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SHS/YES/IBC-21/14/3
Paris, 15 May 2014
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CONCEPT NOTE ON UPDATING THE IBC’S REFLECTION
ON THE HUMAN GENOME AND HUMAN RIGHTS
In response to the rapid advancements in genetics and genomics, and
within the framework of its work programme for 2014-2015, the
International Bioethics Committee (IBC) decided that it is now necessary
to update its reflection on the issue of the human genome and
human rights, building upon the considerable work done on this topic by
the IBC in the past, and in particular, taking into account the Universal
Declaration on the Human Genome and Human Rights (1997), the
International Declaration on Human Genetic Data (2003), and the
Universal Declaration on Bioethics and Human Rights (2005).
This concept note was prepared by a small working group of the
Committee in order to provide a preliminary outline of potential areas of
reflection for this topic. It is important to emphasize that the issues
identified in this concept note are only potential areas of reflection, and
there should be no expectation that they will be covered by a report to be
eventually prepared and adopted by the IBC at a later stage.
As it stands, this concept note does not necessarily represent the final
opinion of the IBC and it is subject to further discussions within the
Committee. This concept note also does not pretend to be exhaustive nor
prescriptive and does not necessarily represent the views of the Member
States of UNESCO.
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I.
INTRODUCTION
1.
In response to the rapid advancements in genetics and genomics, and within the
framework of its work programme for 2014-2015, the International Bioethics Committee (IBC)
decided that it is now necessary to update its reflection on the issue of the human genome
and human rights, building upon the considerable work done on this topic by the IBC in the
past, and in particular, taking into account the Universal Declaration on the Human Genome and
Human Rights (1997), the International Declaration on Human Genetic Data (2003), and the
Universal Declaration on Bioethics and Human Rights (2005).
2.
This concept note was prepared by a small working group of the Committee in order to
provide a preliminary outline of potential areas of reflection for this topic. It is important to
emphasize that the issues identified in this concept note are only potential areas of reflection,
and there should be no expectation that they will be covered by a report to be eventually
prepared and adopted by the IBC at a later stage.
3.
As it stands, this concept note does not necessarily represent the final opinion of the IBC
and it is subject to further discussions within the Committee. This concept note also does not
pretend to be exhaustive nor prescriptive and does not necessarily represent the views of the
Member States of UNESCO.
II.
PURPOSE OF THIS CONCEPT NOTE
4.
The purpose of this concept note is to invite feedback on the potential areas of reflection
identified so far, as well as suggestions on additional issues that could be considered by the
Committee. In particular, the Member States of the Intergovernmental Bioethics Committee
(IGBC) are invited to submit written suggestions on policy-related needs, gaps and interests
concerning this topic, which might be useful for the IBC to strengthen the policy focus of its
report. Members and Associate Members of the United Nations Interagency Committee on
Bioethics (UNIACB) are also invited to submit written suggestions for the IBC’s consideration.
The comments received will be contained in a working document for the 21st Session of the IBC
and the Joint Session of the IBC and the IGBC (UNESCO Headquarters, Paris, September
2014), during which this topic will be discussed by both Committees in more detail.
5.
At this point, the independence of the IBC in taking its own decisions concerning the
eventual direction of its reflection on this topic must be emphasized. Feedback and suggestions
provided at this preliminary stage of the IBC’s reflection will definitely enrich the upcoming
discussion on the topic, but there should be no expectation that these comments are required to
be fully or even partially incorporated by the IBC in its work. Once a draft report on this topic has
been prepared by the IBC, it will be made available for further comments (during the 22nd
Session of the IBC and the 9th Session of the IGBC in 2015), and as per usual practice, the IBC
will take into consideration the feedback received at that stage, especially the opinions of the
IGBC, in finalizing its report.
III.
BACKGROUND
6.
The IBC has performed in-depth analysis of many ethical problems which have arisen
because of the development of medicine. The most important outcomes of this work have been
the three bioethics Declarations – on the Human Genome and Human Rights (1997), on Human
Genetic Data (2003) and on Bioethics and Human Rights (2005); but many other documents
have emerged including the Reports of the IBC on Consent (2008) and on Confidentiality and
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Genetic Data (2000). However, developments in the field of biology and medicine, in particular
genetics, over the last 5 to 10 years have been so rapid that a reflection on some of their ethical
aspects may be worthwhile. Reflection on all such developments will probably not be possible
but some of these are listed below as suggestions for further discussion on the possible
direction(s) of the Committee’s future work on the topic of the human genome and human rights.
In fact, the last 5 years or so have brought new developments which have ethical implications
that the IBC has either not yet addressed, or if it has, such reflection was carried out over 6
years ago.
IV.
POTENTIAL AREAS OF REFLECTION 1
A.
The Human Genome
7.
The human genome comprises 3 billion base pairs, and the idea that sequencing an
individual’s genome would be affordable and possible seemed like a fairy tale even 10 years
ago. The USD$1000 genome sequencing may not quite be here yet, but sequencing of the
coding part of the DNA called the exome is already available at around this price. This decrease
in pricing is due to technical achievements in sequencing methods and the development of
bioinformatics, as raw sequence data has to be analyzed to make any sense of them.
8.
With these rapid advances, the genome can be sequenced if someone wishes to. Such a
service, though without bioinformatics analysis, is available through a private company for
USD$6995 (data for autumn 2012; sequencing of the exome cost as low as USD$895). It has
become a routine part of the diagnostic process for unknown neurological diseases. In cases
when a disease is known but many different genes can be responsible for it (in the sense that
one of 30 or so genes could be mutated as was shown in a well-documented case of CharcotMarie-Tooth disease), it is cheaper to sequence the genome or exome than to analyze several
dozen genes individually.
9.
This type of data yields more information than was asked for – and the problem of
incidental findings has been addressed to some extent in the Report of the IBC on the Principle
of Non-Discrimination and Non-Stigmatization (2014), but this certainly could be addressed in
more depth.
B.
Direct to Consumer Tests (DTC tests)
10. Increased education and access to information in the West has resulted in people taking
genetic analyses into their own hands. Commercial operators are providing services to those
who want them and are willing to pay. This may not be the way forward and, in general, the
legal situation is unclear as this is something new that the law may not have been able to
foresee.
11. DTC tests have been a problem as they analyze all sorts of things – from real diseasecausing mutations to gene variants which may or may not slightly affect the risk of having a
disease. Many of these tests do not give the same risks for a given analyzed condition if done
by different companies. There are no regulations for this in most countries and, moreover, some
attempts to regulate are met with disapproval from persons interested in determining their own
genetic predispositions. In many cases no genetic counselling is associated with the obtained
result and if any interpretation is given it may not be adequate or truly understandable.
1
A Glossary of Technical Terms can be found in the Annex of this concept note
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12. The problem is that there is a conflict between the wish to know and the ability to provide
understandable data; moreover some of the results are clear-cut – you do or do not have a
gene which gives a high cancer risk; but on the other hand what does it mean that your risk for
X is 1.2 times that of the population? Such results often take into consideration only one or a
few of the genes involved together with environmental factors, and very often give results which
are misleading.
C.
Cloning as such and nuclear transfer to avoid mitochondrial diseases
13. The IBC’s work on the issue of human cloning and possible means for its international
governance began in 2008 at the request of the Director-General. The IBC finalized its Report
on this issue and transmitted it to the Director-General in 2009 before pursuing its reflection on
analyzing the use of terminology and its ethical impact; formulating different options for legal
regulation of human reproductive cloning; and suggesting options for the dissemination of
activities concerning the issue of human cloning and its governance. However, due to divergent
positions amongst members of the IBC concerning the ethical implications of techniques of
human cloning as well as the best option for international governance, the Committee was
unable to reach a consensus on a final statement on human cloning and international
governance at its 18th Session. It was therefore decided that the IBC would not pursue its work
on this issue, but would instead entrust one or two members of the Committee to follow
developments in scientific research in this field for the period of 2012-2013. If considered
appropriate, those members can communicate relevant information to the Committee so that its
members can anticipate newly emerging ethical challenges and inform the Director-General.
Since then, there have been further developments in this field which make it worth revisiting the
issue, as, until last year, human cloning to obtain embryonic stem cells seemed to be impossible
and there was a general consensus that reproductive cloning should be banned.
14. Two very important developments pertaining to cloning took place in 2013: the first
successful cloning of human cells was performed, leading to the obtaining of pluripotent stem
cells; and the initiation of serious discussions both in the United States of America and the
United Kingdom of Great Britain and Northern Ireland on the use of nuclear transfer or some
variant of it for the purpose of preventing transmission of mitochondrial diseases – an in-depth
analysis of this has been published (also available online) by the Nuffield Council on Bioethics,
entitled Novel techniques for the prevention of mitochondrial DNA disorders – an ethical review.
15. The obtention of pluripotent human stem cells by nuclear transfer makes a hypothetical
possibility real. So far all the discussions did not have to face the fact that this has only been
achieved in a few laboratories, but the question, which is essentially an ethical one, is again
whether obtaining embryonic stem cells by what has, in general, been called therapeutic
cloning, is ethical or not. A consensus will probably not be reached on this point.
16. The prevention of passing on mitochondrial diseases to the next generation is a problem
of something which is not quite human cloning as has been generally discussed (making a copy
of an already existing individual) but does lead to the formation of a genetically manipulated
embryo – as a nucleus is transferred either before or after fertilization from an oocyte with
defective mitochondria to an oocyte without a nucleus but with normal mitochondria.
17. Mitochondrial diseases are caused in general by mutations in mitochondrial DNA (these
organelles which are mainly responsible for respiration have their own DNA, and are inherited
exclusively from the mother). Two new methods to avoid these diseases have been postulated.
One is called pronuclear transfer; the second is maternal spindle transfer. The former involves
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fertilizing an oocyte from the mother (who has a mitochondrial disease) with sperm from the
father. Another oocyte from a healthy donor is fertilized also with the father’s sperm and the two
pronuclei (nuclei of the two gametes) are removed from the first fertilized egg cell and placed in
the second one from which the pronuclei have also been removed. The second method is to
transfer the nucleus of the mother’s oocyte into another unfertilized oocyte from a healthy donor
from which the nucleus has been removed and then the reconstructed oocyte is fertilized with
the father’s sperm. This has also been described as germline gene therapy. More data of these
methods have recently been submitted to the IBC Secretariat by the Scottish Council on Human
Bioethics (15 April 2014).
18. Considering the history of the IBC’s reflection on human cloning, it is anticipated that there
is no easy way to obtain consensus on this issue. Moreover, the vote that took place at the UN
General Assembly on the UN Declaration on Human Cloning (A/RES/59/280, 8 March 2005)
also seemed to indicate that consensus was not yet possible amongst Member States (although
the resolution passed, the votes were split with 84 countries supporting it, 34 countries voting
against and 37 abstaining). However, it would be difficult to ignore the fact that human cloning
may now be possible and a discussion of the bioethical implications may be necessary.
D.
Personalized Medicine and Data Protection Regulation
19. This is a theme which overlaps both genome analysis and DTC tests but is a different
matter as it seems that medicine is at the beginning of a new era – to misquote Gilbert and
Sullivan – to make the therapy fit the disease. The commonly used term is personalized
medicine but the terms predictive and preventive medicine are also popular. This concerns
diagnosis and therapy and may involve tests for mutations, in particular, genes or genome
sequencing to find mutations, but also such things as prediction of the course of a disease,
finding appropriate treatment for a given type of cancer and avoiding adverse reactions to
drugs. This is not a separate ethical problem and perhaps is more one of distribution and
access, as these methods are still expensive and not universally available. However, there is
another problem linked to this. Collection of data which makes it possible to determine markers
or mutations important for a given disease or to allow proper disease stratification may also
involve collecting very large amounts of samples to look retrospectively for markers of disease.
To obtain new data on diseases, extremely large numbers of samples may be required and both
the samples (sources of DNA; most commonly blood) and the derived data have to be stored,
raising the problem of data access and confidentiality. They also raise the problem of informed
consent which is difficult to address, as both very narrow and very broad consent may lead to
problems – in the first case it would be necessary to constantly recontact the donor if new
analyses were to be performed; in the latter the donor would have no possibility of refusing tests
which s/he did not wish to be performed on her/his DNA.
20. There are serious concerns that legislation aimed at the protection of human data may
lead to problems with conducting large scale epidemiologic research based on biobanks,
registries and electronic records. Recently, for instance, the European Parliament has shown
very strong support for the Data Protection Regulation (621 votes in favour, 10 against and 22
abstentions). What the IBC perhaps should aim at would be to show that the protection of data
is necessary but there is also a right – the reference is in Article 27 of the UN Universal
Declaration of Human Rights – to participate in and derive benefits from scientific activity. We
have addressed this to some extent in the biobanks section of the latest Report of the IBC on
the Principle of Non-Discrimination and Non-Stigmatization (2014) but finding a balance
between data protection and research is a delicate and difficult task. Moreover many people are
more aware of the fact that data needs to be protected than of the need to collect DNA samples
–6–
and store information about them in order to continue to advance our knowledge in
understanding human diseases.
V.
FEEDBACK AND SUGGESTIONS
21. The IBC would like to invite feedback on the potential areas of reflection identified in this
concept note, as well as suggestions on additional issues that could be considered by the
Committee.
22. In addition, the Member States of the IGBC are invited to submit written suggestions on
policy-related needs, gaps and interests concerning this topic, which might be useful for the IBC
to strengthen the policy focus of its report.
23. Members and Associate Members of the UNIACB are also invited to submit written
suggestions for the IBC’s consideration.
24. Finally, the independence of the IBC in taking its own decisions concerning the eventual
direction of its reflection on this topic is emphasized once again. There should be no expectation
that comments submitted at this preliminary stage are required to be fully or even partially
incorporated by the IBC in its work. All feedback and suggestions are intended to enrich the
discussion of the Committee on this topic. Once a draft report on this topic is prepared by the
IBC, it will be made available for further comments (during the 22nd Session of the IBC and the
9th Session of the IGBC in 2015), and as per usual practice, the IBC will take into consideration
the feedback received at that stage, especially the opinions of the IGBC, in finalizing its report.
25. All written comments must be in either English or French, and must be submitted to the
Secretariat via email (preferred method) or regular mail before 31 July 2014. Contact
information for the Secretariat is as follows:
International Bioethics Committee (IBC)
Social and Human Sciences Sector, UNESCO
1, rue Miollis
75732 Paris Cedex 15
France
Email: [email protected] (submission by email is preferred)
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ANNEX
GLOSSARY OF TECHNICAL TERMS
2
Bioinformatics: 2
A scientific discipline encompassing all aspects of biologic
information acquisition, processing, storage, distribution, analysis,
and interpretation that combines the tools and techniques of
mathematics, computer science, and biology with the aim of
understanding the biologic significance of a variety of data.
Cell nucleus: 3
The nucleus is a membrane-enclosed organelle found in
eukaryotic cells. It contains most of the cell's genetic material,
organized as multiple long linear DNA molecules in complex with
a large variety of proteins, such as histones, to form
chromosomes.
Disease marker:2
A substance or measurable parameter that can be used to
identify the presence of a condition or assess the status of known
disease.
Disease stratification: 4
Stratification is the identification of a group of patients with shared
“biological” characteristics by using molecular, biochemical and
imaging diagnostic testing to select the optimal management for
the patients and achieve the best possible outcome in terms of
risk assessment and prevention; and achievement of the optimal
treatment outcome (based on the category and disease
characteristics).
Embryonic stem cells:3
Embryonic stem cells are pluripotent stem cells derived from the
inner cell mass of a blastocyst, an early-stage preimplantation
embryo. Human embryos reach the blastocyst stage 4–5 days
post fertilization, at which time they consist of 50–150 cells.
Isolating the embryoblast or inner cell mass results in destruction
of the blastocyst.
Exome:2
The sum total of the exons in a genome, which comprise about
1% of human DNA. The exome is regarded as the most
functionally relevant DNA, as it encodes proteins and gene
products.
Exon:
Most human genes are composed of parts which encode proteins
(exons) and sequences which separate them (introns).
Genetic counselling: 5
A procedure to explain the possible implications of the findings of
genetic testing or screening, its advantages and risks and where
applicable to assist the individual in the long-term handling of the
consequences. It takes place before and after genetic testing and
screening.
Germline gene therapy:3
In germline gene therapy, germ cells (sperm or eggs) are
Quoted from TheFreeDictionary by Farlex
Quoted from Wikipedia
4
Quoted from "Biomarkers for Patient Stratification", European Commission, DG Research (2010)
5
Quoted from UNESCO’s International Declaration on Human Genetic Data (2003)
3
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modified by the introduction of functional genes, which are
integrated into their genomes. Germ cells will combine to form a
zygote which will divide to produce all the other cells in an
organism and therefore if a germ cell is genetically modified then
all the cells in the organism will contain the modified gene. This
would allow the therapy to be heritable and passed on to later
generations.
Human genetic data:5
Information about heritable characteristics of individuals obtained
by analysis of nucleic acids or by other scientific analysis.
Human genome:3
The human genome is the complete set of genetic information for
humans. This information is encoded as DNA sequences within
the 23 chromosome pairs in cell nuclei and in a small DNA
molecule found within individual mitochondria. Human genomes
include both protein-coding DNA genes and noncoding DNA.
Incidental findings: 3
Incidental findings are previously undiagnosed medical or
psychiatric conditions that are discovered unintentionally and are
unrelated to the current medical or psychiatric condition which is
being treated or tests being performed. Incidental findings may be
uncovered in a variety of settings such as in test subjects during
medical research during the course of an autopsy or during
genetic testing, etc.
Mitochondria:
Parts of the cell (organelles) which contain their own genetic
material (DNA) and are responsible for energy production.
Changes (mutations) in mitochondrial DNA are inherited only
from the mother and can cause diseases mainly affecting nerves
and muscle.
Nuclear transfer:2
The transfer of the nucleus of one cell to another cell whose
nucleus has been removed.
Oocyte:2
Pluripotent stem cells:
The female reproductive cell prior to fertilization.
6
Pronucleus (plural
Pronuclei):3
6
Quoted from Biology Online
Stem cells having the ability to differentiate into more than one
cell type.
The nucleus of a sperm or an egg cell (oocyte) during the process
of fertilization, after the sperm enters the oocyte, but before they
fuse.