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Health Privacy in Genetic Research: Populations and Persons

DOI:10.2990/28_2_99
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Bartha Maria Knoppers at McGill University
Bartha Maria Knoppers
Ma'n H. Zawati at McGill University
Ma'n H. Zawati
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Health
privacy in genetic research
Populations
and
persons
Bartha
Maria
Knoppers
Centre of Genomics
and
Policy
Department
of
Human
Genetics
McGill University
Montreal,
Quebec
Canada
H3A1A4
bartha. knoppers@mcgill. ca
Ma'n
H.
Abdul-Rahman
Centre of Genomics
and
Policy
Department
of
Human
Genetics
McGill University
Montreal,
Quebec
Canada
H3A1A4
man.abdul-rahman@mcgill.ca
The last decade has witnessed apolicy shift in
the ethics framework surrounding genetic
research moving from an emphasis on auton-
omy
and
privacy
towards
including more communi-
tarian
values, such as reciprocity, mutuality,
and
solidarity.1 Today, the era of
open
access databases
and
personal genomics via the Internet could again
affect this framework. As
both
longitudinal, popula-
tional studies
and
"virtual"
personal genomics strain
the confines of deontological
and
legal parameters of
consent to health privacy, it becomes
important
to ask:
What
are the convergent
and
divergent elements of
health privacy in these
new
contexts? And, is there a
need to reconstruct privacy?
Historically, the legal
and
ethical framework sur-
rounding the protection of privacy has been centered
on the right of the individual to control
and
limit the
flow of personal information. Indeed, the protection of
privacy is traditionally viewed as stemming from a
unilateral emphasis on
autonomy
as underscored by
article 12 of the 1948 Universal Declaration
of
Human
Rights:
"No
one shall be subjected to
arbitrary
interference
with
his privacy, family, home or corre-
spondence,
nor
to attacks
upon
his
honour
and
reputation. Everyone has the right to the protection
of the law against such interference or
artacks.i"
In parallel, health privacy is traditionally translated
and
protected under medical confidentiality within the
deontological confines of a physician-patient or a
researcher-participant relationship, as noted in, for
example, article 23 of the
World
Medical Association's
Helsinki Declaration, which states that: "Every pre-
caution
must
be
taken
to protect the privacy of
research subjects
and
the confidentiality of their
personal information
and
to minimize the impact of
the study on their physical, mental,
and
social
integrity.
,,3
But,
with
the emergence of large-scale populational
databases where individuals are viewed as members of
alarger community or population,
and
with
the
surfacing of virtual personal genomics, where the
physician-patient relationship is largely inexistent,
there is a necessity to review the social values
traditionally anchored in health policies.
More
urgency
arose
when
arecent
paper
exposed the possibility
that
SNP (single nucleotide polymorphism)
data
from a
participant in a Genome-Wide Association Study could
be used to "re-identify"
that
same individual in
another
POLITICS
AND
THE
LIFE
SCIENCES
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SEPTEMBER
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VOL.
28,
NO.2
99
Health privacy in genetic research
study," thereby igniting discussion over privacy
and
the
policies framing its protection.
In brief, three new realities are urging apolicy
review: the need for large-scale
populational
studies to
achieve statistical significance
and
agreater under-
standing of
normal
genomic variation; the shared
nature
of genetic information; and, the concept of
genomic databases as global public
goodsr'
Not
long ago, the practice of medical genetics was
limited to the study of
Mendelian
disorders or
chromosomal
anomalies." Recent research initiatives
have evolved from the study of single genes to the study
of the whole genome, efficiently concentrating on
genetic risk
factors.f
Likewise, large-scale biobanks
that
aim to study
normal
genomic variation across
healthy populations
and
pharmacogenomic studies
allow researchers to individually tailor drug type
and
dosage.f Research itself has become increasingly
collaborative
and
international.9
While the
protection
of privacy remains the
most
valuable asset of trust-seeking professionals
and
researchers, the recognition of new players such as
communities, societies, or
populations
as a whole
opens the gates to a more participatory
and
social
approach
to policymaking. In
populational
studies, for
instance, researchers
not
only strive to
protect
partic-
ipant
privacy (a unilateral dynamic)
but
do so while
collaborating
with
the
community
(a bilateral
and
multilateral dynamic). To cite one example, the
International
HapMap
Project has collected blood
samples
and
data
from families
and
communities
whose ancestors came from different
parts
of the
world
and
put
the results online.
The
goal
was
to
develop ahaplotype
map
of the
human
genome, which
will describe via ancestral blocks of SNPs (single-
nucleotide polymorphisms) the
common
patterns
of
human
genetic
variation.l"
To provide preliminary
consultation
and
ongoing
information
on the project, 11
the project set up
community
advisory groups com-
prised of people from the
participant
communities
and
asked the groups to suggest ways to limit any possible
harm
to thern.l'
The
ethical principle of reciprocity, which calls for
recognizing the
contribution
of the research
participant
through
ongoing
communication
and
transparency-
extending even to the
community
the
participant
represents-eharacterizes
the
HapMap
Project ap-
proach. In this case, privacy is no longer seen
exclusively as an obligation of the researcher
towards
the
participant
but
is given a more collective value by
the involvement of
community
members in the
process. 13
Moreover,
with
the potential benefits arising from
genetic information, the parameters of its disclosure
have shifted
towards
a
trend
that
advocates mutuality,
as for example,
when
family members of the partici-
pants
could be affected. In fact,
when
genetic
information could have an
impact
on family members,
traditional parameters proscribe disclosure to
third
parties (often presumed to include family members).
But, if confronted
with
such cases, Quebec's
Network
of Applied Genetic Medicine's Statement
of
Principles
on
Human
Genomic Researcb'" calls for researchers to
disclose genetic information to the biological members
of the family of the participant, in spite of the refusal of
the latter,
when
nondisclosure could lead to a serious,
foreseeable,
and
preventable
harm
to an identifiable
family member.F' This information, however,
would
not
be shared
with
employers or insurers.
Finally, the emerging concept
that
genomic databas-
es are global public goods adds a new element to the
risk/benefit balance since it is based on the concept of
solidarity, which recognizes the need for maximizing
the statistical value of the
data
by sharing.
The
protection of privacy is in no
way
lessened by this
new reality
but
rather
the
broad
consent to unspecified
future research is respected
and
protected
through
increased security measures
and
governance mecha-
nisms. This is reflected in the privacy policies of such
ventures as the
1000
Genomes Project, which clearly
states that:
although
... we will take
many
measures to
protect
your
privacy, we will generate lots of genetic information
about
each person whose sample is studied... As
technology advances, there may be new ways of linking
information back to you
that
we
cannot
foresee
now
...
We believe
that
the benefits of learning more
about
human
genetic variation
and
how
it relates to health
and
disease outweigh the
current
and
potential future
risks.i"
The
fact
that
there may be new, unforeseen ways of
linking information back to a
participant
brings to
light the technological reality
that
the traditional
emphasis on
data
protection (e.g., by removing or
100
POLITICS
AND
THE
LIFE
SCIENCES
•
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2009
•
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NO.2
Knoppers and Abdul-Rahman
coding sample identifiers) or on informed consent
alone to safeguard personal
data
has become unreal-
istic in the
context
of
open
access genomic
databases.I"
Hence, there is a need for increased security
and
governancc.l"
In conclusion, there is no
doubt
that
prospective
policies are needed
with
regard to genetic research. In
the case of
health
privacy, prospective policies
that
encourage transparency
and
good
governance will be
crucial in
promoting
the altruism of participants
and
in
bridging the mistrust sometimes associated
with
privacy issues in genetic research. As this brief
discussion has highlighted, the
notion
of privacy
cannot
continue to be interpreted
and
examined
through
lenses
that
only
protect
the individual rights
of the research participant.
Rather,
health privacy
should be dealt
with
through
a
more
comprehensive,
multilateral,
and
participatory
approach
that
reflects
the
current
dynamics
surrounding
the
world
of
modern
genetic research.
Bartha
Maria
Knoppers is Professor of Medicine at McGill
University
and
Director of the Centre of Genomics
and
Policy.
Ma'n
H. Abdul-Rahman is a lawyer
and
Professional
Associate at the Centre of Genomics
and
Policy.
References
1. B. M. Knoppers
and
R. Chadwick,
"Human
genetic
research: Emerging trends in ethics," Nature Review
Genetics,
2005,
6:
75-79.
2. United Nations, Universal Declaration
of
Human
Rights,
G.A. Res.
217
A (III), U.N. Doc Al810 at 71. Accessed online:
http://www.un.org/en/documents/udhr, 1948.
3.
World
Medical Association, Declaration
of
Helsinki:
Ethical Principles for Medical Research Involving
Human
Subjects, adopted by the
59th
World
Medical Association
General Assembly, Seoul, South Korea. Accessed online:
http://www.wma.net/en/3Opublications/1 Opolicies/b3/index.
html, 2008.
4. N.
Homer,
S. Szelinger, M. Redman, D. Duggan, W.
Tembe, et al. "Resolving individuals contributing trace
amounts of
DNA
to highly complex mixtures using high-
density SNP genotyping microarrays," PLoS Genetics, 2008,
4: e1000167. doi:10.1371/journal.pgen.1000167.
5.
Human
Genome Organization (HUGO) Ethics
Committee: Statement on Human Genomics Databases,
Recommendation 1. Accessed online: http://www.
hugo-international.org/img/genomic_2002.pdf, 2002.
6. F. S. Collins and V. A. McKusick, "Implications of the
Human
Genome Project for medical science,"
fAMA,
2001,
285:
540-544.
7. B. M. Knoppers, M. H. Abdul-Rahman, and K. Bedard,
"Genomic
databases and international collaboration,"
KLf,
2007,18:
291-311.
8. C. Maldrup, "Ethical, social
and
legal implications of
pharmacogenomics: Acritical review,"
Community
Genetics,
2001, 4:
204-214.
9. See the Public Population Project in Genomics (P3G)
website. Accessed online: http://www.p3g.org. See also the
International Cancer Genome Consortium website. Accessed
online: http://icgc.org/home
10. See the International
HapMap
Project website. Accessed
online: http://hapmap.ncbi.nlm.nih.gov
11. R. R. Sharp
and
M. W. Foster, "Involving study
populations in the review of genetic research,"
fLME,
2000,
28:
41-51.
12. See the International
HapMap
Project's consent form
template. Accessed online: http://hapmap.ncbi.nlm.nih.gov/
downloads/elsi/consent/Consent_F
orm_
Ternpla te.
pdf
13. P. M. Regan, Legislating Privacy: Technology, Social
Values,
and
Public Policy (Chapel Hill: University of
North
Carolina Press, 1995), p. 231.
14. The Quebec
Network
of Applied Genetic Medicine
(RMGA), Statement
of
Principles:
Human
Genome Research
(ver. 2000). Accessed online: http://www.cartagene.qc.ca/
docs/enonce.pdf, 2000.
15. The Quebec
Network
of Applied Genetic Medicine
(RMGA), "Confidentiality" section, Procedure 3.
16. See
1000
Genomes Project's informed consent form
template. Accessed online: www.1000genomes.org
17. P3G Consortium, G. Church, C. Heeney, N. Hawkins, J.
de Vries, et aI., "Public access to genome-wide data: Five
views on balancing research with privacy and protection,"
PloS Genetics, 2009, 5:e1000665. doi:10.1371/
journal.pgen.1 0000665.
18. S. Wallace, K. Bedard, A. Kent, and B. M. Knoppers,
"Governance mechanisms and population biobanks: Building
aframework for
trust,"
GenEdit, 2008, 6:
1-11.
Accessed
online: http://www.humgen.org/int/GE/en/2008-2.pdf
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Human FTO gene variants are associated with body mass index and type 2 diabetes. Because the obesity-associated SNPs are intronic, it is unclear whether changes in FTO expression or splicing are the cause of obesity or if regulatory elements within intron 1 influence upstream or downstream genes. We tested the idea that FTO itself is involved in obesity. We show that a dominant point mutation in the mouse Fto gene results in reduced fat mass, increased energy expenditure, and unchanged physical activity. Exposure to a high-fat diet enhances lean mass and lowers fat mass relative to control mice. Biochemical studies suggest the mutation occurs in a structurally novel domain and modifies FTO function, possibly by altering its dimerisation state. Gene expression profiling revealed increased expression of some fat and carbohydrate metabolism genes and an improved inflammatory profile in white adipose tissue of mutant mice. These data provide direct functional evidence that FTO is a causal gene underlying obesity. Compared to the reported mouse FTO knockout, our model more accurately reflects the effect of human FTO variants; we observe a heterozygous as well as homozygous phenotype, a smaller difference in weight and adiposity, and our mice do not show perinatal lethality or an age-related reduction in size and length. Our model suggests that a search for human coding mutations in FTO may be informative and that inhibition of FTO activity is a possible target for the treatment of morbid obesity.
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Resolving Individuals Contributing Trace Amounts of DNA to Highly Complex Mixtures Using High-Density SNP Genotyping Microarrays
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Author Summary In this report we describe a framework for accurately and robustly resolving whether individuals are in a complex genomic DNA mixture using high-density single nucleotide polymorphism (SNP) genotyping microarrays. We develop a theoretical framework for detecting an individual's presence within a mixture, show its limits through simulation, and finally demonstrate experimentally the identification of the presence of genomic DNA of individuals within a series of highly complex genomic mixtures. Our approaches demonstrate straightforward identification of trace amounts (<1%) of DNA from an individual contributor within a complex mixture. We show how probe-intensity analysis of high-density SNP data can be used, even given the experimental noise of a microarray. We discuss the implications of these findings in two fields: forensics and genome-wide association (GWA) genetic studies. Within forensics, resolving whether an individual is contributing trace amounts of genomic DNA to a complex mixture is a tremendous challenge. Within GWA studies, there is a considerable push to make experimental data publicly available so that the data can be combined with other studies. Our findings show that such an approach does not completely conceal identity, since it is straightforward to assess the probability that a person or relative participated in a GWA study.
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Involving Study Populations in the Review of Genetic Research
Article
  • Feb 2000
Genetic research can present risks to all members of a study population, not just those who choose to participate in research. The authors suggest that community-based reviews of research protocols can help identify and minimize such research-related risks.
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Implications of the Human Genome Project for Medical Science
Article
  • Mar 2001
The year 2000 marked both the start of the new millennium and the announcement that the vast majority of the human genome had been sequenced. Much work remains to understand how this "instruction book for human biology" carries out its multitudes of functions. But the consequences for the practice of medicine are likely to be profound. Genetic prediction of individual risks of disease and responsiveness to drugs will reach the medical mainstream in the next decade or so. The development of designer drugs, based on a genomic approach to targeting molecular pathways that are disrupted in disease, will follow soon after. Potential misuses of genetic information, such as discrimination in obtaining health insurance and in the workplace, will need to be dealt with swiftly and effectively. Genomic medicine holds the ultimate promise of revolutionizing the diagnosis and treatment of many illnesses.
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Ethical, Social and Legal Implications of Pharmacogenomics: A Critical Review
Article
  • Feb 2001
My aim was to examine the ethical, social and legal implications of pharmacogenomics. I performed a critical review of the literature. The primary focal point is the bioethical principle discussed. The second outcome measure is the perspective of the discussion. This review documents that the pharmacogenomics issues of concern are comparable to issues concerning other genetic developments in general. However, two main issues are particular to the case of pharmacogenomics. Firstly, this review reveals that society, industry, groups and individuals appreciate the prospect of pharmacogenomics very differently. Secondly, there is a lack of research into the post-marketing implications of pharmacogenomics. An extensive focus on the ethical, social and legal implications of pharmacogenomics, in terms of both pre- as well as post-marketing issues, is essential. Also, a multidisciplinary approach which includes individual and group opinions in an upfront manner in the research and development process is essential. Otherwise, there is a substantial risk that the positive prospects of pharmacogenomics will not survive due to fear and a lack of acceptance and understanding on the part of the general public.
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Human Genetic Research: Emerging Trends in Ethics
Article
  • Feb 2005
Genetic research has moved from Mendelian genetics to sequence maps to the study of natural human genetic variation at the level of the genome. This past decade of discovery has been accompanied by a shift in emphasis towards the ethical principles of reciprocity, mutuality, solidarity, citizenry and universality.
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LINE-1 ORF1 protein enhances alu SINE retrotransposition
Article
Retroelements have contributed over one third of the human genome mass. The currently active LINE-1 (L1) codes for two proteins (ORF1p and ORF2p), both strictly required for retrotransposition. In contrast, the non-coding parasitic SINE (Alu) only appears to need the L1 ORF2p for its own amplification. This requirement was previously determined using a tissue culture assay system in human cells (HeLa). Because HeLa are likely to express functional L1 proteins, it is possible that low levels of endogenous ORF1p are necessary for the observed tagged Alu mobilization. By individually expressing ORF1 and ORF2 proteins from both human (L1RP and LRE3) and rodent (L1A102 and L1spa) L1 sources, we demonstrate that increasing amounts of ORF1 expressing vector enhances tagged Alu mobilization in HeLa cells. In addition, using chicken fibroblast cells as an alternate cell culture source, we confirmed that ORF1p is not strictly required for Alu mobilization in our assay. Supporting our observations in HeLa cells, we find that tagged Alu retrotransposition is improved by supplementation of ORF1p in the cultured chicken cells. We postulate that L1 ORF1p plays either a direct or indirect role in enhancing the interaction between the Alu RNA and the required factors needed for its retrotransposition.
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Legislating Privacy: Technology, Social Values, and Public Policy
  • Jan 1995
  • 231
  • P M Regan
P. M. Regan, Legislating Privacy: Technology, Social Values, and Public Policy (Chapel Hill: University of North Carolina Press, 1995), p. 231.