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Back
to basics
Balancing
fundamental and applied research for the future of
the health and life sciences
ACTIP, the
Animal Cell Technology Industrial Platform,
comprises representatives of many major European
companies as well as a number of SMEs. It was
established in 1990 at the request of the Euopean
Commission in order to follow the progress of
research in ECfunded projects in animal cell
technology, which is an important generic
technology underlying many advances in health and
the life sciences. Another objective was to liase
with project contractors and to provide input to
the European Commission regarding topics most
likely to benefit from funding in this field.
Through numerous meetings, networking activities
and position papers, ACTIP has become a respected
and internationally recognised forum of industrial
expertise for European scientists and the European
Commission.
The first century
of this new millennium has been predicted from many
informed sources, indeed from no less an authority
than Bill Gates, as the 'Age of Biotechnology'. The
ACTIP membership, comprised of representatives of
this technology from European Industry, will be
pleased to remain a source of industrial expertise
and a channel to facilitate technology transfer
from academia to industry. ACTIP can and will
provide a forum of communication, co-operation and
co- ordination between government, academia and
industry for an optimal exploitation of the
scientific, technological and commercial success of
biotechnology.
In order to support
this role, the ACTIP members have prepared this
position paper, intended as input for discussions
with the Commission Services on Framework Programme
6. It contains ACTIPës view on a number of
research policy actions and specific research
topics likely to benefit most from EU funding in
the area of health and the life sciences. The
following Executive Summary contains a synopsis of
our proposal; the underlying argumentation and full
proposal follow in the position paper.
Executive
Summary
Continuing
need for research in animal cell
technology
Despite major
achievements over the past 10 years, there is a
continuing need for research in animal cell
technology, a generic technology underlying many
advances in health and the life sciences. The
surface of this powerful enabling in-vitro
technology has barely been scratched and many more
important discoveries and applications are emerging
as fundamental questions are being answered by
basic research, performed in various
interdisciplinary organisations.
Full social and
economic benefits of new technologies can only be
achieved against a background of solid scientific
infrastructure and the ability to identify and
transfer science to products, in particular since
it is widely recognized that basic science gives
new products! Further arguments in favour of an
EUwide effort to support fundamental and
missionoriented research in animal cell technology
are the following:
* many fundamental
questions relevant for technological applications
remain unresolved, despite obvious progress in
animal cell technology;
* basic skills and
appropriate tools must be further developed in
order to achieve meaningful academic, biomedical
and industrial goals;
* a greater
understanding of cell physiology is needed to take
full advantage of the progress made in the human
genome project;
* clinicians and
industry are calling for more animal cell based
approaches and products. These products and
approaches are used:
- - for the
production and safety testing of
biopharmaceuticals and vaccines;
- - in tissue
engineering
- - in cell and
gene therapy approaches;
- - in advanced
research programmes;
- - in human
genome projects.
Recommendations
Because of the
complexity of biopharmaceutical research, large
pharmaceutical companies focus their research
efforts on their core competencies. In addition,
they frequently enter research alliances with
specialized biotechnology SMEs to increase
long-term innovation. Another solution to secure
future growth is through fundamental research,
since experience and history show that this type of
research frequently generates new product concepts
and the establishment of new SMEs. Both SMEs and
larger pharmaceutical companies, the members of
ACTIP, recognize the importance of pure and
mission-oriented fundamental research; they
therefore propose long-term approaches/developments
in research with interest for applications, whereby
research support should be on a pre-industrial
level. The ACTIP membership in particular proposes
support for:
1. Fundamental
research in addition to missionoriented
research;
2. Early
identification of usable results, with a focus
on:
(a) links between
contractors of EUfunded research
projects;
(b) practical
applicability of results;
(c) good and
meaningful cooperation, communication and
coordination between academia, industry and the
Commission Services;
3. Increased
funding and simpler procedures, in particular
an improved balance between fundamental and applied
research and separate evaluation
procedures;
4. Support for
specific research topics, including suggestions
for research topics to be financed by the European
Commission in the field of animal cell technology
in the Framework Programme 6 (2003-2007). These
specific research topics can be divided
into:
(a) the cell
- new cell lines and model systems, stem cell
technology, reverse genetics, metablic pathway
engineering, expression systems;
(b) the
process - i.e. new and reliable production
processes, control methodologies, preservation
methods;
(c) applications
for the cells and/or their products - i.e.
recombinant proteins, vaccinology, cell and gene
therapy, artificial organs, functional
genomics/proteomics, in vitro methodologies,
virtual methodologies.
The full paper
following this executive summary contains
suggestions for specific research topics, as
identified by the ACTIP members.
Full
text ACTIP position paper, August
2000
A
proposal for funding by the European Union of
research in the field of animal cell technology and
related areas, to be incorporated into the 6th
Framework Programme
Back
to basics
Balancing
fundamental and applied research for the future of
the health and life sciences
In the late 1980s,
the European Commission recognised the importance
of animal cell technology for emerging
biotechnology applications in the areas of
biopharmaceuticals and vaccines. Between 19901999,
it funded in its consecutive programmes a total of
18 projects in animal cell technology (including
two large T and G projects) and 14 projects in the
emerging field of gene therapy. In addition, 36
projects were funded in the area of transdisease
vaccinology. ACTIP, the Animal Cell Technology
Industrial Platform, was established in 1990 to
follow the progress of research in ECfunded
projects in animal cell technology, to liase with
its contractors and to provide input to the
European Commission regarding topics most likely to
benefit from funding in this field. Through
numerous meetings, networking activities and
position papers, ACTIP has become a respected and
internationally recognised forum of industrial
expertise for European scientists and the European
Commission.
In the past ten
years, the efforts of the European Commission, the
industry and academia to improve basic knowledge in
animal cell technology has not been in vain. A
critical mass of researchers has been created,
networks between academia and industry have been
established and fundamental and mechanistic
knowledge of animal cells has increased
substantially.
Continuing need for
research in animal cell technology
There is, however,
no reason for complacency. Full social and economic
benefits of new technologies can only be achieved
against a background of solid scientific
infrastructure and the ability to identify and
transfer science to products, in particular since
it is widely recognized that basic science gives
new products! Further arguments in favour of an
EUwide effort to support fundamental and
missionoriented research in animal cell technology
are the following:
1 Because of the
complexity of animal cells, many fundamental
questions in animal cell technology remain
unresolved. This contrasts with the situation in
other industrially important cell factories, i.e.
those based on fungi, bacteria and yeast: in these
systems molecular genetics, metabolic pathways,
cellular biology and optimal cell culture
conditions are much better
characterised;
2. Basic skills and
appropriate tools must be further developed in
order to achieve meaningful academic, biomedical
and industrial goals;
3. A greater
understanding of cell physiology is needed to take
full advantage of the progress made in the human
genome project. Europe needs to maintain an
intellectual and infrastructural critical mass so
that the EU can respond rapidly to new
opportunities rather than lose the initiative in
this vital area of science and technology to the
USA or Japan;
4. Clinicians and
industry are calling for more animalcell based
approaches and products. These products and
approaches are used for the production and safety
testing of biopharmaceuticals and vaccines, in
tissue engineering, in cell and gene therapy
approaches, in advanced research programmes and in
genomic and proteomic projects.
The area of animal
cell technology is thus characterised by a market
need which cannot as yet be fully met by the
existing technology. To progress further, the field
needs answers to fundamental questions: mechanistic
knowledge is required to expand the set of skills
necessary to develop novel approaches with emphasis
on the translation of knowledge into products. In
addition, a greater emphasis on basic research in
animal cell technology is required to take full
advantage of the knowledge generated by such
initiatives as the human genome project.
Recommendations
The ACTIP
membership proposes that increased support is given
to research in animal cell technology and related
areas, with emphasis on:
(1)
Fundamental research in addition to
mission-oriented research;
For the past 10
years, ACTIP has consistently emphasised the
importance of fundamental research in addition to
applied research in the field of animal cell
technology. ACTIP published position papers to that
effect in 1992, 1993, 1995, 1996, and 1997, and
reinforced the message in letters and personal
messages to representatives of the European
Commission in 1998 and 1999.
Mainly through
fundamental research will the science base be
sufficiently broad to deliver the insights, which
form the basis for new approaches and innovations
in academia, the clinic and industry.
ACTIPs consistent
call for reinforcement of fundamental research has
been echoed by important academic institutions,
such as ESACT (the European Society for Animal Cell
Technology), the EUs own intergovernmental European
Molecular Biology Organisation (EMBO), and most
recently the ELFS (European Life Sciences Forum).
All these organisations have emphasised the
importance of basic research, and in several
communications they argue that basic research and
confidence in its value must be restored to a prime
position on the agenda of research policy in
Europe.
The call for
reinforcement of basic research is also a
recognised socioeconomic priority. In 1998, the US
Committee for Economic Development found that US
economic growth is fed by the enormous federal and
industrial investment in basic research. In the
same year, the US Congressional Budget Office
concluded that the financial return on public
investment in academic research and development is
2040%. In its January 2000 Communication, Philippe
Busquin, EU Commissioner for Research, recognised
the socioeconomic importance of scientific progress
and argued that ".....Europe would be quite wrong
to reduce its investment in this area". As a
consequence, he has put forward ideas of how to
create a coherent, coordinated European policy on
research, the European Research Area.
Recommendation:
ACTIP
supports the initiative to arrive at a European
Research Area and again makes the case to give
priority to fundamental research in addition to
missionoriented research, in particular in the life
sciences. Animal cell technology, including
research into non-mammalian species, should be one
of the priorities in the life sciences because
activities in this field have a wideranging impact
on European citizens and society.
(2)
Boosting early identification of usable
results
To help science
provide the tools to satisfy the commercial and
sociological need, extensive focus should be placed
on novel technology transfer schemes. In our
perspective, technology transfer should
embrace:
(a) Links
between contractors of EUfunded research
projects. In earlier (up to Framework 4
Programme) EUfunded programmes, there was a strong
emphasis on clustering of projects on certain
themes, whether in the form of T (tripartite), G
(generic) projects or by means of sectoral
meetings, where contractors working in related
areas could exchange information and extend their
network. For Framework Programme 5 such established
channels have not been foreseen. Any links which
have been forged have only developed due to the
initiatives of the contractors themselves or
through third parties such as ACTIP and other
platforms. This approach leaves a great deal to
chance.
Recommendation:
For
FP 6, ACTIP supports the inclusion of established
mechanisms that will facilitate exchange of
information between contractors working on related
topics. Preferably, such mechanisms take account of
the International nature of research, allowing
frequent and in some cases intensive exchange of
European researchers with worldleading US and
Japanese scientists. These goals fit extremely well
into the ideas launched for the European Research
Area, such as ..."networking of centres of
excellence", ...." bringing together the scientific
communities, companies and researchers of Western
and Eastern Europe, ", ...."greater mobility of
researchers in Europe", ....."improving the
attraction of Europe for researchers from the rest
of the world", etc.
(b) Practical
applicability of results. In the past, many
ideas have been put forward to promote technology
transfer and industrial applicability of research.
Many of the schemes have focused on the later
stages of research such as stimulating patenting
awareness or innovation and the creation of a more
favourable climate for startup companies. Not
enough has been done in the earlier phases of
research projects, for example, providing guidance
to researchers regarding potential applicability of
their results. Experience has shown that 40% of
fundamental research projects give rise to
practical applications (EMBO, 1998).
Recommendation:
For
FP 6, ACTIP supports a fixed percentage (i.e. 510%)
of a project's budget be allocated to assessment of
technology transfer activities. ACTIP particularly
favours the option whereby EUapproved consultants
with industrial experience closely follow a
project's progress, preferably from an early stage
onwards. Together with the project's coordinator,
these consultants may report back to a forum of
scientists and industrialists, for example,
industrial platforms, as was done for FP 4 but
missing for FP 5. ACTIP would also favour official
EU recognition of the function of an industrial
platform, to allow early exchange of information
and access to publiclyfunded research
results.
(c) Good and
meaningful cooperation, communication and
coordination between academia, industry and the
Commission Services is essential in order to fulfil
expectations for the future industrial and
socioeconomic wellbeing of Health and Life Sciences
in the European Union.
Recommendation:
ACTIP,
together with the Commission, would anticipate
playing a pivotal role in the establishment and
maintenance of good and meaningful cooperation,
communication and coordination activities between
industry, academia and Commission Services. ACTIP
also offers the environment for the assessment of
technology transfer activities.
(3)
Increased funding, simpler
procedures
During FP 5, the
emphasis was on linking the ability to discover to
the ability to produce. Thus the majority of
projects selected so far are application
orientated. While laudable in itself, this has
reduced the chance that fundamental projects have
been or will be selected for funding. In addition,
the selection procedure is very time consuming, and
when a project is finally started, its execution is
accompanied by heavy administrative procedures. All
this has resulted in an erosion of faith in the
EUFP system among scientists working in academia
and industry alike.
Recommendation:
ACTIP
strongly proposes an increase in the budget for
research and in particular an improved budgetary
balance between fundamental and applied research.
It also proposes that fundamental research projects
be evaluated separately from more
applicationoriented projects. While projects have
to be executed in an accountable, transparent way,
it is proposed that purely administrative
procedures are lightened to free scientific minds
for research rather than
administration.
(4)
Specific research topics
In addition to
above general remarks, the ACTIP membership has
identified a number of areas within the field of
animal cell technology and closely related fields,
where it believes that funding by the EU will be
most effective.
Funding of these
topics will stimulate research and serve to
establish new networks among European scientists,
including those from Eastern Europe. It will
reinforce contacts between the industrial and
academic research in Europe and create the
opportunity for European industry to improve
competitiveness, employment and growth in a global
market.
As argued at length
in the preceding paragraphs, we believe that
fundamental research and applied research should be
stimulated in concert. At the same time it is
necessary to foster greater collaboration between
academia and industry. Finally, an important aim
must be the early identification of results with
potential industrial applicability.
(a) The
cell
In order to allow
for further progress in its applications, cellular
research should focus on:
1. Development of
new, mammalian virus-free cell lines that are not
transformed;
2. Identification
of factors involved in the immortalization of
cells; establishment of conditional immortalization
procedures;
3. Development of
stem cell technology, thereby e.g. facilitating
tissue engineering and target finding;
4. Development of
(non-tumorigenic/virus free) continuous cell lines
from other species than vertebrates, e.g.
invertebrates (insects, crustaceans) or avian cell
lines;
5. Development of
methods allowing isolation or induction of cell
lines that keep their differentiated
characteristics and that can be grown in large
scale culture;
6. Development of
efficient methods for site specific modifications
in mammalian cells (other than embryonic stem
cells);
7. Improvement of
efficient expression systems, especially for toxic
proteins;
8. Development of
reverse genetics as a tool to develop defined RNA
and DNA viruses for use in vaccinology and gene
therapy programmes;
9. Metabolic
pathway engineering;
10. Identification
and removal of the bottlenecks in cellular
secretion pathways including intracellular
transport, intracellular degradation and
folding;
11. Wherever
possible, use of yeast (or an other eukaryotic
organism like Drosophila or C. elegans) as a model
system to take advantage of the vast knowledge of
microbial genetics and the complete genome sequence
(especially relevant to points 1 and 2)
(b) The
process
In order to develop
novel production processes meeting industrial
requirements, the ACTIP membership
suggests:
1. Development of
new efficient, safe, largescale expression systems
allowing high productivity combined with a short
development time;
2. Development of
animal cell cultures using serum-free/animal
product free media to avoid possible contamination
of industrial production processes with animal
derived material;
3. Development of
improved reliable measurement and control
technologies;
4. Development of
improved bioseparation systems;
5. Development of
novel protein 'tags' permitting the design of
efficient and versatile integrated bioproduction,
downstream processing and validation of
product;
6. Development of
methods that permit the viable preservation of very
large numbers of animal cells or organs;
7. Development of
technologies for gene therapeutic virus
production;
8. Development of
organ-like cell culture.
(c) The product and
applications
The following
research topics have been identified by the ACTIP
membership to promote the development of specific
products or applications based on animal cell
technology:
I Recombinant
Proteins
1. Study of the in
vivo function of posttranslational modifications
including N and O linked glycosylation.
II
Vaccinology:
1.Transdisease
vaccinology with emphasis on both prophylactic and
therapeutic vaccines;
2. Continuing study
of the immunology of vaccination;
3.Development of
new efficient adjuvants;
4.Further
development of nucleic acid vaccination for both
human and veterinary applications (see also under
III);
5. Identification
of vaccine targets;
6. Studies on
host-pathogen interactions.
III Gene and cell
therapy:
1. Alternative
direct DNA therapies (using the injection of
'naked' DNA for the delivery of recombinant
proteins);
2. Development of
celltargeted specific vectors;
3. Development of
safe, immune nonreactive cells;
4. Development of
new packaging technologies;
5. Further
development of expansion technologies for primary
cells;
6. Methods for the
storage and in vitro and in vivo expansion of stem
cells (i.e. from umbilical cord) to be used in
human therapy;
7. Further
development of cellmediated gene
transfer.
Biosafety aspects
will have to be an integral part of the projects
funded.
IV Artificial
organs
1. Studies leading
to the development of artificial organs such as
liver, pancreas etc;
V Functional
genomics/proteomics
1. Development of
the cell as a vehicle for functional
genomics;
2. Methodology to
translate genomics into diagnosis and therapies
including improving methods of gene expression from
newly discovered chromosomal DNA (verification of
genes, exploration of gene function) and
improvement of knock-out technology on cells to
explore gene function.
VI In Vitro
methodologies:
1.Development, and
validation, of in vitro toxicology
methods;
2.Development of in
vitro methods for the study of drug metabolism and
pharmacokinetics;
3.Studies aimed at
the (partial) replacement of in vivo preclinical
drug development by in vitro methods;
4.Development of
cellular models for metastasis induction, tumour
and normal function;
5.Studies on
cellular signal transduction pathways leading to
the development of in vitro models that are used
for the identification of lead
compounds;
6. Development of
tools that will facilitate High Throughput
Screening and assay development in today's drug
discovery programmes;
VII. Virtual
methodologies
1. Establishment of
a virtual database of certified cells and vectors
used in the industrial production of marketed
therapeutics and diagnostics to foster R&D,
exchange of material, standardisation of cell lines
and regulatory procedures.
Inishturkbeg,
August 2000
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