Playing god

WRITTEN BY ABIGAIL ABLANG & PAENG AMBAG

ILLUSTRATED BY TIFFANY UY

THE CONCEPT OF MANMADE evolution in itself is not innovative. Humans have been “editing” life since the advent of agriculture and breeding. Using artificial selection, we consciously make the choice to breed the variants that possess good traits, allowing us to optimize the kinds of crops we harvest and meet the needs of our ever-growing population. In a span of only thousands of years, we have drastically altered the structure of certain crops such as corn, banana and eggplant that would otherwise take centuries of chance mutations to naturally develop into the forms we are familiar with.

Since their use of artificial breeding 10,000 years ago, humans have never looked back and continued to zero in on manipulating the deoxyribonucleic acid (DNA), the code of life itself. Humans have adopted a multitude of methods focused on editing the DNA even just after it was discovered

more than fifty years ago. Scientists have tried trial-and-error methods such as DNA irradiation, but were discouraged by its one-in-a-million chance of success, wasting a hefty amount of time and resources. But in the late 1960s, restriction enzymes in E. coli bacteria were discovered. These restriction enzymes can cut specific sites on the DNA, enabling scientists to use these enzymes like scissors. After cutting the sites on the DNA which they want to cut, the scientists can then replace these removed segments with DNA sequences from other organisms. The method is far more efficient than relying on chance.

The drawback however was that restriction enzymes can only cut over select sites on the DNA. Each site on the DNA are bound by unique proteins which fold like knots on a rope. The problem is each “knot” has a unique way of folding which requires the development of new and

specific enzymes that can cut through the proteins of each site.

Thus, not all restriction enzymes can be used to cut desired sites on the DNA and not all desired sites on the DNA can be cut by restriction enzymes. The way proteins fold into unique forms has yet to be understood, rendering the development of new enzymes time-consuming and expensive.

In the early 2000s, DNA segments called Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein-9 (Cas9) genes were first discovered in action at the immune systems of bacteria, which acquire viral resistance by inserting DNA segments of an infectious virus into their own CRISPR arrangement. During a viral attack, ribonucleic acid (RNA) segments, normally paired with DNA for the synthesis of proteins are produced from the CRISPR to target the genome of the virus. The Cas9 protein then cuts the DNA apart, disabling it in the process.

It was the women tandem of geneticists Jennifer Doudna and Emmanuelle Charpentier from University of California Berkeley which finally found how CRISPR-Cas9 can be used as a kind of “scissor” that can cut through any kind of “knot” on the DNA.

The first replication of the said system was made by Doudna and Charpentier using a guide RNA as a mailman to a target DNA sequence (Buhr, 2017; U.S. National Library of Medicine, 2017). In a classic DNA model, billions of base pairs (A-T or C-G) can be depicted as billions of rungs that comprise a single continuous ladder. CRISPR-Cas9 works by having a guide molecule (RNA) paired with the Cas9 protein that goes through all the rungs of the ladder and will only stop until it finds its specific target address. Once it finds its target, another molecule cuts off the said DNA region and can even replace it with another one. Now, imagine that the target region is a DNA mutation that codes for cancer. Theoretically, CRISPR-Cas9 has the ability to find that mutation and actually cut it off, and replace it with another DNA sequence that is cancer free.

While selective breeding does not employ the machinery of modern gene editing, the idea itself is the same, only made leagues more efficient by technological advancement. CRISPR-Cas9 has seen rapid progress in different fields of research, already considered significantly more efficient than the previous genome editing tools such as ZFN (zinc finger nucleases) and TALENS (Transcription activator-like effector nucleases) in only less than five years of study. Doudna asserted that the discovery was analogous to trading a pair of rusty scissors for a laser beam cutter; it was just more accurate and time-saving. What took farmers thousands of years to develop and pass down can now be replicated on different crops in a relative snap of a finger.

Today, the gene editing system attracts the most attention in its potential to correct “flaws” in the human genome. In vitro and animal experiments have been used to model human genetic diseases such as hemophilia, Lou Gehrig’s disease and Huntington’s disease, with promising results toward a cure. Actual human experimentation has already occurred as well despite warnings from the scientific community. Only two years after the technology was publicized, Chinese researchers removed, altered and then infused back kidney, lung, liver and throat cancer cells from 36 patients.

However, the implications and possible impact of CRISPR-Cas9 has led to a multitude of ethical concerns as tropes of science fiction dystopia bleed into our own reality, the most urgent being editing reproductive cells, which will affect the next generations. While most human genome editing has been done only on other cells, which affects only certain tissues and the test subject, few studies have explored editing actual embryos or egg or sperm cells. Consent comes into question when embryos and future generations are edited not only for the treatment of diseases, but also for non-therapeutic applications such as editing height, intelligence or speed to create either runway models or super soldiers. With this in mind, one has to assess on what areas can the said technology cross and on what aspects of life do we perceive its use as humane and moral. Will the use of such technology elevate the overall health of mankind or only create further division amongst its classes through the promotion of eugenics, a belief concerned with the use of selective breeding to improve the composition of the human race? Such methods will take at least a century of testing before they are deemed safe for use on human beings, as anything altered could bring unintended consequences for the succeeding generations.

Amid the hazards posed by gene-editing technology, there is currently no international body regulating CRISPR-Cas9 studies and applications amid researchers continuing to question the ethics surrounding its use. Given the situation,

a notable difference regarding the tem- perament of countries for its usage can be observed. The US for example is rather lenient, permitting germline research as long as it is not intended for hereditary use. In contrast, Germany, for example, does not allow such research practices, even imposing rules with threat of crim- inal charges. The genome editing system, albeit a recent innovation, already argues for the need of a clear set of rules agreed upon by members of the scientific com- munity in order to control how it is used and who gets to use it. upon by mem- bers of the scientific community in order to control how it is used and who gets to use it.

In fact, the need for awareness regarding the ethics of gene-editing gained world- wide traction when just last November 2018, a Chinese scientist named He Ji- ankui sent shockwaves upon claiming that he helped create two gene-edited babies using CRISPR technology. Jiankui said that his goal was to make the two twins resistant to HIV infection. Mem- bers of the scientific community quickly stood up to condemn the claim, which was against the established consensus at the International Summit on Human Gene Editing. Doudna said that “it is im- perative that the scientists responsible for this work fully explain their break from the global consensus that application of CRISPR-Cas9 for human germline editing should not proceed at the present time.”

The development of CRISPR-Cas9 marks the evolution of mankind’s understanding of life through the mechanisms that con- sists of millions of years of change as well as the tools in their arsenal that can be used to speed them up. It is predicated upon the fact that maybe nature does not harness all the power, that maybe nature has already lost its regulatory control to select who shall stay and who shall per- ish. Though the potential of the system to drastically improve life may outweigh ethical risks if handled responsibly, fun- damental issues will undoubtedly arise when gene editing is used to pursue per- sonal or commercial interests against the common good.

Humanity has controlled life in more ways than it should have. Blessed with the rev- olutionary advantage of an advanced brain, we have controlled our environ- ment to keep us well fed. We also formed societies in order to optimize production of goods, and maintain peace and order. We edited other species in order to suit our needs, and now the question is if we are to are to actually edit ourselves to serve us our needs. What He Jiankui and his team did for creating CRISPR babies can now only be seen as a wakeup call for the limitless possibilities that can be done with the technology but also the glaring need for cautious ethical actions towards progress. ●

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