Memorandum by the Academy of Medical Sciences
1. The Academy of Medical Sciences represents
many of the UK's most distinguished researchers in medicine and
2. Fellows of the Academy are associated
with many different types of genetic database, within the definition
of "collections of genetic sequence information, or of human
tissue from which such information might be derived". Time
has not permitted a full survey of members' involvement, and details
of individual projects will presumably be supplied by the relevant
3. This response therefore concentrates
on the general types of collections of which we are aware, and
the purposes and constraints on research involving these databases.
4. TYPES OF
Genetic collections may be derived from research,
or from clinical practice.
4.1 Clinically derived collections include:
4.1.1 Every molecular diagnostic laboratory
will have banked DNA from patients who have been clinically tested
for any of a wide variety of genetic disorders. These include:
Samples from individuals known to
be affected with a genetic condition, where the present state
of scientific knowledge or service development does not allow
molecular diagnosis. When such diagnosis becomes available, other
family members may want testing to see if they have inherited
the mutation. Without material from an affected person, it is
impossible to interpret negative mutation studies.
Samples from individuals with undiagnosed
abnormalities (including babies with congenital abnormalities),
stored in the hope that future research may allow a definitive
diagnosis and hence accurate counselling for family members. Many
of these samples are stored from individuals who are no longer
4.1.2 The majority of pathology laboratories
(such as histopathology and haematology) will retain portions
of tissue taken for diagnostic purposes. These samples are retained
predominantly in order to allow subsequent confirmation or refinement
of diagnosis, for the benefit of the patient or the patient's
family, as new techniques evolve. However, they also form a potentially
valuable research resource. Archived tumour samples are particularly
important for genetic studies. These tissue samples can generate
4.1.3 Guthrie cardsregional neonatal
screening programmes receive Guthrie cards, with a number of drops
of blood on them, from virtually every newborn child in the United
Kingdom. Some of these samples are stored for protracted periods
of time; regrettably, long term storage has become less frequent
over time. Although limited in quantity of material per person,
these form a potentially very large source of DNA samples for
some types of research.
All these collections are funded as part of
the NHS service, are linkable to NHS notes on the individual,
with NHS service arrangements for confidentiality and access.
Such collections are not subject to research ethics approval.
Research use of these samples is (and should be) subject to search
ethics review and approval.
4.2 Research derived databases
These may be divided into collections of information
and material relating to individual diseases, and multi-purpose
collections (often populations collected as epidemiological cohorts).
Large numbers of both types of study have been carried out in
the past, and material from many of them is still stored. These
studies will normally have been conducted under protocols agreed
by research ethics committees. The samples often come from a mixture
of two sources. The researcher will seek out suitable subjects
and ask them to take part. Service departments will also have
suitable material from subjects previously seen in clinic, stored
with appropriate consent for future research use.
5. PURPOSES OF
5.1 The samples collected for clinical purposes,
and in accordance with the standards required for accreditation
of clinical laboratories, may be used for diagnosis, mutation
analysis, and counselling of families with genetic diseases. Because
they are carefully characterised, and can be associated with clinical
information, they also have potential as research.
5.2 Research collections have been assembled
for a variety of purposes, in general with the approval of a research
ethics committee, and often with external funding. However, where
clinical samples have been used for research purposes, or have
been secondarily assembled into research collections, issues of
consent may be less clear. Where samples have been specifically
collected by research laboratories, for research purposes, they
may secondarily give rise to clinically relevant information.
It is widely accepted that such information should only with great
caution be fed back to patients or used for clinical purposes,
unless it has been independently confirmed to the operating standards
accepted in clinical diagnostic laboratories. Although this is
widely accepted we are not aware that formal guidelines are in
place to ensure uniformity of practice in this area.
5.3 The great majority of such studies are
intended to clarify the relationship between variation in human
health, development, or behaviour with specific genetic variation.
This is an area of very significant promise for the future, in
terms of understanding the biological basis of medical conditions,
from which may flow new diagnostic and therapeutic modalities.
5.4 Most of these research studies are funded
by external research funding organisations, such as the MRC and
medical research charities.
5.5 We do not consider that there are at
present any alternative practicable ways of unravelling the biology
of human health and disease, other than by studies correlating
phenotype with genetic variation in one way or another.
5.6 Our Fellows anticipate that research
of this nature will expand in the future. They anticipate that
current early exploratory studies will allow more focussed questions
to be addressed particularly in relation to interactions between
environmental factors such as diet or exercise, or toxic compounds
in the environment or drugs, and particular genotypes.
5.7 It is also widely expected that technical
capabilities for genotyping will become very, very much improved,
and that costs of genotyping will come down dramatically over
the next five years.
6. Several Fellows pointed to the important
opportunities raised by the MRC and Wellcome calls for new case-control
and cohort studies. It is expected that these will be carried
out in accordance with the MRC's recently issued ethical guidelines.
7. A number of potential constraints
on this type of research either exist or can be anticipated. The
costs of recruiting participants, collecting data and undertaking
large numbers of genetic typings is considerable. The technology
for preserving and maintaining an adequate supply of DNA for very
large numbers of typings is as yet imperfect.
The collection of clinical data in large prospective
studies would be considerably enhanced if more effective electronic
records were available in the NHS. This would entail developing
mechanisms for obtaining appropriate patient consent. Without
attention to these matters the value of the NHS as a research
base, for the benefit of the health and economy of the country,
will be greatly diminished.
8. It is of the utmost importance that the
reasonable and appropriate concerns about privacy and confidentiality
and appropriate use of genetic information should be openly discussed
and resolved, to allow research for the benefit of society to
go forward under proper control. While fully recognising the importance
of public assent and individual consent to studies of this sort,
there is some concern that it may be retarded by excessive conservatism
on the part of some ethics review bodies. Fellows have experiences
of Research Ethics Committees being extremely anxious about relatively
straightforward genetic linkage studies on clinically derived
samples because of a confusion between research and diagnostic
tests, and the belief that research studies are likely to generate
predictive health information which is only infrequently the caseclinical
samples generally already have diagnostic information attached
to them. An exaggerated perception of the extent of "genetic
determinism" leads to undue fear about genetic studies. Many
of the studies under consideration must deal with identifiable
samples because of the need to correlate laboratory and genetic
information, but once correlated the data are analysed and published
in aggregate anonymised format and mechanisms for ensuring appropriate
individual confidentiality are not excessively hard to devise.
Research based on archived and anonymous samples is exceedingly
unlikely to lead to any form of harm to individuals, and consent
procedures should be set at levels appropriate to the risk of
harm. This research will often require very large numbers, and
will therefore be facilitated by access to diagnostic databases
such as cancer registers. Considered over-regulation of privacy
issues may damage these, without any corresponding gain to the
9. The purpose of these studies is to generate
information relevant to health. Turning this basic research into
usable health products will require commercial involvement. This
should generally be of an open, non-exclusive nature, and must
be fully explained to research subjects as part of the consent
procedure before participation.
This response was prepared on behalf of the
Academy by Professor Martin Bobrow, FMedSci, Professor of Medical
Genetics at the University of Cambridge, with contributions from
Professor Patricia Jacobs, FMedSci, Director, Wessex Regional
Genetics Laboratory, Salisbury, Professor David Porteous, FMedSci,
Western General Hospital, Edinburgh, Professor Andrew Read, FMedSci,
St Mary's Hospital Manchester, and Professor Ellen Solomon, FMedSci,
Head, Division of Medical & Molecular Genetics, Guy's, Thomas'
School of Medicine, London.