Two years ago, a group of Chinese scientists shocked the world with a groundbreaking – and arguably chilling – achievement. They modified genes in human embryos with the latest gene editing technique, showing that designer babies, technically speaking, were no longer science fiction.
A new tool unveiled last week takes the precision of this technology to a whole new level. Named adenine base editor, the gene editing tool can pin-point at the exact DNA molecule that needs fixing. The base editor “corrects” a class of mutations responsible for thousands of diseases like blindness, sickle-cell anemia, and cystic fibrosis.
Super-precise targeting
In short, the base editor replaces adenine (A) – one of the bases that make up DNA – to guanine (G). It’s a modified form of CRISPR/Cas9, the famous technology that cuts chunks of DNA to add, delete, or replace genes.
“CRISPR is like scissors, and base editors are like pencils,” explained study author Dr. David Liu, who is a chemical biologist at Harvard University.
While CRISPR physically snips away at DNA strands, the new base editor dodges the need to cut by shuffling the structure of molecules that make up DNA. To instill edits, the base editor rearranges atoms in adenine to resemble guanine instead. This tricks the cells into fixing the other DNA strand to make the change permanent. It offers a cleaner, more efficient solution when the goal is simply to fix one specific “typo” in the genetic code.
This new method is a game-changer for genetic diseases caused by mutations in which guanine is replaced by adenine; this accounts for about half of the 32,000 single-letter “typos” associated with human disease.
Hereditary haemochromatosis (HHC), a disease that prompts the body to extract and store too much iron from food, is one of them. With the base editor, the team was able to “correct” the mutated gene back to the normal version in cells derived from patients with the disease.
How far are we from designer babies?
The first priority for this research is to establish a machine that can be used to treat existing patients.
“Creating a machine that makes the genetic change you need to treat a disease is an important step forward, but it’s only one part of what’s needed to treat a patient,” said Dr. Liu. “We still have to deliver that machine, we have to test its safety, we have to assess its beneficial effects in animals and patients and weigh them against any side effects. We need to do many more things. But having the machine is a good start.”
But this new technology may also lower the bars for germline editing, or the making of heritable modifications in eggs, sperm, or embryos.
Experts agree that there’s far too little known about how the edits could affect humankind over the long term for germline editing to be considered ethical. One major caveat of the CRISPR method was that physically slicing through DNA invited some unintentional edits with unknown consequences. In fact, a handful of countries now have a ban on germ-line engineering, and the EU’s convention on human rights and biomedicine has declared that this would be “a crime against human dignity”. In 2015, UNESCO made an international call to temporarily ban human germline editing until a thorough public debate ensues.
Without the need to chop up DNA, however, the base editor has less than 0.1% risk of making unwanted mutations. There’s already a supportive environment for further research on germline editing with this technology. Influential organizations in the US and on the international scale have been endorsing research and clinical trials on germline editing, on the condition that the reason for research is justifiable and that the use of the technology is strictly limited with specific criteria. Working on just that are at least three centers in the US, as well as scientists in China and biotech companies in the UK.
To what extent do we, as a collective, want to allow genetic engineering of our offspring? The day we have to come up with an answer might just be around the corner.