Editing the body

There’s a new way to alter the human body beyond exercise or surgery. It’s called gene editing, and it promises to not only end disease but reshape humans. Mahsa Fratantoni takes a closer look at this game-changing technology. 

The recent news that a team from Oregon Health and Science University was able to correct a gene in a human embryo that’s linked to a heart condition was a real indicator to what’s coming as a result of gene editing: the ability for us to start tampering with the building blocks of the human body, potentially to cure cancer, wipe out disease and even edit life itself.

Gene editing is one of the fastest growing research fields of the decade — and at its heart is CRISPR technology — Clustered Regularly Interspaced Short Palindromic Repeats. It’s an exciting and powerful technique that is completely transforming how scientists approach health and disease.

But what is it, exactly? And how is the technology being used? Here’s a glimpse at what’s in store for future generations.

Cut-and-paste genetics

While genetic engineering has been around for some time, CRISPR is an inexpensive, simple and quick “cut-and-paste” tool that has done more for the genetic field in four years than any other technique has in four decades. It can edit genes in humans, animals and plants, and has potential applications ranging from human therapeutics to agriculture in the future.

Interestingly, CRISPR is not a machine or a device, but a naturally occurring bacterial defence system that slices DNA much like a pair of genetic scissors.

By editing DNA, scientists are able to change the way proteins are made, fix them, or remove them completely.

“Conceptually, for a scientist, it’s a simple process,” says Dr Matthew Porteus, a stem cell biologist from Stanford University. “Take out the stem cells from a patient who has the disease, use genome editing to change the mutation back to a letter that doesn’t cause the disease and give those stem cells back to the patient so that they no longer have the disease.”

No room for error

While you’d be forgiven for a cutting mishap on an art project or gift-wrapping exercise, there’s really no room for an unruly chop when it comes to DNA.

Each DNA molecule is made up of a long string of four chemicals, or bases: A, T, C and G, which are arranged in a unique sequence. The sequence of these bases determines the information necessary to build a living organism.

One shaky snip in the genetic code can lead to unpredictable consequences. That’s because genes, which are sections of DNA, act as instructions to make molecules called proteins. This influences our physical traits, such as height or eye colour, and how our bodies work.

Far from your standard cutting shears, CRISPR is made up of two sophisticated parts – a GPS-like navigator that guides the enzyme Cas9 to the precise location, then Cas9 makes the snip.

It’s faster, too. While the research community was slowly making progress with other gene editing techniques — zinc-fingers and TALENs are two examples — they were complex and time-consuming, taking several months to years to work with.

Now, scientists can design a new CRISPR to target a sequence in a particular genome then commence testing multiple genes in as little as one to two weeks, says Porteus, who is using CRISPR to pave the way for a potential cure for sickle cell disease.

In late 2016, scientists Dr Alessandro Bertero and Professor Ludovic Vallier at Cambridge Stem Cell Institute took the CRISPR technology one step further. By enhancing it with a unique “knock out, knock down” mechanism, they are now able to see how a stem cell develops into an adult cell.

This allows researchers anywhere in the world to rapidly and accurately explore the changing function of genes as the cells develop into tissues such as liver, skin or heart.

“By allowing the gene to operate during the cell’s development and then knocking it out with sOPiTKO, the knock out system, we can investigate exactly what it is doing at that stage,” says Vallier.

Is gene editing necessary?

Each of us has approximately 20,000 to 25,000 genes. While most naturally occurring mutations in our body are harmless, a small defect or mutation in one of these genes or a set of genes can cause disease or increase the risk of life-threatening conditions in some people.

“Just living causes mutations to occur. The DNA of our cells is changing all the time,” Porteus explains.

The type of disease depends on the degree of gene mutation. For example, sickle cell disease, an inherited form of anaemia, is caused when one gene stops working. Down Syndrome occurs when the entire chromosome is altered. And some diseases, such as diabetes, can be caused when mutations in multiple genes are coupled with environmental factors.

The potential to one day wipe out these and other diseases altogether is part of CRISPR’s allure — however, the technology comes with a warning label.

“The precision of the CRISPR system massively exceeds the precision of simply living, and this is at the cutting edge of the discussion around this technology,” says Porteus.

Fast and furious

With the technology moving so fast and fears of designer babies or super-humans in the future, CRISPR does raise many ethical and safety concerns.

“Genome editing could be used to modify human embryo and the human germ line to ‘improve’ the human race,” says Vallier. “Those applications are currently impossible but the scientific community and broader society needs to have regulations in place.”

And in theory, what’s to say the same technique used to prevent or treat muscular dystrophy couldn’t one day be used in healthy individuals? For example, in athletes to improve their fitness ability?

“This concern is not limited to genome editing,” replies Porteus. “Gene therapy in general might be used to enhance muscle strength or regeneration or flexibility — basically, genetic doping.

“As we move forward we have to think about the ethical issues of equity and fairness around whether people should be using such therapies, not just to treat disease, but to enhance some sort of feature or trait,” he adds.

While next-generation CRISPRs are in the works, the technology is still far from being used in the doctor’s office.

“Gene editing has the potential of curing certain genetic disorders, however these applications are still years away from the clinic and will require much more work to increase efficiency and establish their safety,” says Bertero.

“Timing will depend on the general progress of the gene-editing field and on how quickly safety of these methods will be established.”