CRISPR Technology

Context: A Chinese researcher recently claimed that he had altered the genes of a human embryo that eventually resulted in the birth of twin girls. The genes were claimed to be “edited” to ensure that they do not get infected with HIV, the virus that causes AIDS. 

Relevance
Prelims: Science & Technology: CRISPR- features and significance
Mains: GS III – Scientific Innovations, Technology, and Ethics 

Background

• He Jiankui Chinese researcher shocked the scientific community in 2018 after announcing he had successfully altered the genes of twin girls born in November to prevent them from contracting HIV.
• He had “privately” organized a project team that included foreign staff and used “technology of uncertain safety and effectiveness” for illegal human embryo gene-editing, investigators said.
• But such gene-editing work is banned in most countries, including China.

• Nobel Prizes for Physics, Chemistry, and Medicine are proof of scientific achievement. It honours life-changing discoveries and great minds.
• The chemistry was the most important science for Alfred Nobel’s own work. The development of his inventions, as well as the industrial processes he employed, were based upon chemical knowledge. The chemistry was the second prize area that Nobel mentioned in his will.
• The Nobel Prize in Chemistry is awarded by The Royal Swedish Academy of Sciences, Stockholm, Sweden.
• Emmanuelle Charpentier of France and Jennifer Doudna of the U.S. won the Nobel Chemistry Prize for the gene-editing technique known as the CRISPR-Cas9 DNA snipping “scissors” tool. It is the first time a Nobel science prize has gone to a women-only team.

• CRISPR-CAS9 is a technology that allows scientists to essentially cut-and-paste DNA, raising hope of genetic fixes for disease. However, there are also concerns about its safety and ethics.
• CRISPR is a dynamic, versatile tool that allows us to target nearly any genomic location and potentially repair broken genes. It can remove, add, or alter specific DNA sequences in the genome of higher organisms.

• Unusual but repeated DNA structures that scientists had been observing for some time were given a name. This name assigned was “Clustered regularly interspaced short palindromic repeats” or CRISPR.
• In 2012, scientists discovered that CRISPR is a key part of the “immune system”. For instance, when a virus enters a bacterium, it fights back by cutting up the virus’s DNA.
• This kills the virus but the bacterium stores some of the DNA.
• The next time there is an invasion, the bacterium produces an enzyme called Cas9 which matches the stored fingerprints with that of the invaders.
• If it matches, Cas9 can snip the invading DNA.
• The CRISPR-Cas9 gene-editing tool thus has two components. They are:
  • a short RNA sequence that can bind to a specific target of the DNA and
  • the Cas9 enzyme which acts like molecular scissors to cut the DNA.
• To edit a gene of interest, the short RNA sequence that perfectly matches with the DNA sequence that has to be edited is introduced. Once it binds to the DNA, the Cas9 enzyme cuts the DNA at the targeted location where the RNA sequence is bound.
• Once the DNA is cut, the natural DNA repair mechanism is utilized to add or remove genetic material or make changes to the DNA.

• Disease modelling:
  • Disease animal models have been essential resources in advancing the biomedicine field.
  • With the help of genome editing technologies, many applicable models with specific mutations that could mimic clinical phenotypes have been generated.
• Cancer models:
  • With the help of genome editing tools, numerous studies have been carried out through modifying key genes for generating accurate and specific cancer models.
  • Cancer models are the most effective ways to study mutational functions which result in cancer.
• Productivity improvement:
  • The continuous decrease in the availability of land and water for agriculture, uncertain weather conditions, and a growing population are signals for the urgent need for an alternative approach in the country.
  • In this scenario, scientists are optimistic about the possibilities of genome editing for enhancing crop productivity to overcome the shortcomings of traditional transgenic methods like irregular breeding cycles, lack of precision in intended trait selection, and uncertainty in getting desirable mutations.
• Genome editing technologies are not only used for generating disease animal models but also destined to enter the therapeutic area. There are plentiful means for genome editing based therapy:
  1. inactivation or correction of harmful mutations
  2. introduction of protective mutations
  3. insertion of therapeutic exogenous genes
  4. destruction of viral DNA

1. CRISPR could be used to modify disease-causing genes in embryos brought to term, removing the faulty script from the genetic code of that person’s future descendants as well.
2. Genome editing could potentially decrease, or even eliminate, the incidence of many serious genetic diseases, reducing human suffering worldwide.
3. It might also be possible to install genes that offer lifelong protection against infection.
4. CRISPR may prove useful in De-Extinction Efforts.
   • For example, Researchers are using the powerful gene-editing tool to recreate the woolly mammoth.
5. CRISPR Could Create New, Healthier Foods- In agricultural crops, Crispr has the potential to impact yield, disease resistance, taste, and other traits. Few experiments have been done. If successful it can help us to eradicate the problem of hunger and malnutrition.

1. Making irreversible changes to every cell in the bodies of future children and all their descendants would constitute extraordinarily risky human experimentation.
2. There are issues including off-target mutations (unintentional edits to the genome), persistent editing effects, genetic mechanisms in embryonic and fetal development, and longer-term health and safety consequences.
3. Altering one gene could have unforeseen and widespread effects on other parts of the genome, which would then be passed down to future generations.
4. Many consider genome alterations to be unethical, advocating that nature should be left to run its own course.
5. Few argue that after permitting human germline gene editing for any reason would likely lead to its ignorance of the regulatory limits, to the emergence of market-based eugenics that would exacerbate already existing discrimination, inequality, and conflict.

• In the 2016 Worldwide Threat Assessment of the US Intelligence Community statement United States Director of National Intelligence, James R. Clapper, named genome editing as a potential weapon of mass destruction, stating that genome editing conducted by countries with regulatory or ethical standards “different from Western countries” probably increases the risk of the creation of harmful biological agents or products.
• Low cost and accelerated pace of development of this technology and its deliberate or unintentional misuse might lead to far-reaching economic and national security implications.
• It could lead to the manufacture of biological weapons by potential bioterrorists who might use the knowledge to create vaccine-resistant strains of other poxviruses, such as smallpox, that could affect humans.

• India has not permitted the trials of CRISPR-Cas9 technology to edit the human germline. The Department of Biotechnology and the Indian Council of Medical Research (ICMR) discusses the social and ethical implications of genome editing in India.
• “Our main concern is that the technology should not be used for human enhancement”, said ICMR Director Dr. Soumya Swaminathan said.
• Ethical concerns are a little more important in India than in other countries, but strict laws can help regulate it. Prenatal sex determination was banned by The Pre Conception and Pre-Natal Diagnostic Techniques (PCPNDT) Act, 1994, and The Surrogacy (Regulation) Bill, 2016, which has been introduced in the Parliament, seeks to prohibit commercial surrogacy- in India's ethical legal environment, germline editing is unlikely to have an easy passage.
• The technology can be used by the rich to customize a baby with desired traits and allowing human genome editing could make India a hub for a certain kind of medical tourism, rather than surrogacy has done.
• The concept of gene editing can slip into prenatal testing, fetal management, and IVF. Developing and underdeveloped countries that face social barriers such as a preference for male children need to tread carefully. 
• Another ethical challenge germline cell and embryo genome editing brings up includes whether it would be permissible to use this technology to enhance normal human traits (such as height or intelligence).
• There are growing concerns about trying to produce “designer” babies or altered human beings.
• Based on concerns about ethics and safety, germline cell and embryo genome editing are currently illegal in many countries.

• Experts recommend that germline editing should be done only on genes that lead to serious diseases and when no other reasonable treatment alternatives exist.
• Among other criteria, they stress the need to have data on the health risks and benefits and the need for continuous oversight during clinical trials. They also recommend following up on families for multiple generations.
• CRISPR technology is indeed a path-breaking technology, to alter genes in order to tackle a number of conventional and unconventional problems.
• The most promising use of CRISPR technology is in the treatment of diseases. For example, sickle cell anaemia.
• However, experiments and tests to validate its use must be subjected to appropriate scrutiny by the regulators, and their use must be controlled to prevent commercial misuse.
• Scientists across the world are still working to determine whether the CRISPR technology is safe and effective for use in people.