The age of CRISPR

Keep your enemies close, the saying goes, but some bacteria—mainly E. coli, which proliferate in human and animal intestines—do better: They keep bits of dangerous viruses in their genome, their genetic blueprint. They do this so that when these viruses attack them, their immune systems can recognize them easily and launch counterattacks.

These curious genetic stretches—a bit of DNA repeated over and over with distinctive sequences in between—in E.coli were first discovered in 1987 and officially termed Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR.

Two decades later, science realized their purpose: these helical curiosities were protective of genetic memories.

Today, we know that CRISPR is one part of a clever and ruthless defence system. If CRISPR is the brains, the enforcer is a collection of enzymes called CAS (CRISPR-associated proteins).

The best-known enzyme bunch is called CAS9, found in bacteria that cause sore throats. Using CRISPR’s knowledge of invading viruses, CAS9—on CRISPR’s orders—acts as a scissor, chopping viral DNA and blocking its ability to reproduce.

In January 2013, two teams of scientists first described how the CRISPR-CAS9 team could be deployed as a precise, easy tool to edit all manner of genes. It was an idea that caught on almost immediately. Within nine months, 1,500 papers refined and expanded the idea. Since then, over the past two years, CRISPR-CAS9 has revealed as possible what was once the domain of science fiction—genes made-to-precise-order.

The word precise is important. Genes have been edited, re-engineered and spliced with other techniques for many years, but the mutations tended to be unpredictable and hard to control. If an older method was a blunt knife attempting to cut paper, think of CRISPR-CAS9 as sharp scissors.

The advances jumped rapidly from mice to rats to monkeys to—whisper it—humans. In May this year, scientists in China said that, using CRISPR-CAS9, they had achieved the ability to repair genetically damaged human embryos. This means that it is now within the realm of possibility that babies can be “designed”, a fraught term that brings visions of humans playing god (if, of course, you believe in the divine).

To be sure, redesigning ourselves is not as easy as it sounds. Even using the sharp molecular scissors of CRISPR-CAS9, there are many formidable scientific—let alone the ethical—hurdles to overcome before you can log into Amazon and order a baby with red hair, the intellect of Einstein and the speed of Bolt.

A more relevant question is, how long before we can order genes that could kill cancers, stop Alzheimer’s or get the body to accept a pig’s heart?

Let’s talk about the pig’s heart because it is there that the most exciting CRISPR-CAS9-driven leap was announced this week in the journal Science. As many as 62 simultaneous edits, 10 times the number previously accomplished, were made to a pig’s genome to squelch hostile retroviruses—viruses that insert copies of their DNA into their host’s genome—opposed to the use of porcine organs in humans.

By the turn of the century, the actions of such viruses had almost brought to a standstill the once-promising field of xenotransplantation, the transplantation of tissues, cells or organs from one species to another. Many mammals, including pigs, have in their genomes dormant but repeating bits of retrovirus DNA. The xenotransplantation of, say, a pig’s heart—biologically similar to a human’s—carries the risk that these retrovirus bits, harmlessly floating about in all porcine cells, will cause disease when transplanted.

By removing these retroviruses in one move, a team of scientists led by George Church, a professor of genetics at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School (HMS), has opened wide the closed gate heading towards the frontiers of pig-to-human transplantation. It was Church, and the paper’s lead author, Luhan Yang, a post-doctoral fellow at HMS and Wyss Institute, who in 2013 had first explained to the world how CRISPR-CAS9 could be used as molecular scissors.

What Church and his team will now have to do is to insert their cleansed DNA into cell lines, use these genetically engineered cells to grow pig embryos and eventually clone pigs bereft of retrovirus fragments. Although many creatures have been cloned—from sheep to pigs (the latter now mass-produced in, where else, China)—cloning genetically modified beings is not an easy task.

Eventually, it will be, and one day humanity will doubtless be faced with the immense benefits and dangers of genetic engineering.

However that turns out, my bet is on the use of CRISPR-CAS9 as one of the turning points of the age of genomics: Human ingenuity, aided by some luck and bacteria. Whether divinity or serendipity, the hottest thing in modern biology is nothing more than one of nature’s most ancient and ingenious survival tricks.

Samar Halarnkar is editor of Indiaspend.org, a data-driven, public-interest journalism, non-profit organization. He also writes the column Our Daily Bread in Mint Lounge.

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