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A. Draft
recommendation
(open)
Report | Doc. 14328 | 24 May 2017
The use of new genetic technologies in human beings
Committee on Social Affairs, Health and Sustainable Development
Summary
New genetic technologies are developing very rapidly: recent discoveries related to the human genome have opened the door to new opportunities and unprecedented ethical concerns. The current scientific consensus is that these techniques are not yet “safe” enough to establish a pregnancy with germline cells or human embryos having undergone intentional genome editing, but deliberate germline editing in human beings would also cross a line viewed as ethically inviolable.
The Parliamentary Assembly should thus recommend a five-step plan to the Committee of Ministers:
- urging member States which have not yet ratified the Oviedo Convention to do so without further delay, or, as a minimum, to put in place a national ban on establishing a pregnancy with germline cells or human embryos having undergone intentional genome editing;
- fostering a broad and informed public debate;
- instructing the Council of Europe Committee on Bioethics (DH-BIO) to assess the attendant ethical and legal challenges;
- developing a common regulatory and legal framework;
- recommending that member States, on the basis of the other steps, develop a clear national position on the practical use of new genetic technologies, setting the limits and promoting good practices.
A. Draft
recommendation 
(open)1. Genetic engineering techniques
have been applied in the medical field for several decades now. However,
new technologies are developing very rapidly: recent discoveries
related to the human genome have opened the door to new opportunities
and unprecedented ethical concerns. On the one hand, this improved knowledge
of our make-up as human beings brings with it welcome potential
to diagnose, prevent and eventually cure diseases in the future.
On the other hand, it raises complex ethical and human rights questions, including
– but not limited to – unintended harm which may result from the
techniques used, access and consent to such techniques, and their
potential abuse for enhancement or eugenic purposes.
2. In particular, recent advances in genome editing are bound
to result in germline interventions in human beings quite soon,
for example with the birth of children whose genome has been altered
with some unforeseeable consequences in such a way that their descendants
are also affected. The scientific consensus at the moment is that
these techniques are not yet “safe” enough, leading to a de facto moratorium until a germline
intervention could meet the risk/benefit standard for authorising
clinical trials. However, other techniques, such as pronuclear transfer
technology (the “three-parent” technique to avoid maternal inheritance of
mitochondrial diseases), have already resulted in babies being born,
despite considerable scientific uncertainty about long-term effects.
3. Deliberate germline editing in human beings would cross a
line viewed as ethically inviolable. Indeed, the 1997 Council of
Europe Convention for the Protection of Human Rights and Dignity
of the Human Being with regard to the Application of Biology and
Medicine: Convention on Human Rights and Biomedicine (ETS No. 164,
“Oviedo Convention”), binding on the 29 member States which have
ratified it, posits in its Article 13 that “an intervention seeking
to modify the human genome may only be undertaken for preventive,
diagnostic or therapeutic purposes and only if its aim is not to
introduce any modifications in the genome of any descendants”. The
convention does, however, also establish a specific procedure for
its amendment (Article 32), which should be read in conjunction
with Article 28, which imposes on States Parties to see to it that
“the fundamental questions raised by the developments of biology
and medicine are the subject of appropriate public discussion in
the light, in particular, of relevant medical, social, economic,
ethical and legal implications, and that their possible application
is made the subject of appropriate consultation”.
4. Numerous scientific and ethical bodies are starting to make
recommendations to establish an appropriate regulatory framework
for genome editing and germline interventions in human beings, including most
recently the United States National Academy of Sciences and National
Academy of Medicine, and the European Academies Science Advisory
Council (EASAC). The current prohibition on interventions aimed
at modifying the germline in human beings in all European Union
and many Council of Europe member States is not going to stop genome-edited
babies from being born elsewhere.
5. The Parliamentary Assembly thus recommends that the Committee
of Ministers:
5.1. urge member States
which have not yet ratified the Oviedo Convention to do so without
further delay, or, as a minimum, to put in place a national ban
on establishing a pregnancy with germline cells or human embryos
having undergone intentional genome editing;
5.2. foster a broad and informed public debate on the medical
potential and possible ethical and human rights consequences of
the use of new genetic technologies in human beings;
5.3. instruct the Council of Europe Committee on Bioethics
(DH-BIO) to assess the ethical and legal challenges raised by emerging
genome editing technologies, in the light of the principles laid
down in the Oviedo Convention and the precautionary principle;
5.4. develop a common regulatory and legal framework which
is able to balance the potential benefits and risks of these technologies
with the aim of finding cures for serious diseases, while preventing
abuse or adverse effects of genetic technology on human beings;
5.5. recommend that member States, on the basis of the public
debate, the DH-BIO assessment and the common regulatory and legal
framework devised, develop a clear national position on the practical use
of new genetic technologies, setting the limits and promoting good
practices.
B. Explanatory memorandum by Ms Petra De Sutter, rapporteur
(open)1. Introduction
1. New technologies in the medical
field are developing exponentially: recent discoveries related to
the human genome and in the science of genetics have opened the
door to a new paradigm. While this improved knowledge of our make-up
as human beings brings with it welcome potential to diagnose, cure
or even eradicate diseases in the future, it also creates ethical
and human rights risks related to the techniques used.
2. I believe it is urgent to have a political debate on new genetic
technologies – some of which are already being applied to human
beings. This is why I encouraged the Committee on Social Affairs,
Health and Sustainable Development to table a motion for a recommendation on the subject in November 2015,
and welcome the two hearings organised by our committee on the subject:
the first on “Manufacturing a new human species?” in October 2015
with the participation of scientists, politicians and a representative
from the Council of Europe’s Committee on Bioethics (DH-BIO), and
the second on “The use of new genetic technologies in human beings”
in January 2017, with a different set of experts and representatives.
on the subject in November 2015,
and welcome the two hearings organised by our committee on the subject:
the first on “Manufacturing a new human species?” in October 2015
with the participation of scientists, politicians and a representative
from the Council of Europe’s Committee on Bioethics (DH-BIO), and
the second on “The use of new genetic technologies in human beings”
in January 2017, with a different set of experts and representatives. 3. My aim in this report is to study the health, ethical and
human rights risks and challenges related to the techniques’ use
and regulation with a view to making the appropriate recommendations
to the Committee of Ministers on possible action to be taken to
provide a common framework for the use of these technologies.
2. The current situation
2.1. International law and the work of international and regional organisations
4. The mandate of the Council
of Europe encompasses the promotion and protection of human rights, democracy
and the rule of law. Also, its recognition of subsidiarity, and
its mission of promoting good practice amongst member States, places
the Organisation in an ideal position to address any possible violation
of human rights at the European level.
5. The 1997 Council of Europe Convention for the Protection of
Human Rights and Dignity of the Human Being with regard to the Application
of Biology and Medicine: Convention on Human Rights and Biomedicine (ETS
No. 164, “Oviedo Convention”), establishes a European legal framework
for the protection of human rights in the field of biomedicine,
which is binding on the 29 member States which have ratified it.
6. This convention should be used as the reference guiding instrument
with regard to the use of genetic technologies. Article 13 of the
convention establishes that “an intervention seeking to modify the
human genome may only be undertaken for preventive, diagnostic or
therapeutic purposes and only if its aim is not to introduce any
modifications in the genome of any descendants”. In addition, “where
the law allows research on embryos in
vitro, it shall ensure adequate protection of the embryo”
(Article 18.1), and the creation of human embryos for research purposes
is prohibited under Article 18.2.
7. The Oviedo Convention does not take any position on genome
research on human embryos. Its Article 13 is, however, generally
understood as de facto prohibiting
the transfer of an embryo with (intentional) genome modification
into the uterus of a woman with a view to giving birth to a child.
8. Article 28 of the convention requires that Parties see to
it that the “fundamental questions raised by the developments of
biology and medicine are the subject of appropriate public discussion”.
Monitoring of scientific developments is foreseen under Article
32.4, and is carried out by the Committee on Bioethics, which represents
47 European States. At its 8th meeting, from 1 to 4 December 2015
in Strasbourg, the Committee adopted a “Statement on genome editing
technologies”, in which it declared itself “convinced
that the Oviedo Convention provides principles that could be used
as reference for the debate called for at international level on
the fundamental questions raised by these recent technological developments”
and agreed, as part of its mandate, “to examine the ethical and
legal challenges raised by these emerging genome editing technologies, in
the light of the principles laid down in the Oviedo Convention”.
This work is ongoing, and could possibly lead to an amendment of
the convention, as is foreseen in its Article 32.
in which it declared itself “convinced
that the Oviedo Convention provides principles that could be used
as reference for the debate called for at international level on
the fundamental questions raised by these recent technological developments”
and agreed, as part of its mandate, “to examine the ethical and
legal challenges raised by these emerging genome editing technologies, in
the light of the principles laid down in the Oviedo Convention”.
This work is ongoing, and could possibly lead to an amendment of
the convention, as is foreseen in its Article 32.9. The Parliamentary Assembly started working on the issue at
hand more than thirty years ago, and adopted two texts: Recommendation 934 (1982) on genetic engineering and Recommendation 1512 (2001) on the protection of the human genome by the Council
of Europe.
10. The United Nations Educational, Scientific and Cultural Organization
(UNESCO) has provided several related recommendations on the issue,
including the Universal
Declaration on the Human Genome and Human Rights in 1997, the International
Declaration on Human Genetic Data in 2003, and the Universal
Declaration on Bioethics and Human Rights in 2005. Indeed,
UNESCO’s International Bioethics Committee has proposed a moratorium
on germline applications and hereditary modifications.
Indeed,
UNESCO’s International Bioethics Committee has proposed a moratorium
on germline applications and hereditary modifications. 11. Shortly thereafter, an international group of scientists meeting
in Washington in December 2015 for the “International Summit on
Human Gene Editing” also called for a moratorium on making inheritable
changes to the human genome. The meeting was convened by the National
Academy of Sciences and the National Academy of Medicine of the
United States, the Chinese Academy of Sciences and the Royal Society
of London.
12. Finally, there are national regulations, although very few
countries legislate on new technologies, mainly because technology
is moving at a faster pace than regulators can keep up with. However,
the consequence of the lack of regulation is the absence of technology
control. Often, the actors involved “auto-regulate” the technology,
which jeopardises the accepted principle of the need for control
by an independent (and transparent) authority.
13. Most recently, the Committee on Human Gene Editing of the
US National Academy of Sciences and the National Academy of Medicine
finalised a report on “Human Genome Editing: Science, Ethics, and Governance”
which includes a number of principles and recommendations for governance
of human genome editing, which may come
to set the de facto global
standard in time. Concomitantly, the European Academies’ Science
Advisory Council (EASAC) also finalised a report on “Genome editing:
scientific opportunities, public interests and policy options in
the European Union”, setting out different policy recommendations,
especially regarding human germline (heritable) genome editing.
which may come
to set the de facto global
standard in time. Concomitantly, the European Academies’ Science
Advisory Council (EASAC) also finalised a report on “Genome editing:
scientific opportunities, public interests and policy options in
the European Union”, setting out different policy recommendations,
especially regarding human germline (heritable) genome editing. 2.2. State of the developments of the use of new genetic technologies on humans
14. The human genome is the complete
set of DNA within the 23 chromosome pairs in cell nuclei and in
a small DNA molecule found within individual mitochondria. After
the mapping of the human genome was completed in 2003, approximately
three billion bases of the DNA code were analysed, and around 20 000 human
genes were identified and mapped (using bioinformatics and experimental
research). However, there are still many gaps in the sequence, and
the function of many genes is totally unknown, including the basic
gene regulation for growing and reproducing cells.
15. A genetic disease is any disease that is linked to an abnormality
in an individual’s genome. Some genetic disorders are inherited
from the parents, while other genetic diseases are caused by acquired
changes or mutations. The defect will only be passed down if it
occurs in the germline. Over 4 000 human diseases are caused by
single-gene defects with recognisable patterns (autosomal dominant,
autosomal recessive, and X‑linked), but the majority of diseases
are related to the implication of several genes and the influence
of the environment.
16. The recent development of a new technology, CRISPR-Cas9, a
genome editing tool, has made it possible to edit DNA faster, more
cheaply and more accurately than with previous such techniques. It acts like “molecular
scissors” in a “specific” place of the DNA, and it is supposed to
excise a gene mutation which can then be replaced by the correct
genetic sequence. However, while the excision is quite effective
for a target gene, the homologous recombination step that happens
later in the reproduction of the cells is more critical to repair
than the defective gene, leading to potential problems of accuracy
with unintended consequences (so-called “off-target” effects).
It acts like “molecular
scissors” in a “specific” place of the DNA, and it is supposed to
excise a gene mutation which can then be replaced by the correct
genetic sequence. However, while the excision is quite effective
for a target gene, the homologous recombination step that happens
later in the reproduction of the cells is more critical to repair
than the defective gene, leading to potential problems of accuracy
with unintended consequences (so-called “off-target” effects).17. In the case of (rare) genetic diseases linked to the maternal
inheritance of mitochondrial diseases, mitochondrial replacement
therapy has been used to avoid passing down such diseases. There
are two ways: pronuclear transfer technology and maternal spindle
transfer. A
child born from this latter procedure has three genetic parents
(with one providing the new genes of the healthy mitochondria).
Although the traits of a child are inherited from the nuclear DNA
of its parents and not the mitochondrial DNA, the interrelation
and function between the genome of the nuclei and the mitochondria
is still uncertain.
and maternal spindle
transfer. A
child born from this latter procedure has three genetic parents
(with one providing the new genes of the healthy mitochondria).
Although the traits of a child are inherited from the nuclear DNA
of its parents and not the mitochondrial DNA, the interrelation
and function between the genome of the nuclei and the mitochondria
is still uncertain.18. The first baby with genes that came from pronuclear transfer
(the three parents technique) was recently born in Mexico, the second in Ukraine. The United Kingdom became the first
country in the world, as of 29 October 2015, to permit such babies
to be born from pronuclear transfer technology (while in the United States
it is completely forbidden), and has also licensed the research
use of embryos that have been genetically modified (by gene editing).
the second in Ukraine. The United Kingdom became the first
country in the world, as of 29 October 2015, to permit such babies
to be born from pronuclear transfer technology (while in the United States
it is completely forbidden), and has also licensed the research
use of embryos that have been genetically modified (by gene editing).19. New technology is also blurring the previous strict dichotomy
of somatic and germline cells, as somatic cells can now be reprogrammed
into pluripotent stem cells, and possibly in the future further
into gametes. Changes can even be made with a combination of in vivo and in
vitro technology, leapfrogging conventional approaches
in relation to in vivo gene
therapy.
20. Similarly, there is a problem with the blurring of the lines
between basic and applied research in genetics. There used to be
a great difference between basic research in the laboratory or on
embryos, and clinical trials with applications leading to pregnancy
and the birth of a child. In the past, new genetic technologies
were only used in very developed countries, but today biotechnology
is more accessible, low-cost and makes inserting, removing, and
editing human genes much easier. Also, with globalisation, it is
possible for patients and scientists to travel easily to private
clinics in countries without (strict) bioethics regulations.
21. In May 2015, a first paper was published using genome editing
(CRISPR-Cas9) on non-viable human embryos in China. February
2016 saw the world's first endorsement of a national regulatory
authority for research on human embryos using genome editing, in
the United Kingdom. In the United States, the National Institute
of Health decided, however, not to fund any use of gene-editing
technologies in human embryos. But all this demonstrates
how human germline gene modification is starting to move out from
the theoretical field to clinical research applications.
February
2016 saw the world's first endorsement of a national regulatory
authority for research on human embryos using genome editing, in
the United Kingdom. In the United States, the National Institute
of Health decided, however, not to fund any use of gene-editing
technologies in human embryos. But all this demonstrates
how human germline gene modification is starting to move out from
the theoretical field to clinical research applications.22. As regards future developments, pre-implantation genetic diagnosis
is generally used to avoid the transfer of embryos carrying a genetic
disease to the uterus, but it cannot be used in all cases. In
those cases, in order to prevent passing the defect mutation to
further generations, a new technology may be required for treatment
purposes.
In
those cases, in order to prevent passing the defect mutation to
further generations, a new technology may be required for treatment
purposes. 3. The potential benefits and risks of new genetic technologies
23. There are many possible positive
uses of new genetic technologies, which could be applied to infectious diseases
stemming from viruses, bacteria, prions and fungi (for example by
making cells resistant to infection by Hepatitis B and HIV). Also,
in relation to the fight against vectors of diseases like zika or
malaria, there are already several developments which aim to stop
the reproduction of certain types of disease-carrying mosquito. In
oncology, a new type of advanced therapy using specific immune cells
reprogrammed to target and kill cancer cells looks promising. Add
to this the use of patient-specific induced pluripotent stem cells (undifferentiated
cells which can differentiate in any given direction) in combination
with genome editing, which offers unique opportunities for developing
personalised disease models for research.
24. There are also many promising uses for the CRISPR-Cas9 technology: the therapeutic potential
would combine the latest technological developments in the field
of stem cells and future clinical applications. The use of patient-specific
induced pluripotent stem cells (iPSCs) in combination with bioengineering
advances and genome editing offers unique opportunities for developing
personalised disease models and tissues for regenerative medicine.
the therapeutic potential
would combine the latest technological developments in the field
of stem cells and future clinical applications. The use of patient-specific
induced pluripotent stem cells (iPSCs) in combination with bioengineering
advances and genome editing offers unique opportunities for developing
personalised disease models and tissues for regenerative medicine.25. However, unwanted and inaccurate (off-target) mutagenesis
is a major concern, because this may produce cancer or rare and
unknown diseases. This risk may be minimised by optimising the procedure
in the future, but even small changes can be very dangerous for
the patient and future generations, with unknown consequences. “Mosaicism”,
the presence of two or more populations of cells with different
genes, can also create several problems, including rare diseases,
as well as practical problems related to the DNA identification for
diagnosis, paternity tests and forensic identification.
26. The problem of the impact of the genetic modification of human
germline cells is that it may not be fully known until a certain
number of generations have inherited these mutations. There are
also risks concerning future generations arising from patients who
have the new genetic condition and who reproduce amongst themselves,
due to the creation of a variety of unknown combinations of genes.
27. The scientific call for a moratorium on the gene editing of
embryos leading to pregnancy concluded that it would be “irresponsible
to proceed”, until the risks were better understood and that there
was “broad societal consensus” about the research – and also because,
up to now, we lack precise knowledge about many genes. This position
was recently confirmed once more by both the US National Academy
of Sciences and National Academy of Medicine and EASAC. Additionally,
so far there are no clinical trials of somatic genetic correction in situ using the newest gene editing
techniques. The gene therapy research and clinical trials with thousands
of studies running every year worldwide have not yet succeeded in
determining survival rates and life expectancy outcomes.
concluded that it would be “irresponsible
to proceed”, until the risks were better understood and that there
was “broad societal consensus” about the research – and also because,
up to now, we lack precise knowledge about many genes. This position
was recently confirmed once more by both the US National Academy
of Sciences and National Academy of Medicine and EASAC. Additionally,
so far there are no clinical trials of somatic genetic correction in situ using the newest gene editing
techniques. The gene therapy research and clinical trials with thousands
of studies running every year worldwide have not yet succeeded in
determining survival rates and life expectancy outcomes.28. Future regulation depends on the respective context and aim
pursued, not solely on the presumed ontology of the cell or tissue. The
physiological regulation of the changed genes and the role of epigenetics must
be considered. There are changes in gene expression (active versus
inactive genes) that do not involve changes to the underlying DNA
sequence (like in gene editing technology). Furthermore, changing
genes may provide only temporary inhibition of certain functions.
The
physiological regulation of the changed genes and the role of epigenetics must
be considered. There are changes in gene expression (active versus
inactive genes) that do not involve changes to the underlying DNA
sequence (like in gene editing technology). Furthermore, changing
genes may provide only temporary inhibition of certain functions.29. In addition, there are grave concerns about possible misuse
and abuse of the technology with the intention to produce individuals
or entire groups endowed with particular characteristics and required qualities. Germline
gene therapy could lead to the acceptance of gene therapy for genetic
enhancement – which could lead, in turn, to the spectre of eugenics
(genetic selection in order to improve genetic traits). I believe
history has taught us where this may lead.
Germline
gene therapy could lead to the acceptance of gene therapy for genetic
enhancement – which could lead, in turn, to the spectre of eugenics
(genetic selection in order to improve genetic traits). I believe
history has taught us where this may lead.30. Since 1980, it is possible to patent micro-organisms under
international agreements. In fact, even during the genome project,
the human DNA was intended to be patented. In a landmark decision
in June 2013, the Supreme Court of the United States determined
that DNA in its natural form cannot be patented, but patents of procedures detecting
certain human genes, even the ones able to produce cancer, are possible.
There are several cases in court, taking many years to resolve,
on claims for intellectual property rights regarding technologies
identifying (only the patent holder has the right to sequence that
DNA) or changing the human genome, including the controversy regarding
the patenting of the CRISPR-Cas9 technology itself.
but patents of procedures detecting
certain human genes, even the ones able to produce cancer, are possible.
There are several cases in court, taking many years to resolve,
on claims for intellectual property rights regarding technologies
identifying (only the patent holder has the right to sequence that
DNA) or changing the human genome, including the controversy regarding
the patenting of the CRISPR-Cas9 technology itself. 31. Although this is beyond the focus of this report, I would
like to comment in passing that the use of genetic technology in
animals and plants indicates a worrying commercial interest with
possibly grave environmental consequences .
At the moment, public investment in this technology is providing
benefits to small public entities or to private companies instead
of to society as a whole. Multiple patent-holder claims across the genome
are stopping the translation of genetic discoveries into health
care benefits, compromising the accessibility and affordability
of high-quality health care, which has human rights implications.
.
At the moment, public investment in this technology is providing
benefits to small public entities or to private companies instead
of to society as a whole. Multiple patent-holder claims across the genome
are stopping the translation of genetic discoveries into health
care benefits, compromising the accessibility and affordability
of high-quality health care, which has human rights implications.32. In addition, there is a natural tendency for scientists to
want to be the pioneers of genetic technology developments, to endeavour
to publish papers thereon and to reap economic benefits from their
research (for example by participating in technological companies).
This raises the question of possible conflicts of interest. In my
opinion, science provides knowledge, but it should not be left to
scientists alone to decide on research policies (for example on
where to set the limits of such research) and how the research is
used.
33. It is often argued that full transparency in research and
clinical trials would compromise patient confidentiality and intellectual
property rights. While patient anonymity must be respected, medical
knowledge should be published and shared, also in this field. It
is, in fact, one of the difficulties of the “gene editing” technology
that it is impossible to identify that changes have been made artificially.
This creates not only a problem regarding the treatment of patients
with genetic changes, but also of traceability in animals and plants.
34. Research on animals is mostly performed on mice, but most
of the recent advances in genetic technology have not yet even been
tested on apes or primates (who share 96% of common DNA with human beings,
but also have 40 million differences). Instead, research has jumped
directly to research on patients or human embryos. Furthermore,
there is a lack of experience in animal research, and the tendency
to stop animal research continues to create a barrier in the field
of genetics. However, it may be necessary to increase animal research
in the genetic field in order to avoid consequences dangerous to
humans. On the other hand, research on animals and human embryos
alike have the drawback of not allowing a thorough analysis of possible
consequences on psychological and behavioural characteristics of
genetic modifications.
4. The need for international regulation and respect of the precautionary principle
35. The Asilomar Conference on
recombinant DNA, held in California in 1975, and led by the United
States, discussed potential biohazards, as well as possible regulation.
It was the first time that genetic dangers were brought into the
arena for public debate. At the time, the Conference focused on
the study of the biohazards and made recommendations about the necessary
containment of research on hybrid DNA – but those recommendations
were made without a prior political, independent, pluridisciplinary,
balanced, and transparent assessment, which would have been desirable.
36. The scientific community has so far agreed on two arguments
regarding interventions on the human genome: safety concerns, mainly
due to the off-target effects of gene editing (i.e. affecting other
genes), and human rights concerns, in particular with respect to
the effects on future generations (changing the genome means changing
the common heritage of humanity). However, so far, international
regulation is sorely lacking.
37. In 4th century BC, Hippocrates established the idea of “to
help and do no harm”. The basic principles of bioethics are nonmaleficence,
beneficence, respect for autonomy and justice. It is important to
explain that the autonomy of the patient is mainly linked to informed
consent (absent in the case of future generations) and also the
principle of justice (equity of access to treatment) which is linked
to fair treatment. Other bioethical principles have been developed
regarding health care, like equity and accessibility to new technology,
the responsibility of scientists and health professionals, the confidentiality
of patient information and the necessary compensation in cases of
harm. All of these principles should be balanced with each other,
as in the Council of Europe Oviedo Convention.
38. The Committee of Ministers and the Parliamentary Assembly
agree that it is necessary to advocate “a culture of precaution
incorporating the precautionary principle into scientific research
processes, with due regard for freedom of research and innovation”. In
this context, the Committee of Ministers recalled in 2008 the undertakings
given by the Heads of State and Government of the Council of Europe
in the Final Declaration of the 3rd Summit of the Council of Europe
to “ensure security for our citizens in the full respect of human
rights and fundamental freedoms” and to meet, in this context, “the
challenges attendant on scientific and technical progress”.
In
this context, the Committee of Ministers recalled in 2008 the undertakings
given by the Heads of State and Government of the Council of Europe
in the Final Declaration of the 3rd Summit of the Council of Europe
to “ensure security for our citizens in the full respect of human
rights and fundamental freedoms” and to meet, in this context, “the
challenges attendant on scientific and technical progress”.39. The European Union defines the precautionary principle as
enabling a rapid response through preventative decision taking in
the case of risk, such as a possible danger to human health, in
particular where scientific data does not permit a complete evaluation
of the risk. Zero
risk does not exist, which is why measures must be proportionate
to risk in accordance with the precautionary principle. Due to the
lack of evidence-based knowledge regarding the consequences of new
genetic technologies, the risk calculation in this area is, however,
quite difficult. Nevertheless, any regulation in this area should
apply the precautionary principle rather than the prevention principle, which
does not go as far in protecting against possible dangers.
Zero
risk does not exist, which is why measures must be proportionate
to risk in accordance with the precautionary principle. Due to the
lack of evidence-based knowledge regarding the consequences of new
genetic technologies, the risk calculation in this area is, however,
quite difficult. Nevertheless, any regulation in this area should
apply the precautionary principle rather than the prevention principle, which
does not go as far in protecting against possible dangers.40. On this point it is very helpful to have advisory bodies,
such as national academies, colleges of scientists or others, able
to undertake risk assessments of possible uses of the technology,
considering the consequences for the newborn babies, future generations,
patients themselves or the environment. Such risk assessments should
be made public, also in order to highlight certain dangers and the
limits of the research.
41. Unfortunately, this is not what is happening today: A Chinese
group has had the first clinical trial approved using the revolutionary
CRISPR–Cas9 technique. They
modified immune cells in vitro to
attack cancer cells, but these changes to the cell genome will not
pass on to the next generation, meaning that any side effects (e.g.
attacking normal cells) will impact only the patient. The United
States is following the approval procedure for a similar clinical
trial through an advisory panel of the US National Institute of
Health, which already approved the project, the US Food and Drug
Administration (FDA) and the license of the University Review Board.
However, China mainly follows the hospital internal review board
system for approval, without due transparency or respect for human
rights. There is a very real danger that countries are running a
race to be the first, without considering the human rights perspective,
bioethical analysis or possible consequences.
They
modified immune cells in vitro to
attack cancer cells, but these changes to the cell genome will not
pass on to the next generation, meaning that any side effects (e.g.
attacking normal cells) will impact only the patient. The United
States is following the approval procedure for a similar clinical
trial through an advisory panel of the US National Institute of
Health, which already approved the project, the US Food and Drug
Administration (FDA) and the license of the University Review Board.
However, China mainly follows the hospital internal review board
system for approval, without due transparency or respect for human
rights. There is a very real danger that countries are running a
race to be the first, without considering the human rights perspective,
bioethical analysis or possible consequences.42. In Europe, some countries have special committees dealing
with reproductive medicine: for example, in the United Kingdom,
the Human Fertilization and Embryology Act created the Human Fertilization
and Embryology Authority (HFEA) in 1990, which gives legal answers
to scientific progress. Few other countries have a national body
regulating new scientific developments, or specific legislation
on gene editing.
43. The report on “Human Genome Editing: Science, Ethics, and
Governance” of the Committee on Human Gene Editing of the US National
Academy of Sciences and National Academy of Medicine proposes
seven overarching principles which should “undergird the oversight
systems, the research on, and the clinical uses of human genome
editing”: promoting well-being, transparency, due care, responsible
science, respect for persons, fairness, and transnational co-operation .
While it is difficult to disagree with these principles (except that
other principles of equal or higher importance in my view are missing,
such as a human rights perspective and the precautionary principle),
their application to the field of “heritable genome editing” leads
to more questionable recommendations. The report concludes, for
example, that “[h]eritable germline genome editing trials must be
approached with caution, but caution does not mean they must be
prohibited” , and thus formulates recommendations
on what is entailed by a “robust and effective regulatory framework”
which should permit clinical trials using heritable germline genome
editing. However, the Committee on Human Gene Editing itself admits
that “it would be surprising if everyone were to agree with this
recommendation”. Indeed, the President of EASAC has categorised
these recommendations as “controversial”, and requiring “considerable further
public engagement by the scientific and medical communities to debate
issues and perspectives”.
proposes
seven overarching principles which should “undergird the oversight
systems, the research on, and the clinical uses of human genome
editing”: promoting well-being, transparency, due care, responsible
science, respect for persons, fairness, and transnational co-operation .
While it is difficult to disagree with these principles (except that
other principles of equal or higher importance in my view are missing,
such as a human rights perspective and the precautionary principle),
their application to the field of “heritable genome editing” leads
to more questionable recommendations. The report concludes, for
example, that “[h]eritable germline genome editing trials must be
approached with caution, but caution does not mean they must be
prohibited” , and thus formulates recommendations
on what is entailed by a “robust and effective regulatory framework”
which should permit clinical trials using heritable germline genome
editing. However, the Committee on Human Gene Editing itself admits
that “it would be surprising if everyone were to agree with this
recommendation”. Indeed, the President of EASAC has categorised
these recommendations as “controversial”, and requiring “considerable further
public engagement by the scientific and medical communities to debate
issues and perspectives”. 44. Interestingly, the final criterion of the recommendation (5-1)
is “reliable oversight mechanisms to prevent extension to uses other
than preventing a serious disease or condition” .
Again, the Committee admits that there are “those who think the
final criterion … cannot be met, and that once germline modification
had begun, the regulatory mechanisms instituted could not limit
the technology to the uses identified in the recommendation”. Indeed,
the committee concluded that if it were not possible to satisfy
the criteria in the recommendation, in the committee’s view “germline
genome editing would not be permissible”.
.
Again, the Committee admits that there are “those who think the
final criterion … cannot be met, and that once germline modification
had begun, the regulatory mechanisms instituted could not limit
the technology to the uses identified in the recommendation”. Indeed,
the committee concluded that if it were not possible to satisfy
the criteria in the recommendation, in the committee’s view “germline
genome editing would not be permissible”. 45. The committee also admitted that heritable germline genome
editing “also raises concerns about premature or unproven uses of
the technology”, and thus the emergence of “regulatory havens” that
would “tempt providers or consumers to travel to jurisdictions with
more lenient or non-existent regulations to undergo the restricted
procedures”. The committee, in consequence, highlights the need
for comprehensive regulation –
which, I would argue, would ideally be international, and based
on a Council of Europe model.
–
which, I would argue, would ideally be international, and based
on a Council of Europe model.46. As regards the possible clinical use of germline interventions,
EASAC comes to a similar conclusion: “These applications pose many
important issues including the risks of inaccurate or incomplete
editing, the difficulty of predicting harmful effects, the obligation
to consider both the individual and future generations who will
carry the genetic alterations, and the possibility that biological
enhancements beyond prevention and treatment of disease could exacerbate
social inequities or be used coercively. It would be irresponsible
to proceed unless and until the relevant ethical, safety and efficacy
issues have been resolved and there is broad societal consensus.”
5. Conclusions and recommendations
47. Genetic sciences are developing
quickly, but we are only just beginning to understand them, with
much research trying to find out the genetic functions and possible
treatments for genetic and hereditary diseases. We need to evaluate
the possible risks and consequences of the application of these
new technologies through a pluridisciplinary, independent, balanced,
transparent and political assessment. The general public needs to be
properly informed in order to have a broad public debate on the
state of scientific knowledge regarding new genetic technologies.
Human rights, including bioethical principles, the rule of law and
democratic principles should be an integral part of this debate.
48. Specific and independent bodies (with the necessary knowledge
on the new developments in science) should advise parliamentarians,
the regulatory authorities and public institutions. Member States
should develop a clear position on the practical use of new genetic
technology, setting the limits and promoting good and accountable
practices in full respect of the precautionary principle. The absence
of regulation should not be an option. It would be appropriate to
take a position (including preventive measures) sooner rather than later,
otherwise technologies will be widely applied without appropriate
analysis.
49. There is an explosion of genetic studies and information on
“big bio-data” that needs to be better understood before being applied
to human reproductive cells or to newborn babies, with unknown consequences.
To create an embryo with a genome modification and to transfer it
into a womb cannot yet be considered a safe practice. Humans should
not be used as experimental entities without there being an existing knowledge
of the consequences following tests on animals, because there is
not enough research and animal experiment experience using new genetic
technology. The current self-declared and self-imposed moratorium on
making inheritable changes to the human genome should thus be upheld.
In States which do not yet have a de
jure moratorium or a ban in place, this moratorium should
be included in legislation/regulation on the matter, in order to
ensure that it is the State (rather than an individual scientist
or a group of scientists) which has the power to lift that moratorium.
Unfortunately, with the pace of scientific progress, this may be
unrealistic.
50. Arguably, deliberate germline editing in human beings would
cross a line viewed as ethically inviolable. However, I do not believe
we are going to be able to agree amongst ourselves on whether there
should be only a moratorium or rather a ban on the deliberate use
of germline editing in human beings, as proscribed in the Oviedo
Convention. However, the current prohibition on interventions aimed
at modifying the germline in human beings in all European and
many Council of Europe member States is not going to stop genome-edited
babies from being born elsewhere. The US National Academy of Sciences
and National Academy of Medicine have recently enunciated a number
of principles and recommendations for governance of human genome
editing. These may in time come to set the de
facto global standard, if Europe cannot offer a better alternative.
and
many Council of Europe member States is not going to stop genome-edited
babies from being born elsewhere. The US National Academy of Sciences
and National Academy of Medicine have recently enunciated a number
of principles and recommendations for governance of human genome
editing. These may in time come to set the de
facto global standard, if Europe cannot offer a better alternative.51. I believe that an international legal framework is necessary
to set the limits and complement national legislation/regulation,
and that Europe should lead the way with a common regulatory and
legal framework which is able to balance the potential benefits
and risks of these technologies with the aim of enabling the eradication
or cure of serious diseases, while preventing abuse or adverse effects
of genetic technology on human beings. The Council of Europe is
the ideal organisation to develop this framework, which – if sufficiently compelling
and widely accepted in Europe –, may well become the global standard.
52. A fifth of the human genome is subject to patent claims, generating
a huge barrier for research, diagnosis and therapeutic use. We need
new legislation to prevent intellectual property rights being recognised
in relation to the identification and modification of the human
genome. Public investment in this technology is providing benefits
to small public entities or to private companies instead of to the
whole of society, while human sciences and medicine should be an
open source of shared knowledge. The public interest should prevail
over the interests of third parties, while taking into consideration
the danger of “sacrificing” individuals for a perceived common good.
53. I thus believe that the Parliamentary Assembly should recommend
a five-step approach to the Committee of Ministers which is compatible
with the divergent views in and amongst the Council of Europe’s 47
member States while assuring an outcome which is consistent with
Council of Europe values and principles. Step 1 would be to urge
those member States which have not yet ratified the Oviedo Convention
to do so without further delay, or, as a minimum, to put in place
a national ban on establishing a pregnancy with germline cells or
human embryos having undergone intentional genome editing.
54. Step 2 would be to foster a broad and informed public debate
on the medical potential and possible ethical and human rights consequences
of the use of new genetic technologies in human beings, so that
there is a fact-based and democratic basis for Step 3 – an assessment
by the Council of Europe Committee on Bioethics of the ethical and
legal challenges raised by emerging genome editing technologies,
in the light of the principles laid down in the Oviedo Convention
and the precautionary principle.
55. Step 4 would be the development by the Council of Europe of
a common regulatory and legal framework which is able to balance
the potential benefits and risks of these technologies with the
aim of enabling the eradication or cure of serious diseases, while
preventing abuse or adverse effects of genetic technology on human
beings. Finally, Step 5 would hand the power back to the member
States, on the basis of the public debate, the assessment of the
Committee on Bioethics and the common regulatory and legal framework devised,
to develop a clear national position on the practical use of new
genetic technologies, setting the limits and promoting good practices.
The only challenge will be time, which is not on our side.