All theory, dear friend, is gray, but the golden tree of life springs ever green.
Johann Wolfgang Goethe
Motto
“omnis cellula e(x) cellula” (“Every cell is derived only from a preexisting cell”).
Rudolf Virchow
Introduction
The objective of tissue engineering is to create or recreate living body parts or
organs that will fully integrate with the recipient's body. The advent of tissue engineering
as a new field of research with a high potential towards the clinical care of patients
from bench to bedside has involved numerous different scientists in various fields
of cellular and molecular medicine, material research, engineering, physics, chemistry,
computational research and allied disciplines [1–5]. Due to a potentially enormous
impact on the health of our society – that is as a whole continuously becoming older
– tissue-engineered solutions to circumvent natural degenerative processes have become
of great interest. They may aid to maintain a high quality of life in the elderly.
This issue has been widely acknowledged, but has created numerous debates also. Many
of the techniques applied in research and in practical applications of nowadays tissue
engineering approaches [3] with direct or indirect relation to the care of human beings
seem to be straight forward and do not offer a sufficient potential for ethical debates
[6–8].
Nevertheless, innovative medical research and new technologies always raise ethical
and policy concerns. In biomedical research, these issues include the ethical conduct
of basic and clinical research as well as the equitable distribution of new therapies
[7]. While questions of intellectual property have been widely published in this context,
there is limited literature on ethics in cellular and molecular medicine and for the
field of tissue engineering [6, 9, 10].
With respect to the ethics of tissue engineering, Derksen and Horstman [11] have suggested
that one can roughly distinguish two perspectives. On the one hand, this technology
could be considered morally good because tissue engineering is ‘copying nature’. On
the other hand, tissue engineering could be considered morally dangerous because it
defies nature: bodies constructed in the laboratory are seen as unnatural. The tremendous
public attraction that the implantation of cultured chondrocytes in the form of a
human ear cartilage (which was implanted under the skin of a nude mouse and that was
eventually called auriculosaurus [1]) gained rapidly all over the world is a vivid
testimony to the perception of people when confronted with such spectacular and obvious
research efforts. Based on the discussion of the engineering of heart valves, authors
have proposed that the ethics of tissue engineering should be framed not in terms
of ‘natural’ or ‘unnatural’ but in terms of ‘good embodied life’ and ‘lived integrity’[11].
Historical aspects
While research with stem cells from the very beginning has evoked many controversial
debates worldwide not only within the recent years (especially when those cells are
derived from embryos), there is comparatively little public debate on ethical issues
in cellular and molecular research, when it is not directly correlated to clinical
applications.
A survey of the literature reveals that the term ‘ethics' in cellular and molecular
medicine is not covered in a database such as PubMed, while the term ethics and cellular
medicine offers 608 papers published between 1967 and 2008. Decades ago, early papers
such as Vogels report on: ‘Can we count on the possibility of manipulation in the
field of human genetics? May we and are we permitted to breed people?’[12] or Hirschhorn's
comment on ‘re-doing man’[13] were discussing the principle question and the fear
of any manipulation of the human genetic information at all. At that time even reproductive
medicine was in its childhood as Ramsey's considerations on the medical ethics of
in vitro fertilization show [14, 15]. However, it has to be remembered that at the
same time the first successful clinical heart transplantation was made public in 1967.
The public confusion of transplanting organs from one human being into another – especially
the human heart – was considerable. It is widely recognized that despite better knowing
about the function of the brain even nowadays feelings are literally more associated
with the heart than the brain. The famous quotation of Antoine De Saint Exupery ‘It
is only with the heart that one can see rightly; what is essential is invisible to
the eye’ may serve as a vivid example of this phenomenon. Looking back into this field
of scientific publication nowadays such questions seem to have been more or less answered
over the time, although it is clear that they cannot be definitely solved for every
opinion and for all times.
For instance, the field of in vitro fertilization to overcome human infertility has
become a clinical routine worldwide and is currently being financed by many social
security systems in developed countries.
Genetic manipulation of the human genome seems nothing spectacular today. The human
genome has been decoded in many aspects and DNA fingerprint tests are popular practice
in many fields of our daily life. This demonstrates that parallel to any progress
in cellular and molecular research the debates also are subject to changing perceptions
over time. Issues that have been extremely controversial decades ago have become less
critical in the public perception today and new challenges arise with the ever-progressing
efforts in cellular and molecular research. Ethically of course the acclimatization
to habits that have become daily practice does not mean that they are ethically unobjectionable
by themselves. However, an ethical reflection should not be addicted to fashions and
should keep in thinking critically.
Nevertheless, due to the translational character of cellular and molecular medicine
[16–19] many critical questions can arise from this field of research that may pose
ethical problems.
Stem cell research in cellular and molecular medicine and tissue engineering
It is always difficult to estimate the true benefits to individuals and to society
that are gained by the introduction of new drugs or medical technologies. As an example
it may be recognized that the introduction of antibiotics and vaccines has enormously
increased our life spans and improved the health conditions of people all over the
world. Nevertheless still major illnesses such as cancer, diabetes mellitus, Alzheimer's
disease, heart disease are ongoing and challenging conditions, which desire continuous
research on a cellular and molecular basis. Research in human developmental biology
has led to the discovery of human stem cells that have been described for many decades
and that have been subject to multiple investigations. Human stem cells are precursor
cells that can give rise to multiple tissue types, including embryonic stem (ES) cells,
embryonic germ (EG) cells, and adult stem cells. The discovery of techniques for the
in vitro culture of stem cells has provided unprecedented opportunities for studying
and understanding more about human biology [20]. In human beings, transplants of haematopoietic
stem cells following chemotherapeutic treatments for cancer, for example, have been
routinely administered for many years now.
It has been proposed by scientific communities that persons considering donating their
excess embryos for research purposes should be afforded the highest standards of protection
for the informed consent and voluntariness of their decision [21]. But if the human
embryo is seen as a human being – and there are a lot of reasons to do this – there
remains the question why medicine does not prevent supernumary embryos at all from
the ethicist's standpoint. In view of the moral concerns surrounding the uses of embryonic
and foetal tissue voiced by a segment of the American population, it has been proposed
by the AAAS (American Association for the Advancement of Science, Science magazine)
that strengthening federally and privately funded research into alternative sources
and/or methods for the derivation of stem cells, including further initiatives on
adult stem cells, should be encouraged [21]. According to their statements human stem
cell research can be conducted in a fully ethical manner, but it is considered to
be true that the extraction of embryonic stem cells from the inner mass of blastocysts
raises ethical questions for all those who consider the intentional loss of embryonic
life by intentional means to be morally wrong. Also, the derivation of embryonic germ
cells from the gonadal tissue of aborted foetuses is problematic for those who oppose
abortion [21]. From an ethical point of view there are enough objections at the moment
to the process of deriving stem cells to consider AAAS recommending against its public
funding.
In contrast, adult stem cell research is more broadly acceptable to the population.
Generally there seems to be no discussion in the media about the so-called adult stem
cells, since the potential benefit appears to be very high and the utilization of
the patient's own cells poses no serious ethical conflict.
Although it is impossible to predict the potential outcome, momentarily worldwide
many experiments carried out that aim towards the determination of the mechanisms
underlying the conversion of a single, undifferentiated cell into the different cells
comprising the tissues and organs and of the human body. A high potential of therapeutic
effects has been claimed for this field of research, but is still not sufficiently
understood or proven. Given the widely unsolved ethical, legal, religious and policy
questions, the potential use of stem cells to generate replacement human tissues and,
perhaps, whole human organs, remains a subject of ongoing public debate. For the majority
of problems arising from embryonal stem cell research, we want to refer to the pertinent
literature that is ample and multidimensional [21–27].
There is already preliminary existing evidence from animal studies that stem cells
could potentially differentiate into cells of choice, and it is hoped that these cells
then would act properly in their transplanted environment. Further, somewhat cruder
experiments (e.g. the transplantation of foetal tissue into the brains of Parkinson's
patients) could indicate that the expectation that stem cell therapies could possibly
provide robust treatments for many human diseases may be a reasonable one, although
this has not been definitely proven today. It is only through controlled scientific
research that the true promise will be understood.
Recent publications on the re-programming of adult cells into embryonal-like cells
(gPS, “germline derived pluripotent stem cells”) that behave similar to stem cells
[28] may well bridge the gap between current controversial stand points. The different
ways to reprogram adult cells might offer the possibility to produce customized stem
cells with the genetic material of the individual patient [27]. This method would
not need the harvest of stem cells from embryos that then necessarily have to be destroyed
– an act that is forbidden by law in many countries, such as Germany for instance.
For the moment, in tissue engineering the application of embryonic stem cells is not
a commonly accepted practice, while human adult stem cells are the object of frequent
investigations [29, 30].
Ethical aspects of mixing human and animal tissues
Many experiments in various fields of research in cellular and molecular medicine
are performed worldwide on a daily routine without a thorough discussion of ethical
implications. In tissue engineering, it is common practice to seed human cells on
bio-materials. Cultured or non-cultured human cells are frequently seeded onto experimental
animals [4, 31–34]. Ethically this creates a combined human-animal being, also called
chimera. Such chimeras are commonly perceived as individuals, organs, or parts of
an organism consisting of tissues of diverse genetic constitution [35]. However, it
remains controversial how much diverse genetic constitution is needed to be allowed
to call it chimera. The question has been brought up by the ethical committee of first
author's former University how it has to be considered if chimeric animals with incorporated
human cells are still alive and subject to experimental studies while the original
cell donor may have deceased due to any reason. Although this question seems to be
artificial there is no clear answer how such a chimera has to be considered, since
it carries tissues or stromal cells from a former human being and may potentially
reproduce itself and theoretically propagate the parts of the initial cell donator.
In the current literature, this issue has not been addressed so far [36].
With regard to tissue engineering such models have been and are used frequently for
experimental purposes and have been reviewed by numerous ethical committees to be
unproblematic. This holds true as long as confidentiality and patient privacy is secured
when working with tissues or cells in such models and ensuring appropriate use of
the material for scientific reasons only.
If stem cells are applied in this way, a plethora of ethical questions arise immediately.
Karpowicz et al.[22] addressed the question if it is ethical to transplant human stem
cells into non-human embryos. They postulated that in the future human or non-human
stem cell chimeras will be increasingly applied to study human cells in developing
non-human animals. Such experiments raise a number of issues that may create further
controversy in the stem cell field. These authors tried to outline the scientific
value and ethical ramifications of such studies. In addition, they try to give suggestions
how such experiments may be conducted ethically. It is proposed that the transplantation
of human stem cells into prenatal non-human animals would allow researchers to study
human cell development without directly using human embryos. Intrinsic value and animal
integrity are two key concepts in the debate on the ethics of the genetic engineering
of laboratory animals. These concepts have, on the one hand, a theoretical origin
and are, on the other hand, based on the moral beliefs of people not directly involved
in the genetic modification of animals [35]. In a study comparing the moral experiences
and opinions of people directly involved in the creation or use of transgenic laboratory
animals to people not directly involved in the genetic modification of animals it
has been strongly suggested that these concepts would not have to be adjusted or extended
in the light of the moral experiences and opinions from practice [35]. Nevertheless
from the ethicist's point of view it remains a question whether such chimeric organisms
have to be created at all. Even the aim to create chimeras could theoretically be
seen as an ethical assault.
In order to regenerate dysfunctional human tissues, the observation of large-scale
human cell actions in comparative animal models is deemed necessary to advance future
research. This may help to investigate human stem cell plasticity. Because embryonic
stem cell transplants have been reported to form tumours in postnatal rats [24], researchers
have successfully begun to assay human embryonic stem cell function using prenatal
chimeras [37]. As an example, retinal stem cells (RSC) found in the adult mammalian
eye [38] form an adult somatic cell population that represents a potentially valuable
therapeutic tool. RSC transplants are believed to eventually restore sight, and perhaps
treat otherwise intractable diseases, such as macular degeneration and retinitis pigmentosa.
Understanding the specification of retinal fate during human development, from embryonic
cell to early neuroec-toderm and later retinal lineages, is useful and necessary before
replacing large areas of the human eye becomes possible [22, 23].
According to Karpowicz et al.[22] for molecular biologists, chimeric DNA refers to
sequences derived from two sources and combined into one; for cell biologists, there
are nucleocytoplasmic hybrids involving somatic cell nuclear transfers (cloning) within
or between species; for embryologists, chimeras are prenatal combinations of cells
derived from different zygotes, either intraspecies or interspecies; for geneticists,
there are interspecies genetic hybrids such as the mule; and finally, there are interspecies
xenografts of tissue into postnatal hosts. When we use the term ‘chimera’ here, we
mean transplants of human stem cells into prenatal non-human animals, although more
broadly speaking, any of the above combinations can use this analysis [22, 23].
It has been formulated that two hypothetical human/non-human RSC chimera experiments
could be undertaken: (i) transplants of adult human RSCs into early embryonic mice
at the blastocyst stage, or (ii) transplants of adult human RSCs into the eye and
brain of foetal monkeys. The first of these would be a preanatomic chimera assay,
a test of whether human cells can participate in the morphogenesis of non-retinal
mouse tissues. The second would be a late chimera assay, a restricted and postanatomic
analysis of human RSC contributions to preformed tissue types [22]. These authors
have referred to the Aristotelian teleological philosophy, which maintains that all
living things have an inner tendency to reach their appropriate ends or goals, and
that their biological functions enable them to achieve this. Contemporary proponents
of this approach argue that although the proper ends of humans may differ radically
from that of mice or monkeys, the intentional alignment of each with their respective
ends is a moral good. According to this view, it would be wrong to tamper with nature
in ways that prevent living beings from achieving their natural ends or pursuing their
natural way of flourishing [39, 40]. If the merger of human and non-human tissues
within chimeras frustrates the ends of the beings involved, it would be unnatural
and therefore wrong.
Interestingly it can also be objected that, in principle, teleological guidance may
also leave us to speculate endlessly about the ‘natural’ purposes of virtually all
living things. On the other hand, it can offer only few clues as to what decisions
are right [22]. Thus purely teleological arguments do not give a clear-cut answer
to the question if it is ethically right to prohibit or to support the making of chimeras
as ethically acceptable with any assurance.
Accordingly, there has been reasonable dispute in the past about limits of medical
actions when we do interfere with the dysfunctioning human organism by surgery, medical
interventions and transplantations for instance. Therefore, it cannot be generally
regarded to be wrong to intervene into these functions or keep them from reaching
certain ends. The context in which such interventions are carried out, not just the
biological function of the organism and its components, has import on assessing whether
that intervention is considered right or wrong [22].
Although it is doubtful, for example, whether human functions could ever arise in
an embryonic mouse host, the entire prenatal development time of which is a mere fifteenth
of a human being's, Karpowicz and co-authors have proposed some limits to chimeric
experiments [22]. They suggested that the number of human cells transferred should
be limited, that the choice of host animals for early blastocyst chimeras be deliberate,
and that dissociation of human cells, rather than postanatomical tissue transplants
should be applied for later embryonic chimeras. According to these suggestions, fewer
human cells, in principle, would reduce the degree of ‘humanization’ in early chimeric
experiments, as the host cells would outnumber the human cells. To ensure any potential
psychological impact of neuronal alterations in chimeric organisms, the use of non-human
animals that are closely functionally or morphologically related to humans should
be only attempted during later embryonic development, when the host's unique neural
networks have already formed to the point that human incursion could not occur. Dissociation
of human stem cell xenografts into early or later embryonic hosts could be regulated
if necessary, to guard against the possibility of human characteristic pattern formation
and development [22].
The mixing of genes, human and animal cells or tissues from humans with those of animals
has been studied for many years. In reality, techniques involving human-animal combinations
have been used in the laboratories for decades. For instance, the utilization of animal
cells (irradiated mouse fibroblasts) as carriers for the culture of human keratinocytes
has been common practice for decades by now. The transplantation of cultured human
keratinocytes propagated on animal cell feeder layers has also been published to be
life saving in extensively burned patients [41–46]. Serum-free culture techniques
and utilization of biomaterials have been introduced to circumvent animal influences
on cultured human cells [43, 44, 46]. Suggestions that animal eggs should, for example,
be used to create hybrid human-animal embryos have elicited some strong reactions
in the international news. Guidelines and regulations have to be discussed freely
in the scientific community and should be brought on their way with the help of ethicists.
Gene therapy in cell science and tissue engineering
It is quite obvious that the potential market for gene-specific pharmaceuticals is
huge. Hence, research in cellular and molecular medicine involving alteration of the
genome is one of the cornerstones of scientific progress. Ethically, the idea of gene
therapy is to introduce or to alter genetic material to compensate for a genetic mistake
that causes disease. By doing so, it is hoped that one day by means of gene therapy
diseases can be treated or cured for which up to now no other effective treatments
are available.
However, many unique technical and ethical considerations have been raised by this
comparatively new form of treatment [47]. Consecutively several levels of regulatory
committees have been established to review each gene therapy clinical trial prior
to its initiation in human subjects. Ethical considerations include the decision which
diseases and/or traits are eligible for gene therapy research, how gene therapy can
be safely tested and evaluated in humans, which cell types should be used, what components
are necessary for informed consent.
Several ethicists have argued that genes and genetically modified organisms should
be considered part of the common heritage of all people. Other thinkers and advocates
have raised equity issues about the role of patents in impeding development and access
to beneficial technologies. The World Health Organization has reminded member states
that ‘justice demands equitable access to genetic services’. WHO has also stated that
‘Genetic services for the prevention, diagnosis and treatment of disease should be
available to all, without regard to ability to pay, and should be provided first to
those whose needs are greatest.’[48]
While the fascination of genetic information has rapidly come to be appreciated by
societies at large, it is also narrowly perceived that only analyses involving nucleic
acids (i.e. DNA, RNA) yield genetic information. The fact that superficially ‘non-genetic’
analyses, e.g. of proteins, hormones, metabolites and even radiologic imaging may,
in certain situations, be equally informative as genotyping appears to have escaped
many [49]. This may explain the individual tendency to handle what is wrongly perceived
to be ‘non-genetic’ medical information with much less care and attention to bioethics
concerns than overtly ‘genetic’ information. Given the relatively large corpus of
medical information not derived from DNA or RNA analysis, this issue is by far more
complex and continues to challenge items of privacy in cell and tissue research with
regard to individual and epidemiological data acquired from such research [50].
Although a considerable discussion about gene therapy has been reported long before
the first approved human gene therapy trial in 1990 was initiated on severe combined
immune deficiency patients the debate remains controversial [26, 51–56].
Internationally, numerous policy statements on human genetic intervention have been
published, all of which support the moral legitimacy of somatic-cell gene therapy
for the cure of disease. The debate over the ethical issues related to somatic-cell
gene therapy has evolved over a 10-year period [56]. When lay perceptions about gene-based
therapy are explored there are differences in the perception in various countries
and societies. A survey in Iceland, following an intensive public debate on the consequences
of the Human Genome Project over the next 40 years, revealed that the lay public was
relatively optimistic with regard to the future of drugs and gene-based therapy. Reasons
for this optimism were considered to be found in a basic trust and belief in the welfare
state and the health system of this country. These results are not consistent with
studies carried out in other countries where the public appears to be focused on the
negative effects of genetic research and the threats to privacy [55].
Since the hallmark of ethical medical research is informed consent it has been considered
to be important that voluntary consent be imperative in this context. The dilemma
can arise when gene therapy may be the only possible treatment, or the treatment of
last resort, for some individuals. In such cases, it becomes questionable whether
the patient can truly be said to make a voluntary decision to participate in the trial.
These criteria do not apply when genetic alterations are performed in a strictly experimental
laboratory setting and when there is no application to human beings [50].
Richter and Bacchetta [47] have proposed a three-dimensional framework for the ethical
debate of gene therapy where they added the genomic type (nDNA versus mtDNA) as a
third dimension to be considered beside the paradigmatic dimensions of target cell
(somatic versus germ-line) and purpose (therapeutic versus enhancement). According
to their considerations somatic gene therapy can be viewed today as generally accepted.
They conclude that many of the supposed ethical questions of somatic gene therapy
today were not new at all, but should be considered as rather well-known issues of
research ethics.
Tissue banking for cellular and molecular science and tissue engineering
Although tissue banking in some form or another has been practised for well over a
century, it is only in the last decade that tissue banking has come into the public
limelight with the recent surge of interest in the new life sciences, and in particular,
in the fields of human genetics and genomic research. Tissue banking as a means to
provide material for medical research is by far not a new phenomenon. The German pathologist
Rudolf Virchow [58] for instance initiated the first known repository in 1847. He
eventually amassed more than 23,000 human tissue specimens. Ever since that time a
large number of (mainly pathology or dermatology) departments in academic medical
institutions and hospitals around the world is housing temporary or permanent collections
of preserved human tissues and or organs. In his ground-breaking book ‘Die Cellularpathologie
in ihrer Begrundung auf physiologische und pathologische Gewebelehre…’ (‘Cellular
Pathology in its foundation on physiological and pathological tissue science’) (see
Fig. 1), published in 1858, he set a cornerstone of modern medicine and biology based
upon physiological and pathological histology with his postulate: ‘omnis celula e(x)
cellula’ (‘Every cell is derived only from a preexisting cell’. He originated the
idea that each cell in each living organism, both plant and animal, originates from
another cell and that the origin of disease can only be located in the cell.
Fig 1
Photograph of infamous mouse with the human ear, depicting new tissue-engineered cartilage
generated in the shape of a human ear (C. A. Vacanti. Ref. [1]).
Essentially, it has to be reminded that Rudolf Virchow, with his book, changed abruptly
the scientific thoughts and conceptions in the whole field of medicine and biology
at his time.
Presumably, for the father (or founder) of pathology the (human) body is like a ‘cell
state’ in which each cell acts as a ‘citizen’! Accordingly, this could metaphorically
be called a ‘cell democracy’. Virchow's assemblage of tissues was an invaluable tool
for his research efforts.
There is no doubt that tissue samples in such collections that were originally sampled
for patient-related diagnostic procedures now serve as an invaluable tool and resource
for research purposes. Concurrent with the enormous advancement of genomic research
it now seems very realistic that large-scale genotyping and the investigation of the
human genome with new techniques for high capacity molecular characterization will
yield a plethora of discoveries to both academia and industry. For instance, vital
epidemiological information about the pattern and incidence of occurrence of various
forms of diseases such as cancers has been (and continues to be) gained from human
tissue research, and through the analysis of such information, important discoveries
about the prevention, control and treatment of such diseases have been made for the
benefit of humankind [49].
Currently, there are no clear guidelines as to whether referring or sending physicians
have a right to demand the return of these tissue samples. At the Singapore University,
it has been suggested that if non-institutional collections have to be made for any
reason (for example, collections of a specific kind of tissue pursuant to a specific
research project), such collections should only be assembled on the understanding
that the human tissues collected will eventually be consolidated with the larger collections
of institutions (for example, by a hospital, a university or a research institution)
[49]. Institutional human tissue holdings should then set up a current database of
all human tissue holdings within that institution. Such a database could be part of
the institution's database of research projects, with information fields such as the
research area, disease, human tissue collected, where they are stored within the institution,
and the units and persons responsible for these human tissues. This is recommended
because the size of holdings is also an important benefit of consolidation: a large-scale
collection is believed to be more useful (particularly for population studies) than
a small and limited collection [49].
Ethically one can discern the collection of tissues or cells in such banks into therapeutic/diagnostic
tissue collections (samples are kept only as a part of the medical records of patients
and are not applied towards research purposes) from the collection of cells and tissue
for research purposes. If the latter aspect is pursued in combination with diagnostic/therapeutic
sampling, adequate informed consent of the individual has to be obtained to fulfil
ethical requirements.
There has also been a parallel trend towards the establishment of collections of human
tissue in which the biological material remains viable or potentially viable, at least
in some respects, at the cellular level. For instance, human tissue samples may be
flash-frozen, and/or living cell lines may be propagated on culture media. This greatly
increases the value of the samples for many lines of research. Institutions such as
the Singapore University have taken the view that such purposed-assembled research
banks are to be encouraged, provided that all appropriate ethical and legal considerations
and concerns are appropriately met and addressed, as they promote and enhance research,
which offers the promise of immense benefit in the future for humankind.
At the present time, there does not appear to be any uniform approach to the governance
and regulation of tissue banking internationally. The Draft Discussion Document entitled
Data Storage and DNA Banking for Biomedical Research: Informed Consent, Confidentiality,
Quality Issues, Ownership, Return of Benefits: A Professional Perspective issued by
the Public and Professional Policy Committee of the European Society of Human Genetics
as part of the EUROGAPP Project 1999–2000 offers an illuminating survey of the gamut
of existing opinions, legislation, guidelines and other policy statements applied
in or issued by EC institutions, 18 European countries, the United States, and international
organisations. Except in the case of the United States, and possibly France, the majority
of the jurisdictions surveyed are notable more for the absence of specific agreed
national guidelines or legislation than by the presence of such in relation to storage
of data derived from human tissue research and DNA banking. One of the prerequisites
from an ethical standpoint seems to be that informed consent should be obtained from
any potential donor of tissue or cell samples if there is any possibility that donated
tissue samples may in the future be made available for commercial research with consequent
financial benefit or gain to third parties, then this possibility must be made clear
to donors at the very outset even if the arrangement is to be that the donors completely
renounce their rights to any share of these gains or benefits [49].
It can be also recommended that all research using human tissue samples should be
approved by an appropriately constituted research ethics committee or institutional
review board. In addition it should be common sense that researchers and all those
involved in the conduct of tissue banking have an obligation to protect the confidentiality
of the personal information of donors entrusted to them, as well as the privacy of
donors.
Fig 2
With his publication of ‘Die Cellularpathologie in ihrer Begruendung auf physiologische
und pathologische Gewebelehre‘ in 1859, Rudolf Virchow (1821–1902) originated the
idea that each cell in each living organism, both plant and animal, originates from
another cell and that the origin of disease can only be located in the cell. This
book is widely believed to have laid the foundations for cell pathology as a scientific
discipline.
Legal and intellectual property considerations
Ex vivo tissue-engineered products have been around for the last decade and are now
increasingly entering clinical trials. Autonomous decision making on their participation
is believed to be a prerequisite to allow prospective recipients of such tissue-engineered
products to decide upon any legal and ethical aspects of such procedures. Compared
to current practice in cell and tissue transplantation there are new elements in the
transplantation of ex vivo tissue-engineered materials. These can be summarized into
(i) the source and manipulation of the cells in the product, (ii) the implantation
of the product and (iii) the additional risks and benefits due to the construction
of the product and its activity in the body [9].
Thorough informed consent should be reached that takes the specific aspects of tissue
engineering into account. The delicate nature of specific cell types and the various
complexities of the tissue engineering process as well as its implications have to
be made clear. When a clinical trial is conducted with such tissue-engineered products,
any crucial issue, potential benefits and specific and general risks have to be made
clear to the potential recipient according to his capacity to understand the whole
procedure. The assistance of informed third parties has been proposed to help participants
in their decision-making processes [9].
Attempts of governmental regulatory boards such as the European Commission to develop
a directive to regulate all tissue-engineered products in a comprehensive yet flexible
framework have been criticized from an ethical viewpoint [10]. It has been argued
that there are shortcomings to such proposals because of disjunctures at various regulatory
levels and because responsibilities of several authorities have not been clearly established.
The appropriateness of patenting gene patterns, DNA sequences and life forms has been
a source of considerable controversy. Generally before the advent of modern genomic
research, until 1980, life forms were considered to be ‘products of nature’ and ineligible
for patent protection. In the 20 years since the first biotechnology patents were
granted, various critics have claimed that the patenting of living things promotes
a reductionist conception of life that removes any distinction between living and
non-living things. Some scientists and lawyers have questioned whether these patents
promote the future biomedical research [48, 49].
Conclusion
There is no doubt that numerous advancements of science have transformed our lives
in a way that would have been unthinkable of just a century ago. While many aspects
seem to be common sense today, the field of embryonic or adult stem cell research
raises a lot of severe ethical questions. It is unclear at the moment if results of
stem cell research will have a similar effect than other scientific achievements,
but the promise is so great that it seems wise to consider seriously how best to further
such research in a manner that is sensitive to ethical objections. Public perceptions
and conversations and ethical objections about research and use of human stem cells
should be recognized and embedded into an ongoing dialogue. The authors want to bring
to the public awareness that not always a clear-cut separation of the ethical problems
and the pragmatic approach to biomedical decisions – including the field of molecular
and cellular medical interventions – can be easily made.
Similar to others [49] we take the view that the vast majority of scientists and researchers
in cellular and molecular medicine are responsible and are acutely aware of potential
ethical concerns in the work that they do, and in that which they may propose to carry
out. Scientists do not presume to know all the answers and ramifications of basic
research in human cells. Most wish to do what is ethically right. Indeed, many may
be inhibited from participating in some areas of research (which may in fact be entirely
acceptable to the community, and in the public interest) by the lack of clear ethical
direction or agreement on a given point, or by uncertainty generated by controversy
in related areas.
Therefore, it is important to promote continued dialogue among all segments of society
concerning the implications of cellular and molecular research. Ongoing educational
processes fostered by public institutions and supported by researchers that informs
such public dialogue seems desirable. As stated by the AAAS it should be recognized
that science does not exist in isolation from the larger community that feels its
effects, whether perceived as good or bad. The work of scientists is, and should be,
conditioned and directed by consideration of broader human values. This means that
the development of public policy, especially where highly controversial matters are
involved, must take all interested sectors of the public into account. It is only
through broad-based participation that the values of all stakeholders in the research
enterprise can be carefully considered and weighed [21].