CELEX: 51988PC0424
Language: en
Date: 1988-07-20
Title: Proposal for a COUNCIL DECISION adopting a specific research programme in the field of health: Predictive Medicine: Human Genome Analysis (1989-1991) (presented by the Commission)

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 ---pagebreak--- COMMISSION OF THE EUROPEAN COMMUNITIES
                                            COM(88 ) 424 final - SYN 146
                                            Brussels , 20 July 1988
                             Proposai for a
                            COUNCIL DECISION
   adopting a specific research programme in the field of health :
             Predictive Medicine : Human Genome Analysis
                              ( 1989-1991 )
                    ( presented by the Commission )
 ---pagebreak---        PROPOSAL FOR A COUNCIL DECISION ADOPTING A SPECIFIC RESEARCH
                        PROGRAMME IN THE FIELD OF HEALTH ;
                   PREDICTIVE MEDICINE s HUMAN GENOME ANALYSIS
                                     CONTENTS
0.          SUMMARY
1.          REASONS FOR PROPOSAL :
1.1         What is Predictive Medicine ?
1.2         The scientific basis for Predictive Medicine
1.2.1             The organization of genetic information :
                  Mapping human genes                                  3
1.2.2             The occurrence of genetic disease                    4
1.2.3             Technologies for mapping genes                       6
1 ., 22 .. 3 . 1  Genetic linkage maps                                 6
1 ., 22 .. 3 . 2  Physical maps                                        7
1 ., 2 . 3 . 3    Ordered clone libraries                              7
1 ., 2 . 3 . 4    Sequencing                                           7
1.2,2.3.5         Management of information and materials              8
1.2.4
   ,2.            Applications of gene mapping in Predictive Medicine
   ,2.4 .1        Diagnostic applications                              8
   , 2 . 4.2      Identification of genes associated with disease      9
1.2 . 4 . 3       Gene therapy                                         9
1.3         Social and ethical considérations                          9
2.          THE PREDICTIVE MEDICINE PROGRAMME : HUMAN GENOME ANALYSIS 10
3.          JUSTIFICATION OF THE CONFORMITY OF THE PROGRAMME WITH
            THE OBJECTIVES AND METHODS OF THE EUROPEAN COMMUNITY
3.1 . Conformity with the objectives of the framework
            programme of research and technological development       12
3.2 Justification of the scientific content of the programmes
            the international challenge and European scientific
            cohesion                                                  13
3.3         Relation to other Community research programmes           13
3.4         Precompetitive nature of the research                     14
3.5         Management and évaluation                                 14
4.          IMPLEMENTATION AND FINANCIAL MEANS                        15
4.1 . Networks of facilities                                          15
4.2 Research contracta                                                16
4.3         Training                                                  16
4.4         Scientific Management                                     17
4.5         Commission Staff                                          17
4.6         Summary of Financial Means                                17
                  PROPOSAL FOR COUNCIL DECISION AND ANNEX             18
                  FINANCIAL RECORD                                    26
                 IMPACT ON SMALL AND MEDIUM-SIZED ENTERPRISES         30
                                  A &-V!>
 ---pagebreak---                                 SUMMARY
Infectious disease is no longer the major cause of illness or
death in the Western world . Instead , much disease has a genetic
component : it may be the result of inheritance of a single
defective gene ( monofactorial ) or of the interaction of multiple
gene defects ( multifactorial ) with environmental factors . Many
common and debilitating diseases such as coronary artery disease ,
diabetes and the major psychoses , fall into the latter category ,
i.e. the disease results from the exposure of genetically
susceptible people to environmental factors . Predictive Medicine
seeks to predict susceptibility to diseases with a view to their
prevention and early diagnosis , as well as to improved prognosis
and , eventually , treatment .
The human genome is the complete set of genetic material
( deoxyribonucleic acid , or DNA ) which embodies the instructions
describing each human being .     It is now possible to analyse , or
map , the genome in such a way that one can " read " these
instructions and , in so doing , locate the genes which , when
altered , give rise to particular diseases . Along the way it will
be possible to make fundamental new discoveries in biology and
acquire new technology for medicine .
The   Predictive Medicine    Programme will  contain the  following
strands   :
    improvement of the resolution of the human genetic map , i.e.
    creation of a map of the human genome , consisting of DNA
    markers , which would enable researchers to locate genes easily
    and quickly ;
    the setting up of ordered clone libraries ,            i.e.   of
    collections of ordered sets of DNA fragments which fully
    represent the DNA present in the entire genome , selected
    chromosomes or chromosomal fragments ;
    the improvement of advanced genetic technologies and , through
    a training programme , the spreading of these advanced
    technologies throughout the Member States .
The programme is a European response to the international
challenges presented by the large-scale biological research
projects in the United States ( Mapping and Sequencing the Human
Genome ) and Japan ( Human Frontier Science Programme ). Although
it is a programme of basic precompetitive research , both new
information and new materials of potential commercial value will
result ; new technological processes will also be developed .
These will all contribute to the development of Europe 's
biotechnology industry - often based in small and medium-sized
enterprises .
                                   1 tjLn.
 ---pagebreak--- As the title implies , the content of the programme will have the
ultimate aim of identifying genes involved in disease , with a
view to their isolation and structural analysis .
The enormous increase in genetic information - or rather the uses
to which it may be put - does raise ethical questions . Aspects
such as personal privacy must be weighed against general health
care considerations ; the ability to diagnose disease will outrun
the possibilities of treating it . These and many other issues
must be given serious consideration .
                                2
 ---pagebreak--- RESEARCH PROGRAMME IN THE FIELD OF HEALTH s PREDICTIVE MEDICINE-
                        HUMAN GENOME ANALYSIS
I.           REASONS FOR PROPOSAL
1.1          WHAT IS PREDICTIVE MEDICINE ?
Fifty years ago the principal cause of morbidity and mortality
was infectious disease but with the discovery of antibiotics , and
improvements in hygiene and pest control , it is now a minor one
in industrialized countries .      Apart from the consequences of
accident or war , much disease today has a genetic component which
may be of greater or lesser importance . Over the past few years
a great deal has been learned about those diseases which are due
to the inheritance of a single defective gene , though in most
cases we are still very far from a remedy .
However , when it comes to the common diseases such as coronary
artery disease , diabetes , cancer , autoimmune diseases , the major
psychoses and other important diseases of Western society , the
position is far less clear .        These conditions have a strong
environmental     component and although genetic       factors are
undoubtedly involved , they do not follow any clear-cut pattern of
inheritance .     Put another way , the disease results from the
exposure of genetically susceptible individuals or populations to
environmental causes ; prevention will depend on reducing the
levels of exposure either in populations or , more probably , in
susceptible individuals . As it is most unlikely that we will be
able to remove completely the environmental risk factors , it is
important that we learn as much as possible about the genetically
determined predisposing factors and hence identify high-risk
individuals . In summary , Predictive Medicine seeks to protect
individuals from the kinds of illnesses to which they are
genetically most vulnerable and , where appropriate , to prevent
the transmission of the genetic susceptibilities to the next
generation .
1.2   SCIENTIFIC BASIS FOR PREDICTIVE MEDICINE
1.2.1   THE ORGANIZATION OF GENETIC INFORMATION :
        MAPPING HUMAN GENES
The human genome is the complete set of genetic material -
deoxyribonucleic acid ( DNA ) - which embodies the instructions
describing each human being . It is now within the realms of
possibility to " read " these instructions in their entirety and ,
in doing so , to make fundamental new discoveries in
biology , to learn to predict and ultimately treat genetic
diseases , and to acquire new technology for medicine .
Each human being has two sets of 23 chromosomes along which are
arranged an unknown number of genes (a sequence of bases in DNA
which codes for one protein ), the best total estimate of which is
50,000 to 100,000 . Each gene is composed of DNA , which is a
                                   3
 ---pagebreak--- thread-like substance made up of nucleotides (a purine or
pyrimidine base attached to a sugar and phosphate group ), and
generally found as two strands wrapped around each other in the
form of a double helix . The two strands are held together by
bonds between base pairs of nucleotides . The linear pattern of
nucleotides in the genome is known as the DNA sequence and its
length is measured in base pairs of DNA . The human genome
contains about 3,000 million base pairs .
A variation in this hereditary set of instructions occurs when
there is a mutation , or change in the sequence or number of
nucleotides in one or more genes . The challenge is to find the
genes which , having mutated , give rise to a particular disease .
Logically , this must be achieved by first locating the position
of the genes along the chromosomes and then defining the
sequence    of    nucleotides      that   determine    normal    genetic
characteristics ;    only by defining the normal genetic structure
can the abnormal then be recognized . Such a genetic map is the
equivalent of a dictionary since it provides a unique ordering of
the genes . We need only think of the problem of looking up a
word without a dictionary or of finding a book in a library
without a catalogue .       Having access to this          " human gene
dictionary " is thus absolutely fundamental to the speed with
which we can analyse human genetic variation and to our
understanding of the complex ways in which genes interrelate to
determine human development .
1.2.2    THE OCCURRENCE OF GENETIC DISEASE
Genetic variation giving rise to disease can be present in all
body cells , including the germ ( egg and sperm ) cells , and can be
transmitted from one generation to the next . Other variation is
present only in somatic ( non-sexual ) cells and has consequences
only for that person . Many types of cancer arise as a result of
mutations of the latter type .
In broad terms , disease involving inherited genetic factors can
be divided into three categories :
   single gene defects         ( monofactorial )   which show simple
   Mendelian inheritance patterns . Most of these conditions are
   rare in themselves but since there are many of them , they
   represent in total a substantial burden of disease . Currently
   some 4,200 single gene defects are recognized and manifest in
   2.5% of all liveborn in Western European populations ;
   multiple    gene  defects   ( multifactorial ),  in  which   multiple
   genetic and environmental factors are involved . Many common
   debilitating diseases fall into this category ;
   abnormalities of chromosome number and structure , as in Down 's
   syndrome .
                                     4
 ---pagebreak--- The incidence of some diseases which are due to single gene
defects is given in Table 1 ; that of some common diseases of
multifactorial origin is in Table 2 .
Table 1   s Occurrence  of some single gene       defect diseases in
            Europe
Disease                   Occurrence related       to   Prognosis
                          number of births
Cystic fibrosis               1 / 2,500                Life rarely
                                                       exceeds 20 years
Sickle cell disease           1 / 6,000 *              Variable serious ¬
                                                       ness , often lethal
Phenylketonuria               1 / 15,000               Favourable if early
                                                       diagnosis
Le sch -Nyhan Syndrome         1 / 16,000               Kidney and brain
                                                       disturbance ,
                                                       generally lethal
Beta-thalassemia                  **                   Life rarely exceeds
                                                       20 years
Duchenne muscular             1 / 7,000 ***            Myopathy after the
dystrophy                                              the age of four ,
                                                       fatal outcome
                                                       around 20 years
Immunodeficiencies                                     High death rate
* Infrequent in Europeans , sickle cell disease (a haemolytic
anaemia ) may have a frequency exceeding 1 / 100 in some African
populations , 1 / 400 in Caribbean islanders and 1 / 2,500 in black
Americans .
** Infrequent in Northern Europe , beta-thalassaemia ( another
haemolytic anaemia ) is widespread in the Mediterranean basin ,
with a maximal occurrence in Cyprus (1 to 2 / 100 ).
*** Linked to the X chromosome , this disease occurs only in boys ,
with a frequency of 1 / 3,500 ( 1 / 7,000 for all births ).
**** The occurrence of genetic immunodeficiencies is low .
Table 2 s Common chronic diseases with a multifactorial
           genetic component
Disease                            Frequency          Frequency in 1st
                                   in general         degree relatives
                                   population         of affected persons
Peptic ulcer                            1 / 25              1 / 10
Rheumatoid arthritis                    1 / 50              1 / 20
Diabetes mellitus :
 insulin-dependent                      1 / 500             1 / 33
 insulin-independent                    1 / 50              1 / 10
Ischaemic heart disease < 65 yrs        1 / 50              1 / 10
Severe manic-depressive    psychosis    1 / 100             1/6
Epilepsy ( errand mal )                   1 / 200             1 / 25
                                     5
 ---pagebreak--- 1.2.3      TECHNOLOGIES FOR MAPPING GENES
There are different ways of constructing maps of the human
genome .     In its most simple form gene mapping means assigning a
gene to a specific chromosome . The first such assignment , made
in 1911 , was of the gene for colour-blindness to the X chromosome
and this depended on the observation that males and not females
were affected .      In the same way , several other X-linked genes
were discovered but some fifty years passed before the
development of new techniques allowed the assignment of genes to
the other 22 pairs of chromosomes . Even then there was no way of
locating genes whose product was unknown until , in the 1970s ,
recombinant DNA technology         provided a new approach .    This
approach , called reverse genetics , depends on first localizing a
disease gene to a particular chromosome by its association with
genetic markers ( identifiable regions on a chromosome ) within
families exhibiting the disease .       This process is expedited by
the availability of genetic linkage maps for each chromosome .
1.2 . 3.1    GENETIC LINKAGE MAPS
A genetic linkage map shows the distance between genes , and
other genetic markers , on the basis of the frequency with which
they are inherited together . Genes that are close together on a
chromosome usually stay together , or linked , during the division
of egg and sperm cells , a process during which some parts of the
chromosomes recombine .        The distance along      genetic maps ,
represented by recombination frequency , is measured by how often
a particular gene is inherited separately from some marker and is
expressed in centimorgans . If a gene and a marker on the same
chromosome are separated only 1% of the time , the distance
between them is 1 centimorgan and this distance is on average 1
million base pairs of DNA , although there will be major
differences from this depending upon which chromosome region is
under consideration .     Such observations are made by studying the
cosegregation of genetic markers within families , and very
large pedigrees are required to establish linkage relationships
between genetic markers with sufficient reliability .            For
example , currently about 600 individuals in 40 large families
have been used to establish a linkage map to the 9 centimorgan
level .     An improvement to between 1 and 5 centimorgans will
necessitate an expansion of the total number of large families by
a further 20 .
Recombinant DNA technology introduced a new dimension to genetic
linkage mapping .     Scientists discovered that restriction enzymes
- the tools used to recognise a particular , short DNA sequence
and cut it at that site - sometimes failed to cut the DNA of some
people in the expected places .        As a result , fragments of a
different length were produced and these variations were
inherited .     Known as restriction fragment length polymorphisms
( RFLPs ) , they are used as reference points along the genome
                                    6
 ---pagebreak--- To identify RFLPs generated from very large pieces of DNA , it is
necessary       to   use    radioactively    labelled ,  single-stranded
sequences of DNA called DNA probes , which form base pairs
( hybridize ) with complementary sequences in the RFLP markers .
Some useful probes for RFLP mapping are fragments of genes ,
others are complementary to a . new generation of markers ,
" variable number tandem repeats ", which make use of the clusters
of repetitive DNA sequences found , in varying numbers , throughout
the human genome .
1.2 . 3 . 2 PHYSICAL MAPS
A physical map of the human genome shows the actual distance ,
measured in base pairs of DNA , between genes or markers . Various
low resolution methods of physical mapping are known which are
dependent upon dividing single human chromosomes into several
fragments .      However , they locate only very large pieces of DNA ,
into which either a few or thousands of genes might fit .
Mechanisms for finding a gene of interest in long stretches of
DNA remain primitive .
New methods of separation of very large DNA fragments produced by
restriction enzymes which cut at very rare sites allow the
construction of long-range restriction fragment maps , which have
a considerably higher resolution and bridge the gap between the
single gene and the entire chromosome .
1.2 . 3 . 3 ORDERED CLONE LIBRARIES
Development of higher resolution physical maps is extremely
valuable in helping to locate genes of medical importance . Also ,
for physical mapping projects , it is necessary to have access to
large stocks of DNA and clone libraries can provide such a
source .
Cloning is making multiple copies of a DNA fragment by
incorporating it into a self - replicating molecule which can then
be   introduced     into  a  host  cell . Libraries  are  collections  of
cloned DNA fragments from a common source . To construct a
physical map , the order of the cloned DNA fragments relative to
one another along the chromosomes must be known . The goal is to
create a complete set of overlapping clones , whose order is
known , to cover the entire human genome . Once the physical
relationship between cloned fragments has been established , their
nucleotide sequence can be determined .
1.2 . 3 . 4 SEQUENCING
The ultimate physical map will be the total DNA sequence of the
human genome . Although it is feasible to consider sequencing the
genome , to determine the total sequence of 3,000 million base
pairs in a reasonable time would require a very considerable
improvement in existing techniques .
                                      7
 ---pagebreak--- However , there is a case for first sequencing those regions of
the genome which are believed to be clinically or scientifically
important . These would include chromosome regions in which
clinically important genes are either expressed - i.e.
transcribed into messenger ribonucleic acids ( mRNAs ) which are in
turn translated into proteins - or serve some regulatory
function . One method which has been proposed is first to sequence
DNA copies ( cDNA ) of cellular messenger RNA transcripts , with a
view to using that information to identify which genes are
expressed in the genome .
1.2 . 3 . 5  MANAGEMENT OF INFORMATION AND MATERIALS
The production of higher resolution genetic and physical maps
will each generate an enormous amount of data ; establishing the
correlations between them will generate even more . In both cases
there will also be a considerable requirement                 for the
distribution and collection of materials , e.g. probes , DNA
clones . The efficient management ( and integration ) of the
information and of the handling of materials will be of prime
importance , and argues for the identification of a number of
central      facilities  each  to become  the  centre   of  a  research
network .
1.2.4       APPLICATIONS OF GENE MAPPING IN PREDICTIVE MEDICINE
1.2 . 4.1 DIAGNOSTIC APPLICATIONS
Tests for genetic disorders are generally used in prenatal
diagnosis of abnormalities such as Down 's syndrome or in
screening the newborn for conditions amenable to treatment , such
as phenylketonuria . They are also used in screening             adults
( often from particular ethnic groups ) for increased risks of
transmitting genetic disease to the next generation - for
instance , by identifying carriers of diseases such as sickle cell
anaemia , beta-thalassaemia , Tay-Sachs disease , etc .
Most of the currently available tests are based not on
identifying the abnormal gene(s ) but on detecting - the gene
product ; hence they are limited to some 200 disorders where a
gene product or biochemical marker is known , a small number in
comparison to the 4,200 known single gene defects . Other
limitations to this approach lie in the inaccessibility of some
tissues to sampling ( eye , brain ) and the probability that the
disease will have manifested itself - perhaps irreversibly - by
the time that the genetic defect is detected . Tests which
directly detect the genetic lesion in the DNA overcome many of
these limitations .
In the last five years , 400 or more genetic disorders have been
mapped to a particular chromosome ; of these , some 40 have been
defined in depth and include Huntington 's disease ( chorea ),
cystic fibrosis and Duchenne muscular dystrophy . In each of
these cases , a diagnosis can be made by a DNA-based test without
knowing the gene 's product or function .       Further , the test can
be used for preclinical diagnosis of a disease of late onset
                                    8
 ---pagebreak--- ( such as Huntington 's ), for prenatal diagnosis and for detecting
carrier status .
1.2 . 4 . 2 IDENTIFICATION OF GENES ASSOCIATED WITH DISEASE
Importantly , detection of the gene by reverse genetics can lead
tc our understanding its function and its role in the pathology
of the disease concerned . Examples where this has already
occurred        include     Duchenne      muscular  dystrophy ,   chronic
granulomatous disease           (a white blood cell disorder )        and
retinoblastoma (a form of eye cancer ). It can be expected that
in the coming years many other disease genes will be isolated ,
including those involved in such disorders as colon carcinoma and
severe mental retardation .            The availability of a higher
resolution genetic linkage map would simplify considerably the
identification of the genes involved in many common diseases
which , as mentioned above , are caused by multiple gene defects .
Computational methods exist which permit the subpartitioning of
genetic       linkage    data    and   identification   of  those genes
contributing to multiple gene detects .
This       information ,   when    combined    with  that  derived   from
overlapping clone libraries , will permit the rapid isolation and
structural analysis of the genes concerned . Improved prediction
of disease susceptibility will result . One of the most important
disease categories is that involving heart and vascular disease .
1.2.4.3       GENE THERAPY
It is hoped that eventually it may be possible to correct a
defective gene by inserting normal DNA directly into a cell - a
process known as gene therapy . This ultimately depends on the
discovery of safe methods of inserting the DNA and of a means of
ensuring that the DNA corrects the target defect without
producing any other adverse effects . Gene mapping will not have
any direct effect on the prospects for gene therapy but the
knowledge gained about the function of genes may have an
indirect benefit .
1.3       SOCIAL AND ETHICAL CONSIDERATIONS
Information about human genetic make-up will increase enormously
in the course of mapping the human genome ; simpler , faster and
less costly methods of screening for genetic susceptibility to
disease will be developed . This will provide the possibility of
therapeutic intervention to prevent the manifestations of
disease . As genes are identified which are associated with an
increased risk of common diseases , such as heart disease ,
diabetes and arthritis , population screening will become a
possibility . In Western Europe , where there is a steadily ageing
population and an associated ever-increasing cost of health care ,
the prospects both of cheaper testing and of earlier intervention
making possible a decrease in morbidity are very attractive ones .
This enormous increase in genetic information does raise ethical
questions . Improvements in diagnosis and risk prediction will
                                        9
 ---pagebreak--- inevitably precede the development of therapeutic remedies ,
creating a growing gap between diagnosis and treatment . The
information about an individual 's genetic constitution will be
more precise , more detailed and more easily obtained ; it will
benefit individuals by informing them about health risks but it
could also be used to their detriment by third parties such as
employers or insurance companies . Further ethical considerations
will arise from the increased range of prenatal diagnoses which
will become easily available - parents may seek to choose the
sex of their children , for instance . These questions do not
arise directly from the information which is collected but from
the uses to which it is put . This implies that , independently of
the technical possibilities and benefits offered by human genome
analysis , it is vital that politicians and Society as a whole
consider seriously the dilemmas presented . Aspects such as
personal privacy , including the right of the individual to know
or not to know , must be weighed against general health care
considerations .
Dialogue and information transfer on the social consequences and
ethical aspects of such research will be organised , in a
systematic manner , with the various interested parties .
There is a unanimous opinion that , also for ethical reasons ,
there must be a rejection of any possibility of modifying the
genetic constitution of human germ cells , even for purely
therapeutic reasons ; this topic will be excluded from this
European Community research programme .
2.     THE PREDICTIVE MEDICINE PROGRAMME : HUMAN GENOME ANALYSIS
The framework programmed ) originally stated that the technical
content of the Predictive Medicine Programme would " mainly be
oriented towards better knowledge of the human genome , immunity
techniques     ( applicable    to   cancer , autoimmune       diseases ,
infections ), genetic engineering processes aiming at repairing
DNA defects ( e.g. in congenital diseases of genetic origin ) and
development of diagnostic test kits ( e.g. for AIDS )". Since a
choice has to be made , it seems appropriate to concentrate
endeavours on definition of the human genome .
The programme will have these aims :
1)      To achieve a high-resolution genetic map         ( at   1 to 5
centimorgan level ) of the human genome . This will require an
increase from 40 to 60 in the number of large families currently
under study in Europe , the extra 20 , where possible , to be
families known to have a genetic modification of medical
interest ; the setting up of a network of 10 to 15 European
laboratories with both the interest in and the capability of
working with material from these families ; the establishment of
1 Framework Programme for Community Activities in the field of
   Research and Technological Development ( 1987-1991 ).
   OJ N° L 302 , 24.10.1987 , p. 1-23 .
                                   10
 ---pagebreak--- one or two centres which would provide DNA prepared from the
families to the members of the collaborating network , and also
maintain and distribute to them a collection of the necessary
probes ; and consideration of the role of computing facilities
both to enable participants to handle the collection and
reduction of these data and also to carry out the preparation of
the map .
2)    To set up collections of ordered DNA clones either from the
entire genome or from selected chromosomes . These ordered clone
libraries , which might be produced in several centres , will
require the establishment of facilities for maintaining the
stocks of cloned DNA fragments , and for distributing DNA - free
of charge - to a network of European laboratories interested in
matching genetic material to these cloned fragments . A related
project could be the sequencing of cDNA clones isolated
independently and mapping them with an ordered clone library .
3)     To improve advanced genetic technologies , with the further
aim of spreading them more evenly among European laboratories .
Examples ares production of new biochemical reagents ( restriction
enzymes ), procedures for labelling DNA probes , amplification of
genes , vectors for the transfer of human genes , methods of
cloning long DNA segments , development of software to help
sequencing , development of new strategies for sequencing , and
creation of overlapping clone banks . The best way to support
this kind of work is by research contracts , with priority given
to collaborations between laboratories in different Member States
working on a common subject , and also to those where there is
participation by industrial laboratories . Communication between
the contracting laboratories will be so managed as to achieve a
collaborative research network .
In the process of improving the genetic map and creating the
ordered clone libraries , due attention will be given to those
chromosomes or chromosome regions known to contain the genes
responsible for specific genetic diseases , especially where this
will optimize the use of existing family material . There is also
a  need   to learn more  about  the location and   function of  the
currently unknown groups of genes involved in the multi ¬
factorial disorders which form the major part of the burden of
disease and where risk prediction is particularly important . A
pragmatic approach will be adopted to maintaining a suitable
balance between these objectives , and to avoiding unnecessary
overlaps with other genome analysis programmes .
A European pilot network for the prevention of one particular
disease taken as a model would be a valuable goal for medical
research in the Community , but this kind of project would need
careful preparation ( both in choice of target and of methods ),
and the setting up of a large-scale programme would be premature .
However , the Predictive Medicine Programme could support the
organization of a collaborative action for the preparation of a
more detailed project . The development of an extensive European
network might be an objective for the follow-up to this
                                 11
 ---pagebreak--- programme . Diseases of particular interest in this respect might
be cystic fibrosis and phenylketonuria .
3.     JUSTIFICATION OF THE CONFORMITY OF THE PROGRAMME WITH THE
       OBJECTIVES AND METHODS OF THE EUROPEAN COMMUNITY
3.1    CONFORMITY WITH THE OBJECTIVES OF THE FRAMEWORK PROGRAMME OF
       RESEARCH AND TECHNOLOGICAL DEVELOPMENT
The Predictive Medicine Programme involves both technological
research and training actions which will contribute to the
achievement of many of the aims listed in the framework
programme .
1)      The activity " Quality of life " includes the Predictive
Medicine Programme in its " Health " line . This aspect is obvious ,
because the development of Predictive Medicine will decrease the
prevalence of many diseases which are very distressing for the
patient and his family , ( incapacitating or painful chronic
diseases , often with a fatal outcome ), as well as being socially
very expensive for the Community .
2)    The goal " to promote scientific research and technological
development at Community level in order to strengthen the
scientific and technological basis of its industry " is also
explicitly addressed by the programme , which aims to promote
advanced technologies with a high added value ( e.g. DNA probes
for diagnostic kits ) . Informed estimates of the potential
European market for DNA probes in the next decade suggest that it
is worth between 1,000 and 2,000 million ECU/year .
3)      The goal of " participation of small and medium-sized
enterprises " will also be met because most of the high
technology enterprises which are able and willing to collaborate
in the programme are in this category .
4)    The goal of " harmonious development of the Community with a
view to strengthening its economic and social cohesion " is
especially important in this field , where the state of scientific
development differs widely between Member States . The provision
of a large number of grants for intra-Community exchanges of
scientists ,      together    with     obligatory    trans-national
collaboration , will aim at promoting greater contact between
individual scientists and at technology transfer to the currently
less advanced laboratories in Member States .
For the future , a follow-up to this programme might include the
launching of a large-scale operation concerning one of the main
diseases of children ( coordinated action including research ,
forecasting , prevention and treatment ). This would be the best
way to convince Europeans in general that the creation of a
" Europe of health " is not merely a matter of public relations but
a living reality .
                                  12
 ---pagebreak---   3.2    JUSTIFICATION OF THE SCIENTIFIC CONTENT OF THE PROGRAMME :
         THE INTERNATIONAL CHALLENGE AND EUROPEAN SCIENTIFIC
         COHESION
  The justification of the scientific content of the programme was
  set out in the discussion of the scientific basis for Predictive
  Modicine ( cf . 1.2 ). It is argued that the ability to understand
  normal genetic function , and hence to recognize the abnormal and
  then predict disease susceptibility , rests on having access to a
  " human gene dictionary ", i.e. a detailed map of the position of
  the genes on the chromosomes . This involves improvement of the
  genetic map and the physical map , and the setting-up of ordered
  clone libraries of the human genome - in the short-term perhaps
  of either selected chromosome regions or genes . The total
- sequencing of the genome , which is the next logical step , is
  still a remote goal because existing techniques are too slow to
  allow the sequencing of the 3,000 million base pairs in an
  acceptable time ; a start could , however , be made on sequencing
  the cDNA .
  The Predictive Medicine Programme would thus enable Europe to
  accept     the challenge of remaining a vital           international
  scientific force in human genetics .
  The United States ( US ) report " Mapping and Sequencing the Human
 Genome " ( 2 ) is a wide-ranging plan which includes the genetic map ,
  the physical map , an ordered DNA clone library and , ultimately ,
  sequencing . This impressive and prestigious programme - it has
 been compared to the " Apollo " project in the field of space - has
  captured the imagination of many scientists and politicians . For
 Japan , the " Human Frontier Science Programme " is a proposal for
  an international research programme in basic biology and the
 development of associated key technologies . At the time of
 writing the content of this programme has not been agreed , but it
 may well include a commitment to human genome analysis and / or the
  development of fast automatic DNA sequencing equipment .
 Whatever view one may have of these projects , the European
  Community cannot remain indifferent . Furthermore , in the case of
  the American programme ,        active European participation is
  explicitly sought . The Predictive Medicine Programme provides the
 means for Europe to participate in an exciting project in one of
  the most advanced sectors of biological research .
  3.3   RELATION TO OTHER COMMUNITY PROGRAMMES OF RESEARCH
 Within the framework programme , the Predictive Medicine Programme
 will be coordinated with the following specific Community
  programmes of research and technological development , in order to
  avoid overlap and to ensure coherence of research efforts :
  2 " Mapping and Sequencing the Human Genome ", Report of the Board
     of Basic Biology Commission on Life Sciences , National Research
     Council . National Academy Press Publisher , Washington D.C. , 1988 .
                                     13
 ---pagebreak---      The " Medical and Health Research " Programme 1987-1991 , and
     especially its area 1.1.4 " Early detection and diagnosis of
     Cancer " which is closely related to the genetic field
     through the topic of oncogenes .            Both programmes form an
     important part of the " Europe against Cancer " Programme , ( 3 ) .
     The " Advanced Informatics in Medicine in Europe " ( AIM )
     programme , especially its Action Line II " Strengthening
     Europe 's position in Medical and Bioinformatics ( MBI ) and
     health care ", which could give support for the development of
     effective communication and information processing within the
     proposed networks .
     The biotechnology programmes ,            especially the programme
     BRIDGE , being prepared at present , with which it would be
     carefully coordinated in respect of expression vectors , gene
     transfer and , more generally , the           genetic engineering of
     animal and human cells .
     The   " Environmental      Protection "  Programme ,    especially   its
     research areas : " Environment and Human Health " and " Genetic
     Effects of Environmental Chemicals ".
     The     " Radiation    Protection "     Programme ,    especially    its
     mutagenesis area .
     The         " Stimulation "      Programme ,        especially       its
     " Biocommunication " area .
The programme will also benefit from synergy                     with other
activities of the Community in the field of                       Information
Technology and Telecommunication ( IT&T ).
3.4 PRECOMPETITIVE NATURE OF THE RESEARCH
The programme is one of basic precompetitive research . However ,
both new information and new materials of potential commercial
value will result . It is generally agreed that all the mapping
and sequence information should be freely available but that
associated        technological     developments     -     of   instruments ,
equipment , reagents or software - should be protected in the
usual way by patents , copyright , etc .
3.5 . MANAGEMENT AND EVALUATION
The existing CGC on Medical and Health Research should deal with
the Predictive Medicine Programme and will advise the Commission
in the manner defined in the Council decision creating CGCs . The
programme will be submitted to evaluation procedures in
accordance with the " Community plan of action relating to the
3 Decision of the Council and of the representatives of Member
  States of 7 July 1986 , concerning an action programme of the
  European Communities against cancer . O.J. N° C 184 , 23.7.87 , p.19 .
                                       14
 ---pagebreak--- evaluation of Community research and development activities "           ).
The CGC may wish to obtain specialized advice and meet                  in
variable configurations ; it may also wish to set up a Working
Party to advise the Commission            on  the  management    of  the
Predictive Medicine Programme .
4.    IMPLEMENTATION AND FINANCIAL MEANS
After the approval of the Medical and Health Research Programme ,
15 million ECU remain on the sub-activity " 1.1 Health " of the
framework programme for the implementation of the Predictive
Medicine Programme . Four main chapters of expenditure are
proposed , for two networks ( human genetic map and ordered clone
library of the human genome ), research contracts for work in
advanced genetic technologies , and training grants . In addition
there would be overheads and staff expenses . The indicative
budget distribution is :
CHAPTER                               MODE OF ACTION         BUDGET
                                                        ( Million ECU )
Improvement of the human        Support to a network of       4.0
genetic map                     centralized facilities
Ordered clone library               As above                  4.0
Research on advanced            Research contracts            3.5
genetic technologies :
e.g. reagents ( restriction
enzymes ), gene detection , gene
vectors , cloning , computer
software , cDNA cloning and
sequencing .
Grants ( particularly post -          Grants                  2.5
doctoral , 100 scientist-years )
Scientific management , including                             0.45
évaluation
Staff                                                         0.55
                                      TOTAL                  15.0
4.1 . NETWORKS OF FACILITIES
Progress with the human genetic map and the creation of ordered
clone libraries of the human genome will be achieved most
effectively by building on existing laboratories through the
creation of networks . Efficient management , both of information
and of biological materials , will be of prime importance for both
4 Communication to the Council concerning a Community plan of
   action relating to the evaluation of Community research and
   development activities for the years 1987 to 1991 .
   O.J. N° C 14 , 20.1.87 , p. 5 .
                                    15
 ---pagebreak--- actions , and it is proposed therefore to identify a central
laboratory in each case to act as the focus for management , i.e.
to become the centre of a network of laboratories .
Four million ECU will be used for the development of a European
network for the improvement of the human genetic map , and another
four million ECU for setting up a network of laboratories
concerned with an ordered clone library of human DNA . These sums
amount to approximately 10% of the sums suggested in the report
of the US Office of Technology Assessment as appropriate for the
US Human Genome Project . Although modest , at least in the
exploratory phase of these activities , Europe 's contribution to
the international effort will be a significant one .
4.2    RESEARCH CONTRACTS
The basic research on advanced genetic technologies in the
programme will be funded through cost-shared and marginal cost
contracts with public and private institutions in the Member
States . The contribution to research contract funding from the
Community budget is estimated at 3,500,000 ECU . This figure is
based    on  an   estimate of  20  research contracts  on  advanced
technologies , of about 150,000 to 200,000 ECU per contract ( for
three years ) according to the size of the project . It corresponds
to the expected response from European laboratories in the field .
In the selection process , priority will be given to proposals
involving a number of Member States and /or participation by
private enterprises . The management of communication between the
various contracting laboratories will be a first step towards the
establishment of a European network in molecular genetics .
Although the sum involved in each contract may seem small , the
impact will be amplified by the complementarity of the programme
to national research efforts . It should be noted that no single
European country would be able to develop the complete range of
research facilities and networks described above .
4.3 . TRAINING
An average estimate of the requirements for training in the
period under consideration is about 100 scientist-years , i.e.
2,500,000 ECU . Two aspects deserve special consideration :
(i)    Steps must be taken to ensure that those Member States which
       currently lack a capability in the techniques of modern
       molecular genetics are given the opportunity to acquire it ;
( ii ) Only if there are very compelling reasons will scientists be
       permitted to train outside the proposed European networks ;
       in order to smooth the path for the transfer of technology ,
       and for the return of the individual newly-trained
       scientist , it is expected that 30 to 50% of such a
       scientist 's time will be spent introducing the new
       techniques into his own laboratory setting .
                                  16
 ---pagebreak--- 4.4 . SCIENTIFIC MANAGEMENT
Budgetary provision of 450,000 ECU is considered necessary for
the external scientific management of the programme . This
assessment , based upon an analysis of current annual needs in
similar     programmes ,  covers    the     expenses    of    meetings ,
participation in symposia , travel and subsistence costs of
experts     and   Commission    staff ,    visits    to    laboratories
participating in the programme ( two visits to each contracting
laboratory , i.e. about 50 visits in the course of the programme ),
and the convening of six workshops during the same period . Funds
are also included for the preparation of a follow-up to the
present programme ( studies and preparatory meetings ) which might
include inter alia the setting up , as mentioned previously , of a
large network of research , forecasting , prevention and treatment
for one of the major genetic diseases of children .
The cost for scientific management amounts to 3% of the total
budget requested for the programme , including the cost of
evaluation .
4.5   COMMISSION STAFF
Expenditure of 550,000 ECU for a staff of two is considered
necessary for the execution of the programme .           This estimate
includes new staff only , i.e. one official of category A ( 93,000
ECU /year ) and one of category C ( 37,000 ECU /year ), inflation
being estimated at 4% per year ; this estimate includes only the
minimal requirements necessary for the             management of the
programme .
4.6   SUMMARY OF FINANCIAL MEANS
                                        ( Million ECU )
Networks of facilities                           8.0
Research contracts                               3.5
Training                                         2.5
Scientific management                            0.45
Staff                                            0.55
                              TOTAL             15.00
 ---pagebreak---                                     1
                    PROPOSAL FOR A COUNCIL DECISION
  Adopting a research and technological development programme in
             the field of health : Predictive Medicine :
                  Human Genome Analysis : ( 1989-1991 )
THE COUNCIL OF THE EUROPEAN COMMUNITIES
Having regard to the Treaty establishing the European Economic
Community , and in particular to Article 130 Q ( 2 ) thereof ,
Having regard to the proposal from the Commission (•*•) ,
In cooperation with the European Parliament ( 2 ) ,
Having regard      to   the  opinion  of  the   Economic  and  Social
Committee (   ,
Whereas Article 130 K of the Treaty stipulates that the framework
programme shall be implemented through specific programmes
developed within each activity ;
Whereas by its Decision of 28 September 1987 ( 4 ) the Council has
adopted    a    framework programme of      Community research and
technological development ( 1987-1991 ), in which it provided for
activities to be undertaken in the field of health ;
Whereas , for the evaluation of each specific programme and the
selection of Community actions , the framework programme sets out
criteria among which is that of contributing to the strengthening
of the economic and social cohesion of the Community , consistent
with the pursuit of scientific and technical quality ;
Whereas two successive pluriannual programmes of research and
training of the European Economic Community in the field of
1 OJ N°
2 OJ N°
3 OJ N°
4 OJ N° L 302 , 24.10.87 , p.l .
                                   18
 ---pagebreak---                                      2
biotechnologies ( ^ ) , of which the second is still in progress ,
have shown the possibility and usefulness of a Community action
promoting the utilization of modern biology for scientific and
industrial purposes ;
Whereas the biotechnology programme presently in progress does
not include some fields of research important for human health
and the quality of life , for the industrial development of
biotechnologies with medical aims and for the control of the
increase of social and health expenses ;
Whereas the framework programme has foreseen in its activity
" Quality of life " under the " Health " line 1.1 , the " Initiation of
new activities relating to the development of predictive
medicine " ;
Whereas , as a result , a specific research and technological
development programme is necessary in the field of predictive
medicine and , in particular , that it is necessary to :
- develop the basic technologies concerning the study of the
   human genome , as a prerequisite to a large number of
   developments in biotechnology for health , and to ensure the
   distribution    of     these   technologies   widely   in   European
   laboratories , and
- improve the resolution of the human genetic map and to refine
   the physical map by the creation of ordered clone libraries , as
   a basis for locating genes of medical importance and for a
   better general understanding of gene function ;
Whereas the carrying out of the above-mentioned goals require the
undertaking at Community level of actions aiming at :
     filling some existing gaps in scientific and technological
     knowledge , gaps      which prevent the full development of the
     resources of modern biotechnologies in the medical field ,
     and
     promoting , through concerted actions between private and
     public    laboratories ,    European   transnational   cooperation
     aimed at speeding up the implementation of technologies
     already available while promoting European scientific areas
     which will encourage new approaches to be developed ;
5 OJ N° L 375 , 20.12.1981 , p.l ;
   OJ N° L 83 , 25.3.1985 , p.l .
                                     19
 ---pagebreak---                                            3
Whereas the Scientific and Technical Research Committee              ( CREST )
was consulted on the following measures ,
HAS ADOPTED THIS DECISION t
                                    Article 1
A specific research and         technological development programme for
the European Economic          Community in the field of Predictive
Medicine : Human Genome          Analysis , as defined in the Annex , is
hereby adopted for a            period       of three  years commencing    on
1 January 1989 .
                                    Article 2
The amount deemed necessary for the execution of the programme
is 15 million ECU , including expenditure on a staff of two
persons .
                                   Article 3
Detailed rules for the implementation of the programme are set
out in    the Annex .
                                    Article 4
1.  In the second year of the programme implementation , the
    Commission shall undertake a review of the programme and it
    shall report to the Council and to the European Parliament
    on the results of this review , together , if necessary , with
    any proposals for modification or prolongation .
2.  An evaluation of the results achieved shall be conducted by
    independent experts and shall be published in the form of a
    communication to the Council and to the European Parliament .
3.  The above-mentioned reports shall be established having
    regard to the objectives and evaluation criteria set out in
    the Annex to this decision and in conformity                   with the
    provisions of Article 2(2 ) of the framework programme .
                                     Article 5
1.  The Commission shall be responsible for the execution of the
    programme and shall be assisted in its implementation by the
    Management and Coordination Advisory Committee ( CGC ) on
    Medical       and    Health       Research ,    set   up  by    Decision
    84 / 338 / Euratom/ ECSC / EEC ( 6 ) .
6 OJ N° L 177 , 4.7.1984 , p.25
                                           20
 ---pagebreak---                                    4
2.  The contracts entered into by the Commission shall regulate
    the rights and obligations of each party , and in particular
    the methods of disseminating , protecting and exploiting the
    research results .
                             Article 6
In conformity with Article 130N of the EEC Treaty , the Commission
is authorized to negotiate agreements with non-member States and
international organizations , particularly with non-member States
taking part in European cooperation in the field of scientific
and  technical  research  ( COST )   and with  countries  which  have
concluded   scientific   and     technical    framework   cooperation
agreements with the Community , with a view to associating them
fully or partially with the programme .
                              Article 7
This Decision is addressed to the Member States .
Done at                                        1988
                                                     For the Council ,
                                                     The President .
                                   21
 ---pagebreak---                                     5
ANNEX
     for a specific research programme in the field of health :
             Predictive Medicine : Human Genome Analysis
1 . OBJECTIVES
Use and improvement of new biotechnologies for risk-forecasting ,
early diagnosis , prevention , prognosis and treatment of some
human diseases , and for a better understanding of the mechanisms
of heredity .
2.   CONTENT
Precompetitive Community research , setting up and reinforcement
of networks of European laboratories , and training intended to
allow the use of modern biotechnologies for the improvement of
risk-forecasting , early diagnosis , prevention , prognosis and
treatment of some human diseases ( in particular hereditary
diseases and cancers ).
2.1 IMPROVEMENT OF THE GENETIC MAP OF MAN
Establishment of a Europe-based network , with a worldwide extent ,
for the collection of the DNA of large families , in order to
provide free of charge to research scientists well-characterized
genetic material and a set of probes to determine the location of
the relative positions of genes on the chromosomes .            Possible
provision of computer facilities to handle the data .
2.2    SETTING UP OF AN ORDERED CLONE LIBRARY OF HUMAN DNA
Setting up of a European network of laboratories working on
establishing overlapping cloned libraries , and support for
limited sequencing of cDNA .
2.3   RESEARCH ON THE IMPROVEMENT OF ADVANCED GENETIC TECHNOLOGIES
New     biochemical     reagents     ( restriction    enzymes ,   etc .).
Improvement of methods for the detection and localization of
genetic     markers    ( techniques     for   labelling   DNA    probes ,
amplification of genes , etc .). Development of new vectors for
the cloning of large DNA fragments and of procedures for the
transfection of chromosomes . Development of model systems for
the reproducible and stable expression of medically important
genes both in vivo and in vitro . Development of new computer
software for the collection and manipulation of data from genome
sequencing and mapping .
                                    22
 ---pagebreak---                                   6
2.4  TRAINING
Setting up a training programme to assist with the technology
transfer of molecular genetics methods to Member States in which
these techniques are currently underdeveloped and , in particular ,
the transfer of techniques into the clinical field .
3.  IMPLEMENTATION
The programme shall be implemented through cost-shared or
marginal cost contracts , support to centralized facilities and
networks ,   training   contracts ,    training     grants ,  courses ,
consultations with national experts , organization of study-group
meetings ,   participation   in     seminars    and    symposia ,  and
publications .
The Commission participation may range from about 50% in the case
of cost-shared contracts and may reach 100% in other cases .
Participants may be research institutions , universities , private
enterprises , or combinations of them , located in Member States or
in the third countries referred to in Article 6 .
Projects must be carried out by participants from more than one
country , and include at least one participant from one Member
State .
                                 23
 ---pagebreak---                                    - 7 -
                            EVALUATION CRITERIA
The    Community   plan   of  action   relating to the evaluation of
Community research and development programmes ( 7 ) states that the
milestones and objectives for each research programme have to be
set out in verifiable and , where appropriate , quantitative form .
These are listed below :
1.    The long-term objective of this programme is to contribute to
      the fight against human diseases arising from genetic
      variation ( including genetic diseases sensu stricto and many
      common diseases with a genetic component , such as heart
      disease and cancer ), through forecasting the risk , early
      diagnosis ,    prevention ,   improvement   of  prognosis   and ,
      ultimately , therapy . The Commission proposes to achieve this
      objective by :
- the management of a network of laboratories set up around
    European facilities for ( a ) the improvement of the human
    genetic map and ( b ) the setting up of ordered clone libraries
    of human DNA , either of the complete genome or of selected
    chromosomes , together with cDNA sequencing ;
 - the launching of a programme of precompetitive             research
    contracts on advanced genetic technology ;
 - the setting up of a programme of training to increase the
    distribution of modern genetic technologies in Europe , and to
    improve technological know-how in European laboratories .
 2 . The primary short-term objective is that the programme should
     succeed in establishing the above-mentioned European networks
     of laboratories in the field of :
     - the human genetic map
     - ordered clone librarles of human DNA and cDNA sequencing
     - advanced genetic technologies .
     These objectives should be verifiable in 1990-1991 .
 3.    Particular objectives to be attained within three years of
      the programme implementation are as follows :
 3.1    Concerning the human genetic map :
 - the present total of 40 well-studied large families which form
    the basis for the genetic map should be increased to 60
    families ;
 - genetic material from these families , and DNA probes , should be
    made available       free of     charge to    interested European
    laboratories ;
 7 OJ N° C 14 , 20.1.87 , p.5
                                      24
 ---pagebreak---                                  - 8 -
- a central facility should be set up to pool the results and
    establish an improved genetic map at the 1 to 5 centimorgan
    level ;
3.2 The strategies for setting up ordered clone libraries of
      human DNA should be compared and an approach defined ;
      facilities for maintaining the stocks of cloned DNA fragments
      should be established and the available clones dispatched
      free of charge to interested European laboratories .
3.3 Substantial improvements should be obtained in the following
      advanced genetic technologies :
    - New reagents , such as restriction enzymes ,
    - Methodology for cloning large     DNA  fragments     and  for  the
      transfection of chromosomes ,
    - Gene vectors adapted to human cells in vitro .
    - Methodology for the detection of a particular gene in a cell
      ( examples : how to make the use of DNA probes and gene
      amplification easier ),
    - Localization ,   cloning   and   seguencing     of    new   genes ,
      especially those which are disease-related ,
    - New computer software for the         storage ,    collation   and
      analysis of DNA sequence data .
4.    In addition , the programme should ensure that the following
      general criteria are met :
4.1 That throughout the execution of the programme , the projects
      should have taken adequately into consideration the complex
      ethical aspects of human genetics , avoiding any manipulation
      of human germ cells , and any risk to the environment .
4.2 That medical developments are actually              or   potentially
      facilitated by the results obtained .
4 . 3 That potential opportunities for commercial developments are
      obtained .
4 . 4 That the overall technological level of       the participating
      European laboratories has been increased .
4.5 Taking account of the results of Community , national or
      private sector research activities in human genetics , the
      evaluation panel shall consider whether the Predictive
      Medicine Programme has contributed to the application of the
      results of the said activities in regions of the Community
      other than those in which the research was conducted .
                                    25
 ---pagebreak---                                   1
FINANCIAL RECORD
PREDICTIVE MEDICINE PROGRAMME
1.   RELEVANT BUDGET HEADING
   - Posts    Line 7312
   - Titles      Specific research and technological development
     programme in the field of health - Predictive Medicine .
2.   LEGAL BASIS
     Article 130 of the Treaty ,
     Council Decision .
3.   DESCRIPTION OF ACTION AND OBJECTIVES
3.1 Description
     Community programme (1 January 1989-31 December 1991 ) for
     research and training in predictive medicine , carried out by
     means of implementation of laboratory networks , research and
     training contracts , consultancies by experts , organization
     of workshops , contribution to symposia , and studies .
3.2 Objectives
     The objectives of the programme are the followings Community
     research and technological development in molecular genetics
     to achieve a better understanding of genetic disease and
     hence improve the prospects for diagnosis and therapy .
4.   JUSTIFICATION OF ACTION
     The choice of predictive medicine as one of the targets for
     Community efforts in health matters takes into account three
     elements s
     - The priority to be given to advanced technologies , and
       particularly to modern biotechnologies , the importance of
       which for European economic development is an indisputable
       fact .
     - The seriousness of the human and social aspects of some
       diseases - in particular the common diseases which result
       from a combination of genetic factors interacting with the
       environment .
     - The economic importance of health expenditure , which is
       constantly increasing in Europe and is a serious problem
       for the governments involved .
                                  26
 ---pagebreak---                                      2
These three elements come together in the definition of a
research action programme in the field of biotechnologies to be
applied to predictive medicines this field covers diseases often
of long duration , socially expensive and very distressing in
hutian terms , where it is now possible to anticipate their early
detection . This will lead to their prevention and eventual
treatment , through using the resources of modern biotechnology
while stimulating European industry .
5.    FINANCIAL INCIDENCE OF ACTION ON EXPENDITURES
      ( including costs for staff and expenses for administrative
      and technical management )
                                                            Million ECU
5.1 .    Total cost over the whole of the expected duration        30
5.2 .       Participation in funding :
          - From the Community budget                              15
          - From national budgets and other sectors
            at national level                                      15
5.3 .       Multiannual Schedule of Commitment Appropriations and
            Payments from the Community budget
5.3.1 . Commitment Appropriations
                             1989   1990    1991         TOTAL
Staff                        0.14   0.20    0.21           0.55
Administration               0.20   0.12    0.13           0.45
Contracts and
training     grants          1.66   6.68    5.66          14.00
Total                        2.00   7.00    6.00          15.00
5.3.2 . Payments
                        1989   1990    1991   1992  1993         TOTAL
Staff                   0.14   0.20    0.21           _          0.55
Administration          0.20   0.12    0.13      -    -
                                                                 0.45
Contracts and
training grants         0.46   2.98    5.36    4.10  1.10       14.00
Total                   0.80   3.30    5.70    4.10  1.10       15.00
                                     27
 ---pagebreak---                                        3
5.3.3 . Methods of calculation
5 . 3 . 3.1 . Staff expenditure
The staff requirements for the implementation of this programme
are :
1 category A staff , (*)
1 category C staff . (*)
The above-mentioned calculation of staff expenses is based on the
following annual figures for 1989-1991 : 93,000 ECU for an A post ,
37,000 ECU for a C post , inflation being allowed for at 4% per
year . Expenditure for missions of Commission staff , for national
experts and auxiliary staff are also included under this heading .
5 . 3 . 3 . 2 . Expenditure for administrative and technical operation
This heading covers the expenses of meetings , participation in
symposia , and travel and subsistence costs of experts , as well as
the publication and dissemination of results and information ,
together with the cost of           scientific and technical assistance
whenever it proves necessary             for the implementation of the
programme .
5 . 3 . 3 . 3 . Expenditure in respect of contracts
The budget foreseen for contracts and training grants < 14 million
ECU ) should permit the conclusion of research and development
contracts         ( for a total   amount  of 11.5 million  ECU ) with an
average length of 2.5 years ( the duration of the programme being
three years , but allowance being made for the period of the call
for proposals and the period of administrative negotiation ), and
for a variable amount according to the subject of the research .
With regard to training contracts and the short-term training
grants , the method of calculation is based upon an average cost
of 29,000 ECU per year per scientist . It is foreseen that
approximately 20-22 training contracts and 10-15 short-term
training grants will be allocated each year . The total amount
devoted to training actions will be 2.5 million ECU .
6.      Financing of expenditure
The appropriations required to cover the Community 's contribution
to this project are to be entered in the Community 's future
budgets .
 (*) 6 months in 1989 .
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 ---pagebreak---                           4
Type of Control
Administrative control by the Director-General for
Financial     Control      ( DG XX )       as    regards    budget
implementation , and by the Contracts Division of DG XII .
Scientific Control by the            responsible     officials  in
DG XII assisted by the CGC .
Audit by the Court of Auditors in accordance with the
provisions of the Treaty .
Evaluation   in  accordance     with    the   Community plan of
action *  See also the Evaluation Criteria in the Annex
to the Council Decision .
Financial Record
Summary
Action i Research and technical development in
          Predictive Medicine .
                                 Expenses           Staff
                           ( Million ECU )          ABC
                                               ( Number of posts )
                  TOTAL :             15 .          1-1 .
                          29
 ---pagebreak---     STATEMENT ON THE IMPACT ON SMALL AND MEDIUM-SIZED ENTERPRISES ,
                      COMPETITIVENESS AND EMPLOYMENT
  Although not primarily aimed either at the support of small and
  medium-sized enterprises or at the solution of the problems of
  industrial     competitiveness and employment ,       the Predictive
  Medicine Programme should nevertheless have some positive results
  in this respect :
  1.        The improvement in advanced genetic technologies should
            lead to worthwhile developments :
               The production of new reagents ( such as restriction
               enzymes ) could provide a good opportunity for the
               commercialization of high added value substances .
               The    obtaining    of     new   DNA  probes ,  and    the
                simplification of their practical use , should permit
                the development of new diagnostic kits . Informal
                estimates of the potential market for DNA probes in
                the next decade in Europe indicate that it is worth
                between 1,000 and 2,000 million ECU/year .
                New techniques for gene amplification might also give
                rise to development of commercial kits .
  2.        Most of the high technology enterprises which are both
            able and willing to collaborate belong to the category
            of small and medium-sized enterprises , and should be
            stimulated by the implementation of the programme .
  3.        In the longer term , the Predictive Medicine Programme
            can   be  considered  as    a  valuable contribution   to  an
            alternative approach to the problem of steadily
            increasing health expenditure in European society , and
            this should ultimately result in an increase in the
            competitiveness of the Community .
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