Michel Morange
email: michel.morange@ens.fr

Pseudoalleles and gene complexes: the search for the elusive link between genome structure and gene function

After their discovery in the first decades of the XX th century, pseudoalleles generated much interest among geneticists: they apparently violated the conception of the genome as a collection of independent genes elaborated by Thomas Morgan's group. Their history is rich, complex, and deserves more than one short contribution. I will focus on two issues: the way the phenomenon of pseudoallelism suggested that the genome was more than a simple addition of independent genes, and the connection established between the formation of pseudoalleles during evolution and their functional roles. I will successively consider the first explanations for the origin of pseudoalleles elaborated in the mid-1930s, the metabolic/developmental sequential model proposed by Ed Lewis in the 1950s, the disappointments encountered with the T-complex in the 1970s, and the fading of the previous models after the molecular characterization of the pseudoallelic gene complexes in the 1980s. Genomes are more than collections of genes, but their structures are the result of a complex evolutionary history that leaves no place for simplistic models.

Pseudoalleles are closely linked genes that have similar functions. Their proximity on the chromosome makes their distinction by the complementation tests traditionally used by geneticists difficult. For this reason, and because they have similar functions, they were initially often considered as allelic forms of the same gene, hence their name. The Hox cluster is an emblematic example of a pseudoallelic gene complex. The history of research on pseudoalleles is rich and complex. The first observations were made very early, but remained puzzling until a simple model explaining their formation and characteristics emerged in the middle of the 1930s: pseudoalleles originated by gene duplication, the two copies of the gene remaining closely associated on the chromosome, but progressively diverging in structure and function. This model did not prevent the active discussion of new observations on pseudoalleles in the following years. There is an additional, more important reason for a historian to be interested in this system. The study of pseudoalleles was an unsuccessful attempt to bridge the gap between genes and genomes, and to find in the structural organization of the genome clues to how genes function. As Edward B. Lewis put it in 1955: -The phenomenon of pseudoallelism promises to contribute much to our understanding of the genehow it functions, how it mutates, how it evolves‖ [START_REF] Lewis | -Some aspects of position pseudoallelism[END_REF]. The history of pseudoallelism illustrates the difficulty of demonstrating that genomes are more than the addition of individual genes. Research on pseudoalleles has characteristics that are worth underlining at the outset. There was a pre-eminence of a limited number of experimental systems (Bar (an ensemble of mutations affecting the shape of the eyes), achaete-scute, bithorax (a part of the Hox cluster) in Drosophila, the T-complex in mice) that attracted the most eminent geneticists (for Bar, Alfred Sturtevant, Theodosius Dobzhansky, Calvin Bridges, Hermann Muller, Sewall Wright, A. A. Prokofyeva-Bolgovskaya, K. V. Kossikov) over a long period of time. The study of pseudoalleles was a dual issue, concerning both functional and evolutionary biologists, the mechanism of their formation being linked with the functional role they played in the organism. This is probably why so many different issuesposition effects (i.e. the fact that the activity of genes may change according to their position on the chromosomes), the mechanisms of gene duplication, the role of chromatin and the regulation of gene expression-were, transiently or not, associated with their study. I will successively discuss four episodes in this complex history: the early observations on pseudoalleles and gene complexes, and the mechanistic models provided to explain their formation; the metabolic/developmental sequential model proposed by Ed Lewis in the 1950s; the long and tumultuous history of the T-complex (1927-1980); and the -golden age‖ of gene complexes (1980)(1981)(1982)(1983)(1984)(1985)(1986)(1987)(1988)(1989)(1990) with the precise description of their structure at the molecular level. A full history of pseudoalleles would require more than a book!

I. The early observations on pseudoalleles

To understand why the existence and functions of pseudoalleles have always been problematic, it is necessary to bear in mind the vision of the genome held by Thomas Morgan and by most American geneticists: -So far as we can judge from the action of mutated genes, the kind of effect produced has as a rule no relation to location of the gene in the chromosome. A gene may produce its chief effect on the eye colour, while one nearby may affect the gene structure, and a third, in the same region, the fertility of the male or of the female. Moreover, genes in different chromosomes may produce almost identical effects on the same organs. One may say, then, that the position of the genes in the hereditary material is inconsequential in relation to the effects that they produce‖ [START_REF] Morgan | Nobel lecture[END_REF]. Given this view, it is quite remarkable that the early observations on the existence of pseudoalleles were made by collaborators of Morgan, Alfred Sturtevant and Hermann Muller, as well as by the Russian geneticist A. S. Serebrovsky. A mechanism for their formation and extension by unequal crossing over was rapidly proposed. This was confirmed by Calvin Bridges in 1936 through the direct observation of these pseudoallelic complexes on the giant chromosomes of Drosophila [START_REF] Bridges | -The -BAR‖ gene a duplication[END_REF], and simultaneously by Hermann J. Muller in a Russian publication. This phenomenon, occurring at the gene level, had clear analogies with other phenomena described at higher levels of organization in animals: repetition of parts of the organism was a well-known phenomenon revealed by comparative anatomy, and used by evolutionary biologists to explain some of the evolutionary transformations observed in organisms. The origin of life was identified with the formation of the first genes by Muller: therefore, it was not surprising to obtain evidence that new genes originated from pre-existing ones, as every cell comes from the division of a pre-existing cell, and life always originate from life [START_REF] Muller | Bar duplication[END_REF]. In this evolutionary conception, the formation of pseudoalleles was seen only as a transient step, a hypothesis in contradiction with the observation that at least some of these gene complexes seemed to have been conserved in evolution. The existence of pseudoalleles also received attention from the rare geneticists who opposed the particulate conception of the gene, such as Richard Goldschmidt. For them, the existence of pseudoalleles was a strong argument against the -theory of the gene‖ [START_REF] Goldschmidt | Spontaneous chromatin rearrangements and the theory of the gene[END_REF].

II. The metabolic/developmental explanation of the functions of pseudoalleles

In 1945, Norman Horowitz proposed an evolutionary scenario for the formation of long metabolic pathways [START_REF] Horowitz | On the evolution of biochemical syntheses[END_REF]. His model was a consequence of the experiments of George Beadle and Edward Tatum who had confirmed in Neurospora a relation beween genes and enzymes that was implicit since Cuénot and the early steps of genetics [START_REF] Beadle | Genetic control of biochemical reactions in Neurospora[END_REF], but also of the model for the origin of life proposed by Alexander Oparin [START_REF] Oparin | The origin of Life[END_REF]. He suggested that metabolic pathways had grown during evolution in a stepwise process from the end product to the substrate of the first enzyme by the progressive recruitment of mutations generating new enzymes catalyzing each of the steps of the metabolic pathway. This article was important because it was the first to address the issue of the evolutionary origin of the stepwise pathways described in metabolism. The main contributor to the metabolic interpretation of the functions of pseudoalleles was Ed Lewis. He had acquired considerable experience of pseudoalleles, which he had been studying for more than ten years [START_REF] Lewis | Another case of unequal crossing-over in Drosophila melanogaster[END_REF][START_REF] Lewis | The pseudoallelism of white and apricot in Drosophila melanogaster[END_REF]. He proposed the sequential reaction model. Since an enzyme catalyzing a reversible reaction recognizes both the substrate and the product of the reaction, a simple mutation was able to orient the conversion of the product into another product, elongating the metabolic chains. After duplication, the different genes present in a pseudoallelic complex diverged to generate these long metabolic pathways [START_REF] Lewis | Pseudoallelism and gene evolution[END_REF]. Lewis adapted this model to the pseudoallelic bithorax complex. This pseudoallelic complex was involved in the development of Drosophila. By transposing a hypothesis on the origin of metabolic pathways to developmental pathways, Ed Lewis established a link between embryological mechanisms and the evolution of genomes. It was not a big leap, since developmental steps were often considered to be identical to metabolic steps. The metabolic model also explained why pseudoallelic complexes are not transient, but are stable during evolution. Since the products of the genes (enzymes?) were probably physically very close to the genes themselves (a hypothesis that still remained acceptable for eukaryotes at that time), keeping the genes in close proximity meant keeping nearby the enzymes produced by these genes, an obvious kinetic advantage in a metabolic pathway since it limits the time of diffusion of the substrates and products. By extension, the physical association between the different genes involved in the same developmental pathway was also considered as beneficial. Ed Lewis also distinguished position pseudoallelism from other forms of position effects effective over long distances (variegation). At the end of the 1950s, it was discovered that genes involved in the same metabolic pathway were often grouped on the bacterial genome in a structure later called operon, and transcribed into a unique RNA species. The existence of operons seemed to support the previous metabolic model of pseudoallelism [START_REF] Lewis | Genes and developmental pathways[END_REF], although nothing demonstrated that the genes present in an operon had a common evolutionary origin, and further experiments even demonstrated the opposite. At the end of the 1960s, many debates took place on the existence (or not) of operons in eukaryotes. Their absencewith few exceptionsbecame evident only in the 1980s when genetic engineering tools permitted the isolation and characterization of genes and mRNAs, definitively breaking the relation between operons and pseudoalleles.

III. The T-complex

In the words of Virginia Papaioannou (1999), the T-complex educated a generation of developmental biologists [START_REF] Papaioannou | The ascendency of developmental genetics, or how the T complex educated a generation of developmental biologists[END_REF]. Mutations in the genes of this pseudoallelic complex were described as early as 1927 (Dobrovolskaia-Zavadskaia 1927), and the list of geneticists devoting time to the study of this complex included Leslie Dunn, Salomé Gluecksohn-Schoenheimer, Ernst Caspari, Mary Lyon, Dorothea Bennett and many others. The phenotypic characteristics of the mutations were complex. The T-mutation was responsible for a short tail at the heterozygous state, and was lethal at the homozygous state. The different t-mutations were lethal for homozygotes, but heterozygotes were indistinguishable from wild-type animals [START_REF] Bennett | Abnormalities associated with a chromosome region in the mouse[END_REF]). However, a t-mutation combined with a Tmutation generated tailless mice, which constituted a simple way to isolate new t-mutations. In addition, there was a biased transmission of the t-mutations that was interpreted as the effect of the expression of the products of the T-complex on the membranes of spermatozoa. A battery of different tmutations was progressively described, interrupting early embryological development at different successive steps. In 1975, Dorothea Bennett proposed a model that described the role of the T-complex in development and explained the characteristics of the different t-mutations [START_REF] Bennett | The T-locus of the mouse[END_REF]). The T-complex encoded a family of membrane proteins: each of them controlled one early step in embryogenesis. These membrane proteins generated new interactions between embryonic cells that transformed the characteristics of the cells and led to the expression of a different gene of the Tcomplex, allowing new intercellular interactions. The process was repeated as many times as there were different genes in the T-complex. There were various reasons for proposing that the T-complex encoded membrane proteins, but some of them came from a collaboration between a student of Dorothea Bennett, Karen Artz, and the laboratory of François Jacob, who had recently abandoned the study of bacteria and bacteriophages for that of mouse development [START_REF] Morange | François Jacob's lab in the seventies: the T-complex and the mouse developmental genetic program[END_REF]. The experimental approach was to raise specific antisera against embryonal carcinoma cells. These were stem cells of tumours of the gonads called teratocarcinomas, and they were considered to have characteristics in common with early embryonic cells. One of these antisera bound to a membrane protein of the embryo called the F9-antigen, from the name of the embryonal carcinoma cell line used to obtain it. It prevented the compaction of the embryo, a major step of development preceding the formation of a blastocyst, and the first differentiation event. It suggested that the F9-antigen might be involved in this process. By using complex immunocompetition experiments, Karen Artz demonstrated that the expression of the F9-antigen was reduced in embryos bearing the t 12 -mutation, the mutation of the T-complex that had the earliest phenotypic effect on development [START_REF] Artzt | Primitive teratocarcinoma cells express a differentiation antigen specified by a gene at the T-locus in the mouse[END_REF][START_REF] Artzt | Analogies between embryonic (T/t) antigens and adult major histocompatibility (H-2) antigens[END_REF]. Additional experiments performed by Karen Artz suggested that the F9-antigen contained a chain of 2-microglobulin, a protein associated with the H2 immunocompatibility complex of the mouse, the equivalent of the HLA system of humans. The H2-and T-complex might have originated by duplication of a unique ancestral complex involved in the control of early embryogenesis. Even before these results, Walter Bodmer had elaborated an evolutionary scenario in which the genes of the H2/HLA complex were a by-product of the duplication of genes involved in the control of differentiation [START_REF] Bodmer | Evolutionary significance of the HL-A system[END_REF]). This functional model of the T-complex combined a precise mechanistic model of development and an evolutionary explanation of the way this genetic system (and development) progressively became more and more complex. Somehow it fulfilled the dreams that had been supporting the study of pseudoalleles since their discovery: to provide simultaneously an evolutionary and mechanistic explanation of their functions. Unfortunately, the observations on which this model had been based were wrong: the expression of the F9-antigen was not altered in the t 12 -mutation, and 2-microglobulin is not associated with it. But worst of all was the discovery that the T-complex did not exist! The different mutations thought to be in the same gene complex were scattered on the chromosome. Their apparent proximity was the artefactual result of a past chromosomal inversion that prevented genetic recombination and generated deformed genetic maps. These negative results sounded the death knell of the excessive hopes that had been invested in the pseudoallelic gene complexes. Pseudoalleles were not the keys that would open the door to an understanding of genome structure.

IV. The golden age of pseudoallelic gene complexes (1980-1990)

This decade corresponded to the molecular characterization of pseudoallelic gene complexes, made possible by the newly introduced tools of genetic engineering. Particular attention was focused on the HLA and H2 gene complexes [START_REF] Klein | Genetics of the major histocompatibility complex: the final act[END_REF], the globin gene complex [START_REF] Collins | The molecular genetics of human hemoglobin[END_REF], the mouse and human Hox gene complex (homologous to the bithorax and antennapedia gene complexes of Drosophila) [START_REF] Duboule | The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes[END_REF], and more recently the odorant receptor gene complex [START_REF] Kratz | Odorant receptor gene regulation: implications from genomic organization[END_REF]. The situation was shown to be different for each complex. In the HLA and H2-complexes, genes such as those encoding some of the components of the complement (a complex of proteins involved in the destruction of infected cells), structurally unrelated to the major histocompatibility genes, had been associated with the complex during evolution for functional reasons. In most cases, the existence of a complex was the result of a process of gene duplication, the importance of which was reemphasized by Susumu Ohno in 1970 [START_REF] Ohno | Evolution by gene duplication[END_REF]. The different genes present in the complex had often acquired different functions and regulation. The existence of a complex was clearly the consequence of the mechanism of generation of new genes; but the genes having become independent, the future maintenance of a complex was problematic. In some cases, the close association of the genes and their position on the chromosome remained important for their correct expression in the time and space of the organism. Such is the case of the globin gene complex, and even more significantly of the famous Hox gene complex. The position of a gene in the complex is related to its timing and level of expression along the anterior-posterior axis of the embryo (as well as in the limbs); and the structural organization of the complex has been conserved -from Drosophila to humans‖ [START_REF] Duboule | The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes[END_REF]. Gene complexes are a by-product of an important phenomenon for the evolution of genomesgene duplication but also of the complex mechanisms of gene regulation that were progressively brought to light. The most significant step for a reappraisal of the physiological significance of the existence of gene complexes was the discovery of enhancers by Walter Schaffner in 1981 [START_REF] Banerji | Expression of a -globin gene is enhanced by remote SV40 DNA sequences[END_REF][START_REF] Morange | Enhancers: their existence and characteristics have raised puzzling issues since their discovery‖[END_REF]. These DNA sequences activate gene expression at a long distance, in one or other orientation, in the 5' or 3' position relative to the gene they regulate. These enhancer sequences are formed of binding sites for transcription factors. Activation of transcription requires the direct interaction of enhancers with promoters through the formation of loops. Recently, thanks to a huge accumulation of data on gene regulation as well as to the development of specific programs such as ENCODE, which is designed to provide a full description of regulatory elements in a genome, a new vision of enhancer action has emerged [START_REF] De Laat | Topology of mammalian developmental enhancers and their regulatory landscapes[END_REF]. Enhancers are highly abundant in a genome like the human genome, 20 to 30 times more abundant than the genes themselves. According to Chromosome Conformation Capture (3C) studies, enhancergene contacts might be predominantly restricted to topologically associated domains (TADs), coherent chromatin domains (or blocks) along the linear genomic DNA. The existence of gene complexes is the result of four unrelated and independent phenomena and processes: duplication of genes, their progressive functional divergence, the conservation (or not) of enhancers during evolution, and the organization of chromatin in different TADs. The existence (or inexistence) of a complex and its functional integration are the results of the relative weight of these different processes.

Conclusion

Thomas Morgan was not utterly right. The functions of genes can depend on their position in the genome, and on their integration in gene complexes. Gene duplication is an important mechanism of genome evolution. But acknowledging the existence of these phenomena only yields ambiguous clues to the relation between genome organization and gene function. The difficulty of apprehending the complex relations between genome structure and gene function is another example of the difficulty of dovetailing evolutionary (historical) and functional explanations in biology. Whereas functional approaches would favour simple solutions, the long evolutionary history of organisms clouds the picture and prevents any generalization.

Acknowledgements:

I am indebted to Ute Deichmann, David Marsh and the anonymous reviewer for critical reading of the manuscript.


Aouatif El Fakir

South Korean System of Innovation: From Imitation to Frontiers of Technology, Successes and Limitations

In this chapter, we use an analytical framework based on the "national system of innovation" approach to understand how South Korea acquired technological capabilities, increased the effectiveness of its national system of innovation and became a major player in many hightech industries.

Introduction

Some developing countries have emerged as serious competitors in new areas of technology. How did they acquire the necessary capabilities to use technology and even to develop it? And how did they make their systems of innovation more sophisticated?

This chapter will examine the case of South Korea to understand how it has acquired technological capabilities and increased the effectiveness of its national system of innovation to become a major player in many high-tech industries.

We use an analytical framework based on the "national system of innovation" approach to clarify this process. We assume that countries acquire capabilities to produce new goods, services and technologies through interactive learning spaces (ILS). The effectiveness of these spaces depends on how technologies, institutions and organisations evolve simultaneously.

Section 1 contains a critical review of the literature on the acquisition of technological capabilities. In section 2, we present the analytical framework based on the national system of innovation approach. In section 3, we use this framework to examine the case of South Korea. We conclude with a discussion on developing countries in terms of the relationship between technology and development.

The Acquisition of Technological Capabilities in Developing

Countries: Theories and Approaches

The study of technology in developing countries started in the 1960's.

Until the mid seventies, the main corpus of literature was called the Theory of Technological Dependency. This theory considers that technologies that are already developed elsewhere should not be reinvented but must be exploited under the following two conditions: the technology should be appropriate to a country's needs and it should be available at a reasonable cost. The theory also highlights the role of foreign investments and multinationals companies in the transfer of technology [START_REF] Gerschenkron | Economic Backwardness in Historical Perspective: A Book of Essays[END_REF][START_REF] Helleiner | The Role of Multinational Corporations in the Less Developed Countries' Trade technology[END_REF].

From the mid seventies to the mid eighties, many scholars assumed that indigenous science can be more responsive to national needs than technology imports. The effectiveness of the National System of Science, Technology and Innovation (S&T&I) depends on some conditions like long term investments, efforts to accumulate knowledge, and skills and know-how, selection of the right R&D fields, effective institutional support and international [START_REF] Jones | The role of science and technology in developing countries[END_REF][START_REF] Cooper | Science, technology and development: the political economy of technical advance in underdeveloped countries[END_REF][START_REF] Herrera | Social Determinants of Science in Latin America: Explicit Science Policy and Implicit Science Policy[END_REF][START_REF] Sagasti | Knowledge and Innovation for development, the Sisyphus challenge of the 21st Century[END_REF].

The 1980's witnessed the emergence of the Theory of Technological Capabilities. It stipulates that imported technology cannot be used if it does not match the scale, skills and material needs of the new environment. Therefore, developing countries can not take advantage of imported technologies without a threshold of technological capabilities [START_REF] Bell | Learning and the Accumulation of Industrial Technological Capacity in Developing Countries[END_REF][START_REF] Dahlman | Managing Technological Development: Lessons from the Newly Industrializing Countries[END_REF]Fransman and King, 1984;Katz, 1987;[START_REF] Lall | Learning to Industrialize: The Acquisition of Technological Capabilities by India[END_REF].

At the end of the 1980's, the Windows of Opportunity Theory assumed that co-evolution of technology, institutions and organisations is essential for catching up and growth. The time needed to learn and the perspectives for growth depend on the technology. Developing countries must identify clearly the current stage of the technology and acquire the suitable combination of productive and institutional infrastructure, scientific/technical knowledge and experience. The cost of these components changes in each stage of the technology life cycle. It is lower in the emerging and mature stages of technology and higher in the growth phase [START_REF] Perez | Catching up in technology: entry barriers and windows of opportunity[END_REF][START_REF] Perez | Technological change and opportunities for development as a moving target[END_REF].

While all these approaches and theories have illuminated many fundamental aspects on the technology transfer to developing countries, they lack an overall vision of how developing countries can acquire capabilities to use, adapt, improve and even develop technologies.

As a consequence, we propose to use the National System of Innovation (NSI) approach, because it could help to identify the actors and the mechanisms that determine the success of innovation and technological development processes. This approach emerged in the 1980's and the 1990's as an analytical framework in developed countries. It assumes that innovations result from interactive learning processes and the co-evolution of technologies, institutions and organisations. Here, innovations mean using new technologies, adapting, improving and even developing them [START_REF] Lundvall | National systems of Innovation: Towards a theory of innovation and Interactive learning[END_REF]Nelson, 1993).

The National System of Innovation (NSI) Approach

According to NSI approach, innovations (not inventions) occur within a specific system in which stakeholders interact and learn from each other to take advantage of technological and market opportunities.

Interactive learning is the main process leading to innovation because it enables individuals and organisations to acquire new knowledge and new skills to improve their performances, to seize opportunities and to face pressures [START_REF] Lundvall | National systems of Innovation: Towards a theory of innovation and Interactive learning[END_REF][START_REF] Mckelvey | Using Evolutionary theory to Define Systems of Innovation[END_REF] Moreover, this approach emphasizes the uncertainty of the innovation process and the need for an appropriate institutional framework [START_REF] Nelson | An evolutionary Theory of Economic Change[END_REF][START_REF] Saviotti | Innovation systems and Evolutionary Theories[END_REF].

Although the NSI approach highlights systemic and dynamic aspects of the innovation, it has some limitations. It is based on the observation of sophisticated and complex innovation systems in developed countries. As a consequence, we had to adapt it to the context of developing countries because of the following reasons. First, the behaviour and objectives of the corresponding organisations and institutions differ. Second, the NSI indicators for developing countries deal with systems under construction. Finally, developing countries are operating in the context of a globalized R&D where technological alliances can play a significant role in technology acquisition.

Empirical studies of NSIs in developing countries, such as the comparative study of [START_REF] Dahlman | Social absorption capability, national innovation systems and economic development[END_REF], have confirmed that the macroeconomic environment and incentives regime determine technological and economic performance. In addition, resources like appropriate human capital, foreign technologies, industrial infrastructure, public support and funding are crucial for the acquisition of technological capabilities.

Arocena and Sutz's theoretical works about innovation in developing countries highlighted that developing countries lack "interactive learning spaces" which are "interactive activities and processes where individuals and organisations generate, transfer and use systemically knowledge to enhance their ability to learn and to resolve problems." [START_REF] Arocena | Innovation Systems and Developing Countries, DRUID Working[END_REF]. These interactive learning spaces (ILS) facilitate the resolution of pressing problems of production by the encounter of actors owning the problems with "knowledge" actors So, we assume here that these ILS cannot emerge if there are no incentives and pressures on firms to be more competitive and if they do not have the resources to participate in processes to generate, transfer and use knowledge. We also assume that in these learning spaces, firms acquire new technological capabilities and the national system of innovation emerges. As these spaces become systemic, firms strengthen their technological capabilities and the NSI becomes more sophisticated and effective.

The Acquisition of Technological Capabilities in South Korea

South Korea achieved a very fast development process in the last forty years and emerged as a competitive supplier in many medium and high tech industries. First, we note the incentives/pressures that pushed Korean firms to enter in ILS. We then examine the resources they used to resolve production and innovation problems. We will observe how spaces, resources and capabilities have evolved from 1960 until now. Our study is based on the works of [START_REF] Kim | Stages of development of industrial technology in a developing country: a model[END_REF][START_REF] Kim | National System of Industrial Innovation: Dynamics of Capability Building in Korea[END_REF][START_REF] Kim | Korea's National Innovation System in Transition[END_REF], [START_REF] Westphal | Sources of Technological Capability in South Korea[END_REF], [START_REF] Westphal | Reflections on the Republic of Korea's Acquisition of Technological Capability[END_REF], [START_REF] Kim | The dynamics of R&D in Industrial Development: Lessons from Korean Experience[END_REF], [START_REF] Kim | Patterns of Technological Change in a Rapidly Developing Country: A Synthesis[END_REF] and [START_REF] Lim | Technology and Productivity, the Korean Way of Learning and catching up[END_REF]. Table 1 provides figures on the growth the GDP (gross domestic product) and GDP per capita in South Korea from 1960 to 2000. Table 2 shows the evolution of exports from 1966 to 2000. It seen that, in addition to their dramatic growth over the last four decades, their technological content has continuously progressed to higher values.

The South Korean technological, industrial and economic progress has gone through 4 stages. In the 1960's, South Korea was oriented to import substitution before switching to export promotion. This phase witnessed the set up and strengthening of production capabilities 2 . The 1970's was the period of increasing exports, the establishment of heavy industries and the development of investment capabilities 3 . High-tech industries and local R&D activities emerged during the 1980's. In the third phase, industries and activities were strengthened during the 1990's despite the financial crisis and some industrial and institutional failures. In the current phase, which started in 1997, South Korea has undertaken many reforms which put it on a new growth virtuous spiral, but some limitations prevent it from becoming a knowledge and innovation economy.

Keys of success

This success cannot be objectively explained without speaking about the U.S. assistance during the cold war and the major role of Korean government nationalism and culture. In fact, during 1950's, American aid was vital for the reconstruction and industrialization of South Korea after Korean War. Until 1961, 70% of public investments were funded by U.S. aid (military aid from 1953 to 1961 amounted to 1561 million U$) [START_REF] Toussaint | Banque Mondiale, le coup d'Etat permanent[END_REF]. In the 1960's, South Korea firms supplied the U.S. military in the region with construction services, machinery and some finished products (tire, wood). This helped them improve their management, organizational and technical skills [START_REF] Westphal | Sources of Technological Capability in South Korea[END_REF].

The U.S. has remained an important source of technology. Moreover, thanks to Korean Diaspora in the U.S, joint ventures with U.S. firms and research structures allowed South Korean firms to assimilate new technologies, especially in electronics, particularly during the 1980's.

During the totalitarian regime , the South Korean government pursued an active industrial development policy which was continued after the democratic transition in 1987. Reforms of the agricultural regime, investments in infrastructure and education, public funding, subsidies, tax incentives and strong protectionism were the main tools that the South Korean government used to achieve technological and industrial development.

South Korean nationalism and culture played an important role, particularly in the early stages [START_REF] Koo | Socio-cultural Factors in the Industrialization of Korea[END_REF]. According to [START_REF] Song | The Rise of The Korean Economy[END_REF], new Confusionism in South Korea encouraged personal achievement (education and discipline), family values, patriotism, harmony and community spirit.

We will now highlight the ILS that improved technological capabilities of Korean firms and lead to the production of new goods and the use of new technology in each period. Our objective here is to clarify the link between ILS and the technological and industrial development of South Korea.

The 1960's: The acquisition of production technological capabilities

In this decade, South Korea had three major handicaps: a small local market, lack of natural resources and low technological capabilities to compete locally or abroad. The Korean government switched rapidly from import substitution to export promotion to encourage the acquisition of production capabilities in many new industries. Public incentives (subsidies, domestic market protection, fiscal incentives and so on) and attractive market opportunities encouraged Korean firms to acquire technological capabilities even in industries in which they had no competitive advantage. In general, the technology in these industries was mature except for electronics. Korean firms took also advantage of qualified workers who were able to assimilate new knowledge and to acquire new skills rapidly. They benefited from available foreign technologies in the form of capital goods, turnkey plants, technical assistance and licences. Large firms (chaebols or Chaebols, please be consistent throughout the paper) benefited from attractive financial terms from Korean banks. Lastly, the government set up many measures to increase the bargaining power of Korean firms.

To acquire technological capabilities, Korean firms entered deliberately in many ILS that involved different actors according to the production process and scale as well as the size of the firms.

In small batch industries (shipbuilding, machinery), large firms favoured capital goods, licences imports and technical assistance. They were involved in interactive learning spaces with foreign suppliers and experts through training and in situ technical assistance. Korean engineers and technicians learned how to manufacture effectively large quality of quality products with varying technical specifications. Small firms applied imitative reverse engineering. In addition, they interacted with local users to improve their copies of foreign products. Lastly, in new industries, technical staff moved from the pioneer firms to latecomers and interacted with their inexperienced personnel. Thus, foreign technologies were rapidly disseminated.

In large batch industries (electronics, automobile), large and small firms set up ILS with foreign suppliers of sophisticated products to acquire knowledge through training and technical assistance. Small firms preferred imitative reverse engineering of simple products. Foreign technologies have been disseminated in the same way as in small batch industries.

In industries using process production (chemicals, cement, pharmaceutical), firms purchased turnkey plants to acquire initial production capabilities. Korean technical personnel entered in interactive learning spaces with foreign technical experts to assimilate technology and to perform production, maintenance and repair operations.

In summary, in this period, the learning spaces were dominated by foreign sources of technology. Large firms imported technologies to acquire production capabilities and small firms preferred imitative reverse engineering. However, all tried to improve their capabilities to be more autonomous and to enhance quality and sophistication to go to next stages.

The 1970's: The emergence of innovation capabilities

During the 1970s, the Korean companies improved rapidly their technological capabilities in production and in product design. Interactions with foreign customers enhanced the know-how of local companies and new technologies, some mature and some growing, were acquired.

The output of large production facilities set-up in many industries to achieve economies of scale economies was larger than the local market could absorb, so Korean firms had to open new markets. To have competitive exports, they had to reduce costs, differentiate products and improve their quality. A large percentage of Korean firms worked under Original Equipment Manufacturing (OEM) agreements and had to meet tight specifications. To do so, they had to acquire more sophisticated engineering capabilities. Also, OEM relationships constituted precious sources of information about international markets.

Finally, the South Korean government provided attractive incentives in heavy industries like chemicals, the automobile industry, steel or shipbuilding.

The combination of all these factors resulted in a more technically qualified labour force. Korean firms could then import or assimilate more complex and newer technologies. Even while they continued to use some of the old spaces, Korean firms could also engage in new interactive learning spaces in the following manner.

First, in many established industries, new firms hired the technical personnel of pioneering firms to benefit from their experience and skills. Moreover, the new entrants avoided the inherent risks of technology selection by taking advantage of adaptations achieved by the pioneers.

Secondly, large Korean companies involved in OEM agreements entered in a specific interactive learning space with their costumers.

Lastly, large Korean firms continued to import sophisticated and complex technologies through specially licences. Hence, interactive learning space between licence suppliers (especially Japanese) and Korean firms aimed at acquiring production capabilities in new technologies and/or design capabilities in established areas. In short, the acquisition and mastery of production technologies progressed during this phase through "learning by doing" and "learning by using" as well as by adaptations of the foreign technologies. The mobility of qualified workers and other formal and informal mechanisms made the dissemination of technologies easier. Simultaneously, the acquisition of design capabilities continued through the transfer of foreign knowledge, NSI was more and more embedded in economic system, interactions between actors became more systemic and Korean firms reinforced their international competitiveness and enhanced the range of their products.

The 1980's: The emergence of high-tech industries and the expansion of R&D

At the beginning of the 1980's, South Korea faced a dramatic change.

The economic crisis pressed the U.S. and Europe to set up protectionist measures against new industrialised countries. South Korea also lost its competitive advantage in labour intensive industries as real wages increased. Moreover, foreign suppliers of technology became reluctant to supply it to their Korean competitors. Lastly, imitative reverse engineering became more difficult as South Korea tightened regulations regarding the protection of intellectual property. Many emerging hightech industries, however, provided new opportunities. Among them, South Korea chose semiconductors, optical fibre, robotics, computer and aircraft.

During this decade, large Korean firms had to increase their reliance on indigenous resources in R&D with government assistance through exportations subsidies, technology monitoring, financial assistance and so on. Yet, the supply of highly qualified engineers and scientists at this time was not adequate for the needs. To fill this gap, Korean firms attracted Koreans expatriates (from the United States, Europe and Japan). Korean-American engineers and scientists provided the necessary bridges with foreign experts on specific R&D projects. Moreover, large firms like Samsung, Hyundai and LG invested in foreign technological outposts to monitor technological changes and work with foreign firms and R&D institutes within technology clusters. Korean foreign subsidiaries and outposts contributed to the dissemination of foreign knowledge and know-how particularly in electricity, electronics and chemicals. All these interactive learning spaces, particularly those that involved Korean and U.S companies, were extremely beneficial in leading-edge technologies such as semiconductors, computer and biotechnology.

In many industries, such as robotics and computers, companies (notably Chaebols) continued to use their usual ILS. New interactive learning spaces involved Chaebols and multinationals firms (MNFs) through joint ventures. The latter were interested in technological cooperation with Korean firms with large production capabilities. While Korean firms aimed to strengthen their innovative capabilities.

In this decade, Korean companies started to work with government research institutes (GRIs). National R&D Projects (NRP) and Industrial Base Technology Development Projects (IBTDP) set up by the Korean government involved the GRIs and firms in selected technologies.

In short, during the 1980s, Korean companies (particularly Chaebols) moved from reverse engineering to international cooperation and local R&D to acquire the knowledge associated with the emerging industries. Reverse engineering and internal R&D was for relatively simple technological tasks in robotics, computers at the beginning. Interactions with foreign companies and indigenous R&D structures were reserved for more complex cases. The ILS helped to establish new industries to replace those that lost their competitive edge and to take advantage of new opportunities. The NSI became more autonomous, innovations more endogenous. As a consequence, the Korean economy was radically transformed in this critical decade.

The 1990's: The expansion of high-tech industries and the strengthening of innovation capabilities

The Korean slowdown during the 1990's had many reasons, both internal and external. Nevertheless, after the financial crisis, favourable conditions accelerated Korean recovery. Foreign investors' confidence was re-established, many large companies were restructured and currency was re-stabilized. Moreover, favourable global demand, and information and communication technology expansion encouraged Korean firms to increase their efforts towards more creativity and inventiveness in order to take advantage of new innovation-intensive industries.

In addition, large investments in basic research in universities, venture capital availability, attractive public incentives and the needs of more flexible firms in many industries encouraged the setting-up of hightech and innovative SMEs.

By and large, Korean firms achieved internal R&D and kept their relationships with Korean diaspora to improve their innovative capabilities. They also maintained cooperation with MNFs and GRIs. In addition, the government continued to support firms through subsidies, financial assistance and so on. Lastly, in the case of more complex capabilities, Korean companies increased their patent portfolio to enhance their negotiation position with international parties through cross-licensing and similar intellectual protection schemes.

Korean firms, notably Chaebols, reorganized themselves to encourage new "creative spaces." For example, to stimulate innovation, employees with new ideas could set up experimental spaces involving persons of various domains to find profitable projects in the short and medium terms.

Furthermore, outsourcing needs of Chaebols strengthened semipermanent relations between them and their SME suppliers of components and machinery. This cooperation resulted in cost reduction, and improved the design and production capabilities for complex technologies.

Also, Korean SMEs were involved together in many interactive learning spaces through R&D cooperation, common equipment and inputs purchasing, common marketing in order to improve their efficiency and quality.

Korean companies continued to be involved with GRIs in new hightech industries, such as artificial intelligence, advanced robotics and so on. Lastly, Chaebols kept interactive learning spaces through joint ventures with MNFs to strengthen their innovative capabilities.

In this stage, ILS led to the acquisition of more complex engineering and innovative capabilities in order to keep pace with technology frontiers and to generate new technologies in specific industries.

Figure 1 summarizes the technological catch-up process of South Korea.

The 2000's: South Korean System of Innovation limitations

Many studies and reports in the 2000's have indicated that South Korea is not a producer of radically new knowledge. Chaebols do not have enough capabilities to innovate radically and there are only few technological SMEs. Basic and applied researches are not promoted enough and scientists and researchers are not equally distributed between GRIs and universities [START_REF] Kim | Korea's National Innovation System in Transition[END_REF]OECD, 2005).

To fill the gaps of its system of innovation, OECD recommended that South Korea focus on three major areas of improvements. First, basic research, especially within universities, must be strengthened to increase the chances of new discoveries and to develop new technologies. More interactions between different innovation actors (firms, GRIs, universities) are also required. Moreover, scientific and technological cooperation with others countries must be intensified to take advantage of their previous experience. Second, education policy must be reformed to diversify higher education and develop creative and high quality expertise in strategic areas. Third, industrial policy must lead to a more balanced structure between SMEs and Chaebols and to more intensive learning and innovation through more business services, venture capital development, support networks, enhancement of creativity culture and so on.

In recent years, Korea has followed many of these recommendations. In fact, R&D expenditures reached 2.63% of GDP in 2003 (24321.3 million U.S.$), higher than the OECD average. New R&D public programs and higher universities budgets (to intensify basic research) lead to the rise of public expenditures. Moreover, the number of researchers reached 6.2 per 1000 workers, which is close to the OECD average in 2002 (OECD, 2006). Furthermore, in the early the 2000's, South Korean government restructured the national system of innovation to encourage creativity an innovation such as upgrading academic and industrial laboratories.

Consequently, South Korean scientific and technological outputs increased significantly in recent years. As shown in Table 3, patent applications and patents granted to South Korean inventors increased dramatically between 1995 and 2005. The percentage of high-and medium tech exports rose respectively 36.1% and 32.2% of the total South Korean exports. In contrast, low and medium-low tech exports declined to respectively 11.4% and 20.3% (OECD, 2006; STAN database).

Discussion and Conclusions

The common pattern of Asian success in manufacturing (Japan, South Korea, China…) shows two main characteristics. First, firms are able to integrate and evolve from an interactive learning space to another to get the technological capabilities required for each stage of development. Second, institutional framework and organisational arrangements supported the technological effort.

Like Japan earlier, South Korea imitated and integrated the existing technological systems. Similarly, Chinese firms in the field of mobile telephone technology, entered in several ILS and had joint ventures with Multinational companies to acquire basic manufacturing skills and hone their adaptive capabilities [START_REF] Von Zedtwitz | Process of Technological Capability Development: Cases from China's Mobile Phone Industry[END_REF]. Unlike Korean firms, however, Chinese firms moved quickly to establish joint ventures and R&D to keep pace with rapid change of 3G technology.

South Korean strategies were particularly effective in the assimilation, adaptation and improvement of technologies developed outside Korea. Organisation arrangements and the institutional framework were adapted to fit the technology needs. This experience illustrates, however, that a successful pattern of technological assimilation does not necessarily help in producing new technologies and that contributing to radically new knowledge and technologies requires another set of strategies.

The failure of other developing countries can be attribute to the lack of interactive learning spaces and to the absence of a supportive institutional framework. Firms in these countries rarely have the internal and external resources to integrate and evolve from one interactive learning space to another. Thus, they cannot solve their pressing production problems; stagnate at a level of low technological capabilities and insufficient competitiveness in local and international markets. This inability to integrate interactive learning spaces and to evolve among them results from the disjunction of the institutional framework and organisational arrangements from technology evolution.

Accordingly, we propose that technological and economic development is possible only if developing countries make their institutional framework and organisational arrangements compatible with the technology life cycle. More studies of catch up processes are needed to clarify whether it is the political regime, institutional arrangements and culture aspects that determine the accumulation of capabilities and the production of new knowledge or whether the latter depends on each national experience and the history of the various national innovation systems.

Figure 1 :

 1 Figure 1: Technological development process of South Korea

Table 1 :

 1 GDP and GDP per capita of South Korea 1960-2000.

	Year	GDP	GDP per
		(current	capita,
		billion. US$)	Purchasing
			Power Parity
			(current
			international
			($)
	1960	3.9	155
	1965	3.0	108
	1970	8.9	275
	1975	21.5	599
	1980	63.8	1632
	1985	96.6	2290
	1990	263.8	5893
	1995	517.1	10850
	2000	511.7	9763
	Source: World Bank.World Development Indicators Database.

Table 2 :

 2 Structure of exports of SouthKorea 1966Korea -2000

	Type of Export (%)	1966	1976	1987	1995	2000
	Primary products	37.9	10.1	6.4	3	2
	Resources based manufactures 12.5	6.2	3.4	7	11
	Low tech manufactures	41.8	55.5	52.3	20	17
	Medium tech manufactures 0.4	4.4	13.7	35	33
	High tech manufactures	1.3	6.7	21.8	30	36

Source: Calculated from international trade statistics, SITC Rev.2. OECD. 2005.

Table 3 :

 3 Patent applications and patents granted of SouthKorea 1995Korea -2005. .

		Patent applications			Patents granted
	Year	1995	2000	2002	2005*	1995	2000	2002	2005*
	Number 78,499 116,886 106,136 160,921 12,512 34,956 45,046 73,512
	Source: World International Property Organisation WIPO. * Last data available.

The Author is grateful to Mostafa Hashem Sherif for the support received in the preparation of the manuscript.

Production capabilities include the supervision of production facilities, raw materials control, production planning, quality control, production problems resolutions, process and product adaptation, facilities repairing and maintenance and marketing[START_REF] Westphal | Sources of Technological Capability in South Korea[END_REF].

Investment capabilities include labour force training, feasibility studies, projects implementation, management and engineering, specific studies, basic and specific engineering and purchasing. Ibid.