Memorandum by the Royal Society of Edinburgh
1. The Royal Society of Edinburgh (RSE)
is pleased to respond to the House of Lords Science and Technology
Committee's Inquiry into Human Genetic Databases. The RSE is Scotland's
premier Learned Society, comprising Fellows elected on the basis
of their distinction, from the full range of academic disciplines,
and from industry, commerce and the professions. This reponse
has been compiled by the General Secretary with the assistance
of a number of Fellows with substantial experience of genetics
and genetic databases.
2. The specific questions identified by
the inquiry are addressed below:
Q1: What current projects involve collecting
genetic information on people in the UK? What other projects are
about to start? Are there collections of material (eg tissue samples)
that could be used to generate databases of DNA profiles?
3. Diagnostic laboratories (such as the
Wessex Regional Genetics Laboratory) are sent specimens from patients
suspected of having a genetic abnormality detectable by cytogenetic
or DNA analysis. These laboratories can handle about 8,500 diagnostic
specimens a year and of these about 5,000 have DNA extracted and
stored for an indefinite period. DNA is also collected by large
regional cohorts, such as by the Avon Longitudinal Study of Parents
and Children (ALSPAC), and by Police Forensic Science Laboratory
Dundee, and the UK National DNA Database at the Forensic Science
Service Laboratory in Birmingham.
4. In terms of new projects, the Division
of Molecular and Clinical Medicine at Edinburgh University is
in discussions with the Imperial Cancer Research Fund about the
creation of a genetic database for patients with a family history
of cancer. In addition, they are exploring the concept of creating
a database with tumour material from patients presenting to their
hospitals in Edinburgh with a diagnosis of cancer, where they
may wish at some stage to apply genetic tests to the material.
There is also an initiative planned by the Wellcome Trust and
Medical Research Council to take a representative sample of the
5. With regard to collections of tissue
samples, DNA could be extracted albeit with difficulty from fixed
cells from specimens sent to diagnostic laboratories. Such specimens
are stored for a number of years (varying with local laboratory
practice, but sometimes up to 90 years). However, these specimens
have been collected as part of the diagnostic process on individual
patient and there has never been any attempt for such specimens
to form part of a collection organised on a population basis.
There are also extensive collections of cervical cytology specimens
in all NHS Regions collected in the process of screening for pre-malignant
and malignant lesions of the cervix. These preparations consist
of relatively small numbers of cells fixed as smears to glass
microscope slides. DNA will be sparse, but in many regions these
will be fairly representative of the female population of reproductive
Q2: Why are these genetic databases being
assembled? How are these activities funded? What practical considerations
will constrain developments? Are there alternative ways of fulfilling
6. Human DNA/genetic databases and tissue
banks are essential resources that are invaluable for diagnostic
purposes and in research projects designed to improve our understanding
of the human genome.
7. Research projects are contributing to
the knowledge of the relationship between disease and genetic
make-up, with implications for quality of life and the relief
of human suffering. Diagnostic laboratories use diagnostic specimens:
(i) to diagnose conditions for which the specimen was submitted,
and (ii) anonymously as control material for other investigations.
They use research specimens only: (i) to undertake research on
the condition for which the specimens were obtained, or (ii) anonymously
as control material for other investigations.
8. With regard to funding, genetic databases
assembled for diagnostic purposes are funded by the NHS, while
those for research purposes are funded by Research Councils and
charitable organisations. Genetic databases are also used and
funded in other areas such as forensic science, where DNA databases
are contributing significantly to the detection of crime.
Q3: What is the genetic information that is
being collected? How is it being stored and protected?
9. Collections of DNA and/or information
from patients from diagnostic laboratories contain information
on a variety of conditions including mental retardation, behavioural
abnormalities, diabetes, reproductive difficulties, cytogenetic
abnormalities and specific malignancies. In addition to DNA, tissues
and cell suspensions, these laboratories collect information on
the immediate or extended family, relevant clinical information
and the results of the various diagnostic tests being undertaken.
The data from these laboratories are stored in computers and are
protected by restricted access, safeguarded by appropriate codes
and the professionalism of their staff.
Q4: How do the organisations involved see
their responsibilities regarding privacy; consent; future use;
public accountability; and intellectual property rights?
10. The RSE believes it will be important
to plan how to maintain individual databases while maintaining
confidentiality, and to ensure that human genetic databases are
made available in a carefully regulated and controlled manner
but in such a way that important research is not inhibited. In
this regard, it is often important to be able to inquire of the
clinical outcome of the patient from whom the material was originally
banked and to be able to know what happened to the patient from
whom the material was taken.
11. In diagnostic laboratories, information
identifiable with a patient is given only to other diagnostic
laboratories, or clinicians on an individual basis, where the
information is necessary to:
(i) make a genetic diagnosis (eg part of
a family being investigated by two different laboratories);
(iii) conduct ethically approved research;
(iv) assist in the clinical management of
the individual from whom the data was collected.
12. Such information is only provided with
the written permission of the referring doctor, and written consent
is obtained from all research subjects and all research protocols
are passed by the relevant Multi-centre Research Ethics Committees
or Local Research Ethics Committees.
13. There are, however, some concerns about
the quality of consent provided, given that the agreement from
a given patient to provide a sample may be relatively or completely
unspecific as to its future use. One question which may need to
be addressed concerns whether or not use of samples, additional
to that first proposed as agreed to, requires that the individual
is re-invited to consent. This issue is significant because subsequent
genetic tests may reveal different information which might ultimately
be of more significance to a patient and his/her family.
14. Questions about tracing individuals
will also need to be addressed. As with anonymised HIV testing
for epidemiological purposes, there is a residual concern thatif
therapy becomes available, or additional information comes to
lightthere may be a tension between the scientific endeavour
and patient care.
15. It would appear that, to a great extent,
intellectual property questions are straightforward, in that the
development of a technique or therapy from human genetic material
does not appear to provide the donor with any rights to benefit
financially from the invention.
16. As for the question of accountability,
arguably this will only be achieved by close monitoring of those
facilities involved in such research, and a strict adherence to
optimal observance of the law of consent and the professional
and legal commitment to confidentiality.
Q5: How do they see their activities in the
area of genetic databases developing in the future? What advances
in sequencing, screening and database technology are they anticipating?
17. It is clear that both molecular and
symptomatic screening for those who may be genetically susceptible
to common cancers are facing increasing demands and this is likely
to extend also to other common diseases with identifiable genetic
components, such as diabetes and degenerative cardiovascular disease.
Genetic predisposition to disease is likely to become important
and the tailoring of treatments to an individual's genetic constitution,
initially by screening for genotype at particular loci, may develop.
A key consideration will be the ethical problems involved in such
screening. These issues are addressed further in the Society's
response on Preimplantation Genetic Diagnosis.
18. The principles that underline decisions
to set up future screening programmes remain unchanged: the disease
is common and of consequence, there is an effective screening
test (irrespective of its nature), and early treatment favourably
alters the outcome. The existing and future national screening
programmes within the various regions should be co-ordinated and
monitored more effectively through a central agency to detect
problems and poor performance before these enter the public domain.
Demands for screening, however, are likely to increase, with a
risk that failure to screen will be perceived as negligence. It
will become correspondingly essential to tackle the ethical question
of who is entitled to have access to the information, particularly
in connection with medical insurance.
19. In terms of future advances in technology,
there is a great deal of activity in the area of DNA screening
that can be divided into low/medium throughput and high throughput.
In the former case it is now possible to analyse DNA for single
nucleotide poloymorphisms reliably and reproducibly and therefore
to gain knowledge of value in the field of clinical diagnostics
(eg to develop screening methods to differentiate between the
many strains of human papilloma virus to diagnose the onset
of cervical cancer). These new DNA-based methods are likely to
be much more reliable, faster and cheaper than existing cytological
methods. With the availability of high-throughput DNA analysis,
significant advances are being made in DNA array technology to
enable several thousand samples to be analysed simultaneously.
Q6: What lessons should be learnt from genetic
database initiatives in other countries?
20. Most common illnesses involve genetic
risk factors but individuals with the critical combination of
susceptibility genes will only develop the disease when exposed
to particular environmental risk factors. The genetics of common
disease, however, is very complicated and poses a huge challenge.
There are two complementary approaches to the problem: (i) to
study large genetically mixed populations, and (ii) to study isolated
populations with reduced genetic heterogeneity (such as Iceland
and Finland, or Sardinia).
21. At a seminar on National Databanks of
Medical Records, on 14 February 2000 at the RSE, Ragnheidur Haraldsdottir,
Deputy Permanent Secretary, Icelandic Ministry of Health and Social
Affairs described how a database has been produced in Iceland
from the medical records of almost the total population, secured
by anonymity and encryption, and funded by a private pharmaceutical
company. The information from the medical records included only
the key features from each record, and any individual who did
not wish to take part had to opt-out in writing to the Department
of Health. It was also expected that a genetic base would soon
be available, linked to this medical database, providing an unprecedented
wealth of information. The major ethical problem presented by
the Icelandic database is that the concept of truly informed consent
for its use in any future project cannot be achieved with the
documentation currently available. The implications of this ethical
dilemma will become more apparent with attempted use of the data
in this database for particular research projects.
22. In responding to this inquiry the Society
would like to draw attention to the following Royal Society of
Edinburgh responses which are of relevance to this subject: Consent
and the Law (December 1997); Review of the Common Law Provisions
Relating to the Removal of Gametes and of the Consent Provisions
in the Human Fertilisation and Embryology Act 1990 (April
1999); Preimplantation Genetic Diagnosis (March 2000) and
Healthcare in 2020 (September 2000). Copies of the above
publications and further copies of this response are available
from the Research Officer, Dr Marc Rands.
Professor P N Wilson CBE FRSE