By Angus Dalton
A perfect bioweapon. The ultimate pandemic. Unprecedented ecological meltdown.
These are the nightmare scenarios scientists fear they may have unwittingly conjured into near reality as they pursued the creation of “mirror life”; a cell or bacterium engineered with the structure of its molecules entirely flipped.
Any attempts to create “mirror life” should be stopped, according to the scientists who were working on the technology.Credit: Nathan Perri
Now 38 luminaries of biotechnology have hit the brakes on their own research with a 300-page technical report and an article in the journal Science calling for a halt to all efforts to create mirror life, citing potential catastrophic risks to life as we know it.
If a mirror bacterium leaked from a lab – or was released maliciously – it would probably be invisible to our immune system, and could replicate so explosively in the body it would cause “conditions similar to septic shock”, they wrote.
A population of mirror microbes could rip through habitats and biospheres, escaping the attention of microbial predators and outcompeting natural bacteria. The organisms could disrupt nutrient cycling on the scale of ecosystems, and possibly interrupt the global carbon cycle.
Early-stage research into mirror life has already been funded in China, America and Europe, although the creation of a mirror cell will be virtually impossible for at least a decade and would require the synthesis of at least 100 mirror proteins. We can’t yet build a normal cell from scratch.
But once created, these mirror organisms would constitute a “radical departure from known life” – which is why the authors have demanded a discussion before mirror life leaps into reality.
“We restrict research involving live smallpox virus, dangerous human psychological experiments, and nuclear explosive testing in the environment because it is too dangerous,” co-author of the report Dr Kate Adamala, a synthetic biologist at the University of Minnesota, wrote in an editorial for The Scientist Magazine.
“We think that the creation of mirror life falls into the same class of research that is simply too risky to conduct.”
To understand what exactly mirror life is – and the related mirror technologies that could actually save lives – we need to understand the biochemical principle of “chirality”. And to do that, we must look at our hands.
Chirality: Why all of nature is left- or right-handed
All biological molecules are “chiral”, which means they exist in either a left- or right-handed form. An object or molecule is chiral if it can’t be superposed on its mirror image.
Picture it like this: hold up your hand to a mirror. Take a snapshot of your real upraised palm, and a snapshot of its reflection. If you printed these two images out and laid them over each other, palms up, they wouldn’t match – the thumbs would be on opposite sides. That makes hands “chiral”; a word that means “hand” in Greek.
If you did the same experiment with a bottle of water or a pencil, the object and its mirror image would match up perfectly. These are achiral objects.
DNA helices are chiral and always right-handed (if a tiny version of you walked down a DNA strand like a spiral staircase, you’d be turning to the right as you descend). Amino acids and proteins, meanwhile, are almost all left-handed.
The bearing of a chiral molecule dictates which biological receptors it can bind to and how it interacts with the other substances, such as drugs and enzymes. Sometimes the difference is profound; the right-handed version of the drug thalidomide, for example, is a sedative, while the left-handed version causes birth defects.
For the chemical compound carvone, used in fragrances, one orientation smells of crushed caraway seeds; the flipped version binds to a different olfactory receptor and smells of spearmint.
Professor Richard Payne, a leading expert in synthetic chemistry at the University of Sydney, works on crafting mirror proteins in the lab in pursuit of new drugs.
There are enormous advantages of using proteins or peptides (which are just mini-proteins) in medicine; they’re very selective in the cellular targets they latch onto, which means drugs made from proteins are extremely precise and less prone to off-target side effects.
But there’s a catch. Our bodies easily recognise the amino acids that make up peptide-based drugs and promptly chops them up. The drugs could also trigger an unwanted immune response.
Professor Richard Payne at the University of Sydney is using mirror proteins to discover promising new anti-inflammatory drugs.Credit: Stefanie Zingsheim
That’s why Payne and others in the field are working on flipping the chirality of different peptides from left to right because our immune systems – primed to detect left-handed proteins – would have a harder time targeting the mirrored peptide.
“From a drug discovery point of view, you get a molecule that doesn’t get deactivated as quickly,” Payne said, adding his lab was focused on discovering mirror-peptide and protein drug candidates that could treat inflammatory lung and bowel disease, psoriasis and eczema.
The gift of fear
Although a scientific paper by Payne about the therapeutic promise of mirror proteins was referenced in the mirror life report, in light of the paper’s apocalyptic tone he’s anxious to emphasise that his research into mirror proteins is a separate pursuit with vastly different goals to those who were working on mirror cells.
“[Our work] does not enable mirror image life at all. It’s just that we’re making some little protein components, and not even the protein components you would need to replicate life.
Almost all biological molecules are “homochiral”, meaning they exist in either a left or right-handed form. Natural DNA is considered a right-handed structure.Credit: Wolter Peeters
“We are going to see, I believe, a mirror image drug molecule in the future. And so you don’t want this sort of report – which is an important report that needed to be written – to curtail the really cool science that’s going on in drug discovery and immunology.”
Other scientists have argued the report was overblown and that the medical community’s wellspring of drugs would be more than capable of cracking down on a rogue mirror bug. Mirror bacteria might also struggle to survive outside the lab because they’d need left-handed sugars to feed on rather than the natural right-handed form.
But Payne said it was courageous and right to open a discussion about the risks. It’s rare scientists call time on their own research, but right to do so while the advent of mirror life is still at least a decade away and stymied by an estimated price tag of half a billion dollars.
Co-author of the report from Stanford University, Associate Professor Drew Endy, said engaging constructively with risks and fear is a necessary duty of scientists forging new ground.
“I see no future for bioengineering that doesn’t include the routine building of entire cells. And, so, we have to talk about the edge cases, like mirror life,” Endy said.
“The gift of fear is the chance to become courageous together.”
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