New Chapter of Superhuman Design


The government and expert associations should set up a committee of experts in charge of compiling all matters regarding genomic research, such as academic studies, research governance, clinical trial procedures.

The human genome has been completely sequenced. This scientific achievement for humanity deserves to be celebrated.

Researchers across countries collaborating in the Human Genome Sequencing Consortium have succeeded in mapping and sequencing the complete human genome, the whole genetic information of human beings.

Made up of superpowers the United States, the United Kingdom, Japan, France, Germany and China, the consortium began the major research project in 1990. They successfully started mapping the human genome in 2003, but 15 percent of the segment remained unrevealed. By the end of March 2022, the genome sequence was complete.

This has paved way for us to know and understand the human blueprint in its entirety, including genetic mutations, physical differences between races, resistance to diseases, such as diabetes, heart disease or schizophrenia.

The genome is a blueprint of genetic information arranged in the form of deoxyribonucleic acid (DNA) molecular bands that are needed for every organism to develop and function. Each human individual is reported to have about 3 billion nucleotides (base pairs) located in 23 pairs of chromosomes in the nucleus of every cell of the human body. Each chromosome contains hundreds to thousands of genes, which carry instructions for producing proteins. Each of the approximately 30,000 genes in the genome make up an average of three proteins.

The composition of each human's genes is different, and this is what makes the diversity of human beings. They diverge into nations and tribes, with various physical characteristics. There are those characterized with big, tall physical builds like races in Africa, Europe and Middle East and smaller ones like those from East and Southeast Asia. There are also different colors of skin, eyes, hair, blood type and fingerprints. Generally, we can identify large racial groups of Africa, Europe and Asia. Interactions between races over thousands of years has resulted in merged races, which have continued merging to become what they are today.

A decade ago, the Eijkman Institute for Molecular Biology conducted a major study involving the DNA of various ethnic groups throughout Indonesia. The study, as reported in the Journal of Human Genetics, showed almost all of the tribes in Indonesia today are the result of intertribal merging that went on for thousands of years. This is Bhinneka Tunggal Ika (unity in diversity) in the biological sense.

Besides affecting physical characteristics, the gene composition of humans also makes each individual different in terms of susceptibility and resistance to certain diseases. This is one field for future research. The complete sequencing enables scientists to design further research to find the DNA sequences that cause specific diseases, and try to counteract the potentially infecting diseases by improving its DNA structure.

Counteraction is done through hypothesis. For example, with an XYXY DNA structure, a baby will be susceptible to polio virus. To improve the baby’s disease resistance, scientists can change the DNA structure to XYXYXY, so that the baby will not be infected with the polio virus when growing up. Another example is DNA editing. If a baby has a specific DNA structure that will mean as an adult it would grow to a maximum height of 150 centimeters, will be sparsely haired and physically weak, by changing the composition of its DNA, the baby, when entering adulthood, is expected to be able to grow taller, have thick hair and be physically strong. Research on DNA editing has been done extensively, although not much is known publicly. There is also a research on the use of DNA to produce “advanced creatures”, but not by editing methods.

 

Genome editing

In the 1990s, research was carried out to produce a physically identical copy of a sheep from a parent sheep through cloning. The Scotland-based Roslin Institute announced on 22 Feb. 1997 that it had successfully produced a cloned sheep, named Dolly, from an adult sheep’s stem cells. It was the first mammal to be successfully cloned from an adult cell. Different from DNA editing, the cloning method does not change the DNA structure, but takes the DNA of the parent adult cell to be developed outside.

The complete genome sequencing and mapping opens up more challenging yet very sensitive opportunities in genome editing research. One of the greatest achievements of genome editing technology has been the invention of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR).

CRISPR has the following stages. First, researchers identify the location and arrangement of the DNA to be modified. Then, researchers design a guiding ribonucleic acid (RNA)”. An RNA is a molecule that plays a role in coding, decoding, regulating and gene expression. Its nucleotide base arrangement is similar to DNA targets so the RNA can immediately recognize and bind to DNA targets.

Also inserted to this guiding RNA is an enzyme that functions to cut the nucleotide chain in DNA targets. This enzyme is named Cas-9, which stands for CRISPR-associated protein 9. After the guiding RNA finds the desired location on DNA targets, the Cas-9 enzyme is activated to cut DNA targets chain.

With the DNA targets being cut, the gene's natural function is temporarily disabled. The next step is to insert a modified DNA chain between the genes as a replacement, or it can also be left to improve naturally, in the hope that it corrects the genetic mutation that previously occurred.

CRISPR-Cas9 has proven to be a more efficient and adjustable genome editing method than the previous genome editing technologies. As the system is capable of cutting DNA strands, CRISPR does not need to be paired with a separate splitting enzyme as done in other methods. The presence of guiding RNA also facilitates matching with the modified DNA targets structure. In addition, CRISPR-Cas9 can also be used to target multiple genes simultaneously.

CRISPR is currently used and being developed in the healing and prevention of disease. CRISPR has entered clinical trials for the treatments including for blood diseases (sickle cell anemia and thalassemia), and cancer. Another application of CRISPR is in eye diseases. For leber congenital amaurosis (LCA), CRISPR is injected directly into the sub-retinal layer of the eye to change the patient's damaged photoreceptor gene where it is expected to be able to form a completely functional protein. When ample healthy protein is formed, the patient is expected to recover their vision.

In disease prevention, CRISPR can be used to slow down the transmission of vector-based disease. In malaria and leishmaniasis for example, CRISPR is used to edit the genomic sequence of disease-carrying vectors to inhibit the transmission or prevent the proliferation (Rostami, Parasite Immunology, 2020).

From the explanation above, we can be more confident that advances in genome editing technology can become the future technology for the prevention and treatment of diseases and the improvement of human physical quality. Genome editing has the potential to prevent and cure disease. If genome editing is conducted on an embryo, for example, it is possible that a person will be spared from having to live with a clubfoot due to the polio virus. A somatic gene therapy, which is done by modifying the patient's DNA, has successfully treated or cured several diseases, such as HIV, sickle cell disease of the anemia group and transthyretin amyloidosis. In addition, treatment for various types of cancer has been improved by genome editing.

From a medical point of view, germline (seed line that passes genes on to progeny) and genome editing can be inherited. The result of a genome procedure on a human embryo can be passed on to the next generation, with heredity traits being modified to produce a higher quality generation.

 

Ethics

The research and development of science and technology facilitates human work, improves health, prosperity and brings benefits to mankind. However, apart from the many benefits, advances in science and technology do not always go in line with the more noble goals.

The development of science and technology ends up being used to kill each other in wars. Dynamite was invented by Alfred Nobel initially to facilitate work in the mining sector before being developed later to be used as war weaponry. Remorseful about his invention, Nobel decided to donate his wealth to pioneering projects that bring benefits to humanity, which we know as the Nobel Prize.

In the case of the Human Genome Project, the researchers were well aware that this research would provide great benefits to mankind, but at the same time have the potential to violate ethics. The US Congress allocated a special budget not only to study the ethical, but also the legal and social implications of human genome research.

From Hollywood films, we know about cyborgs (cybernetic organisms), humans whose organs are replaced or grafted with electronic devices so that they become super humans, such as in the films The Six Million Dollar Man, Terminator and Robocop. The body, brain, feelings and conscience remain as human. Only part of the organ is replaced with an electronic graft.

They are different from The Bourne, Gemini Man, Splice, Dual and other similar films, in which humans have their DNA edited to become, for instance, a super soldier who is very intelligent, strong, swift, pain-resistant and, at the same time, mercilessly vicious and very subservient to an ordering master. The sense of mercy has been banished. In genome editing, there is no electronic robot graft to the organs. Human organs are intact, but the genetic code is changed to produce a human with the character that the programmer wants.

 

Preserving humanity

This is where we come across ethical problems. Having the complete human genome sequence is basically analogous to having all the manuals needed to construct the human body. The challenge for scientists is to determine how to read the contents of all the sheets and then understand how the constituting parts work together. Then, they can try to find out which genetic basis is related to human health and disease pathology.

This will ultimately open up opportunities to develop highly effective and precise diagnostic tools because we can better understand each person's needs based on each individual's genetic makeup. Analysis based on genome sequencing contribute substantially to early prevention. Clinicians can learn about future disease risks based on DNA analysis and focus on the most likely causes in order to protect a particular individual's health. That could mean a change in diet, lifestyle or even medical supervision.

But recognizing that the human genomic sequence is akin to a manual for creating the human body, we need strict regulatory and ethical scrutiny. It needs to be clarified to what extent the limitations of genome editing can be tolerated by ethics. For example, editing human DNA to produce super soldiers who are at the same time cruel and ruthless is certainly against our human values.

Given this potential dilemma, the World Health Organization (WHO) has provided recommendations on the governance and supervision of human genome editing. The recommendation center on nine main areas, namely the registration of human genome editing; international research and international travel for medical purposes; illegal, unregistered, unethical or unsafe research; intellectual property; and education, participation and empowerment. Recommendations focus on improving systems to build capacity to ensure human genome editing is used safely, effectively and ethically.

Complementing these recommendations, a new governance framework is included to identify its methods, tools, institutions, procedures and controls. Following the WHO recommendations, research on hypothetical clinical trial of human somatic genome editing for sickle cell disease will be conducted in West Africa. Also being proposed is a research project on the use of somatic or epigenetic genome editing to improve athletic performance.

In designing sensitive research, we must be able to keep the balance between benefits and risks. The government and expert associations should set up a committee of experts in charge of compiling all matters regarding genomic research, such as academic studies, research governance, clinical trial procedures, surveillance and prevention of illegal research. Thus, research on the development of genome editing remains as a benefit to mankind, not something that violates ethics and human values.

Djoko Santoso
Professor of Medicine, Airlangga University
chair of East Java MUI Health Board

 

This article was translated by Musthofid.



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