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January 2003
PART 1: FOCUS AND RATIONALE
1. INTRODUCTION
The APEC Center for Technology Foresight has received funding from the
APEC Central Fund for a Foresight study of “DNA Analysis for Human
Health in the Post- Genomic Era”. This paper reviews the background
to the study and the available Foresight studies that have been carried
out in the area in order to provide a framework for the present project.
Over recent years there has been intensive
research towards the understanding of genes and their link to diseases
and the mapping of the human genome. This opens the way to a new approach
to biology, a new way to consider human disease, new avenues for drug
development and drastic changes in health care systems. The implications
for the next decades are enormous and there are many issues-scientific,
industrial, social and ethical- which need to be addressed. Foresight
provides a way to tackle such a complex set of issues as demonstrated
in the recent project on “Nanotechnology: the technology for the
21st century” completed in 2002 (APECTF 2002).
2. GENOMICS AND HUMAN HEALTH
The link between genetics and disease requires some discussion. Although
many diseases can be traced through families because they result from
a single defective gene, with few exceptions they are rare and are not
a major health problem. On the other hand most common diseases are the
result of infectious agents or other environmental factors and for many
of these the cause is unknown. However there are two major influences
of genetics in these latter situations. Firstly any disease process can
be explained ultimately in biochemical terms which, in turn, reflect gene
function. Secondly there is a remarkable degree of individual variation
to susceptibility to environmental factors that can be linked to genetic
variations.
Over the past 20 years important steps
have been taken in the understanding of the molecular basis of many single-gene
disorders based on inheritance e.g. congenital malformation and mental
retardation. A start has been made on a better understanding of the genetic
component of diseases such as strokes, diabetes and cancer. This is leading
to the development of therapeutic agents to deal with these diseases.
The announcement of the success of the
Human Genome Project has given an enormous thrust to this field. The project
was carried out independently in the private and public sectors using
different but related approaches. In June 2001 both Celera Genomics, a
private company (Venter et al 2001) and the International Human Genome
Mapping Consortium, funded by governments and charities in several countries
(Lander et al 2001), announced the completion of “working drafts”
of the human genome.
The human genome seems to contain about
32000 genes and it will take a long time to determine the function of
all of them and how they interact. However it appears that human DNA sequences
are 99.9 % identical to one another and it is the 0.1 % of variations
that are of great practical value. Within genes it is possible to identify
DNA markers which are sites (roughly 1 in 1900) at which single nucleotide
bases differ from person to person. These single nucleotide polymorphisms
(SNPs) offer the possibility of linking genetic variations in populations
to specific diseases. The result is that medical treatment could change
to become comprehensive and highly integrated, highly individualised and
focussed more on prevention than on treatment of established diseases.
3. EMERGING TECHNOLOGIES
3.1 Diagnostics
Even when the Human Genome Project is finished, we will still not have
the genome of a single person; the consensus sequence is based on DNA
from 10 different people. The challenge is to develop cheap, fast techniques
which will provide individuals with their own genome sequence. Current
techniques are relatively slow and the consensus of opinion is that it
will take about 5 years before sequencing technology reaches a point where
it is fast enough and cheap enough (say US$ 1000 per person) to make personal
genomics feasible (Westphal 2002). As noted above the variations between
individuals are small and thus accuracy is essential.
One approach is that of DNA micro-arrays
or DNA chips (Anon 2001). The surface of the array (about 1 sq. cm overall)
consists of a glass or silicon substrate on which fragments of DNA strands
from a known source are fixed by chemical reaction. To analyse a sample
the target material, labelled with a fluorescent molecule, is then exposed
to the chip to see whether it will react with any of the complementary
strands. By locating and quantifying the fluorescent signal in each DNA
probe deposited on the chip the nature of the target material can be characterised
in one step. It is possible to analyse tens of thousands of genes simultaneously
on one chip and to compare gene expression patterns in normal vs diseased
samples or in treated vs non-treated samples. The data from these comparisons
can be used to help drug researchers identify drug targets, study potential
toxicities of compounds and define biological pathways.
3.2 Bioinformatics
The efforts of genomic researchers have yielded thousands of genes and
millions of SNPs as well as millions of potential proteins coded by the
genes. The amount of data generated doubles approximately each year. As
a result of the need to process these data there has been a convergence
of information technology and biotechnology into the new field of bioinformatics
(ISR 2002). At its broadest, bioinformatics is the application of information
technology to the organisation, management, mining and use of life-science
information. This takes in bioinformatic databases, genomic data analysis,
proteomic data analysis, protein 3-D structure analysis and clinical and
pharmacological data analysis.
The bioinformatics industry is already
very large and is growing rapidly. On the narrow definition, the world
market of some US$ 470 million in 2000 is predicted to reach US$5000 million
by 2010. On the broad definition the world market of some US$ 22 billion
in 2000 could reach US $ 40 billion by 2005.The need to process extraordinarily
large amounts of data is driving the development of larger and faster
computer systems. The growth of the information technology industry will
be in bioinformatics not in communications. This has significant implications
for the smaller and developing economies in the Asia-Pacific region.
3.3 Proteomics and Drug Development
Proteomics is the large scale analysis of the products of genes. The aim
is to define the protein complement, or proteome, of cells and how proteins
interact with one another. Proteomics is complementary to genomics because
it focusses attention on gene products. By interacting with each other
and the environment in intricate ways, the relatively small human genestock
confers high variability with, for example, single genes expressing multiple
proteins (WHO 2001).
The ultimate aim is to develop new therapies,
particularly in personalised medicine, formulated on personal genetic
make-up. The promise of personalised medicine or pharmacogenomics is based
on the fact that people react differently to certain drugs depending on
their SNP variations. Thus adverse drug reactions could be prevented and
more effective medications could be made available (Bock et al 2001).
To reap the rewards of genomics, pharmaceutical
firms need to computerise and automate the process of drug discovery to
a greater extent than ever before. All the drugs that have been invented
up to now have come from targeting the protein products of some 500 genes.
Although a total of some 32,000 genes has been estimated through the Human
Genome Project only 10% of these are considered to be potential drug targets
i.e. some 3000 targets (Anon 2001a).
While there is scope for improvements
in drug discovery it is sobering to recognise that only 1% of a drug company’s
discoveries ever reach the market, the rest are written off at a loss.
Even if the absolute number of drugs were not increased significantly
the efficiency of the innovation process could be boosted and this could
drastically reduce the cost of producing a new drug (possibly by up to
US$ 300 million).
3.4 Gene Therapy
More advanced knowledge of genes and their interactions offers the possibility
for curing disease by altering the genetic make-up of cells, organs and
individuals through gene therapy. Somatic gene therapy (altering make-up
of body cells not involved in reproduction) involves the modification
of the genome of individual organs or tissues. Although somatic gene therapy
is the subject of intense research there have been few successes.
The main problem is to deliver the “healthy”
gene to the right cells and to insert it in the cell’s genome in
a stable and effective manner. It appears that genetic diseases such as
haemophilia and cystic fibrosis, and possibly certain cancers, can be
treated by gene therapy and it could commonly be used for these by 2010
(WHO 2001, Rowley 2002).
4. FORESIGHT STUDIES ON GENOMICS
AND HUMAN HEALTH
Not suprisingly the implications of the developments discussed above have
prompted many people to speculate on the future of genomics and human
health. A number of national Foresight studies have highlighted issues
for their countries using various techniques. Two of considerable interest
are the Delphi survey and scenario creation.
The Delphi survey technique allows groups
of experts to be consulted on a range of possible future developments
in their respective fields. The questions include such issues as the expected
date of realisation of the development, and demand and supply factors
linked to the developments. The Seventh Japanese (NISTEP 2001) and German
(BMBF/FI 1998) Delphi studies have given likely dates for specific developments
.For example, among the top 20 ranked topics, six are related to genomics
and human health, particularly related to cancer. Thus the rapid and cheap
determination of an individual’s genome is forecast for 2012 while
the diagnosis and treatment of cancer based on genome analysis is forecast
for 2014. Similar dates have been identified in the Technology Timeline
produced in the UK (Pearson and Neild 2002) and the major review by the
Rand Corporation in the USA (Anton et al 2001). An overview of biotechnology
(Rowley 2002) and a review of European Foresight studies (Bock et al 2001)
also have given likely dates based on fuller discussions of the underlying
science.
The scenario creation technique is a
way of envisaging what the future might hold by first identifying the
major drivers likely to shape the future and the impact of these on an
economy, industry or organisation. This analysis is then used to create
scenarios which are stories of future worlds that convey a range of possible
outcomes. Two major studies have recently been carried out in which scenarios
developed by groups of experts have been used to develop strategies for
further research in the area of genomics and human health. The first of
these is the ESRC Genomics Scenario Project, funded by the Economic and
Social Research Council in UK and carried out by the Institute for Alternative
Futures in the USA and the Centre for Research in Innovation and Competition
in the UK (ESRC 2001, Justman et al 2002). The aim was to provide a view
of emerging social research issues and the requirement for social sciences
research to contribute effectively to the evolution of genomics and associated
social processes.
The study identified 12 key drivers
shaping genomics over the next 15 years. In order of importance, they
were: functionality of genomics, regulation of genomics, business forces
and beyond, genomics itself, politics and geopolitics, demand, social
attitudes, social mobilisation, governance of knowledge, events, risk,
and environment. Based on these inputs and an overview paper on genomics
and its application (Rowley 2002), four scenarios were constructed (Justman
et al 2002). Abstracts of these are:
In Genomics
Inc, social science would consider impacts of genomics
on various sectors of society, concepts of well-being ethics and use of
genomics by the National Health Service in UK, the new industrial structure
and property rights, as well as the growing divide to which genomics would
contribute.
In Broken
Promises, as genomics fails repeatedly, social science
research contributions come through re-evaluation of the notion of progress;
research on alternative lifestyles and product use; better understanding
of political change; new concepts of risk.
In Out
of Our Control, China takes the lead in genomic research
and applications in the face of more stringent regulation in developed
countries. Social science would consider the comparative advantage and
disadvantage of states and their relations to multi-national companies
and the nature of international organisation.
In Genomics
for All, social science research supports the development
of international institutions that can regulate bio-weapons ; the identification
of genomic products and applications that will support equity and sustainability;
the comparative analysis of scientific and social change using information
and communication technologies.
Discussion of these scenarios at a workshop
in London in early 2002 identified research issues related to genomics
that would benefit from social science inputs.
The second study was the BIO-EXPRESS
Study funded by the European Commission through CEN-STAR (Comite Europeen
de Normalisation-Standardisation and Research) and carried out by the
Instituto Nacional de Enghario e Tecnologica Industrial in Portugal, the
Joint Research Centre of the EU and the National Physical Laboratory in
UK (BIO-EXPRESS 2002). The aim was to assess the requirements for pre-normative
research in the fields of agri-food, environmental and medical technology,
and the resulting implications for standards, measurement and testing
requirements in the next 5 to 10 years. The scenario creation technique
was used to produce scenarios for each field. The three scenarios for
the medical area highlighted developments in DNA analysis and its application
to health care with reference to harmonised standards, risk management,
screening and bioinformatics.
Both of these studies were directed
to specific areas and there has been no major Foresight study of broader
issues of DNA analysis and human health in a multi-economy context. The
present study will use the scenario approach as a basis for identifying
policy issues for the APEC region.
5. CONCLUSION
The recent sequencing of the human genome as well as the genomes of other
organisms such as pathogens, disease vectors, insects and animals (WHO
2001) points the way to a new approach to biology, a new way to consider
human diseases, a new advance for drug development and a new approach
to health care systems. A number of Foresight studies have identified
emerging technologies that require great effort and investment such as:
diagnostics, bioinformatics, proteomics and gene therapy and several have
forecast expected dates of realisation of application of therapies. However
there has not been a study with a broad approach to issues involving society,
technology, the economy, environment and policy as envisaged in the present
one.
Thus in addition to the technology developments
their application will mean fundamental changes in health care. There
will be an evolution towards more individual medicine with an increase
of prescription based on DNA diagnosis (Rowley 2002). With more and better
diagnostics testing for genetic disposition, emphasis will move towards
preventative rather than curative medicine. This has implications for
the structure of national health systems.
Further, the coming genomics era will
raise important and ethical issues and challenges. Firstly since genetic
information about individuals can be highly predictive of their future
health, it has the potential both to stigmatise them and to be used by
others such as potential employers and insurers as a basis for discrimination.
The extent to which intervention is employed to prevent transmission of
serious genetic disease to children is a highly sensitive issue. Secondly
there is an important dimension in the social context in which genetic
testing is used {WHO 2002). Thus the context may be significantly different
between developed and developing countries and even between developing
counties. The populations of very poor developing countries are especially
vulnerable to exploitation by much richer developed counties or by multi-national
corporations in genetic research or the development and use of genetic
databases. Many developing countries also lack well developed regulatory
mechanisms to deal with these issues.
The present study is a unique opportunity
to consider the current state of genomics and human health and the future
implications for the APEC region.
Greg Tegart, 30.1.03
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