AETOX - Asociación Española de Toxicología

Inventory of the Spanish Institutions and Scientists Involved in Alternatives to the use of Laboratory Animals (Refinement, Reduction or Replacement)+

Inventory: 9. Sources of Financing

As stated before, many scientists involved in adopting innovative models in biomedical and environmental research and stimulated by the impressive information which can be obtained working in these fields have also promoted and introduced in vitro approaches into the highly conservative field of regulatory toxicology, and also into many different areas. At the same time public institutions have paid attention to in vitro approaches, and support has been given to both research in the field and to congresses and meetings. The financing of all these activities has contributed both to technical and scientific advancement.

About 30,000 Spaniards are working in research and development, 12,000 being researchers (40 %), 11,000, technicians, and the remainder, support personnel. Only 23 % of the researchers are working for industry, while the mean is 49 % for the rest of Europe. Although the number of Spanish researchers has doubled in ten years, it represents only 2.7 per 1000 inhabitants, whereas the median in the European Union is 4 researchers per 1000 workers.

As there are more prepared scientists than offers of work (since only a few new positions are created each year), it is very difficult to change from one work-place to another, and the institutions tend to become endogamic, with most of their workers prepared at the workplace. The fulfilment of principles of equality and meritocracy in assessing applicants for a post have recently been discussed (Bosch, 1998a).

Grisolía (1998) has stated that to promote Spanish science, scientists and institutions should be renewed. He also proposed to strengthening the Interministerial Commission of Science and Technology (CICYT) and to creating a Ministry or Vicepresidency of the Government for Research.

In relation to the European Programmes for the promotion of Science, Research and Development, many Spanish institutions have presented proposals for co-ordinated projects within the IV Framework programme, and 6.2 % of the funding has been returned to Spain. For example, in the Biotechnology Programme 1994-1998, corresponding to the objective of Prenormative research: in vitro alternatives to animal experiments in Pharmacology-Toxicology, 11 proposals were approved: one was co-ordinated by a Spanish team, and 3 more Spanish groups were participants in other approved projects. In more detail, two projects were included in topic 711 "In vitro tests for developmental pharmaco-toxicology"; one related to topic 712 "In vitro tests for neuro-pharmaco-toxicology"; three for topic 713 "In vitro tests for immuno-pharmaco-toxicology"; and five to topic 714 "Cell cultures for the development of in vitro tests".

The total investment in R&D in 1997 in Spain represented 0.85 % of the Gross Domestic Product (GDP), less than in 1992 (0.91 %), and was very low in comparison to the European median (1.9 %). Fortunately, for 1999 an increase was expected to 400,000 million pts (Bosch 1998b).

Spain is situated in position 30 worl-wide in relation to technological innovation. Industrial investment in 1997 was 328,000 million pts, representing a 6 % increase of 18,000 million pts over 1996. However,

these figures represent only 0.42 of the GDP, with no differences in either year. The industry with the largest amount of investment was the pharmaceutical (11 %), followed by TV and radio production and communication equipment (10 %). 80 % was financed by industry, 9 % directly from the public sector, 9 % by contracts, and 6 % from other countries.

9.1.- National Programmes

Roush (1997) reports on the low amount of research funding in animal alternatives by the governments of the US, the UK, and the Netherlands. However, the Dutch Alternative to Animal Experiments Platform invested $1.5 million in 1997, and the German government has funded research to develop alternatives at a rate of $3 to $6 million per year for the past 15 years (Spielmann, 1997).

There is not a fixed amount of investment in Spain for alternative methods. From the answers given to the inventory questionnaire, there are only a few exceptions in which Spanish groups were financed by the specific priorities for alternatives.

The main Spanish National Programmes for Research and Development in areas related to alternative methods are:

1 National Programme of Health, covering biomedical research prioritized according to a list similar to that of the European Biotech Programme.

2 Sectorial Programme for the General Promotion of Knowledge, for fundamental research in areas not prioritized in the previous programme.

3 Fund for Health Research (FIS), related to clinical, experimental/clinical and / or public health, according to the needs of the National Health Service.

4 Other programs from the National Plan for Scientific Research and Technological Development, such as those ralated to environment, food, agriculture, etc

TOPIC	YEAR	ORIGINAL TITLE (in Spanish)
PGC	95	Estudio de fenómenos plásticos en un modelo de cerebro íntegro in vitro
PGC	97	Bases moleculares de las interrelaciones entre factores endocrinos y nutrientes: estudios in vivo e in vitro.
PGC	97	Mecanismos antitumorales de la melatonina: control de la proliferación , apoptosis y capacidad invasiva de células tumorales mamarias in vivo e in vitro
PGC	97	Estudios in vitro , in vivo y experimentales sobre mecanismos de desarrollo de la microglia de aves
1.1	94	Expresión de las moléculas de adhesión en los linfomas cutaneos de células T: modulación de la misma in vivo mediante interferón-alfa e in vitro mediante interferón –alfa y etretinato.
1.1	94	Expresión de las moléculas de adhesión en la psoriasis. Modulación de la misma in vivo mediante etretinato e in vitro mediante etretinato e interferón –alfa
1.3	96	Terapia génica in vitro de una inmunodeficiencia humana de CD3
2.1.1	97	Estudio in vivo e in vitro del papel de CD40 en la apoptosis mediada por la IgM de membrana y FAS en linfocitos B.
2.2.1	96	Efecto antitumoral de la melatonina . Estudios in vitro e in vivo
2.2.3	97	Estudio del efecto radioprotector del GHS in vitro e in vivo en células tumorales, epiteliales y fibroblastos.
3.1.1	98	Anisakis simplex: purificación antigénica y desarrollo de nuevas técnicas de inmunodiagnóstico in vivo e in vitro
3.6	93	Influencia de la glicoproteina P-170 inductora de multiresistencia en drogas en los fenomenos de nefrotoxicidad. Farmacología in vitro.
5.1	96	Efecto comparativo de una dieta rica en grasa monoinsaturada y otra pobre en grasa, sobre el metabolismo de la glucosa in vivo e in vitro en hombres y mujeres sanos.
6.2.1	96	Análisis moleculares y celulares in vitro y en modelos animales, con implicaciones en inmunopatología humana.
7.1.2	97	Caracterización y ensayo in vivo e in vitro de la capacidad antitumoral de dos compuestos de azafrán (Crocus stivus L): crocina y un arabinolactano.
7.2.1 (AM)	96	Estudio farmacológico del mecanismo celular de acción de fármacos antiasmáticos en cultivos celulares de músculo liso de vias aereas humanas
7.2.1(AM)	97	Desarrollo de nuevas estrategias para el control de la genotoxicidad de fármacos y para el estudio de su relación con el estrés oxidativo
7.2.1 (AM)	98	Efectos de antioxidantes naturales en modelos de inflamación intestinal en rata
7.2.2	96	Farmacocinética, metabolismo, biodisponibilidad y residuos de nuevas fluoroquinolonas. Evaluación de la seguridad de uso de animales de consumo humano -pollos broiler.
7.2.2	96	Estudio de la participación de linfocitos T en las reacciones alérgicas cutáneas a medicamentos. Producción de clones de células T específicas a fármacos.
7.2.2	96	Predicción de la biodisponibilidad en los estudios de desarrollo de fármacos, nuevas fluoroquinolonas
7.2.2	98	Actividad y estudio del modo de acción leishmanicida y tripanocida de derivados alquilfosfolípidos
7.2.3	96	Estudio del efecto de los antiinflamatorios no esteroides en la activación del endotelio vascular y su papel en el tratamiento del shock endotóxico.

From a practical point of view, the National Programme of Health is the only one that prioritizes the use of alternatives. More than ten years ago, the use of new methods in toxicology was removed as an objective and research task due to the inclusion of the Toxicology Programme in the Programme of Pharmacy and Health. Later on, under the scope of Pharmaceutical Research, and following the point "7.2 Pharmacology and Toxicology of new products of pharmaceutical interest", the point "7.2.1 Development and Validation of molecular and cellular alternative models to the use of animals in pharmacology and toxicology" was included. In the last 3 years, and under the objective 7.2.1., only 3 projects have been approved, with a total cost of 25 million pts, which represents, respectively, 0.8 % of the projects approved and only 0.6 % of the investment of the National Programme of Health.

This data show that the present objective and research task is not very useful in promoting alternatives. From the data it is clear that in vitro studies are approved under other objectives. The answers to the questionnaire also confirm that the groups interested in alternatives obtained grants independently of the subject of the alternatives. Two main reasons must be taken into account in relation to the low effectiveness of the grants devoted to alternative methods. The first one is the reduced scope of the objective within the pharmaceutical research area, limited to new pharmaceuticals, with no provision for institutions working with pesticides, cosmetics, food additives, industrial chemicals, etc. The second reason may be the low cultural baggage of reviewers, mainly of academic origin, in relation to the social, political, legislative and logistical impacts of alternatives. In order to better stimulate alternative studies, the definition of the research tasks in the National Programme of Health should include a wider objective in regard to alternative methods, not restricting them to the pharmaceutical area, and prioritizing their impact on the real world as much as possible.

9.2.- Regional programmes

There are many differences in the Spanish regional programmes to be included in the inventory. Apart from the amount invested, the philosophy follows European and National Programmes in some cases, but not in others. Some are very open, but others are extremely restrictive, such as those, for example, that do not consider the scientists working in public service facilities, as researchers.

As an example of the important difference among regions, the industrial investment of only 3 Spanish community regions --Madrid, Catalonia and the Basque Country-- represents 75 % of the total investment in this area.

Autonomic Community	TOTAL (millions pts)	%
Madrid	113,061	34.5
Cataluña	92,114	27.1
Pais Vasco	46,475	14.2
Andalucia	15,653	4.8
Valencia	12,051	3.7
Castilla-La Mancha	10,279	3.1
Castilla y León	7,769	2.4
Aragón	6,822	2.1
Galicia	6,102	1.9
Navarra	5,678	1.7
Murcia	3,891	1.2
Asturias	3,259	1.0
Canarias	1,857	0.6
Cantabria	1,442	0.4
La Rioja	1,069	0.3
Extremadura	258	0.1
Baleares	142	0.0

9.3.- Industrial support

The amount of private investment aid in Spain is low in comparison to other countries, approximately 15 % less than the European median. The contracts of the institutions with different companies have been confirmed in the Inventory as a major source of funding.

In recent years, industry has been increasingly using, intramura, in vitro methods, at least for preliminary testing, in order to reduce costs and speed up production processes. However, no private open aid or grants directly focused on alternative methods, such as those that exist in many other countries, could be identified in Spain.

Many other activities have been promoted by private entities, acting especially as sponsors or collaborators in the organization of meetings and courses. This small help has been very positive, particularly when it was possible to combine aid from national institutions such as the CICYT, regional institutions, industrial organizations such as Farmaindustria, and other individual organizations.

The main private entities that have collaborated in Spain in the promotion of activities related to alternative methods are: Afora, Boehringer Mannheim, CIDA, Fundació Bosch i Gimpera, Fundación Alive, Fundación Echevarne, Glaxo Wellcome, IFFA-Credo, L'Oreal, Panlab SL, Ropak Europe, SmithKline Beecham and Uriach.

Fuente / Source: Guillermo Repetto, Ana del Peso, Manuel Salguero, Manuel Repetto (1999) Inventory of the Spanish Institutions and Scientists Involved in Alternatives to the use of Laboratory Animals (Refinement, Reduction or Replacement) Revista de Toxicología 16: 50-127.