Letter from SmithKline Beecham
Further to your letter of 20 July, I have pleasure
in enclosing SmithKline Beecham's (SB) response to the above enquiry.
Healthcare systems across Europe are a substantial
but underused research resource. They have much to offer in epidemiology,
technology assessment, outcomes research and population genetics
and there are many ways in which industry together with healthcare
providers and academic groups can use healthcare information databases.
As one of the world's leading research based healthcare companies,
SB is committed to exploring these opportunities. We therefore
welcome the opportunity of responding to this enquiry as it promises
to broaden the debate around a vital element of healthcare databases,
namely the potential offered by the collection of genetic sequence
I hope that the enclosed submission outlining
SB's approach to genetic databases in the UK represents a useful
contribution to this debate. I would obviously be delighted to
elaborate on any of the issues raised in it, if the sub-Committee
felt that might be helpful.
Chairman, Research & Development
SmithKline Beecham Pharmaceuticals
There are many ways in which industry, together
with healthcare providers and academic groups, can use information
generated from genetic databases to meet the challenges of a new
era of medicine and healthcare provision.
SB has several collections of DNA samples in
the UK for use in the search for new disease genes suitable as
targets for drug development and to validate existing targets
using genetic approaches.
The main constraints on SB's work in this area
are the time taken to find suitable clinical cohorts with a high
quality of phenotypic data and ethnically matched controls that
can be used in association studies. Finding academic centres willing
and able to collaborate with industrial partners is also a constraint.
SB acknowledges the requirements of the EC Data
Privacy Directive in relation to the collection, storage and analysis
of patient data.
SB does not believe that the potential of bigger
and more numerous genetic databases raises any new intellectual
property issues for industry, academia or the NHS.
SB treats all DNA samples held in UK databases
in the strictest confidence and implements, where necessary, appropriate
organisational and technical measures against unauthorised or
unlawful use of such data.
The UK should be aiming to establish a non-restrictive
legislative environment which protects the individual while promoting
SB believes that the concerns expressed about
industry involvement in genetic database initiatives can be assuaged
by incorporating the best practice developed by companies such
The basic infrastructure to realise the potential
offered by large-scale genetic databases is already in place.
What is now required is the political will to tackle the issue
of public acceptability.
1. The science and technology of genetics
is advancing at a remarkable rate. The completion of human genome
mapping, the development of a high-density Single Nucleotide Polymorphisms
(SNP) map and associated technologies over the next one-two years
will further the identification of disease susceptibility genes
for common diseases and the identification of genetic markers
which can be used to predict an individual's response to a medicine
(pharmacogenetics). In general, genetic databases represent an
important new resource that will:
2. Facilitate the identification of additional
disease susceptibility genes: For common diseases such as cardiovascular
disease, asthma, osteoarthritis, migraine and Alzheimer disease
there are a number of variants of susceptibility genes which interact
with environmental factors to cause disease. Identification of
these genes involves the study of individuals with and without
the disease and is recognised as an increasingly important aspect
of research to find new medicines.
3. Facilitate an understanding of susceptibility
genes in disease: Genetic databases will enable us to study the
impact of carrying certain variants of susceptibility genes on
disease (eg impact on disease severity and age of onset) and can
also record lifestyle variables which will greatly facilitate
an understanding of the environmental factors which interact with
susceptibility genes to cause disease.
4. Identify genetic markers to predict responses
to medicines: As genetic databases develop, they will include
information about medicines prescribed and patients' responses.
Comparing the DNA of patients who responded in a particular fashion
(eg with an adverse event) with suitably matched controls who
did not experience the adverse event, may enable the identification
of DNA markers to predict that response.
5. Provide a basis for healthcare providers
and governments to estimate more precisely pharmacoeconomic consequences
of healthcare and its management: By collecting information on
the medical management of patients with disease over time and
their outcomes, the value of particular medical interventions
can be evaluated to provide important information to estimate
the pharmacoeconomic consequences of healthcare management. Because
of this tremendous potential in helping to deliver better healthcare,
SB welcomes the proposal of the Wellcome Trust and the MRC to
establish a new genetic database. We believe that it is highly
appropriate for industry to be involved in this, and other, national
initiatives, based upon our shared desire to deliver better healthcare
and the expertise we have already developed in this area. Outlined
below are SB's responses to those questions raised by the Sub-Committee
based upon the principles and practices we adopt when collecting
DNA samples in the UK.
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?
6. SmithKline Beecham (SB) has several collections
of DNA samples for use in population association studies in the
UK. These include nearly 3,000 samples from a cohort of women
in the age range of 45-55 from the Aberdeen region who have had
two bone mineral density scans at five year intervals. In addition,
we have over 5,000 anonymised control samples from the same region.
We have a population collection of individuals with schizophrenia
from Scotland and London, and a collection of controls and patients
with psoriasis from Stoke and Bristol.
7. At present all future plans for further
sample collection are on hold until after the merger to form GlaxoSmithKline,
as we need to compare our portfolios of samples before further
studies are initiated. The DNA samples could feasibly be used
to generate additional genetic databases.
Why are these genetic databases being assembled?
How are these activities funded? What practical considerations
will constrain developments? Are there alternative ways of fulfilling
8. These collections are being used in the
search for new disease genes suitable as targets for drug development
and to validate existing targets using genetic approaches. The
work is funded by SB as part of its Discovery Research programme.
9. The work is constrained by the time taken
to find suitable clinical cohorts with a high quality of phenotypic
data and ethnically matched controls that can be used in association
studies. Finding academic centres willing and able to collaborate
with industrial partners is also a constraint.
10. Our strategy requires sampling from
the human population to search for genes relevant to human disease
processes especially those related to an ageing population, for
example type 2 diabetes and many late-onset neurological disorders.
There are no direct alternatives to studying the diseases in human
What is the genetic information that is being
collected? How is it being stored and protected?
11. Depending on the project, we collect
basic phenotypic information on individuals including age, gender,
racial origin plus medical information necessary for the disease
under study. This might include weight, height and blood pressure.
This phenotype information is stored in a separate database from
any genotyping data generated using the DNA from patients. All
DNA samples are bar-coded and no patient information is available
within the laboratory environment. No names or other personal
identifier information are ever stored in SB. All information
is stored on separate servers and can only be accessed through
a secure password system. There are only a limited number of named
individuals who are able to access the databases with phenotype
information and the genotyping data and this only occurs at the
analysis stage. SB acknowledges the requirements of the EC Data
Privacy Directive in relation to the collection, storage and analysis
of patient data.
How do the organisations involved see their responsibilities
regarding privacy; consent; future use; public accountability;
and intellectual property rights?
12. SB has considerable experience in performing
clinical trials under very closely regulated conditions which
are designed to protect patients from misuse of their personally
identified clinical data. The process of prior consent and practices
to ensure patient privacy and confidentiality are central to patient
protection. SB is therefore very conscious of our responsibilities
for any genetic data that we hold, hence the development of security
systems, like the one described above, which make it extremely
difficult to identify anybody individually. We treat all genetic
data in the strictest confidence and implement, where necessary,
appropriate organisational and technical measures against unauthorised
or unlawful use of such data. Individuals participating in studies
give their prior consent in writing and our procedures meet with
all the current guidelines in the Helsinki and UNESCO declarations
plus the appropriate European laws relating to scientific research
13. All individuals have the right to withdraw
from studies and are now also, following implementation of the
EC Data Privacy Directive, able to decide if their samples can
only be used for specific studies or for a secondary purpose,
for example in a broader analysis of the disease process.
14. The mere identification of the sequence
of nucleotide bases in segments of DNA contained in databases
does not in itself represent a patentable invention. However patents
on DNA (genes) may nevertheless be obtained in appropriate circumstances.
This is clear from the extensively debated European Biotechnology
Directive (98/44/EC), Articles 1 to 11 of which were implemented
nationally in the UK on 28 July 2000. While controversial, patenting
genes is entirely appropriate since the rationale for the patent
system is to stimulate R&D investment. Developing treatments
for presently incurable diseases using the promising but hugely
costly genomics-based approach is only possible within a climate
of strong IP protection.
15. To be patentable an invention must be
novel, non-obvious and have utility. Finding, isolating and purifying
gene segments associated with disease will in most cases represent
inventive activity, deserving of patent protection.
16. It is sometimes argued that patenting
of genes and other research tools stifles research: if a company
obtains a patent on an important gene, no-one else can do research
on the gene and important medical advances may be delayed. This
is a misconception. UK patent law permits non-commercial research
on patented subject matter, so pure research by academic institutions
in the UK is not affected by the existence of patents. Even in
relation to commercial research it does not necessarily follow
that others are irrevocably blocked as it will often be possible
to negotiate a licence under the patentor challenge its
validity. Finally, it is always open to third parties to obtain
"dependent patents"that is to say patent a new
use for an already patented gene. The original finder of the gene
could not then commercialise the new use without a licence under
the dependent patent. This situation, which tends to stimulate
cross-licensing, is inherent in the patent system. It is frequently
encountered with pharmaceuticals and is in principle no different
in the genomics field.
17. In this way, SB does not believe that
the potential of bigger and more numerous genetic databases raises
any new intellectual property issues for industry, academia or
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?
18. It is clear that databases will continue
to develop in the next few years as more work focuses on efforts
to understand the mechanisms involved in the susceptibility to
and progression of complex disease in an increasingly ageing population.
There will be growing emphasis on obtaining specific quantitative
phenotypic measures, for example biochemical markers, as surrogates
of the disease process. This will increase the demands on individuals
participating and lead to increased costs and calls for improved
vigilance in the security of information obtained. The completion
of the human genome sequence and the current efforts to identify
single nucleotide polymorphisms will lead to increased efforts
to find genes involved in the more complex disorders, for example
degenerative diseases. We would expect to see DNA sequencing technologies
advancing in the next 10 years, to a level that enables sequencing
a substantial proportion of an individual's genome in a short
time-frame. This will lead to the ability to diagnose diseases
or the potential risks to health on an individual basis based
on the variants occurring in a particular genome. Thus the goal
of personalised medicine will start to be possible leading to
increased demands on the health service for both screening and
What lessons should be learnt from genetic database
initiatives in other countries?
19. Countries such as Denmark have a long
history of developing population-based databases for genetic epidemiology.
They have one of the longest experiences in Europe of the issues
around such databases of privacy and access to data. These started
with the twin registries and have developed into more population-based
systems of data and blood collection. The Danes have handled such
issues with sympathy maintaining a balance between personal privacy
as well as enabling science to continue. The UK should be aiming
to mirror this approach with a non restrictive legislative environment
which protects the individual while promoting the science.
20. Important lessons can also be learned
from an example of successful industry involvement in a public-private
approach to a genetic project: the SNP Consortium. This international
research initiative, by all measures a successful collaboration,
between industry (initially 10 pharmaceutical companies including
SB) and the Wellcome Trust, contracts with academic institutions
to perform the work that is placed in the public domain. It is
successful because it represents the generation of fundamental
pre-competitive information that also can be used by all parties
for developing standards in order to create the research framework
for the provision of better healthcare.
21. Closer to home, the British NHS represents
a singular but under-utilised resource for population genetics,
and healthcare informatics more generally. It has the potential
to offer unparalleled access to areas of sample acquisition, such
as across primary care, that is not possible in more fragmented
health systems or in the smaller cohorts studies hitherto. A national
structure could provide homogeneity of data acquisition that is
essential for large-scale studies.
22. The likely benefits accruing to the
NHS (and the UK as a whole) include:
Progress in understanding disease
at the public health level.
Provision of new resources to support
Stimulating production of novel therapeutics,
diagnostics and the better targeting of treatment.
Attracting inward investment by companies.
23. Concerns have been expressed by some
on industry involvement as a partner with public bodies in genetic
database initiatives. There is often an implicit assumption that
genetic research conducted by industry is, by virtue of its commercial
nature, ethically questionable. In fact, clinical research studies
performed in academic institutions by academic researchers using
public funds can often discover data of commercial value. Consequently
there is a significant ethical problem in that the original informed
consents for such possible commercialisation may not have disclosed
the possible financial consequence: informed consent for commercial
uses should not be assumed to be implicit for academic investigators
and institutions and explicit only for industry-supported research.
24. We believe that the other concerns expressed
about industry involvement in genetic database initiatives can
be assuaged by incorporating the best practice developed by companies
such as SB:
(i) Protection of patient privacy and confidentiality
and using the "opt-in" approach to participation based
on informed consent.
(ii) Correcting the widespread misunderstanding
that raw gene sequence information can be patented and that the
patent holder in some way owns that sequence as it exists in individuals.
25. Success at a national level within the
UK will undoubtedly require a radical strategy which seeks to
identify and mobilise the appropriate scientific and clinical
skills, to build large-scale computational infrastructure and
to address public concern over many of the ethical issues touched
upon in this paper in the context of medical privacy, use of anonymous
data and consent issues. This will not be easy. It will involve
significant funding and an unprecedented working relationship
between the public and private sector. However, these are not
insurmountable barriers. The basic infrastructure is already in
place, as witnessed by the collaborations already underway, on
a smaller scale, within companies like SB. What is now required
is the political will to tackle the issue of public acceptability.
To date the UK population has been willing to participate in clinical
research. It is important that this willingness to participate
is not lost by confusing issues of genetic modification of foods
with advances in medical diagnostics and therapy.
4 October 2000