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CRISPR – Gene-Editing and Designer Babies

Intro

In November 2018, a Chinese scientist named He Jiankui shocked the world by announcing that he had successfully created the world’s first gene-edited babies. Using a method called CRISPR-Cas9— CRISPR for short— He (name, not “he”) edited the DNA of a set of embryonic twins to make them resistant to HIV. By the time of his announcement, the twins had already been born. Though it seems like something from a science-fiction novel, this development had been in the works for a decade. However, instead of praising He for his landmark experiment, the scientific community lambasted him for testing the technology on humans far before it was ready. He was rebuked by the Chinese government for disregarding state laws and scientific ethics in search of personal fame and fortune. 

Chinese biomedical researcher Dr. Jiankui He

CRISPR is a relatively new technology, and, until He’s experiment, it had only been used in non-human organisms. Those tests have shown the relative ease with which the latest gene-editing technology can modify a living creature’s DNA.

Today, scientists predict a whole host of invaluable uses for CRISPR, from removing genetic diseases to creating so-called “designer babies.” But, with this great power comes immense ethical responsibility. Scientists have discussed using gene-editing to wipe out entire species of dangerous animals. Wealthy parents salivate at the possibility of designing taller, smarter, healthier children. There’s no question of CRISPR’s potential impact; what remains to be seen is whether that impact will be positive or negative.

Let’s explore.

Body

Though relatively simple by the standards of world-class scientists, the technology behind CRISPR is a bit complex. To get a basic understanding of how it works, we need to look at E. Coli. Bacteria like E. Coli survive by constantly fending off viruses with special enzymes called Cas9. Once these enzymes kill a virus, they make a copy of that virus’s remaining DNA. Think of this as a DNA mugshot. When a similar virus arrives, the Cas9 enzymes inspect it, comparing the new virus’s DNA to the mugshot. If they find a match, then the Cas9 enzyme can remove that DNA, neutralizing the threat.

When a team of scientists made this discovery around 2007, they didn’t understand just how impactful it could be. Thankfully, Jennifer Doudna and Emmanuelle Charpentier remained curious about how CRISPR could be used in other ways. Together, the two researchers made one of the most important discoveries of this century. The Cas9 protein could be given a fake mugshot, with which it would scan an organism and boot out the related DNA. In other words, humans could harness CRISPR to alter the genes of any living organism.

Doudna and Charpentier’s 2012 research paper caught the attention of scientists around the world. Just one year later, their research was corroborated by a scientist named Feng Zhang, who laid out the process of altering the genomes of human cells. Since then, studies and experiments involving CRISPR have blown up. The number of CRISPR-related research papers published annually rose from 100 in 2012 to 17,000 in 2018.

Through this increased attention, scientists discovered that this miraculous technology is even more powerful than initially thought. While early studies showed that Cas9 could remove DNA, there was no way to replace it. Now, scientists can similarly manipulate repair enzymes to replace the old gene with a new one. With this discovery came even more possibilities.

Today, testing CRISPR’s applications has become relatively cheap and straightforward. Earlier attempts at genome editing cost thousands of dollars, and it sometimes took months to make a single alteration. With Doudna and Charpentier’s model, the same process can be done in several hours for a cost of about 75 dollars. 

So, with all of this attention and low barriers to entry, what are the realistic applications for CRISPR? 

On the most basic level, scientists can use CRISPR to learn what purposes each individual gene serves. The Human Genome Project of the 1990s already mapped the entire human DNA. Yet, we still don’t know exactly what each gene does. By removing a single gene without replacing it, scientists can observe the differences, revealing that gene’s function. This would dramatically increase humankind’s understanding of how our bodies actually work. More importantly, this could serve other applications of CRISPR, as in-depth gene editing will require more knowledge of which DNA strands to cut and insert. Aside from this primary purpose, there are five generally accepted potential uses.

The first is to alter crops for increased nutrition, flavor, and production. Of course, the world is already familiar with genetically modified food. While GMOs have become a hotly contested topic, scientists tend to look at them in a positive light as a means of ending widespread food shortages across the globe. Still, the process of modifying food genes with CRISPR would be a much more exact science than the current method. 

Food scientists could adjust the nutritional content of common crops like corn to reduce sugars, for instance. But they could also get more ambitious, like by removing allergens from peanuts. A team in Japan is attempting to create a super-banana that could withstand fungal diseases. Dairy farmers have funded efforts to remove the gene that causes dairy cows to grow horns, hoping to reduce cattle-on-cattle killings. 

Unlike traditional GMOs, foods modified with CRISPR technology are almost entirely unregulated at the moment. While this is likely to change soon, it’s indicative of a significant issue. Lawmakers and regulators haven’t been able to keep up with the fast-moving pace of developments in CRISPR-based gene-modified foods.

Not all uses are quite so controversial, though. One intuitive use for CRISPR is as an antibiotic. Every year, bacteria develop greater resistance to existing antibiotics. The medical community spends incalculable time and money developing new antiviral treatments. Yet, fighting viruses and invasive bacteria is among CRISPR’s biological purposes. If scientists can isolate DNA strands unique to these viruses, then CRISPR could become the primary technology for developing antibiotics. There are currently studies underway to determine whether this method could aid the fight against otherwise incurable viruses like HIV or herpes. The biggest obstacle to achieving this is designing a safe delivery system. In fact, the delivery system is considered by most scientists to be the greatest challenge to any CRISPR application.

For the more ambitious types, CRISPR could be used for knocking out genetic diseases altogether by removing genes that allow for them in the first place. This practice is highly controversial, as it would require editing DNA in living humans or at least human embryos. Still, the upside of such an innovation would be infinite. The world could end genetic disorders like Huntington’s disease or cystic fibrosis. Even non-genetic ailments like cancer and HIV could be seriously reduced. While this may seem like the perfect use of the technology, most researchers fear the potential risks. For example, Cas9 enzymes are not 100 percent accurate in the DNA they modify, and designing a delivery system is still a critical issue. 

Side effects could be catastrophic, such as causing cancer or even creating entirely new diseases. In fact, researchers who inspected He Jiankui’s gene-edited twins determined that the babies’ genes were not precisely altered. It remains to be seen just how they respond to the changes long-term.

Perhaps the most aggressive of all the possible uses would be to create “gene drives” within entire species of animals to alter their future offspring. The most common example of this method is with mosquitoes, which pose near existential health risks in Africa by transmitting infections like malaria. Currently, when two mosquitoes mate, the offspring have a 50-50 chance of receiving any gene carried by parents, including genes making the mosquito susceptible to the malaria parasite. Scientists could use CRISPR to ensure a 100% chance of passing a gene on to offspring. So, mosquitoes could be edited to provide, for instance, that every offspring contains a gene coding for resistance to malaria parasites. Better yet, scientists could make it so that mosquitoes only produce male offspring and, before long, the entire population would go extinct, unable to reproduce. While the biggest hold-ups of this use are political, ethicists question whether it’s wise to use technology to drastically modify species. Not only is there the question of committing genocide against an entire species, but environmental scientists warn that we don’t understand the consequences of removing such abundant creatures as mosquitoes.

Of course, the most attention-catching use for CRISPR is the prospect of creating “designer babies.” This is what Jiankui did when he altered human embryos to increase resistance to HIV. Yet, the possible changes of these designer babies go far beyond disease resistance. Researchers envision a day when babies could have their genes altered to improve athleticism, height, or even intelligence. Would-be parents could modify a baby’s eye-color or, perhaps, skin color. Of course, humans still aren’t entirely sure of what genes code for which traits. A single gene may stunt muscle growth or determine eye-color, for instance, making them relatively easy to replace. However, ensuring more complex features like intelligence could be impossible, as there’s currently no knowledge of an intelligence gene. Creating a propensity for higher IQ could require immense changes to an embryo’s DNA. As intriguing as it may be to make designer babies, the most ambitious researchers take it one step farther— some believe that the same technology could be used to alter an adult human’s genome.

No matter how CRISPR is eventually used, we will need to develop new technologies to get us there. Yet, the scientific community seems confident that the creation of those advancements is a question of “when,” not “if.” Scientists have already successfully reduced genetic deafness in mice and believe that the same can be done with humans once delivery methods are perfected. With these innovations potentially right around the corner, the most pressing questions are not technological but ethical.

These issues span fields like bioethics, law, economics, medicine, and even religion. For instance, there are serious concerns about the technology falling exclusively into the hands of massive corporations. The current low cost makes CRISPR accessible to anyone with the technical abilities, but certain businesses will undoubtedly look to keep the technology for themselves. With the possibility of one-day eradicating genetic diseases, there are concerns that profit-seeking companies could do their best to keep this from happening.

If this were to happen and editing human DNA were to become commonplace, the fear is that this would exacerbate inequality. After all, the world’s richest and most powerful people could alter their genes in dramatic ways, ensuring that they and their offspring are born with infinite advantages, not just wealth and opportunity. Over generations, gene-altered one-percenters could gain a monopoly on height or resistance to dangerous diseases. In the most horrific forecasts, authoritative and racist governments could alter the skin color of unborn children to standardize race within their borders. Critically, this type of change could impact more than just the people whose DNA was altered.

That’s because there are two kinds of gene editing, and they hold several vital differences. Somatic editing only affects the patient and isn’t passed on to later generations. Germline editing alters every cell in an organism, including sperm and eggs, so that changes are passed on to later generations. As such, critics insist that it’s unethical to impose drastic changes on future generations, especially when the consequences of some changes are still unknown. 

He Jianking’s designer twins are a perfect example of this. While He altered the babies’ DNA to make them resistant to HIV, researchers believe the change may have made them more susceptible to the West Nile Virus. Many doctors argue that it’s better to leave the human genome as is than to make changes that adjust risk factors so dramatically. Of course, the most damning critique of He’s experiment is that CRISPR simply isn’t ready for use on humans. However, the COVID pandemic may have changed the conversation around this. With disease running rampant throughout the world, at what point does CRISPR become a welcome risk? 

On the flip side, given that CRISPR is currently so cheap, how can we ensure that others, like He Jiankui, don’t use it before the tools are perfected? Even when the technology is ready, how can governments ensure that rogue operators don’t run more tests on human embryos? 

Still, the most crucial moral questions are those that haven’t been asked yet. It’s not too difficult for experts to imagine where CRISPR could be in a decade or two, but fifty years from now, what new applications should shake the scientific and ethical landscape? This question is made harder by the lightning-quick pace of innovation in the field, which has made conversations around ethics and law lag behind the technology. Yet, the scientific community favors continuing down this path to discover just how great a benefit to society CRISPR could provide. 

For now, the choice is yours. Are you optimistic about the future that CRISPR-based gene-editing could provide? Or do you feel that the potential downside far outweighs the upside? In some ways, this question applies to all future technologies, whether artificial intelligence or gene editing. But, as innovation outpaces ethical debate, must we slow down the pace of technological change? Or are those changes necessary to force moral discourse? What are the most intriguing uses for CRISPR? Would you use the technology to alter the genes of your children? What about yourself? What changes would you make to your own DNA?

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