It's hard to think of the Zika virus these days without shedding a tear for its heartbreaking impact on the unborn, who risk being born with significant neurological impairment as a result of the infection.
Tragically – or perhaps, thankfully – this debilitating effect was never observed in any previous Zika virus outbreak. Now a group of researchers from across China think they know why; in 2013, the virus mutated into something far more dangerous.
Unless you're a well-read pathologist, there's a good chance you hadn't heard the name Zika before 2015.
It's not that the virus was unknown – it was first documented way back in 1947, isolated from a monkey in Uganda as researchers hunted for specimens of yellow fever.
The mosquitos that are capable of spreading the virus don't tend to come into contact with the general population in that corner of Africa, limiting its ability to spread.
Even then, cases of Zika infection rarely resulted in noticeable symptoms. When they did, it was little more than a fever and a rash.
In the decades since, the virus has slowly moved from its ground zero to spread to more than 90 countries, and has been found to not only travel via certain mosquito species, but through sexual contact as well.
A 2015 outbreak in Brazil brought word of a radical new effect of the virus's hijacking – infants of infected mothers being born with a condition called microcephaly.
It's been found that Zika virus easily slips inside neural progenitor cells and destroys them.
This isn't a big problem for most of us – our adult brains are practically fully formed, leaving little use for the blank-slate cells that develop into brain tissue.
In fact, this ability to destroy certain kinds of brain tissue could even make the virus useful as a weapon against cancers called glioblastomas.
For embryos relying on those cells to grow new brain structures, it's a whole other story.
Characterised by underdeveloped brains and surrounding bones, children with severe forms of this condition face a lifetime of neurological and sensory impairments, feeding problems, and seizures.
It took the CDC until April 2016 to officially declare there was a link between microcephaly and the Zika virus, but the race was already on to develop a vaccine.
Just how a rather innocuous virus could seem to suddenly give rise to such a severe disorder posed something of a mystery.
Had this condition been missed in previous outbreaks? Or was this an entirely new talent?
To find an answer, the researchers compared a strain of the virus collected from Cambodia in 2010 with samples from Venezuela, Samoa, and the Caribbean in 2015 and 2016.
A handful of differences were identified across in their RNA, each serving as the basis of engineered strains that were then used to infect young mice.
The method allowed the researchers to focus in on a single mutation that forced an amino acid called serine to switch to one called asparagine in one of the virus's proteins.
What's more, they could estimate this mutation took place in mid-2013, months before an outbreak in French Polynesia.
From there the mutated form of the Zika virus spread to Brazil, most probably in the blood of athletes competing in a canoe race world championship in 2014 (and not the 2014 FIFA World Cup).
There's no reason to conclude that this one shift was solely responsible for giving the Zika virus a new talent for breaking and entering brain cells.
It's possible that the virus was capable of causing microcephaly before, especially as the researchers observed instances of minor neurological impairment in mice infected with non-mutated strains.
But the study is strong evidence that a single mutation provided the virus with a useful tool for unlocking the door.
The implications are a sobering reminder – any quiet pathogen could be just a mutation or two away from becoming something far more insidious.
Cases of the virus have continued to plummet with improved awareness and growing immunity, which can only be a good thing for the time being.
It's unlikely we've heard the last of the Zika virus, though. Hopefully if it returns, it won't have any more nasty surprises.
This research was published in Science.