Designer DNA: Will CRISPR-Cas 9 Create a BioHacker Revolution or a Nightmare?

When microbiologist Emmanuelle Charpentier and RNA expert and biochemist Jennifer Doudna met at a conference in 2011, their shared passion for science led to a profound discovery; a new technique to engineer genomes known as CRISPR-Cas9.

The technological and economic revolution that ensued still reverberates through labs around the world. CRISPR-Cas9  has created a seismic shift in how science operates making genome editing fast, flexible, inexpensive and easily accessible to anyone with a modicum of lab equipment. But is CRISPR-Cas9 a bio-hacker revolution or a potential scientific nightmare?

Based on a bacterial CRISPR-associated protein-9 nuclease (Cas9) from Streptococcus pyogenes, CRISPR-CAS9 allows researchers to edit parts of a genome, using the same adaptive immune system mechanism bacteria use to recognize viral DNA and trigger its destruction. The CRISPR-CAS9 kit allows sections of DNA sequences to be snipped out and replaced, giving scientists the ability to essentially mutate the DNA. Further complicating the issue are synthetic elements which can now be added to genomes.

In 2014, the Scripps Research Institute in California added two artificial bases to the genetic code. Synthetic bases X and Y, which could be combined with the natural nucleic acid bases; adenine (A), cytosine (C), guanine (G), and thymine (T). The new six-letter DNA alphabet increases the number of possible amino acids to 172. Then on January 23, 2016, Scripps announced they had created a stable synthetic bacterium using CRISPR-CAS9 to modify the error removal mechanism. As a safeguard straight out of Jurassic Park, the ingredients for the synthetic bases (which don’t exist in nature), must be fed to the bacterium; providing a theoretical fail safe should the organism escape the lab. “We’ve made this semisynthetic organism more life-like,” said Professor Floyd Romesberg, senior author of the study.

Although regulations preclude human experimentation in the United States, Chinese scientists have already used CRISPR-Cas9 to manipulate human embryos to try and make them resistant to HIV. According to a report published in the journal Nature, 26 human embryos were eventually targeted for modification using the process, with four being successfully modified. Of the others, a significant number showed signs of unintended mutations. And on October 28th, 2016, a team led by oncologist Dr. Lu You at Sichuan University in Chengdu injected cells modified with CRISPR-Cas9 into a patient with aggressive lung cancer as part of a clinical trial at the West China Hospital, also in Chengdu.

Ideally, gene editing will lead to targeted gene therapy where scientists will edit out faulty sections of genetic code as easily as writers find and replace a word in their text. On June 21st, 2016, an advisory committee at the US National Institutes of Health (NIH) approved a proposal to use CRISPR–Cas9 to help augment cancer therapies that rely on enlisting a patient’s T cells, a type of immune cell, allowing CRISPR-Cas9 for use in human trials.

But CRISPR-Cas9 is not just a scientific breakthrough, it’s essentially opening genetic engineering up to the masses and this collision of commerce and science is having interesting effects. There are competing brands like zinc-finger nucleases and TALENS; gene editing systems which can deliver a DNA-cutting enzyme to a particular gene. And innovations continue to make the technology of gene editing more accessible and efficient for scientists to experiment with in the form of new kits and pipeline software to make experimentation easier. For example, DECKO was created by Johnson labs to delete non-coding DNA, also known as junk DNA, using two individual sgRNAs to act as molecular scissors.  In response to that development, a master’s degree student, Carlos Pulido-Quetglas, designed a software pipeline for CRISPR deletion experiments called CRISPETa, which allows users to select a DNA region to delete and return a set of optimized pairs of sgRNAs for use by experimental researchers.

Not only are labs across the world using the CRISPR-Cas9 (and competing kits) to conduct genetic experiments and developing innovative software to visualize and manipulate DNA, but a slew of genetic startups are now conducting experiments that would have been unfeasible or too expensive before CRISPR-Cas9 was an option.

And that reality is creating a seismic shift in how science operates. A world of genetic startup companies with easy access to DNA manipulating technology and toothless regulation could lead to a future of independent labs creating mutations.  Think Ridley Scott’s Blade Runner, where Tyrell Corporation farms out the making of Replicant eyes to genetic designers/independent contractors in labs scattered throughout a future Los Angeles.

CRISPR-Cas9 experiments are only limited by the imagination of scientists and the strength of regulating forces, and when it comes to botanical experiments, it’s the wild west out there. Companies are manipulating plant DNA to avoid existing Agriculture Department regulations, which never envisioned such technology. These genetic mutations are being offered up in commercial marketplaces and distributed into the environment. There have already been genetic accidents, such as in 2003, when the Miracle-Gro Company allowed genetically-engineered grass to escape into the wild in Oregon.

In 2015, Yinong Yang, a plant biologist at Penn State using CRISPR-Cas9 to modify white mushrooms to brown less on the shelf, wrote to the U.S. Animal and Plant Health Inspection Service to see if his mushrooms would be a “regulated article” (He was switching off one gene, not introducing foreign DNA). And though the US Dept of Agriculture did not consider the gene tampering to make the grade, the letter shows the battlefield of ethical considerations at play. Penn State Letter.

Another area of ethical controversy is using CRISPR-Cas9 to force a suicidal gene change in a population to drive an entire species to extinction. Scientists are currently debating the merits and dangers of destroying Aedes aegypti, the type of mosquito spreading Zika virus, among other deadly pests.

Even more startling from a cultural perspective is the fact that biohackers can access the technology and manipulate the genetic code of organisms from anywhere. The equipment needed to crack the code of life is available on e-bay and a working lab can be set up using space in any home or garage.

What dangers does CRISPR-Cas9 present? Could biohackers edit the genetic code of human beings or release transgenic organisms capable of propagating edits into the wild?

Yes.

Could biohackers create a modified virus or bacteria? In other words, could bio-hackers create a plague?

Yes, they could.

When we speculate about what could possibly go wrong with this technology, we must consider what we already know of human nature. What would a cult do with this technology? What about an ideologically driven regime or terrorist organization? How about a corporation who controls agriculture or large sectors of the food supply?

What could possibly go wrong?

Everything.

 

 

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