which, in itself, is more than legitimate.

Nevertheless, if knowing cannot be an end in itself, even less can the will to dominate aspire to such a status. To exercise power through the modification, transformation, and manipulation of something can be a very enticing experience that easily lends itself to a distorted, self- interested use. Knowledge communicates itself, but not so with power. If the will to dominate prevails over the will to know, even an activity as noble as medical research is transformed into a competitive arena where, sooner or later, inappropriate methods will be introduced so long as one is able to win. We must have the courage to recognize that globalization within the world of research is not leading us to a wider sharing and participation in new findings and knowledge,

(5)

and that if we do not remedy this situation, we will find ourselves hurried towards a despotic hegemony of a few who wield immense economic resources and a long list of patents.

Modernity has not been sufficiently aware of these issues when it sought to construct a new culture solely on the basis of knowing, a knowing understood as the evident vanquisher of ignorance, superstition, taboos, and irrational, ancestral fears. It is to this founding vision that a so-called freedom of research so often appeals, a freedom understood as a complete lack of any controls or obligations. And while we must admit that research must not be conditioned by extraneous powers – politicians, ideologues, businessmen, moralists and more – we must also note that a unilateral insistence on this point brings with it rejection of any social, cultural, or political context. Such decontextualization seems to suggest a corporate attitude that is not entirely rational and is even dangerous. Why? Because no human activity can be disconnected from the person. Indeed, research will not succeed in presenting itself as a value if, in its logic and as a necessary price of its execution, it foresees or tolerates serious harm for the person in his or her integrity or in his or her dignity. This affirmation is ultimately nothing more than the expression of a self-evident ethical principle: knowing and acting well in biomedicine are inextricably orientated towards the health and well-being of the person. This person, then, is an inviolable limit for the person as such.

FROM A LOGIC OF KNOWING AND A LOGIC OF DOING TO THE RISK–BENEFIT DILEMMA

Let us now return to the epistemological question mentioned earlier and the dual nature of biomedical research. As stated above, this research seeks both to know and to act well. As such, it is an endeavour in which a speculative reason orientated towards the truth and a practical reason orientated towards practice are simultaneously at work. What this implies is that there is an inter- action between two ways of reasoning that pursue diverse objectives and apply diverse rules, but must nevertheless proceed harmoniously. The technician is not interested in the truth of a thing, but that it works. The scientist, however, is attracted by the truth of a thing, even if it does not

‘work’ in this technical sense. Scientific reason responds to the logic of experimentally verifiable truth, while technological reason responds to a logic of efficiency or benefits. These two modes of reason, then, present evident limitations when they take as their object of investigation, the human person. The human being is much more than what can be verified according to the

‘sacrosanct’ rules of the scientific method. This is even more the case if we consider the criterion of productivity, something that serves us nicely when we are dealing with things, but is enormously problematic if we apply it to subjects who are much more than simple productive agents. The true measure of the person is dignity. To apply a methodology to him or her only because it is profitable, without taking into account any possible impact it might have on that dignity is unjustifiable.

A respect for the life, integrity, and intrinsic value of the human person has been one of the cardinal principles recognized by research ethics and, for this reason, a motif for pride in the history of medical research. The exceptions are precisely that, exceptions. With regard to biomedical research on humans, there has always been an awareness that alongside hoped-for benefits, there existed a certain risk for the subject’s physical and psychic integrity and this has contributed to maintaining a high level of ethical sensibility and, in practice, has contributed to the refinement of research protocols. In the past, episodes of self-experimentation showed how researchers, fearful of unforeseeable damage to their patients, preferred to expose themselves to such risks in order to confirm their scientific intuition.

(6)

Nevertheless, today we can no longer take for granted that the risk–benefit dilemma is a principle ethical question. In other words, in the particular area of adult stem cells our moral attention cannot be reduced to a cost–benefit analysis. The situation is more complex. We have the overlapping of various conflicting interests: good of the subject versus scientific utility; profit versus complexities of research; freedom versus ethical and juridical restraints; public versus private; individual versus collectivity; and more. For instance, those who are involved in the field know that priorities in planning and management of research are not dictated by the objective seriousness of an illness, but rather by the potential economic benefits represented by those who are affected by it. The ethics of the researcher must keep such considerations in mind since they bear directly upon his or her own professional survival.

FOUR PRINCIPLES FOR RESEARCH

In conclusion, there are a few broad principles that, on a general level, ought to guarantee humane methods in research on humans. These principles could be formulated in many ways, but it is preferable to do so in personalistic terms.³

1 Personalist Principle. This affirms that a human being is that type of subject that cannot be

‘objectified’, or, even less, used as a means or instrument to arrive at a further end. A human being is a person, and a person cannot be possessed by anyone, but only by him- or herself.

The patient, whether he or she be sick or healthy, must always be the end of any medical intervention. Equally, any research ethically justifies itself to the extent that it is orientated towards the good of every individual who participates in it.

2 Prevalence Principle. The integral good of the subject – whether ill or healthy – precedes and conditions any other collective good, be it social, scientific, political, or religious. The life and integrity of the subject who participates in an experiment cannot be endangered deliberately, not even if there is a possibility of obtaining certain results that would be of great benefit to all of humanity.

3 Principle of Consent. The principles for enrolling anyone in a research programme must be preceded by and accompanied with sufficient information such that the knowing and free consent of every participant is possible. This is an essential principle that is clearly personalistic, and is already to be found in the Nuremberg Code. To not respect this requirement would imply treading upon the sovereignty of the individual, his or her inalienable right to act as the master of him- or herself.⁴

4 Principle of Responsibility and Transparency. This is the principle that directly appeals to the conscience of the researcher. It requires not only careful planning of the protocol and a respect for the universally recognized rules, but also complete transparency regarding the real goals of the research, as well as a declaration of independence and immunity from any unfitting request, and not only those that could be made by the sponsor of the investigation. The researcher must never hide the interests of third parties. He or she enjoys many rights but also assumes just as many obligations, and all rights and all obligations must be respected.

Nevertheless, the principle commitment remains, that of the of the subjects who collaborate and voluntarily put themselves at risk.

It is glaringly obvious that all four of these principles express awareness of the intrinsic value of every single human being. The Ethical Code of the Order of Italian Doctors admits this principal when it prescribes that ‘biomedical research and experimentation on humans must always be inspired by the undeniable principle of inviolability, and of the psycho-physical

(7)

integrity of human life’. Nothing can come before the person. What is more, everything must be submitted to him or her. It is for this reason that biomedical science, having to occupy itself directly with weak and diseased persons has always employed prudential reasoning that is more rigorous and attentive than that required by other scientific areas. We can only hope that this common history will also be our common future.

NOTES

1This opinion clearly emerges also looking at some statements previously made by other National Commissions and Associations. See, for example, National Bioethics Advisory Commission (1999), and American Association for the Advancement of Science (AAAS) and Institute for Civil Society (ICS) (1999).

2“All men by nature desire to know.” Aristotle, Metaphysics I, 1, 980a21.

3The principles that are proposed here are at least implicitly present in the three documents cited earlier – Wma, Belmont, Cioms.

4Certainly, the informed consent issue takes up a central role in ethics research and it needs to be considered in a specific way when it comes to research involving the several types of adult stem cells, from the donation to the use.

See, as an example, Horowitz and Confer (2005).

REFERENCES

Chapman AR, Frankel MS, Garfinkel MS (1999) Stem Cell Research and Applications: Monitoring the Frontiers of Biomedical Research. Washington, DC: AAAS.

Cioms (2003) International Ethical Guidelines for Biomedical Research Involving Human Subjects. Dawson L, et al. (2003) Safety issues in cell-based intervention trials. Fertility and Sterility80, 1077–1085.

Federazione Nazionale degli Ordini dei Medici Chururghi e degli Odontoiatri (2006) Codice Deontologico. FNOMCeO, 46.

Horowitz MM, Confer DL (2005) Evaluation of Hematopoietic Stem Cell Donors, Hematology Am Soc Hematol Educ Program1, 469–475.

Hwang WS, Roh SI, Lee BC et al. (2004) Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science303, 1669–1674. Epub 2004 Feb. 12. Retraction in: Kennedy D (2006). Science311, 355.

Erratum in: (2005) Science310, 1769.

Hwang WS, Roh SI, Lee BC et al. (2005) Patient-specific embryonic stem cells derived from human Sent blastocyst.

Science308, 1777–1783. Epub 2004 May. 19. Retraction in Kennedy D (2006) Science311, 355. Erratum in: (2005) Science310, 1769.

Lersch P (1968) La estructura de la personalidad. Barcelona : Scientia.

Meldolesi A (2006) Il Riformista 13.9.2006 : 3.

National Bioethics Advisory Commission (1999) Ethical Issues in Human Stem Cell Research. Rockville, MD: NBAC.

National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research (1979), The Belmont Report Ethical Principles and Guidelines for the Protection of Human Subjects of Research.

Pontifical Academy for Life (2004) Comunicato finale su “Etica della ricerca biomedical. Per una visione cristia”, in Vial Correa JD, Sgreccia E (eds.), Atti della IX Assemblea della PAV (24–26 febbraio 2003). Cittá del Vaticano:

Libreria Editrice Vaticana.

UK Department of Health (2000) Stem Cell Research: Medical Progress with Responsibility, in http://www.dh.gov.uk/

prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_4065085.pdf.

World Medical Association (1964–2000) Declaration of Helsinki (Ethical Principles for Medical Research Involving Human Subjects).