INTRODUCTION

The Nobel Assembly at Karolinska Institutet for Physiology or Medicine issued a press release on October 7, 2024, announcing the winners of the 2024 Nobel Prize in Physiology or Medicine: Victor Ambros and Gary Ruvkun for their discovery of microRNA and its role in post-transcriptional gene regulation. This year’s Nobel Prize honors these two scientists for their discovery of the fundamental principles of how gene activity is regulated. Meanwhile, the Royal Swedish Academy of Sciences held a press conference on October 8, 2024, announcing the winners of the 2024 Nobel Prize in Physics, which was awarded to John J. Hopfield and Geoffrey Hinton “for fundamental discoveries and innovations enabling machine learning with artificial neural networks.” They trained artificial neural networks using physics. The winners for the field of Chemistry were announced on October 9, 2024, with the winner being David Baker “for computational protein design” and the other half jointly awarded to Demis Hassabis and John Jumper for “predicting protein structures by modeling them using AI.” They cracked the code for the amazing structure of proteins.

It is interesting to notice that for three consecutive years, 2022, 2023, and 2024, the Nobel Prize winners in Physiology or Medicine have always been related to DNA/RNA or genomics. Even when looking at the last five years (2020 to 2024), four Nobel laureates have been associated with DNA/RNA or genomics, namely: 1) In 2020, the Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for their groundbreaking work in developing the revolutionary genome editing method known as CRISPR-Cas9. This discovery allows scientists to “cut” DNA with very high precision, opening up great opportunities for advances in biology, medicine, agriculture, and other fields. 2) In 2022, Svente Pääbo received the Nobel Prize in Physiology or Medicine for his discoveries about the genomes of extinct hominins and the emergence of the discipline of paleogenomics, as well as changes in the history of human evolution and migration. 3) In 2023, the Nobel Prize in Physiology or Medicine was awarded to Katalin Kariko and Drew Weissman for their discoveries regarding “nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19”; and 4) In 2024, the Nobel Prize in Physiology or Medicine was awarded to Victor Ambros and Gary Ruvkun for their discovery of “microRNA” which plays a role in regulating gene activity in cells.

This article reviews the four Nobel Prize-winning topics related to DNA/RNA or genomics in 2020, 2022, 2023, and 2024.]

PURPOSE

This paper aims to:

1. It should be emphasized that DNA, RNA, genes, and genomes are the engines of life at the cellular level that are essential for the life and survival of living things, including humans, animals, plants, and microorganisms, including viruses. Therefore, DNA, RNA, genes, and genomes have always been objects of interest to researchers in genetics, biotechnology, medicine, and agriculture.
2. Recalling that although there have been many research results related to DNA, RNA, genes, and genomes, there are still many more things that are unknown, including their use in food production or in overcoming various infectious diseases such as dengue fever, HIV, and non-infectious diseases such as cancer, etc.
3. To inspire researchers in related fields to utilize or develop research results related to DNA/RNA, genes, or genomes for implementation in various indigenous or endemic species that have economic or strategic value, or for other purposes.
4. Motivating young researchers that the Nobel Prize is the highest prestigious award for intellectual achievement for a scientist in their contribution to the development of science and human life. It is hoped that this will spark interest in becoming persistent, accomplished professional researchers who are active internationally by establishing extensive cooperation.

A BRIEF OVERVIEW OF DNA, RNA, GENES, AND GENOMES

Chemically, DNA (Deoxyribonucleic Acid) is a macromolecule in the form of a polynucleotide composed of repeating nucleotide polymers, arranged in pairs to form a right-handed double helix bond (forming a double helix) found in the nucleus of cells in the form of chromosomes, where there are various genes that are a collection of DNA. DNA is responsible for storing and transmitting genetic information.

RNA (Ribonucleic Acid) is a single nucleic acid molecule that plays an important role in the process of gene expression, including in protein synthesis. In this case, RNA has a role in translating genetic information from DNA into proteins through the processes of transcription and translation. So if DNA is a double molecule that stores genetic information, then RNA is a single molecule that plays a role in gene expression. RNA is produced from DNA through the process of transcription, but physically RNA is not part of DNA; rather, it is a product produced from DNA to carry out genetic functions in cells.

Some terms closely related to DNA are genes, chromosomes, and genomes. Genes are the basic substances of heredity that contain genetic information composed of nucleic acids (DNA) and are found in chromosomes. Meanwhile, chromosomes, which are composed of DNA and proteins, function as storage for the genetic material of life. A gene consists of coding DNA sequences, promoters, enhancers & silencers, terminators, start & stop codons, and regulatory elements. These genes are located along the DNA strand within the chromosomes. Not all DNA is genetic; some DNA is non-genetic. Therefore, genetic information is stored in DNA, which not only functions as a carrier of genetic factors that determine all the characteristics of an organism, but also plays a role in the formation of protein synthesis related to the life processes of an organism.

The genome is the entire genetic material possessed by an organism, containing all the information necessary for the growth, development, function, and reproduction of that organism. The genome includes DNA (deoxyribonucleic acid) or RNA (ribonucleic acid) in some viruses. So the genome includes genes, DNA, non-coding DNA, and chromosomes. Most of the DNA in the genome is not part of genes, but still consists of nucleotide base pairs that have other important functions beyond protein formation.

DNA performs its tasks by, among other things, determining which enzymes or proteins will be produced by cells. The enzymes produced give cells their characteristic chemical patterns with the ability to accelerate and catalyze chemical reactions in certain ways. A detailed explanation of the structure and function of DNA has been researched by relevant scientists, some of whom have won the Nobel Prize. From this description, we can see how important the role of DNA is in the survival of an organism. Therefore, it can also be said that DNA is the chemical engine of living cells.

SUMMARY OF TOPICS RELATED TO DNA, RNA, AND GENOME FOR 2024, 2023, 2022, and 2020

This brief overview of the findings of Nobel laureates related to DNA, RNA, or genomics will begin with the 2024 Nobel laureates, followed by the 2023 and 2022 laureates, and conclude with the 2020 laureates.

1. Victor Ambros and Gary Ruvkun, winners of the 2024 Nobel Prize in Physiology or Medicine for their discovery of microRNA.

Victor Ambros and Gary Ruvkun won the Nobel Prize in Physiology or Medicine in 2024 for their discovery of microRNA in living organisms, including multicellular organisms such as animals and humans. Victor Ambros was born in 1953 in Hanover, New Hampshire, USA, and received his doctorate in 1979 from the Massachusetts Institute of Technology (MIT), Cambridge, MA. He then conducted postdoctoral research from 1979 to 1985. In 1985, he became a Senior Researcher at Harvard University. He then became a Professor at Dartmouth Medical School from 1992 to 2007 and is now the Silverman Professor of Natural Sciences at the University of Massachusetts Medical School, Worcester, MA. Meanwhile, Gary Ruvkun was born in 1952 in Berkeley, California, USA, received his doctorate from Harvard University in 1982, and became a postdoctoral researcher at the Massachusetts Institute of Technology (MIT), Cambridge, MA, from 1982 to 1985. He then became a Senior Researcher at Massachusetts General Hospital and Harvard Medical School in 1985, where he is now a Professor of Genetics.

MicroRNA plays an important role in regulating gene activity in cells. Its discovery began in 1993 when they found microRNA in nematode worms (C. elegans) that could inhibit the formation of proteins from certain mRNAs (Lee, et al., 1993). However, this finding, which was published in 1993, did not attract much attention from other scientists. The attention of researchers and scientists only emerged when Ambros and Ruvkun published their next findings in the 2000s that similar microRNAs were also found in multicellular organisms, including animals and humans, and played a role in regulating gene activity in cells. The attention from various scientists was partly due to the potential of this discovery to be developed in controlling diseases such as cancer (Pasquinelli, et al, 2000). This is because microRNA can regulate to inhibit or stop by blocking mRNA in the post-transcription protein formation process.

In its press release, the Nobel Assembly at Karolinska Institutet explained that Victor Ambros and Gary Ruvkun were interested in how different types of cells develop. They discovered microRNA, a new class of small RNA molecules that play an important role in gene regulation. Their innovative discovery revealed a completely new principle of gene regulation that turned out to be important for multicellular organisms, including humans. It is now known that the human genome encodes more than a thousand microRNAs. Their surprising discovery revealed a completely new dimension of gene regulation. MicroRNAs have proven to be very important for how organisms develop and function (NAKI, 2024).

As is known, there are four stages in the process of gene activity: 1) the process of gene activation through a specific protein that binds to the gene; 2) then the DNA strand of the gene is opened into an RNA strand at the transcription stage, where this RNA strand is copied into mRNA; 3) the mRNA formed in the cell nucleus then moves to the cytoplasm; 4) the ribosomes in the cytoplasm attach to the mRNA and read the sequence of nucleoside bases in the mRNA while carrying the amino acids encoded by the mRNA, thus forming a chain of amino acids that ultimately becomes a protein. MicroRNA plays a role in the final stage of this process, where microRNA binds to mRNA, thereby inhibiting (blocking) the translation or protein formation process (NAKI, 2024).

Ambros and Ruvkun initially discovered microRNA in roundworms (C. elegans) produced by the l-4 gene, and this microRNA does not produce protein and can inhibit l-14 mRNA produced from the l-14 gene. Subsequent studies have shown that hundreds of microRNAs can be found in multicellular organisms such as animals and humans. MicroRNAs are known to play a role in regulating gene activity in cells. If the genes that form these microRNAs are disrupted, it can affect abnormalities in the tissue formation process (Pasquinelli, et al, 2000).

Under normal circumstances, the amount of a particular protein formed by a particular gene will be sufficient to meet the body’s needs. However, if there is a disturbance in the microRNA-coding gene that results in an excessive amount of microRNA, then only a small amount of protein will be produced because the mRNA is bound by the excess microRNA. Conversely, if there is too little microRNA or it is not produced due to a disturbance, then the protein produced will exceed normal requirements, which will also cause health problems. In cancer, the microRNA-encoding gene experiences a disruption/mutation, causing microRNA to be disrupted (slightly) so that cancer cells will continue to grow.

The Nobel Prize awarded to Ambros and Ruvkun took a long time to come, around 30 years, as is the case with most Nobel laureates, because the findings had to be proven to provide significant benefits or prospects both for the development of science and for human life, such as in the treatment of cancer or other diseases.

Similar to what Ambros and Ruvkun did, in 1998, Andrew Fire and Craig Mello, through their studies also on C. elegans roundworms, discovered a phenomenon called RNA interference. In this phenomenon, double-stranded RNA blocks messenger RNA so that certain genetic information is not altered during protein formation. It silences these genes, rendering them inactive. This phenomenon plays an important regulatory role in the genome (MLA-Fire, 2022). In 2006, Andrew Z Fire and Craig Cameron Mello were awarded the Nobel Prize in Physiology or Medicine for their discovery of RNA interference – the silencing of genes by double-stranded RNA, also known as “RNA interference” (MLA-Mello, 2022a). This research was conducted at the University of Massachusetts Medical School and published in 1998 (Mello, 2022).

The Nobel Prize for Fire and Mello is dedicated to work that began in 1998, when Mello and Fire, along with their colleagues Si Qun Xu, Mary Montgomery, Steven Kostas, and Samuel Driver published a paper in the journal Nature detailing how small pieces of RNA trick cells into destroying gene messengers (mRNA) before they can produce proteins, effectively turning off certain genes (Mello, 2022b; Fire, et al., 1998). This finding showed that RNA actually plays a key role in gene regulation. They had discovered a fundamental mechanism for controlling the flow of genetic information.

2. Katalin Karikó and Drew Weissman, winners of the 2023 Nobel Prize in Physiology or Medicine for their discovery of mRNA vaccines

Katalin Kariko and Drew Weissman were awarded the Nobel Prize in Physiology or Medicine in 2023 for their discovery of nucleoside base modifications that enabled the development of effective mRNA vaccines. Katalin Karikó was born in 1955 in Szolnok, Hungary. In 1982, she received her doctorate from the University of Szeged, continuing her postdoctoral research at the Hungarian Academy of Sciences in 1985, at Temple University in Philadelphia, and at the University of Health Sciences in Bethesda. In 1989, she was appointed Assistant Professor at the University of Pennsylvania. She later became vice president at BioNTech RNA Pharmaceuticals. Since 2021, he has been a professor at the University of Szeged and an adjunct professor at the Perelman School of Medicine at the University of Pennsylvania. Drew Weissman was born in 1959 in Lexington, Massachusetts, USA, and received his PhD from Boston University in 1987. He conducted postdoctoral research at the National Institutes of Health. In 1997, Weissman established his research group at the Perelman School of Medicine at the University of Pennsylvania. He is the Roberts Family Professor in Vaccine Research and Director of the Penn Institute for RNA Innovations.

The findings of these two Nobel laureates were crucial in the development of effective mRNA vaccines to combat COVID-19 during the pandemic that began in late 2019 or early 2020. Their research has provided a fundamental understanding of how mRNA interacts with our immune system.

In general, vaccines are produced using whole attenuated viruses, but this often encounters obstacles in growing the virus in culture media. Therefore, other methods that do not use whole viruses are sought, including molecular biology techniques that use only certain proteins from the virus but can be developed into effective vaccines. In the process of utilizing parts of the virus, mRNA is used to form viral proteins that subsequently stimulate the immune response. However, producing mRNA naturally from viruses faces various obstacles. Therefore, Kariko and Weissman tried using mRNA produced in vitro.

Initially, this faced various failures because the mRNA produced in vitro caused inflammatory reactions and viral protein production was also very low. After extensive research, Kariko and Weissman modified the nucleoside bases of the mRNA produced in vitro, and the results prevented inflammatory reactions, as the modified nucleoside bases blocked the activation of inflammatory reactions. In addition, when the mRNA was delivered to cells, there was an increase in protein production (Kariko, et al, 2005; Anderson, et al, 2010; Morais, et al, 2021). Thus, mRNA can be used as a vaccine because, in addition to producing proteins responsible for immunity, it does not cause inflammatory reactions. Kariko and Weissman’s findings paved the way for the development of vaccines using mRNA, which had never been done before. Their research results were published in 2008 and 2010 (Kariko, et al, 2008; Anderson, et al, 2010).

Unlike the production of vaccines from weakened or inactivated viruses, the production of mRNA vaccines only takes a few days or weeks to complete (Pascalo, et al, 2004: Pascolo, 2021). This can be done through in vitro mRNA transcription, where almost all mRNA sequences can be produced from DNA templates (Krieg and Melton, 1984; Melton et al., 1984). Furthermore, mRNA vaccines provide direct instructions to cells to express the desired immunogenic protein through translation in the cytoplasm.

Subsequently, in the 2010s, research on mRNA vaccines began to gain popularity, including their use in developing vaccines against the Zika virus, MERS-CoV, and SARS-CoV-2, which emerged in late 2019 (Szabo, et al, 2022). With the COVID-19 pandemic caused by the SARS-CoV-2 virus, a COVID-19 vaccine using mRNA was developed, resulting in two types of mRNA vaccines against COVID-19 at the end of 2020 (Noor, 2021). Finally, mRNA-based COVID-19 vaccines were mass-produced in billions of doses in an effort to control the pandemic (WHO, 2020).

The Pfizer-BioNTech vaccine (Comirnaty) is the first COVID-19 mRNA vaccine to receive emergency approval in various countries. Pfizer collaborated with BioNTech, a German biotechnology company, to develop this vaccine. Meanwhile, Moderna (Spikevax) is Moderna’s COVID-19 vaccine, which is another mRNA vaccine that works in a very similar way to Pfizer-BioNTech (Polack, et al. 2020; Baden et al. 2021; WHO, 2020; FDA, 2021).

The success of Kariko and Weissman in developing a vaccine using mRNA, particularly in the effort to control the COVID-19 pandemic, led to both researchers receiving the Nobel Prize in Physiology or Medicine in 2023. Once again, the Nobel Prize in Physiology or Medicine was awarded to a field related to DNA (in this case, using mRNA), continuing the Nobel Prize also related to DN  (in this case, the genome) in 2022, which was won by Paabo. The discoveries and technological innovations in mRNA-based vaccine production are expected to continue to be beneficial in addressing various challenges, particularly regarding the potential emergence of new disease outbreaks or in preparing for future pandemics.

The Nobel Committee for Physiology or Medicine in 2023 decided on Kariko and Weissman as the winners after reviewing the results of Kariko and Weissman’s findings in the development of mRNA vaccines, which began in the 2010s. Kariko and Weissman’s efforts to create an mRNA vaccine took years before they discovered how to modify in vitro mRNA nucleoside molecules so that they did not cause inflammatory reactions and could increase protein production in cells, which ultimately led to the creation of a Covid-19 vaccine using mRNA technology that had never been done before. To receive the Nobel Prize, Kariko and Weissman needed more than 10 years from the start of their mRNA vaccine research. The Nobel Committee believes that Kariko and Weissman’s work will be beneficial now and in the future in the development of new vaccines in the event of a pandemic or disease outbreak in the future.

This mRNA vaccine has potential for the future, as research is currently underway using mRNA vaccines in the treatment of cancer, where mRNA is designed to help the immune system recognize and attack cancer cells. Similarly, the development of mRNA vaccines that can protect against various types of coronaviruses, including new variants, is the focus of research. It is hoped that by using the mRNA platform, future pandemics can be responded to more quickly and efficiently. With continuous innovation, mRNA vaccines have the potential to revolutionize the way we deal with infectious and non-infectious diseases in the future.

3. Svante Pääbo, 2022 Nobel Prize in Physiology or Medicine laureate for his discoveries concerning the genomes of extinct hominins.

Svante Pääbo, who won the Nobel Prize in Physiology or Medicine in 2022 for his discoveries about the genomes of extinct hominins and the changing history of human evolution and migration. Svante Pääbo was born in 1955 in Stockholm, Sweden, and received his doctorate in 1986 from Uppsala University. He then became a postdoctoral researcher at the University of California, Berkeley, USA. In 1990, he became a professor at the University of Munich, Germany. In 1999, he founded the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. He also serves as a professor at the Okinawa Institute of Science and Technology in Japan.

In the 1980s and 1990s, Pääbo pioneered techniques for extracting DNA from ancient human remains and other fossils. A major challenge was that the DNA found in fossils was usually largely degraded and contaminated by other DNA or microbes from the environment or the researchers themselves. The hard work of Pääbo and his research team finally paid off in analyzing the DNA sequences of these ancient human fossils. This success was inseparable from his team’s success in developing and using a more advanced third-generation DNA sequencing technique called “High Throughput Sequencing” (Green, et. 2008), which was developed from the second-generation DNA sequencing technique known as NGS (Next Generation Sequencing).

One of Pääbo’s most monumental achievements was in sequencing the Neanderthal genome, which began in the early 2000s. In 2010, his team successfully sequenced almost the entire Neanderthal genome, opening the door to further understanding of the genetic relationship between Neanderthals and modern humans. At around the same time, Pääbo and his team also succeeded in identifying a previously unknown group of ancient humans from a fragment of finger bone found in Denisova Cave, Siberia. They managed to extract DNA from the bone and discovered that this species, named Denisovans, shared ancestors with Neanderthals but were a distinct group.

Neanderthals (Homo neanderthalensis) were an ancient human species that lived approximately 400,000 to 40,000 years ago in Europe, Western Asia, and Central Asia. Neanderthals are close relatives of modern humans (Homo sapiens), and they share a common ancestor with us around 500,000 to 700,000 years ago.

From Pääbo’s findings, it turns out that modern humans, Homo sapiens, did not live alone but coexisted for tens of thousands of years with other human relatives, namely Homo neanderthalensis, especially those living in western Eurasia. According to Wall, et al (2013), Neanderthals contributed more DNA to modern East Asia than to modern Europe.

Pääbo and his research team published their initial findings on the genome of Homo Neanderthal, an extinct human relative that disappeared around 30,000–40,000 years ago (Krings, et al., 1997). In 2010, Pääbo and his research team successfully sequenced the Neanderthal genome more completely (Hublin, 2009, Green et al., 2010; Prufer, et al. 2014). Pääbo also revealed the existence of gene flow from Neanderthals to modern Homo sapiens living today, indicating that interbreeding occurred between Homo sapiens who left Africa and spread throughout the world and lived alongside the ancient Homo Neanderthal for several decades before Homo Neanderthal became extinct.

Pääbo revealed his findings that, in addition to Homo sapiens from Africa, there were also other hominins, namely Neanderthals, relatives of modern humans who lived in Western Eurasia, where fossil bones found in Germany were successfully sequenced after Pääbo’s research team successfully extracted genetic material (DNA) from the fossil bones so that their DNA/genome sequence could be determined. The DNA sequence of Neanderthals is more similar to the DNA sequence of modern/contemporary humans living in Europe or Asia than to that of contemporary humans living in Africa. This indicates that there was interbreeding between ancient Neanderthals and Homo sapiens in Europe and Asia.

Pääbo also succeeded in discovering another previously unknown hominin, Denisova, after finding a 40,000-year-old finger bone fossil in a cave in Denisova, Siberia, in 2008. The bone was successfully extracted and its DNA isolated to determine its gene/genome sequence. From the genome sequence obtained, it was discovered that Denisova was an ancient human who lived in Eastern Eurasia, in southern Siberia (Krause, et al. 2010; Reich, et al., 2010; Meyer, et al. 2012). There was also evidence of ancient gene flow from Homo sapiens to Denisovans, indicating that interbreeding had occurred between Homo sapiens and Denisovans. The findings of Pääbo and his team have given rise to a new discipline called paleogenomics. Denisovans and Neanderthals are ancient humans who became extinct about 30,000 years ago (Hublin, 2009), but Neanderthal genes are found in 1-4% of modern humans in Eurasia, while Denisovan genes are found in up to 6% of modern human populations living in Melanesia in Southeast Asia (Reich, et al. 2011).

The ability of Pääbo’s research team to analyze genomes from fossil bones tens of thousands of years old is crucial in uncovering the origins, evolution, migration, adaptation, and interactions between species in the past. In the future, there may be many more discoveries of ancient humans using the same or even better genome analysis techniques and using the discipline of paleogenomics discovered by Pääbo. Knowledge about DNA and genomes in living things will continue to be interesting and important in the development of science in the fields of chemistry, medicine, and physiology, both for understanding life in the past and for facing the future. Therefore, it is no mistake that the Nobel Committee awarded the Nobel Prize to Pääbo in 2022.

Pääbo’s journey to winning the Nobel Prize was quite long, considering his first discovery in the early 1990s about his initial attempts to analyze the genome of the ancient Homo Neanderthal (Krings et al, 1997). until finally the Nobel committee selected him as the recipient of the Nobel Prize in Medicine or Physiology in 2022 for what is considered a major discovery that will change the history of human evolution and migration, which was previously thought to involve only Homo sapiens. Pääbo’s research has changed the history of early humans, namely Homo Neanderthal, who lived in Western Eurasia and Central Asia, and Denisova hominins, who lived in Eastern Eurasia and Asia. In addition, Pääbo has also given birth to a new discipline, namely paleogenomics. Paleogenomics is a branch of science that studies the genomes of extinct organisms or those that lived in the past using modern techniques in genetics and biotechnology. This science combines the principles of paleontology, archaeology, and genetics to obtain information about the origins, evolution, and adaptation of species from the past, including ancient humans, animals, and plants.

Paleogenomics can be performed by utilizing DNA samples from fossil remains, such as bones, teeth, hair, or other tissues that have been preserved for thousands or millions of years. However, ancient DNA is often degraded, especially in tropical regions, requiring special techniques to extract it. Paleogenomics helps us understand how a species has evolved over time, both genetically and environmentally. By comparing ancient genomes with modern species genomes, researchers can track genetic changes related to adaptation to environmental changes.

Pääbo’s findings are one of the greatest achievements in paleogenomics in the study of ancient humans such as Neanderthals and Denisovans. By studying their genomes, scientists can understand the genetic relationship between modern humans and ancient humans, including the identification of crossbreeding between Homo sapiens and Homo neanderthalensis or Denisovans. With Pääbo’s discovery, it is believed that there will be findings from subsequent researchers on other ancient human fossils that will complete the history of human journey on this earth. The Nobel Committee decided that Pääbo deserved to receive the Nobel Prize after reviewing his various efforts and findings over more than 30 years, and believed that his findings were very beneficial for the development of science.

Through his monumental work, Pääbo has created a new field that combines molecular genetics with archaeology and paleontology. His contributions have changed the way we understand human evolutionary history and interspecies genetic interactions.

4. Emmanuelle Charpentier and Jennifer A. Doudna, recipients of the 2020 Nobel Prize in Chemistry for their discovery of the CRISPR-Cas9 genetic scissors.

The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for their groundbreaking work in developing the revolutionary genome editing method known as CRISPR-Cas9. This discovery enables scientists to “cut” DNA with extreme precision, opening up tremendous opportunities for advancement in biology, medicine, agriculture, and other fields. Emmanuelle Charpentier, a French citizen born in 1968 in Juvisy-sur-Orge, France, is affiliated with the Max Planck Unit for the Science of Pathogens, Berlin, Germany. Meanwhile, Jennifer A. Doudna, an American citizen born in 1964 in Washington, D.C., USA, is affiliated with the University of California, Berkeley, USA, and is a researcher at the Howard Hughes Medical Institute (MLA, 2020).

In a press release from the 2020 Nobel Chemistry Committee on October 7, 2020, for Charpentier and Doudna on genetic scissors: a tool for rewriting the code of life. Emmanuelle Charpentier and Jennifer A. Doudna have discovered one of the sharpest tools in genetic technology: CRISPR/Cas9 genetic scissors. Using this tool, researchers can modify the DNA of animals, plants, and microorganisms with extremely high precision. This technology has a revolutionary impact on life sciences, contributing to new cancer therapies and potentially realizing the dream of curing inherited diseases (MLA, 2020).

CRISPR-Cas9 is a natural immune system found in bacteria. Bacteria use CRISPR to recognize and cut the DNA of bacteriophage viruses that attack them, thereby protecting themselves from infection. Charpentier and Doudna then discovered a way to utilize this system as a tool that can be modified to edit DNA in other organisms, such as plants, animals, and humans. They designed a guide RNA that can be directed to specific locations in the genome, and with the help of the Cas9 enzyme, the DNA at that location can be cut with great precision.

The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technique was adopted from a bacterial immune system against viruses that infect bacteria (bacteriophages), in which bacteria are able to delete parts of the bacteriophage genome through cas proteins mediated by specific RNA (sgRNA). Initially, the CRISPR sequence was identified by Japanese researchers Ishino et al. in 1987 in Escherichia coli bacteria, but its role and function were unknown at that time (Ishino, et al. 1987). It was only around 2008 that researchers discovered that CRISPR is part of the immune system that bacteria acquire against viruses or bacteriophages that infect them (Deveau, et al. 2008; Barrangou, et al. 2007; Horvath, et al. 2008). This has been proven, among others, by Barrangou, et al. (2007) by infecting bacteria with viruses, thereby triggering an immune system in the bacteria.

In 2011, Emanuelle Charpentier from France and Jennifer Doudna from the United States developed a gene editing technique using CRISPR-Cas9 or genetic scissors, which makes it easier for researchers to cut, remove, or insert specific genes from DNA. This development is used to modify or engineer the genetic code of plant, animal, human, or microorganism DNA for specific purposes. Furthermore, in June 2012, Jennifer Doudna and Emanuelle Charpentier reported that CRISPR could be used to edit genomes (Jinek, et al. 2012). This was after they were able to design sgRNA against specific genes and the CRISPR-Cas system from target cells would eliminate those genes.

Thus, the original function of CRISPR-Cas9 has changed or evolved. Initially a bacterial defense mechanism against phages (viruses that attack bacteria), it has become a reliable technique in genome editing tools (Singh, et al. 2017). Furthermore, this CRISPR-based genome editing technique continues to evolve in the field of biology through various living organism models, in the medical and healthcare fields, agriculture, and industry. Thus, CRISPR-Cas9 is the key technology for targeted genome editing in various organisms and cells, as this technique is relatively simple, cost-effective, efficient, and has the potential to be developed for broader biomedical, therapeutic, industrial, and biotechnology applications (Singh, et al. 2017).

This “genome editing” engineering technique has dramatically increased the usefulness of genetic engineering known as CRISPR-Cas9. With this technique, genes/DNA from organisms can be edited by removing certain base pairs and replacing them with other base pairs, resulting in changes to the organism known as synthetic biology. This can be done more accurately, cheaply, quickly, and easily (Nicholas, 2020).

The revolution in genome editing technology brings hope for medical treatments such as overcoming genetic defects or disorders, treating cancer, and treating various other diseases. In agriculture, CRISPR technology offers hope for producing superior seeds more quickly, which can be used to produce more food crops to meet the world’s growing food needs. This is one solution to the food shortage caused by the world’s growing population.

This discovery is considered very important in molecular biology because it offers convenience, flexibility, and efficiency compared to previous genome editing methods. Thus, it is useful for: 1) Medicine: The potential to treat genetic diseases such as sickle cell anemia, muscular dystrophy, and certain types of cancer; 2) Agriculture: Producing crops that are more resistant to pests and extreme weather and have higher nutritional value; and 3) Biology: Accelerating our understanding of gene function and disease.

CRISPR technology has paved the way for faster, safer, and more effective vaccine development. Its applications include various infectious diseases such as COVID-19, HIV, and tuberculosis, as well as cancer immunotherapy. Research continues to ensure the efficiency and safety of this technology before it is widely implemented. Although still in the research and development stage, CRISPR has shown great potential to become one of the innovative methods in cancer therapy. Its success could revolutionize the approach to cancer treatment in the future.

CLOSING REMARKS

The fact that the Nobel Assembly at the Karolinska Institute has selected a number of topics related to DNA/RNA or genomics as Nobel Prize winners in the last five years indicates that the field of DNA/RNA or genomics has attracted the attention of researchers worldwide as a subject for research. This is undeniable, as DNA/RNA or genomics is the most important part of the life of living things, including animals, plants, humans, and microorganisms.

Physics, Chemistry, and Physiology or Medicine are the three fields covered by the Nobel Foundation at the inception of the Nobel Prize in 1901. Indeed, Physics, Chemistry, Physiology or Medicine are interrelated or interdisciplinary sciences that contribute to our understanding of life. Meanwhile, DNA, RNA, and the genome are considered the chemical machinery of living cells that determine the life and sustainability of an organism. Therefore, research related to DNA/RNA or the genome has attracted a significant number of enthusiasts and practitioners.

Ambros and Ruvkun’s important findings on microRNA, or miRNA, which plays a role in regulating gene expression, include binding to specific messenger RNA (mRNA) and inhibiting the translation process or causing mRNA degradation. In the context of cancer, these microRNAs can be used as therapeutic tools due to their important role in regulating genes related to cell growth, apoptosis, and metastasis. These findings are expected to inspire related researchers to adopt and develop this research in Indonesia by collaborating with the research team.

The findings of Kariko and Weissman in developing a vaccine using mRNA to combat Covid-19 may inspire Indonesian researchers to adopt this technology for use in diseases that have not yet been overcome in Indonesia, such as dengue fever, HIV, or other tropical diseases. At the very least, these skills can be utilized in the future if a pandemic occurs. Similarly, the CRISPR-Cas9 gene editing technique discovered by Charpentier and Doudna could inspire our researchers to utilize it in agriculture, health, or other fields.

Svante Pääbo’s discovery may inspire Indonesian archaeological anthropology and paleontology researchers to collaborate with Pääbo’s research team in uncovering the 100,000–50,000-year-old Homo floresiensis fossils discovered in 2003. Homo floresiensis is a hominin species that once lived on the island of Flores, Indonesia. The species was first discovered in 2003 in Liang Bua, a cave on Flores. Due to its small size, Homo floresiensis is often referred to as the “hobbit.” It may eventually reveal the origins, evolution, and migration of humans in the Indonesian region.

On average, Nobel laureates take quite a long time from the publication of their first research. This is because the benefits of their findings are not only assessed based on their publication, but also on their benefits or potential benefits for the development of science and their benefits for the lives and welfare of humanity in the world, such as in overcoming cancer and other diseases. In general, Nobel laureates need 10-30 years from the initial publication of their research results, which are considered important, until it is proven that their findings have significant benefits for human life. Research is generally conducted over a long period of time and is followed by the training of researchers, including continuous funding.

May this article inspire young researchers in choosing research topics that do not necessarily have to be related to DNA, genes, or genomes, but are important in providing significant short-term and long-term benefits for food, health, disease control, etc. May it encourage them to compete and excel, even inspiring them to win a Nobel Prize, build international cooperation networks, and many more.

Written by: Prof. Dr. Sjamsul Bahri