Scissors that won the Nobel prize.

This is a quote from the famous TV show ‘Westworld’. This question was asked by a humanoid robot from a human. When I read about the 2020 Nobel prize-winning technology and its applications, I asked the same question from myself. If we start editing our genome and keep editing it, at what point should we stop? When will that ‘thing’ stop being a human and start becoming something else?

The 2020 Nobel prize for chemistry has been awarded to Emmanuelle Charpentier and Jennifer A. Doudna for the development of a method for genome editing called CRISPR-Cas9. This new genome-editing tool can introduce site-specific double-strand breaks in the DNA and insert the desired gene into that space. What makes this new system stand out from older methods is that it’s high accuracy when it comes to cutting the gene. When it is used with programmed RNA molecules, this can be applied to any gene in any species’ genome. So, in a way, these two scientists invented the worlds’ sharpest and most precise pair of scissors.

The idea for this genome editing mechanism came from the immune response shown by bacteria for a bacteriophage attack. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. Or simply, in a bacterium’s genome, we can find palindromic repeating units with regular intervals. The N-bases that fill these spaces are not the same. These are known as CRISPR associated genes or Cas genes. These genes make Cas proteins. They are either nucleases or helicases. So, when a bacteriophage attacks a bacterium it releases its genes into the bacterium. As a response to this attack, Cas genes make the Cas protein complex and transcribe the Cas genes to CRISPR RNA or crRNA. This crRNA can fit inside the Cas protein complex. This combination can cut the viral genes in several places and deactivate the gene.

What if the incoming viral RNA is not in the bacterial DNA?

Even for this case, there is a different Cas protein that can cut the incoming RNA and embed the transcribed complementary DNA to the bacterial Genome between the palindromes. So, the bacteria can face the infection more successfully in the future.

But this is not the innovation that won the Nobel prize. What Emmanuelle Charpentier and Jennifer A. Doudna did was, in Streptococcus pyogenes there is only one Cas protein, Cas-9. They tried to enter an artificial RNA to this protein called tracrRNA-crRNA chimera or shortly, gRNA. So, now we have Cas protein and gRNA. This combination allows cutting any gene at the place we want of both chromatids. It makes the gene inactivated. In the same way, it also allows combining any gene to any place we want. What is significant in this process is, gRNA is programmable. That means we can add any desired N-base sequence to the gRNA. And it is comparatively easy and more successful than any methods scientists used for genetic engineering so far. Now, this opened a lot of fascinating possibilities.

This new genome engineering mechanism can be used to treat many heritable diseases and genetic disorders such as diabetes, heart disease, schizophrenia, and autism. Because in these cases, a small yet precise cut to separate the gene will stop the showing of phenotype. Not only heritable diseases but viral diseases like HIV also can be prevented from this method. In 2018, Chinese researcher He Jiankui managed to make the first genome-edited human babies who are entirely resistant to the HIV infection.So far, CRISPR Cas-9 technology has been used to improve around 20 crop varieties. Crops resistant to diseases and with improved tolerance for abiotic stresses like drought and salinity, production of bioindicators like Arabidopsis thaliana (used for land mine detection), improved yield and enhancement of nutritional content, Production of biofuels using plants like Glycine max, to delay Ripening process in tomatoes and the list goes on. What we have to remember is that scientists have been doing all these works even before the invention of the CRISPR Cas-9 genetic engineering method. But what makes this new method more attractive is that using this method, all we need is to program a gRNA molecule to carry out the task. In other words, the CRISPR Cas-9 method speeded up the advancement of the whole genetic engineering world.

Now let us talk about all those crazy applications.

The first one is turning pigs into organ donors. As you all know, our body rejects anything foreign entering the body. And this is one of the challenges faced by doctors for a long time when it comes to organ transplants. Scientists believe, using ‘CRISPR human organs’ can be made inside other organisms so that there will be no issues in the transplant.

Another fascinating application is de-extinction. Although we cannot expect mammoth walking on earth during the next couple of years, scientists are planning to bring back passenger pigeons, a species that lived in North America. This is done by adding its genes to modern-day relatives. And yes, Mammoths are a possibility. But after a lot of work.

Finally, designer babies. Lulu and Nana are the first designer babies made using the CRISPR/Cas method. These twins are free from the danger of HIV for the rest of their lives. But this does not end there humans with higher IQ, Higher body strength, and better senses all these are possible thanks to this new technology. But due to the ethical questionability of this technology, in 2015, the International Summit on Human Gene Editing was held in Washington D.C. and concluded to proceed with the genome editing of somatic cells using CRISPR and other genome editing tools only under FDA regulations. And it also banned germline engineering.

As you can already tell, the application of this technology to human embryos raises a lot of questions. For example, He Jiankui, who made the first genetically engineered baby, is now called “China’s Dr. Frankenstein”. After the reveal of his actions, the Chinese government suspended all his activities and kept him under surveillance on campus grounds. Later he was found guilty of forging documents and sentenced to 3 years of prison and a fine of 3million yuan.

People are concerned with the safety of CRISPR. Although this new method is highly precise, the possibility of off-target effects (edits in the wrong place) and mosaicism (when some cells carry the editions, but others do not) is still there. Another concern is taking consent. Because when it comes to human genome editing, it should be done in the embryo stage. So, we have to conduct it without the consent of the embryo. Another concern is how this will affect the future social structure. When rich people design or modify their embryones for better babies, others will not have a chance. And this will create social classes defined by the quality of the genes they have.

Gene editing is not new. It has been in practice for some time now. What CRISPR did was, making the process easier. It is like giving a machine gun to a person who has been using an old pistol or a revolver. In this case, a better, sharper pair of scissors. Scientists have the responsibility of deciding when to use this and for what to use this. Otherwise, it will not be just a misuse of technology. It is a question about authenticity. It is about what is real and what is not.

“My wish is that this will provide a positive message specifically to the young girls who would like to follow the path of science and to show them that women in science can also be awarded prizes. But, most importantly, that women in science can also have an impact through the research that they are performing.”

-2020 Chemistry Laureate Emmanuelle Charpentier (left) on the award of her Nobel Prize-

Reference

• Hsu, P. D., Lander, E. S., & Zhang, F. (2014). Development and applications of CRISPR-Cas9 for genome engineering. Cell, 157(6), 1262–1278.
• Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013). Genome engineering using the CRISPR-Cas9 system. Nature protocols, 8(11), 2281–2308.
• Desalle, R., & Amato, G. (2017). Conservation genetics, precision conservation, and de ‐ extinction. Hastings Center Report, 47, S18-S23.
• Shapiro, B. (2015). Mammoth 2.0: will genome engineering resurrect extinct species? Genome Biology, 16(1), 1–3.
• Kim, H., Kim, S. T., Kim, S. G., & Kim, J. S. (2015). Targeted genome editing for crop improvement.
• https://bit.ly/37pBOBC
• Feng, W., Dai, Y., Mou, L., Cooper, D. K., Shi, D., & Cai, Z. (2015). The potential of the combination of CRISPR/Cas9 and pluripotent stem cells to provide human organs from chimeric pigs. International Journal of Molecular Sciences, 16(3), 6545–6556.
• Vasiliou, S. K., Diamandis, E. P., Church, G. M., Greely, H. T., Baylis, F., Thompson, C., & Schmitt-Ulms, G. (2016). CRISPR-Cas9 system: opportunities and concerns. Clinical Chemistry, 62(10), 1304–1311.

Originally published at https://blog.colombobeacon.com on October 22, 2020.