Indonesia: Genetic diversity 101

The country has the opportunity to cash in on its unique biodiversity – not to mention save itself and perhaps the entire planet

Indonesia: Genetic diversity 101 AFP Photo/Mark Garlick/Science Photo Libra/MGA/Science Photo Library

For Indonesia, a rapidly growing economy is a blessing and curse at the same time. To maintain economic growth using the “business as usual” paradigm, which for the most part disregards environmental impacts, there are bound to be negative externalities. Whether it’s through land conversion, our extensive use of fossil fuels, large volumes of trash, pollution and other activities, there are consequences that we will have to face sooner or later. 

On a global scale, environmental degradation has led to many issues. One of them is the loss of biodiversity. Rapid change in the environment from human activities is one of the culprits behind the mass extinction of species we currently face, known as the sixth extinction. We are now seeing species go extinct at a rate 100 times faster than what is considered “normal.” When species are extinct, we lose them forever. It’s irreversible. And many of these species being lost are not well known. We have not even started scraping the surface of their functions in the ecosystem, let alone their potential medical attributes, potential economic value, the ecosystem services they provide and so forth. 

As a megadiverse country, harboring one of the largest biodiversities in the world, Indonesia is faced with an uphill task in balancing economic growth and conservation of its biodiversity. This essay focuses on the Indonesian narrative for biodiversity conservation, especially at the genetic level. We argue that conservation of genetic diversity in Indonesia does not have a definitive narrative, albeit it has a potential role in building scientific excellence and economic growth. Finding a balance between economic growth and genetic diversity conservation is of the utmost importance and will be beneficial in the long run. 

Before moving any further, we feel compelled to clarify the definition of genetic diversity, which is the variation of genomic information (information in genes) of individuals that belong to the same species. Individuals from the same species have small differences in their gene sequences. The mechanisms behind genetic diversity are not yet well understood, but it’s believed to be important for the survival of species in an ever-changing environment. From a broader perspective, genetic diversity is the diverse genetic material contained in all living organisms, which is responsible for shaping life. The total information contained within a creature’s genetic material is called the genome. The genome is every living creature’s blueprint. A creature’s appearance, physiology, how it reacts to the environment and so forth are all controlled by the information within its genome. Coupled with science and technology, the information in the genomes of organisms can be an indispensable asset.

Indonesia’s megadiversity is reflected in the high diversity of organisms living within its borders. For instance, Indonesia has one of the largest collections of indigenous medicinal plants in the world, only second to the Amazon rain forest; it has 10 percent of all flowering plants in the world; 12 percent of the world’s total mammal collection; 16 percent of its reptiles; and 17 percent of bird species. Indonesia owns this amazing diversity despite only consisting of 1.3 percent of the earth’s total land area. We haven’t even touched the microbial diversity Indonesia owns, which is most likely to be one of the largest in the world.

Every single one of those organisms’ genomes has genes that are key factors in everything produced from it, be it metabolites, enzymes, hormones and other biological products. Some plant products are shown to have anti-cancer, anti-inflammatory, sedative and other medicinal properties, which can be harnessed and even readily produced by better understanding the mechanisms of how they are produced in the plant (ie, how the genome is translated.) We can even reproduce certain fragrances and tastes in plants by utilizing their genes, bypassing the tedious process of planting, mending and harvesting. Thus, genetic diversity (and to a larger extent, biodiversity) has great potential in improving the life of the global community, which in turn gives it limitless economic potential.
 

AFP Photo/Bay Ismoyo

The genetic diversity conservation narrative

The global community has given notice to the importance of biodiversity and initiated efforts for its conservation. These efforts have significantly escalated during the past two to three decades. One of the most notable efforts is the adoption of the Convention on Biological Diversity (CBD) in 1992, which is the first real international agreement on biodiversity management. Signed in Rio de Janeiro, the parties to the CBD pledged to create a mechanism to reduce the decline of global biological diversity, from the species to the genetic level. 

The CBD is unique in many ways, one of them being that it is the first international convention that let the global community independently decide on a global narrative for a certain topic without intervention from the United States or the former Soviet Union. The CBD has hosted 13 Convention of Parties in the 26 years it has been running. Unfortunately, despite some success stories, the decline of global biodiversity and consequently genetic diversity is still very much the norm. The economic growth narrative has nullified conservation efforts, with the loss of conservation areas (such as Indonesia’s vast tropical forests) being prevalent. In fact, Indonesia’s tropical forest loss increased exponentially from 2000 to 2012. Thus, much needs to be thought of in terms of how the global community should proceed in the conservation (and utilization) of the world’s biodiversity. 

Despite being one of the forefronts of efforts on biological diversity conservation, the biological diversity conservation narrative in Indonesia is far from mature.

One way to assess the level of participation and seriousness of the global community toward the CBD is by looking at the number of countries that have ratified and designed conservation plans based on it. As of this writing, 196 countries have ratified the CBD. That number includes nearly all of the countries in the world with the exception of the Holy See and the United States. Unfortunately, from that number, only 148 countries have designed updated National Biodiversity Strategies and Action Plans (NBSAP) in accordance with the latest convention guidelines. The rest have either not designed an NBSAP or have an outdated version of it. Choosing not to ratify/accept the CBD or not submitting a proper NBSAP is most likely due to the priorities of each government, how the country is interconnected with the global community and the influence of other stakeholders in the lobbying process. Nevertheless, it shows a lack of uniformity of belief in the benefits of the CBD.

Indonesia has been a staunch supporter of the CBD. It participated in meetings in the late 1980s and early 1990s that would eventually create the CBD. However, despite being one of the forefronts of efforts on biological diversity conservation, the biological diversity conservation narrative in Indonesia is far from mature. Definitions of key terms are far from being agreed upon. This is particularly true for the definition of genetic diversity. In fact, the definition of genetic diversity in the CBD is also not well defined. In the CBD, a genetic resource is defined as a resource in the form of living beings or genetic material existing in living beings. However, nothing is mentioned about pure genetic matter (DNA or RNA) or the information extracted from those resources – for example, the digital data from the genomes of organisms. This is a loophole that needs to be addressed in the near future, as there is the possibility of inequitable usage of genomic data among nations. 

All regulations in Indonesia, including the NBSAP based on the convention, must stem from the country’s Constitution, where in Article 33 it is stated that the earth, water and all natural resources within belong to the state and are to be used for the utmost welfare/ benefit of the people. The Constitution is then translated into Indonesian Law Number 5/1990 on biological diversity conservation, which is due for revision soon. Unfortunately, the law does not clearly explain genetic resources and diversity. Again, similar to the CBD, the definition of genetic resources is limited to genetic material contained within organisms. Genetic material that has been extracted from organisms or data containing genetic information is not regulated or mentioned. 

The good news is that in 2015, the Indonesian government, through the Ministry of National Development Planning, the Ministry of Environment and Forestry, and the Indonesian Institute of Sciences (LIPI), issued an NBSAP that contains a more complete definition of genetic resources: it states that genetic resources also include pure genetic material extracted from organisms. This is good progress, despite the definition still lacking explanations of in silico/digital and analog genetic data such as genomic sequence data, expressed sequence tags, full genomes or single genes. These genomic data are indispensable for metabolic engineering, artificial biological systems and creating synthetic metabolic pathways. Thus, it is urgent to include genomic data (digital and analog) within the definition of genetic resources. 

Facilities for genetic resource conservation 

The definition of genetic resource/diversity determines the policies and strategies that are designed for its conservation and utilization. With the currently common definition, which is limited to the concept of genetic resources as living organisms, the Indonesian government has been focusing conservation efforts through the establishment of ex situ facilities such as natural conservation zones, zoos, storage facilities, refrigeration and cryopreservation facilities, and in situ facilities such as natural sanctuary zones. 

The goals are to prevent species extinction and protect genetic diversity from shrinking. Such facilities are very difficult to maintain due to their vast areas. The Indonesian conservation zones, mostly made up of rain forests, are shrinking continuously. Many issues are not yet being dealt with successfully, such as illegal logging and illegal poaching, which contribute to the demise of Indonesia’s biological and genetic diversity. 

If the more complete and comprehensive definition of genetic diversity is to be used, which acknowledges pure genetic material and also genetic data (digital and analog) as genetic resources, Indonesia needs to prepare and build more specialized infrastructure and facilities; and perfect (or improve) existing ones. Conservation efforts using this specialized infrastructure require less manpower, but the initial investment is very high. Conservation using such infrastructure can be somewhat of an assurance if the older paradigm of biological conservation (conservation zones, zoos, natural sanctuary zones) fails. Two specialized facilities that will be discussed in this essay are gene banks and genetic information databases, which are currently lacking in Indonesia. The government has not yet paid much attention to the ones that are available. 

Gene banks are traditionally understood as an ex situ genetic resource (from any organism: plant, animal, microbe and so forth) conservation area/facility that stores germplasm using fields, shelters and refrigeration units. The conserved items in gene banks can be a whole individual, embryos or cells (somatic, germ, gonadal). These facilities can conserve known genetic

AFP Photo/Yves Lefevre/Biosphoto pools with better control and protection than in situ methods. However, it is worth noting that gene banks and other ex situ conservation methods should be complementary to, and will not be able to replace, in situ methods, as in situ methods conserve the known and the unknown: the interaction between living beings and between their environment, and possibly unknown species that may be the key to the perplexing mechanism of evolution. 

The gene banks in Indonesia are owned by different research institutions that have their own policies. Each is moving in its own direction, without much-needed coordination. One notable research institute that has a gene bank facility is the Indonesian Center for Agricultural Biotechnology and Genetic Resource Research and Development, which is under the Indonesian Agency for Agricultural Research and Development at the Ministry of Agriculture. It boasts more than 11,000 various crop accessions, mostly in the form of seeds. Large portions of that number are rice accessions, at 4,116. This number is almost one-tenth of the collection owned by the International Rice Research Institute in the Philippines, which is quite an achievement. This important asset needs much attention, as many of the accessions can be utilized as new alternatives for food crops. 

Another gene bank in Indonesia is owned by LIPI. LIPI’s Indonesian Culture Collection currently preserves around 2,800 microbial strains. The facility is one of the few in the world that has 500 or more yeast strains. It is the result of decades of collaboration with Japan’s National Institute of Technology and Evaluation, the University of California, Japan’s Riken research institute, the University of Tokyo and the Japan International Cooperation Agency. The collection in this gene bank can potentially be very influential in determining Indonesia’s biotechnology-based industry development, specifically industries that are based on microbe usage. However, to realize that potential, there needs to be more commitment from the central government, at least first by acknowledging the importance of this facility and other gene banks. 

Despite the achievements, we have to acknowledge the sporadic nature of the genetic resource conservation using gene banks in Indonesia. There needs to be a centralized body to coordinate gene banks and direct research within gene bank-harboring institutions. In addition, to extend research into products that have economic value, the Indonesian government needs to create synergy between different stakeholders, including industry and end users. If we refer to the genetic resource definition that includes genetic data, another important facility lacking in Indonesia is a centralized genetic information database, similar to the United States’ National Center for Biotechnology

Genetic data from Indonesia is still very much in demand as a research subject.

Information, the DNA Data Bank of Japan or the European Nucleotide Archive. As a country with megadiversity, having its own genetic information database will protect Indonesia’s sovereignty in conserving and utilizing the vast genetic information collected within its borders. 

Scientific research on genetic diversity 

The central dogma in molecular biology is that there are two steps in the transfer of information from genetic material to functional proteins in living beings. First, there is the transcription process, in which the DNA in genes is transcribed into RNA. Then, the RNA is translated into proteins, which carry out the various functions of organs in living organisms. Those functions, especially ones that have medicinal properties, are of great interest. This interest triggers much scientific research on the function of genes and their corresponding proteins. 

In the current edition of Nature Biotechnology, a leading scientific journal in biotechnology, at least one out of two sets of research is related to the study of genes, which we will refer to as “genomics” from hereon. Whether it’s about the function of certain genes, the mechanisms of gene expression or methods to manipulate genetic material for specific purposes, the implication of advancement in genomics is that there will be more tools at our disposal to modify and utilize genetic resources for specific purposes. In other words, genes will be a hot commodity in the near future, as we will be discussing in the next section. 

One of the key indicators of the enthusiasm for genomics, particularly in the isolation and characterization of genes from organisms living in Indonesia, is the amount of gene sequences submitted as accessions to online genetic information databases such as GenBank. Using the query word “Indonesia,” there were 470,510 submissions to GenBank between 1990 and 2017. In fact, the number of submissions related to Indonesia has escalated exponentially during the past decade, meaning that genetic data from Indonesia is still very much in demand as a research subject. 

Next-generation gene sequencing is now ubiquitous and has become the staple for genomic research, driving down prices for gene sequencing. As the price for extracting information from genetic material becomes cheaper, more and more information on genes will be available, including the total genome of organisms, which contains all the genes in a certain organism. Indonesia needs to be aware of this trend and set up facilities for extracting genetic information from its immense genetic resources. Research on the characterization of genes and the functional proteins they produce can increase scientific research excellence in Indonesia. Indonesia’s genetic diversity has great potential for improving science and technology development, and that potential can only be realized through the commitment of the Indonesian government and other stakeholders. 

Transforming research 

Biotechnology has paved the road for multibillion-dollar industries. From a handful of microbial resources such as Bacillus spp and Aspergillus spp, and enzymes such as lipases, amylases and proteases, which are used extensively in washing detergents, industries have emerged and been sustained for decades. As mentioned earlier, the central dogma in molecular biology is that the key for the production of enzymes is the genes that encode them. 

The extension of the central dogma in molecular biology is known as metabolomics. It explains that metabolites (products from the metabolism of living organisms) and everything else are produced in living organisms through a series of complex steps. Each step involves proteins produced by the genes of the organism. Thus, the gene, the protein (or enzyme, as enzymes are proteins) and metabolites are three elements that need to be studied in depth in order to understand the mechanisms of metabolite production/biosynthesis. By understanding the mechanisms and genes involved in the process, we will be able to manipulate them according to our needs. We can even produce metabolites and other natural products without the presence of the original organism from which they came. This branch of science is commonly referred to as synthetic biology. 

The use of synthetic biology has been advocated extensively during the last decade. One example is in the production of vanillin. Vanillin is consumed at approximately 16,000 tons annually. Its natural production is done by extraction from seedpods of vanilla crops. However, surprisingly, of the total global vanillin demand, only 0.25 percent comes from vanilla seedpods. The rest of the vanillin we consume is synthesized through chemical synthesis from lignin (a component of wood) and fossil hydrocarbons. This “unnatural” vanillin is dominating the market due to its cheap price (0.3 percent of natural vanillin), despite the environmental stress of its production process. New ways to produce vanillin have been sought out, with synthetic biology being one of them. 

Through synthetic biology, vanillin has been successfully produced using a biological system that mimics the biosynthesis of vanillin in vanilla crops. This biological system involves the use of microbial genes that are similar to genes for vanillin biosynthesis in vanilla crops and fermentation using the microbe Escherichia coli. Simply said, the genes responsible for vanillin biosynthesis were inserted into E coli and used in a fermentation process to produce vanillin. The feedstock (raw material) for the process can be glucose, which is ubiquitous and readily available. 

Evolva, based in Switzerland, is one of the companies that has invested in synthetic biology-based products. Its synthetic biology vanillin is already available in the market and there are market reports that claim Evolva’s vanillin now has a larger market share than natural vanillin from vanilla seedpods. This is understandable due to the fluctuating supply of natural vanillin from vanilla seedpods. The unreliable supply of natural vanillin will only increase with climate change and land conversion, making synthetic biology-based vanillin an obvious choice. 

Aside from vanillin, there are also other fine chemicals that are produced using biotechnology, namely 1,3-Propanediol, Isobutanol, Succinic acid, 1,4-Butanediol, Artemisinin and Omega-3 Eicosapentaenoic. In the near future, more synthetic biology- based products will appear in the market. With the maturation of our understanding of genomics, proteomics and metabolomics, the potential within genes can readily be explored and used with technological innovation. In the Indonesian context, there are opportunities to utilize the immense Indonesian genetic diversity to drive economic development and help Indonesia shift to a knowledge- based economy, which is by far much more desirable than its current trade-based economy. However, there are challenges. 

One of the challenges specific to Indonesia is the lack of a roadmap for genetic resource utilization. There need to be certain basic steps that include resource and data collection; screening of potential hits; a technology assessment process, research, development and prototyping; and marketing of products. For these steps to proceed smoothly, there needs to be strong collaboration efforts among all stakeholders including the Indonesian government, universities, industry/private sector and the Indonesian people. 

The Indonesian government needs to provide more incentives to utilize genetic resources for industrial purposes. It must also do more to facilitate the matching of universities and institutions that keep and do research on genetic resources with relevant industries. The key for building and maintaining a knowledge- and science- based economy is the active involvement of the private sector in scientific research. Unfortunately, this is not the case in Indonesia. The relationship between industry and the research community is somewhat volatile. Industry has no trust in the research community due to continual disappointments, while the scientific community has no trust in the commitment of industry to ensure equitable benefit for both parties. For Indonesia to thrive in scientific research and its utilization in industry, the culture must change. The government can act as a middleman to connect the two stakeholders and ensure positive interaction. Continuous interaction will encourage academic and research institutions to be more open to industry, which in turn will lead to more positive collaborative efforts. 

A strong narrative can help foster a good climate for building a positive collaboration among stakeholders. For example, one narrative that can be used to elevate the importance of genetic resources in research and industry is Indonesia’s traditional herbal drink jamu. Jamu is known to contain herbs that have medicinal attributes. Within those herbs are metabolites that are active chemical compounds, which are synthesized by plants through a biosynthesis process involving the central dogma of molecular biology mentioned earlier. Thus, theoretically, the active compounds can be produced through synthetic biology if the genes and mechanisms in the biosynthesis process are elucidated. The process of elucidating the scientific aspect of active compound biosynthesis in jamu herbs will elevate scientific excellence, while the commercialization of the active compounds will positively contribute to the shift toward a knowledge-based economy. 

Scientific research will never be able to be converted to commercial products without collaboration and strong commitment from relevant stakeholders. In the case of genetic resource-related research and industrialization in Indonesia, the first step is to create a better climate for collaboration, followed by the design of a roadmap for genetic resource utilization and commercialization, legitimization of policies for the roadmap, and a guide for the whole process to ensure its success. 

Conclusions 

The crux of the future of Indonesia’s genetic diversity lies in its definition. The current definition fails to acknowledge data (digital and analog) extracted from genetic materials. This needs to be addressed immediately, as genetic data will be and is already the main currency in biotechnology- based industries. 

In addition, genetic resource conservation and utilization efforts in Indonesia still need improvement, especially coordination among institutions that conserve genetic resources. A centralized ad hoc organization formed by the Indonesian government can help address the issues, at least until a better system is legitimized. 

As for ensuring the realization of the potential of Indonesia’s genetic diversity in the economic and scientific sense, stronger collaboration and commitment needs to be fostered among relevant stakeholders. The process will involve research on genetic resources (including in cutting-edge sciences such as the branch of synthetic biology) and the commercialization of significant findings. Hopefully in the near future, Indonesia’s genetic diversity can truly become a driver for scientific excellence and economic growth instead of remaining as merely “jargon” and “potential.”

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