Science fiction of precise and efficient Gene editing has become reality now with emergence of powerful new technology of CRISPR-CAS9 (Clustered regularly Interspaced Short Palindromic Repeats- CRISPR associated proteins). This technology offers potential to flexibly alter the genetic material of everything from Wheat to an Elephant. Unlike any other previously developed technique of gene editing CRISPR is remarkably simple, fast and cheap. Our dream of curing and eradicating diseases such as Cancer, Huntington’s disease (inherited brain disease), Cystic fibrosis (inherited disease affecting lungs and digestive system), dengue fever, sleeping sickness, yellow fever, West Nile virus, Lyme disease, Alzheimer's (progressive memory loss disease), Obesity, tyrosinemia (genetic disorder affecting amino acid breakdown in body) and Hepatitis (liver infection) could become a reality. It has the potential to change everything from the food we eat to the world we live in.
Very few technologies truly merit the epithet “game changer” — but CRISPR-CAS9 is one of them. Why did this sudden revolution happen? How does CRISPR really work? This is where it gets interesting. Bacteria and viruses have been fighting since the dawn of life. The viruses called as Bacteriophages or phages hunt bacteria. Phages do this by inserting their own genetic material into bacteria. The targeted bacterium tries to resist but fails most of the time because their protein tools are too weak, but sometimes the targeted bacteria manages to survive an attack. When a bacterium successfully negates an attack, it can activate its most effective antivirus system. It saves a part of the phage virus DNA in its own genetic code as a DNA archive called CRISPR. This forms a kind of “immune” memory, which means it can recognize and respond more quickly if it is attacked again in the future.
CRISPR relies on a gene-editing complex composed of a DNA-cutting tool called CAS9 (molecular scissor) and a short RNA strand that guides this tool to a specific area of the DNA, directing CAS9 to specific point where a cut is to be made. When CAS9 and the short guide RNA targeting a disease causing gene are delivered into cells, a specific cut is made in the gene, and the cell’s DNA repair processes glues the cut portions back together, often deleting/eliminating a small portion of the gene. However, if a corrected copy of the gene is also delivered when the cut is made, the DNA repair process can lead to a correction of the disease gene, permanently repairing the genome. What's special about CAS9 is that the protein which is generated in this process acts as a protection against future phage attacks, is very precise and acts almost like a highly trained DNA level surgeon.
CRISPR is also more efficient than two other genome engineering techniques called Zinc Finger Nuclease (ZFN) and Transcription Activator-Like Effector Nucleases (TALENs). ZFN and TALENs can recognize longer DNA sequences and they theoretically have better specificity than CRISPR/CAS9, but they also have a major downside. Scientists have to create a custom-designed ZFN or TALEN protein each time, and they often have to create several variations before finding the one that works. It’s far easier to create a RNA guide sequence for CRISPR/CAS9, and it’s far more likely to work.
Aside from being precise, cheap, and easy, CRISPR offers the ability to edit live cells, to switch genes on and off, and to target and study particular DNA sequences. It also works for every type of cell: microorganisms, plants, animals, and humans. It allows us to swap in DNA wherever we like so as to create targeted tools and fulfill applications. Want a corn to fight bacteria? You can. Want a fish to glow? Grab some DNA from a phosphorescent algae and integrate it with the fish.
CRISPR has the potential to curtail or even eradicate certain diseases. Moreover, multiple genes can be targeted in one manipulation, making this technique an extraordinarily powerful tool for studying complex genetic traits or diseases that involve multiple genes. It is a long road that could eventually lead to eradication of many hereditary diseases ranging from blindness, Down syndrome to sickle-cell anaemia. It holds promise of treating several thousand inherited disorders like Huntington’s disease and Cystic Fibrosis, which currently have no known cure. Over 3,000 genetic diseases are caused by a single incorrect letter in human DNA. With a powerful tool like CRISPR, we may be able to end these in due course.
Scientists are already using CRISPR to introduce genes for disease resistance into wheat and to insert malaria blocking genes into mosquitoes. CRISPR may also be used to engineer infertility in mosquito DNA, thereby driving their population to zero. This could have significant ramifications for India which had 11 lakh cases of malaria in 2014, has $2 Billion of estimated socioeconomic losses annually due to malaria and needs $18 Billion to eradicate the disease by 2030.
The technology has been used to study Candida Albicans (a form of fungus), to modify yeasts used to make bio-fuels and to genetically modify crop making them yield more high-energy foods , and to resist drought and diseases more effectively. Already, a lab in China has used CRISPR to high yielding rice and a group in the U.K. has produced drought-resistant Barley varieties. Indeed, because it’s so easy to do and the plants could avoid the lengthy and expensive regulatory process associated with GMOs, the method is increasingly being used by research labs and industries.
CRISPR could also defeat one of our worst enemies- Cancer. CRISPR gives us the means to edit our immune cells and make them better cancer hunters, without making patients bear the brunt of chemotherapy, radiotherapy and surgery. Getting rid of cancer might eventually mean getting just a couple of injections of a few thousand of your own cells that have been engineered in the lab to heal you for good.
On 28 October 2016, a team led by oncologist Lu You at Sichuan University in Chengdu delivered CRISPR modified cells into a patient with aggressive lung cancer, marking the initial steps in the quest to cure lung cancer. Carl June, scientific adviser for a planned US trial using CRISPR to target three genes in participants’ cells with the goal of treating various cancers, expects the trial to start in early 2017. Additionally in March 2017, a group at Peking University in Beijing hopes to start three clinical trials using CRISPR against bladder, prostate and renal-cell cancers.
As per research by MIT (Massachusetts Institute of Technology), the CRISPR system responds to UV light in the target cells. This kind of control can help scientists study genetic events that influence embryonic development or disease progression. Eventually, it could also offer a more targeted way to turn off Cancer-causing genes in tumour cells.
Harvard geneticist and CRISPR pioneer, George Church believes he can use this tool to genetically modify endangered Indian elephants into “Woolly Mammoths” capable of surviving in the freezing wilderness of Siberia. As a first step for this, Church inserted the mammoth genes for small ears, subcutaneous fat, and hair length and colour into the DNA of lab-grown elephant cells. Other scientists have expressed hopes to resurrect other extinct species such as the passenger pigeons (Jurassic Park, anyone?)
George Church, recently led a team of scientists that used a complex CRISPR molecule to edit 62 genes in pig cells at once. Church believes that this technique could be used to make pig organs suitable for transplantation into humans. The team's experiments also represent a step forward in CRISPR technology by using the tool to edit many genes at once, a method that could be imitated to make more complicated changes to DNA quickly. Researchers have also demonstrated that CRISPR can be used to remove the HIV virus's DNA from the patient's genome and permanently make it inactive.
In a decade or two, we could possibly cure thousands of diseases, forever. But, all of these medical applications have one thing in common, they are limited to the individual and die with them, except if you use them on reproductive cells or very early embryos. But, CRISPR can and probably will be used for much more, the creation of modified humans—designer babies—and will mean gradual, but irreversible changes to the human gene pool. Modified humans could alter the genome of our entire species because their engineered traits will be passed on to their children and could spread over generations, slowly modifying the whole gene pool of humanity
It may start slowly. The first designer babies will not be overly designed. It’s most likely that they will be created to eliminate a deadly genetic disease running in a family. As the technology progresses and gets more refined, more and more people may argue that not using genetic modification is unethical, because it condemns children to preventable suffering and death and denies them the cure.
If you make your offspring immune to Alzheimer, why not also give them an enhanced metabolism? Why not throw in perfect eyesight? How about height or muscular structure? Full hair? How about giving your child the gift of extraordinary intelligence? Huge changes are made as a result of the personal decisions of millions of individuals and these accumulate over time. This is a slippery slope as genetically modified humans could become the new standard.
As per research by Nature.com and BioMed Central , the regulation around genetic modification in human embryos is still largely in flux. Some countries have legislation that bans the practice and violations carry criminal penalties while other countries have unenforceable guidelines around the same. In a survey of 39 countries around regulations on genetic modification of human embryos, 25 countries have "Ban based on legislation", 4 have “Ban based on guidelines” , 9 had “Ambiguous” stance on the practice, and 1 had a “Restrictive” stance.
Specifically on the regulation front on gene editing in human embryos -
- United States does not allow use of Federal funds to modify human embryos but there are no specific bans on genome editing
- India, China, Japan and Ireland forbid the practice based on guidelines that are less enforceable than laws, and are subject to amendment
- Belgium, Bulgaria, Canada, Denmark, Sweden, and the Czech Republic have bans on the grounds that a modified gene may be inherited by offspring or that the gene modification may impair human embryo
- Germany has strict laws on the use of embryos in assisted reproduction. It limits research on human embryos and violations may result in criminal charges
- Argentina bans reproductive cloning, but research applications of human genome editing are not clearly regulated
CRISPR technology is really powerful. While it is tempting to ban genetic editing and related research it is likely to be a mistake. Banning human genetic engineering would only lead to the research and practice wandering off to a place with jurisdiction and rules that we are uncomfortable with as a species. Only by participating ethically can we make sure that further research is guided by caution, reason, oversight, and transparency.
If engineering becomes more "normal" and our knowledge improves, we could solve the single biggest mortality risk factor, Aging. In possession of a modified immune system, with a library of potential threats, we might become immune to most diseases that haunt us today. Even further into the future we could engineer humans to be equipped for extended space travel and to cope with different conditions on another planet, which would be extremely helpful in keeping us alive in the hostile universe.
A big question to ponder is, if in the future we who are a "flawed" species compared to genetically created modified beings will be allowed to exist? The CRISPR technology is certainly a bit scary, but we have a lot to gain, and genetic engineering might just be a step in the natural evolution of an even more intelligent species in the universe. We might end diseases. We could extend our life expectancy by centuries and travel to the distant stars.
Whatever our opinion on genetic engineering, the future is approaching us and fast. What had been insane science fiction is about to become our new reality, a reality full of opportunities and challenges.