The Characteristics Of Gene Modifications In Human

Genetic modification is the process of altering the genetic makeup of an organism. This has been done indirectly for thousands of years by controlled, or selective, breeding of plants and animals. Modern biotechnology has made it easier and faster to target a specific gene for a more-precise alteration of the organism through genetic engineering.

The terms 'modified' and 'engineered' are often used interchangeably in the context of labeling genetically modified, or 'GMO,' foods. In the field of biotechnology, GMO stands for genetically modified organism, while in the food industry, the term refers exclusively to food that has been purposefully engineered and not selectively bred organisms. This discrepancy leads to confusion among consumers, and so the U.S. Food and Drug Administration (FDA) prefers the term genetically engineered (GE) for food. [1]

CRISPR AND CRISPR-Cas9

CRISPR technology is a simple yet powerful tool for editing genomes. It allows researchers to easily alter DNA sequences and modify gene function. [2] Its many potential applications include correcting genetic defects, treating and preventing the spread of diseases and improving crops. However, its promise also raises ethical concerns. [3]

In popular usage, 'CRISPR' (pronounced 'crisper') is shorthand for 'CRISPR-Cas9.' CRISPRs are specialized stretches of DNA. The protein Cas9 (or 'CRISPR-associated') is an enzyme that acts like a pair of molecular scissors, capable of cutting strands of DNA. CRISPR technology was adapted from the natural defense mechanisms of bacteria and archaea (the domain of single-celled microorganisms). These organisms use CRISPR-derived RNA and various Cas proteins, including Cas9, to foil attacks by viruses and other foreign bodies. They do so primarily by chopping up and destroying the DNA of a foreign invader. When these components are transferred into other, more complex, organisms, it allows for the manipulation of genes, or 'editing.'

'CRISPR' stands for 'clusters of regularly interspaced short palindromic repeats.' It is a specialized region of DNA with two distinct characteristics: the presence of nucleotide repeats and spacers. Repeated sequences of nucleotides — the building blocks of DNA — are distributed throughout a CRISPR region. Spacers are bits of DNA that are interspersed among these repeated sequences. [4]

THE SCIENCE BEHIND THE CRISPR BABIES LULU AND NANA

Scientist and Bioethicists are in outrage at the moment. Many posts about how much they are crying for babies, the babies that scientist Dr. Jiankui He claimed to have genetically edited with CRISPR. On Sunday, Nov. 25th, a story was leaked that he claimed to have created the first humans to be genetically modified. Dr. He claimed to have utilized CRISPR gene editing to modify the CCR5 gene to make the children HIV resistant. [5]

The genetic mutation introduced into two babies by a Chinese scientist in 2018 may be associated with a 21 percent higher chance of early death in later life. Controversial scientist He Jiankui's justification for his experiment was to confer HIV immunity to the embryos to avoid infection from the father, who is HIV positive. Dr. He reported using CRISPR-Cas9 technology to edit the human CCR5 gene in an attempt to artificially replicate a natural mutation, called 'CCR5-Δ32'. However, this mutation had previously been linked to an increased susceptibility to certain diseases such as influenza. As the CCR5 gene codes for a protein involved in many body functions, researchers say that there could be many different possible reasons for the risk of early death. [6]

Jiankui is a Chinese biophysics researcher who was an associate professor. He worked in the Department of Biology of the Southern University of Science and Technology (SUSTech) in Shenzhen, China. Dr. He Jiankui became well known after he had claimed that he had created the first human genetically edited babies, known by their pseudonyms, Lulu and Nana (twin babies). The announcement in November 2018 of Lulu and Nana, was met with widespread condemnation, and on 29 November 2018, Chinese authorities suspended all his research activities. Dr. William Hurlbut, Stanford University neuroscientist and bioethicist, reported that He Jiankui is staying in a university apartment in Shenzhen “by mutual agreement” and is free to leave. Nonetheless, He Jiankui may be under some form of surveillance and may face serious consequences. On January 21, 2019, He Jiankui was fired by SUSTech according to the university's announcement. [7]

ADVANTAGES OF CRISPR

CRISPR technology is very simple, easy to use and cheap unlike the previous gene-editing techniques such as Transcription activators-like effective nucleases (TALENS). This technology can be employed to analyze the interaction of genes and the relationship between genetic differences and expression (phenotype). It can also be used to knock out a gene and replaced it with another gene for diseases therapy. [8]

DISADVANTAGES OF CRISPR

CRISPR-Cas9 off-target: The effect of off-target can alter the function of a gene and may result in genomic instability, hindering it prospective and application in the clinical procedure. A Single guide RNA is known as chimeric RNA is the combination of CRISPR RNA (CrRNA) and trans-activating RNA (TrRNA). SgRNA’s 20 base nucleotides are complementary to the target DNA of interest with a trinucleotide known as Protospacer adjacent motif (PAM) adjacent to the sequence which is mostly NGG (where N can be Adenine, Guanine, Cytosine or Thymine). Other studies reported that the PAM can also be NRG (where R is Adenine or Guanine). Even though DNA complimentary is highly specific based on base pair rule (A-T and G-C) there is still occurrence of off-target with 3 to 5 mismatches within the distal part of the PAM. [9]

GENE ALTERATION

Genetic alternations include chromosomal abnormalities and gene mutations. Chromosomal abnormalities generally arise during cell division. They can be numeric, involving the number of chromosomes, or structural, involving the typical configuration of one or more chromosomes. Many different chromosome abnormalities have been identified, some of which are associated with genetic disorders and diseases like cancer. Gene mutations are permanent changes in DNA gene sequence. They can arise during normal DNA replication or in response to environmental factors. There are many classes of gene mutations. Certain mutations cause disease.

SPEED (METHAMPHETAMINE)

Speed (methamphetamine, C10H15N) is an addictive central nervous system stimulant and chemically related to amphetamine, but with greater central nervous system side effects. It is a white, odorless, bitter-tasting powder that easily dissolves in water or also in alcohol. [10] Methamphetamine is classified as a Schedule II stimulant by the U.S. Drug Enforcement Agency (DEA), which means it has a high potential for abuse and is available legally only by prescription.[11] Methamphetamine, when abused, is commonly referred to as “speed”, and has been in use since the early 1960s. When abused, methamphetamine is usually smoked, snorted, injected, or taken orally. [12]

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EFFECTS OF SPEED (METHAMPHETAMINE)

Immediately after smoking or intravenous (IV) injection, the user experiences an intense sensation which often called as 'rush', which lasts only for a few minutes and was described as extremely pleasurable. Oral or intranasal use produces high but not a rush. Snorting methamphetamine will lead to effects within only 3 to 5 minutes, whereas oral ingestion takes 15 to 20 minutes.

Common, immediate effects of methamphetamine abuse include:

• increased activity and body temperature
• wakefulness
• talkativeness
• faster breathing
• increased concentration
• decreased appetite
• elevated blood pressure
• rapid heart rate
• increased libido (sex drive)
• a sense of well-being.

Some users become addicted quickly and abuse it with increasing frequency and doses. As the pleasurable effects of methamphetamine disappear, abusers may use more and more drugs to get the same effect. Using methamphetamine many times over several days, usually without food or sleep, is often called a 'run'.

Methamphetamine (speed) is extremely addicting. Withdrawal from methamphetamine produces:

• severe depression
• anxiety
• fatigue
• psychosis
• Intense cravings for the drug.

The health hazards from chronic use of methamphetamine appear to be at least partially reversible. Recovery of dopamine transporter activity has been shown on brain neuro-imaging studies after roughly 2 years. Motor skills and verbal memory tests showed some recovery, but not all changes have been shown to reverse over time. [13]

TREATMENT FOR SPEED ADDICTED

Behavioral therapy remains the most effective treatment for methamphetamine abuse and addiction, at this time. According to the National Institute of Drug Abuse (NIDA), the combination of behavioral therapy and family education, counseling and 12-step support, drug testing and positive reinforcement for non-drug related activities are effective. There are no specific medications approved for use in methamphetamine addiction. The National Institute of Drug Abuse (NIDA) reports that clinical studies are ongoing looking at medications or vaccine use for the treatment of methamphetamine addiction. Besides, bupropion (Wellbutrin), approved for use in depression, has been shown to reduce low-to-moderate methamphetamine cravings, in combination with behavioral group therapy. Bupropion's proposed mechanism in methamphetamine dependence by inhibiting the reuptake of norepinephrine and dopamine

SIDE EFFECTS WITH SPEED

Methamphetamine is a stimulant. Methamphetamine use:

• increases heart rate
• increases blood pressure
• elevates body temperature
• quickens the breathing rate
• Dilates the pupils.

Other side effects include temporary hyperactivity, insomnia, anorexia and tremors. High doses or chronic use have been associated with increased nervousness, irritability, paranoia, confusion, anxiety and aggressiveness, all typical side effects expected from a high-dose stimulant.

Methamphetamine can cause irreversible damage to blood vessels in the brain, leading to a stroke. Death can result from hyperthermia (elevated body temperature), convulsions and cardiovascular collapse.

Chronic, high-dose methamphetamine abusers are susceptible to violent and erratic behavior, hallucinations, and psychosis similar to schizophrenia. Psychotic episodes may recur for months or years after methamphetamine abuse has stopped. The neurotoxic effect of methamphetamine causes damage to brain cells that contain dopamine. Over time, reduced levels of dopamine can result in symptoms like those of Parkinson's disease, a severe movement disorder.

Other adverse health effects that may occur due to speed abuse include memory loss, severe dental problems (often called “meth mouth”, where the users' teeth rot from the inside out), weight loss, and malnutrition. [14]

HOW TO OVERCOME THIS ISSUES

• To authorize clinical trials
• Awareness camp
• Law
• Enforcement
• Instill religious moral education

CONCLUSION

In conclusion, human genetic modification is the direct manipulation of the genome using molecular engineering techniques. Recently developed techniques for modifying genes are often called “gene editing.” Genetic modification can be applied in two very different ways: somatic genetic modification and germline genetic modification. Genetic alternations include chromosomal abnormalities and gene mutations. Chromosomal abnormalities generally arise during cell division. They can be numeric, involving the number of chromosomes, or structural, involving the atypical configuration of one or more chromosomes. Thus, there are many advantages and disadvantages in this gene modification, humans should aware on this ethical issues in gene modifications.

REFERENCE

1. Baltimore, D., Berg, P., Botchan, M., Carroll, D., Charo, R. A., Church, G., ... & Greely, H. T. (2015). A prudent path forward for genomic engineering and germline gene modification. Science, aab1028.
2. https://medium.com/futuresin/a-simple-way-to-understand-crispr-gene-editing-technology-31b4014e91b
3. Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., ... & Zhang, F. (2013). Multiplex genome engineering using CRISPR/Cas systems. Science, 339(6121), 819-823.
4. Shalem, O., Sanjana, N. E., Hartenian, E., Shi, X., Scott, D. A., Mikkelsen, T. S., ... & Zhang, F. (2014). Genome-scale CRISPR-Cas9 knockout screening in human cells. Science, 343(6166), 84-87.
5. Peterson, J. C. (2019). Gene Editing Lulu, Nana, and Their Children. Perspectives on Science and Christian Faith, 71(1), 1-3.
6. Singh, S. M. (2019). RE: Lulu and Nana (2018) open pandora's box way beyond Louise Brown (1978): Must it remain closed for ever.
7. https://howlingpixel.com/i-en/William_Hurlbut
8. 8. Li, D., Qiu, Z., Shao, Y., Chen, Y., Guan, Y., Liu, M., ... & Zhao, Y. (2013). Heritable gene targeting in the mouse and rat using a CRISPR-Cas system. Nature biotechnology, 31(8), 681.
9. Brooks, C., Nekrasov, V., Lippman, Z. B., & Van Eck, J. (2014). Efficient gene editing in tomato in the first generation using the clustered regularly interspaced short palindromic repeats/CRISPR-associated9 system. Plant physiology, 166(3), 1292-1297.
10. https://www.honeylake.clinic/what-is-speed/
11. https://fellowshipoftheminds.com/find-out-if-you-live-near-a-meth-lab
12. Barr, A. M., Panenka, W. J., MacEwan, G. W., Thornton, A. E., Lang, D. J., Honer, W. G., & Lecomte, T. (2006). The need for speed: an update on methamphetamine addiction. Journal of psychiatry & neuroscience.
13. Cheng, R. K., Hakak, O. L., & Meck, W. H. (2007). Habit formation and the loss of control of an internal clock: inverse relationship between the level of baseline training and the clock-speed enhancing effects of methamphetamine. Psychopharmacology, 193(3), 351-362.
14. Weigmann, D. A., Stanny, R. R., McKay, D. L., Neri, D. F., & McCardie, A. H. (1996). Methamphetamine effects on cognitive processing during extended wakefulness. The International journal of aviation psychology, 6(4), 379-397.