**4. Overview of the global scientific development in biotechnology in Brazil**

### **4.1. Analysis of results and cowords networks**

Government policies to incentive and promote R&D activities in biotechnology in Brazil have started since the 1980s. However, from the late 1990s and the early 2000s, especially in 2001, with the creation of the national fund for biotechnology, the area aimed at real conditions of productivity and competitiveness in R&D. Biotechnology has its amended financing path taking up considerable resources of 97% between 2002 and 2003, with the resources allocation from the National Fund for Scientific and Technological/FNDCT, managed by the MSCT, CNPq, and Studies and Projects Financing Institution (FINEP) [23].

From the data collected in the ISI database, bibliometric indicators have been produced that will help us to understand the scientific activity in the biotechnology area.

With regard to the scientific literature on biotechnology for the period between 1995 and 2015, it was retrieved 102,326 documents containing terms selected by experts in the fields of title, abstract, and keywords, and 69,977 documents where Brazil as the home country (1st author). **Figure 1** shows the evolution of publication number in biotechnology area since 1995.

By analysis, the number of articles published throughout this period was possible to observe that there is an increase in publication trends, which indicates an intensive scientific activity over the past 15 years, mainly in the last 8 years. An exponential growth with increased production greater than 6500% was observed, as shown in **Figure 1**. However, this scenario

**Figure 1.** Historical evolution of biotechnology scientific publishing indexed in Brazil since 1995.

of accelerated growth should be modified in the coming years because of the reduction of R&D investments by government agencies in recent two years (2014–2016); due to the severe economic crisis that Brazil has been facing since 2013, which will reflect in a slowdown of the scientific production in the country for the next years.

**4. Overview of the global scientific development in biotechnology in** 

Government policies to incentive and promote R&D activities in biotechnology in Brazil have started since the 1980s. However, from the late 1990s and the early 2000s, especially in 2001, with the creation of the national fund for biotechnology, the area aimed at real conditions of productivity and competitiveness in R&D. Biotechnology has its amended financing path taking up considerable resources of 97% between 2002 and 2003, with the resources allocation from the National Fund for Scientific and Technological/FNDCT, managed by the MSCT,

From the data collected in the ISI database, bibliometric indicators have been produced that

With regard to the scientific literature on biotechnology for the period between 1995 and 2015, it was retrieved 102,326 documents containing terms selected by experts in the fields of title, abstract, and keywords, and 69,977 documents where Brazil as the home country (1st author).

By analysis, the number of articles published throughout this period was possible to observe that there is an increase in publication trends, which indicates an intensive scientific activity over the past 15 years, mainly in the last 8 years. An exponential growth with increased production greater than 6500% was observed, as shown in **Figure 1**. However, this scenario

**Figure 1** shows the evolution of publication number in biotechnology area since 1995.

**Brazil**

**4.1. Analysis of results and cowords networks**

194 Knowledge Management Strategies and Applications

CNPq, and Studies and Projects Financing Institution (FINEP) [23].

will help us to understand the scientific activity in the biotechnology area.

**Figure 1.** Historical evolution of biotechnology scientific publishing indexed in Brazil since 1995.

A probable cause of this growth seems to be the key role that the activities of biotechnology have gained notoriety on a worldwide scale in recent decades. In Brazil, this increase observed reflects the research government incentives, established the financial investments in the area and the implementation of government policies, as aforementioned.

With respect to the most frequently used terms to screen the biotechnology area in Brazil, it was possible to find a large dispersion in relation to them [2], which means that there are more than 7000 distinct descriptors (keywords) described by the authors in the scientific publications as examples: Vaccine, PCR, DNA, Genome, Leishmania, *Trypanosoma cruzi*, HIV, among others. Some of them were not used as initial descriptors when searching the database.

In the specific evaluation of these terms, we noted that terms such as DNA and PCR are often used since the beginning of the period analyzed, which means that since 1998, these are being associated with modern biotechnology techniques [2]. Other terms such as "genomic," (72 articles) "proteomics," (32 articles), and "stem cell" (37 articles) are further frequent, however, they are related to more advanced future-bearing technologies of modern biotechnology, being mentioned in Brazil by the National Biotechnology Committee as the frontier areas of biotechnology. This observed result is associated with the Brazil collaboration in the genome projects, as example the mapping of the *Xylella fastidiosa* genome in 1997, and later, working in international project such as Human Genome Project (HGP) in 1999. *X. fastidiosa* is a bacterium that attacks citrus agriculture producing "little yellow" and decreasing agricultural productivity, so this project was essential for the control of this pest in Brazilian farming. This project was much important because it was the first phytopathogen sequenced in the world.

According to Santana et al. [2] and Pisano [6], some areas of biotechnology will have a significant impact in the near future on the development of new technologies and its applications, which are the genomics, pharmacogenomics, transcriptomics, biomaterials, bioengineering, and synthetic biology. Some themes related to these terms were detected in this dataset. **Table 2** presents the terms mentioned by the authors (keywords' author) with more than 50 citations related to the field of biotechnology.

From the total of scientific publications found, it can be observed the terms like *Leishmania*, *T. cruzi*, *Schistosoma mansoni*, and Chagas disease, which refer to a potential application. It should be emphasized that the data collected point out that scientific research on biotechnology in Brazil is directly related to the study of some relevant social problems of a country mainly related to tropical diseases.

Neglected tropical disease (NTD) has become an extremely important issue in public health in Brazil, as they profoundly affect the quality of life and generate negative socioeconomic impacts for the population of the poorest countries. Although not unique to developing countries, they arouse little financial appeal from the large pharmaceutical industry, since they do not reach the large consumer market that is the developed countries. In Brazil, the


**Table 2.** Terms with more than 50 citations used by authors in the fields title, abstract and keywords in the articles published by Brazil.

Ministries of Health, Science and Technology and the Health Surveillance Secretariat defined seven neglected tropical diseases based on epidemiological criteria, disease impact, and demographic data. They are dengue, Chagas disease, leishmaniasis, malaria, schistosomiasis, leprosy, and tuberculosis [24].

**Figure 2** presents a network map where the main lines of research stand out. This map representation was obtained using VOSviewer®, taking as the matrix of cooccurrence of the 7000 keywords' and authors standardized by the measure of strength of association [21].

Although the keywords, which represent the domain of cells and genome, show a highly interrelated distribution, the structure can be clearly seen. Analysis of the relations among the most frequent descriptors reveals four well-defined groups, but with a variable degree of dispersion. In the upper part (1), around the nodes infection and vaccine, we find the most compact group of the network. It includes descriptors that represent documents in the areas of immunology, infectious diseases, and tropical medicine, related fundamentally with the application and clinical research into tropical diseases.

This scenario is compounded by the lack of innovation in drug R&D programs in the area of NTD; thus, the situation requires a concentrated global for the creation and maintenance of R&D programs focused on the discovery of new alternative therapies for the control and treatment of these diseases [25, 26]. Modern biotechnological tools (e.g., genomics, functional genomics, proteomics, metabolomics, and cytometry) have provided valuable insights for the discovery and development of new drugs that are extremely useful in coping with these NTDs. Extremely important initiatives are being successfully implemented to include Brazil in an increasingly significant science and technology scenario. According to Guido et al. [25, 26], three examples are presented to illustrate the breadth and diversity of networks and partnerships that have provided great opportunities and challenges in the area of NTD.

**Figure 2.** Map of keywords based on a co-occurrence network on biotechnology in Brazil. *Source*: Map presentation software VOSviewer®.

Ministries of Health, Science and Technology and the Health Surveillance Secretariat defined seven neglected tropical diseases based on epidemiological criteria, disease impact, and demographic data. They are dengue, Chagas disease, leishmaniasis, malaria, schistosomiasis,

**Table 2.** Terms with more than 50 citations used by authors in the fields title, abstract and keywords in the articles

**Articles Top terms** 

324 PCR 83 Diagnosis 69 gene 232 DNA 82 Expressed gene 65 HIV

131 Leishmania 72 Genomics 57 Cancer

54 Chagas disease 53 Epidemiology 50 Drugs

380 Vaccines 99 Cell 71 Molecular marker

 Genetic 85 Genotype 64 Microsatellite Brazil 79 *Trypanosoma cruzi* 66 Chromosome Genome 78 Oxidative stress 61 Apoptosis Polymorphic 75 Cytokine 63 Bovine diseases

**(keywords)**

56 Inflammation 54 Fish

**Articles Top terms** 

**(keywords)**

**Figure 2** presents a network map where the main lines of research stand out. This map representation was obtained using VOSviewer®, taking as the matrix of cooccurrence of the 7000

Although the keywords, which represent the domain of cells and genome, show a highly interrelated distribution, the structure can be clearly seen. Analysis of the relations among the most frequent descriptors reveals four well-defined groups, but with a variable degree of dispersion. In the upper part (1), around the nodes infection and vaccine, we find the most compact group of the network. It includes descriptors that represent documents in the areas of immunology, infectious diseases, and tropical medicine, related fundamentally with the

This scenario is compounded by the lack of innovation in drug R&D programs in the area of NTD; thus, the situation requires a concentrated global for the creation and maintenance of R&D programs focused on the discovery of new alternative therapies for the control and treatment of these diseases [25, 26]. Modern biotechnological tools (e.g., genomics, functional genomics, proteomics, metabolomics, and cytometry) have provided valuable insights for the discovery and development of new drugs that are extremely useful in coping with these NTDs. Extremely important initiatives are being successfully implemented to include Brazil in an increasingly significant science and technology scenario. According to Guido et al. [25, 26], three examples are presented to illustrate the breadth and diversity of networks and part-

nerships that have provided great opportunities and challenges in the area of NTD.

keywords' and authors standardized by the measure of strength of association [21].

leprosy, and tuberculosis [24].

**Articles Top terms** 

56 *Schistosoma* 

published by Brazil.

*mansoni*

**(keywords)**

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application and clinical research into tropical diseases.

To the right, cluster 2, the keywords genome, PCR, and DNA connect with a well-defined cluster of descriptors related to genetics, and molecular biology research related fundamentally with the application and clinical research into the genome of *X. fastidiosa* begun in the 1990s.

Genomics is also closely related to agriculture not only in genetic improvement of species such as transgenic crops (with resistance to pests and tolerance to pesticides), but also in the product quality changes (plants that produce hormone, eucalyptus with higher production cellulose). More recently, Brazil has been developing research on feasibility of plants, animals, and microorganisms as biofactories of molecules of agricultural, pharmaceutical and industrial interest; identification and applications of genes and biological functions that promote tolerance to abiotic and biotic stresses and elimination of contaminants in food; identification and characterization (structural and functional) of new molecules to increase the production capacity of biologically based products with low environmental impact; and identification and applications of genes and biological functions that promote tolerance to abiotic and biotic stresses and elimination of contaminants in food [27].

Meanwhile, the terms of biomass, diversity, and conversation compose the third cluster 3, far right, including areas of biotechnology and biodiversity. To the left, cluster 4, we have the keywords (cell, gene expression, and stem cell) associated with molecular biology and cell biology areas related to the processes of modern biotechnology associated with a medicine, oncology, and neuroscience therapies.

The information obtained through keywords analysis is much more comprehensive and precise. For this reason, even though the two largely coincide or overlap, subject categories (see **Figure 3**) are more general or superficial than the information based on keywords (**Figure 2**). The latter shows, with a greater level of desegregation, the distribution of the descriptors that specifically configure each thematic profile, plus the less productive or incipient research that would otherwise remain hidden [28].

### **4.2. Profile of the scientific sector: biotechnology**

By its intrinsic multidisciplinary characteristics, biotechnology permeates many areas of knowledge. Therefore, when analyzing the frequency of publication of scientific areas, there is a predominance of biochemistry and molecular Biology (12.4%), followed by genetics and heredity (10.94%), immunology (8.66%), microbiology (7.57%), and veterinary science (6.22%) together representing 45.79% of total articles published. However, this study highlights the wide dispersion of scientific publications by all thematic areas. **Figure 3** demonstrates the percentage distribution for all the 20 areas with the number of articles greater than 200 indexed in ISI/Web of Science.

**Figure 3.** Percentage distribution of scientific publications on biotechnology by areas of knowledge indexed on database. Period 1995–2015.

It can be observed that most of the articles found are in the areas like life sciences and health, highlighting specific areas such as molecular biology, genetics, immunology, and microbiology. The predominance of these areas was already expected due to the characteristics of biotechnology, but it is interesting to note that areas such as molecular biology and genetics have a significant interest toward other traditional areas such as chemical and pharmaceutical industries.

The information obtained through keywords analysis is much more comprehensive and precise. For this reason, even though the two largely coincide or overlap, subject categories (see **Figure 3**) are more general or superficial than the information based on keywords (**Figure 2**). The latter shows, with a greater level of desegregation, the distribution of the descriptors that specifically configure each thematic profile, plus the less productive or incipient research that

By its intrinsic multidisciplinary characteristics, biotechnology permeates many areas of knowledge. Therefore, when analyzing the frequency of publication of scientific areas, there is a predominance of biochemistry and molecular Biology (12.4%), followed by genetics and heredity (10.94%), immunology (8.66%), microbiology (7.57%), and veterinary science (6.22%) together representing 45.79% of total articles published. However, this study highlights the wide dispersion of scientific publications by all thematic areas. **Figure 3** demonstrates the percentage distribution for all the 20 areas with the number of articles greater than 200 indexed

**Figure 3.** Percentage distribution of scientific publications on biotechnology by areas of knowledge indexed on database.

would otherwise remain hidden [28].

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in ISI/Web of Science.

Period 1995–2015.

**4.2. Profile of the scientific sector: biotechnology**

Note, also, that a considerable number of articles are classified as multidisciplinary, confirming that research in biotechnology, as mentioned previously, brings together researchers from different areas of knowledge. This, probably, highlights the increasingly important role of biotechnological techniques for the development of new products.

Of the 73,125 articles published in internationally indexed journals it was possible to realize a trend of publication in two main areas: health and life science. It is worth mentioning that both thematic areas coincide with the prevailing keywords previously identified. Besides this fact, an interesting aspect observes the concerns of the regional coverage of the top 20 journals, which means that the majority of Brazilians scientific articles are submitted in Brazilian journals (60%), or particularly in indexed American journals (30%). This indicator illustrates the little dynamics of international cooperation of Brazilian research groups. Among the indexed journals, the Vaccine journal has the highest number of articles (12.65%), followed by other journals such as Memórias Instituto Oswaldo Cruz (10.98%), and genetics and molecular biology (10.58%).

**Figure 4** presents the top 20 journals with a number of scientific publications greater than 40 articles. The list of journals is in accordance with classification presented in **Figure 3**.

An interesting fact observed is the leadership position of Vaccine Journal, which justly gives priority, an analysis of information and knowledge about human vaccines (infectious diseases and noninfectious diseases) and veterinary vaccines, molecular biology, immunology, production and manufacturing, regulatory, and legislation aspects. It is followed by others publications in areas such as microbiology, biology, genetics, life sciences, and others.

Considering the authors´ affiliation, it is observed that there are 441 institutions, showing a high dispersion among the authors´ institutions in Brazil. It is important to highlight the significant number of articles produced by institutions such as the University of São Paulo (USP) representing 32.71%, followed by the Oswaldo Cruz Foundation (FIOCRUZ) with 8.92%, and the Federal University of Rio Grande do Sul (UFRGS) with 7.58% articles, respectively. Another significant topic to be observed is the prevalence of public governmental institutions such as research centers or universities, evidencing a concentration of activities in biotechnology by public institutions or nonprofits corporations at research levels. It is also worth mentioning a few numbers of scientific publications indexed by the Brazilian biotechnology companies in the research period, less than 1%, which indicates a small number of companies working in that area or that they are still consolidating their capacities, according Santana et al. [2]. It is should be highlighted the public institution Brazilian Agricultural Research Corporation (EMBRAPA) Genetic Resources with the 8th institution in the ranking, which is the public company with

**Figure 4.** Main internationally indexed journals with biotechnology-related articles.

leadership in transgenic research in the agricultural area in the country. **Figure 5** shows the top 20 institutions that have published more than 100 articles in the observed period.

The research results present that the most of institutions are located in South/Southeast regions, which are more developed regions of the country. There is little representation of institutions in the Center-West/ Northwest regions, presented only for 4 universities: University of Brasília, Federal University of Pernambuco, University of Goiás and Federal University of Ceará.

In addition, there is the significant presence of the public universities of São Paulo (USP, UNESP, and UNICAMP), which together account for a significant share of national scientific output in the biotechnology area, that is, 46.31% of published articles in journals are from USP. This observed result was expected because since the beginning of projects development in the biotechnology area (*X. fastidiosa* genome and HGP/Brazil), there was an intensive participation of research groups of these universities. Furthermore, we can mention the continuous financial support from FAPESP foundation for the development of projects in the areas such biotechnology and bioprospection.

### **4.3. Maps of knowledge and network collaboration**

According to Santana et al. [2], regarding the analysis of relationships between composing agents of the National Organizational System of S,T&I, many authors refer to the central idea

**Figure 5.** Leading Brazilian institutions with major publications in biotechnology for the period 1995–2015.

leadership in transgenic research in the agricultural area in the country. **Figure 5** shows the top

The research results present that the most of institutions are located in South/Southeast regions, which are more developed regions of the country. There is little representation of institutions in the Center-West/ Northwest regions, presented only for 4 universities: University of Brasília, Federal University of Pernambuco, University of Goiás and Federal University of Ceará.

In addition, there is the significant presence of the public universities of São Paulo (USP, UNESP, and UNICAMP), which together account for a significant share of national scientific output in the biotechnology area, that is, 46.31% of published articles in journals are from USP. This observed result was expected because since the beginning of projects development in the biotechnology area (*X. fastidiosa* genome and HGP/Brazil), there was an intensive participation of research groups of these universities. Furthermore, we can mention the continuous financial support from FAPESP foundation for the development of projects in the areas

According to Santana et al. [2], regarding the analysis of relationships between composing agents of the National Organizational System of S,T&I, many authors refer to the central idea

20 institutions that have published more than 100 articles in the observed period.

**Figure 4.** Main internationally indexed journals with biotechnology-related articles.

such biotechnology and bioprospection.

200 Knowledge Management Strategies and Applications

**4.3. Maps of knowledge and network collaboration**

of networking and the valuable interactions between system components and its main actors in order to promote the dissemination and use of new scientific knowledge [29].

In accordance with these premises, we sought to analyze the links established between the organizations by observing how these actors relate to each other using the number of publications of scientific cooperation between institutions and countries; on a macro level, the international relationships developed by these institutions for R&D. The best representation of these collaborations is the visualization of maps of knowledge, where the existence or not of correlations and the degree of its intensity are clear, which provide to decision-makers some strategic subsidies in future planning of national activities of ST&I [2].

Considering the network map of articles´ authorship in Brazil, for the biotechnology area, it is possible to verify an intensive cooperation between diverse institutions, especially among Brazilian institutions, showing that 66.9% of articles are written with internal collaboration, which subsidize the relevance to develop endogenous capacity of Brazilian groups and publish papers with little support from international cooperation [2].

It is possible to note groups with strong collaboration such as the University of São Paulo (USP), Federal University of Rio de Janeiro (UFRJ), the University of Campinas (UNICAMP), and Oswaldo Cruz Foundation (FIOCRUZ). These collaborations between Brazilian institutions demonstrate that relationship is based more heavily on the model of interaction between universities, research centers, and nongovernmental research centers and of little interaction with companies. It should be emphasized that this scenario will modify since the implementation of the Organic Law of Science, Technology and Innovation in January 2016, where the private sector was encouraged to invest more in partnerships with public institutions and/or in internal activities of ST&I, aiming to promote alliances between the private sector with scientific research center and universities [2, 29]. **Figure 6** shows the collaboration network among institutions with more than 60 articles published.

From a macro perspective, there is a large international collaboration, particularly with five countries: the United States (12.81%), the United Kingdom (2.27%), France (2.22%), Germany (1.43%), and Spain (1.30%). As seen previously, when focusing on Latin America, the block represents only 1.89% of all countries' collaboration, it is possible to identify that Brazil has networks of scientific collaboration and research with almost all countries. Inside this block, Argentina is a major coauthored number of articles (41.94%), followed by Colombia (19.47%), Chile (12.17%), Uruguay (9.92%), and Venezuela (8.80%). **Figure 7** shows the map collaboration network among 40 major countries and Brazil in the biotechnology area.

**Figure 6.** Map of institutional relations on biotechnology for Brazil. *Source*: Map presentation software VOSviewer®.

**Figure 7.** Map of network based on a co-authorship between Brazil and the 40 major countries on the biotechnology area. *Source*: Map presentation software VOSviewer®.
