Updated June 15, 2018 05:27:31
Francisco Mojica is a humble man but his study of simple bacteria in a salt marsh in Spain decades ago has led to one of the biggest scientific breakthroughs of the 21st century.
Mojica discovered something that would allow scientists to edit genomes in virtually whatever way they wanted — giving them the power to rewrite the code of life.
It is called CRISPR and already it has been used to wipe out cancer in people. And in animals it has induced immunity to HIV and cured genetic heart conditions as well as Huntington's disease.
It has also been used to make genetically engineered crops that are resistant to disease and to make modified yeast that when fermented, produces opioid drugs rather than alcohol.
"It was not possible to even imagine this was going to happen," Professor Mojica told the ABC.
He is in Australia as part of an international award for innovation.
Professor Mojica grew up near the Mediterranean port of Santa Pola in Spain, a region famous for its salt lakes and the flamingos that live in them, and one day he noticed something odd.
He was looking at the bacteria that thrived in those marshes, and realised bits of DNA that were repeated many times, with regular spaces in between.
"And that was very unexpected and very amazing — and very peculiar," Professor Mojica.
Most researchers would not have thought much of such a discovery, said Professor Merlin Crossley, a molecular biologist form the University of New South Wales.
Professor Crossley was now one of thousands of researchers around the world working with technology that relies on Professor Mojica's discovery.
"Most repeats are junk — like a computer virus," Professor Crossley says. "If you see something like that it's often fools' gold."
But it was not fools' gold, said Professor Crossley. "He stumbled across a nugget of gold."
Professor Mojica devoted the next decade of his life figuring out exactly what these repeating structures were.
Today, they are known as CRISPR, which stands for "clustered regularly interspaced short palindromic repeats".
And they are the basis of a technology that lets scientists edit genomes of everything from bacteria to humans.
"You can do whatever you like," said Professor Crossley. "Some people say you can make a unicorn … but the problem is you don't quite know what to do to make a unicorn. You don't know what genes to change," he said.
Professor Crossley himself is one of thousands of researchers around the world using CRISPR. He made headlines recently using it to develop treatments for sickle cell anaemia — a genetic disorder.
The technology is still new and not perfect. It can introduce mistakes into genomes and in some cases, if that happens in animal cells, that can lead to cancer developing.
But Professor Mojica was blown away by the variety of ways his discovery has been used. He said among his favourites is work by Harvard's George Church, where an encoding of a movie was written into DNA using CRISPR.
But Professor Mojica's journey from the first discovery in 1993 was long and hard. And he said his motivation was just curiosity, not the desire to produce a world-changing technology.
Then in 2003, he made the most crucial discovery. Professor Mojica noticed that the weird repeating DNA in the bacteria usually sat alongside chunks of DNA that matched viruses that attacked that type of bacteria.
He realised, in effect, the repeats were framing a kind of mugshot in the bacteria's genome, that lets it recognise viruses.
"This is a bit like human antibodies," Professor Crossley said.
"If you've been infected once, you have a snapshot of that and you're ready for next time. And what CRISPR does is take a little piece of the viral DNA and puts it in the bacteria's genome so that next time the virus comes along the bacteria is ready."
Not only that, but as other researchers established, the bacteria's CRISPR system cuts the virus's DNA.
Once that was discovered, others worked out how to direct it to cut DNA where they wanted it cut. And yet others discovered how to get it to do that not just in bacteria, but in plant and animal cells too.
Suddenly, scientists effectively had a cut-and-paste tool for the DNA.
"Now it is like a Google search," Professor Crossley said. "You can search through vast genomes, actually in a test tube. And home in on the region you want, you can cut it, and you can put a new gene there, or you can change the sequence."
Although Professor Mojica's realisation caused a sweeping revolution in biomedicine, his ideas were not immediately welcomed.
The Professor wrote the idea up and submitted it to the top science journal Nature.
But they rejected it, without even getting experts to review it.
"We got these results in August 2003 and we immediately tried to publish it," Professor Mojica said.
"And also we said this was going to have tremendous repercussions in biology, in biotechnology and clinical sciences. They didn't' believe us and the paper wasn't accepted," he said.
"So we tried once again with another journal, and another one and another. Four different journals!"
Following 18 months of rejection — it was finally accepted by a journal.
Professor Mojica said the ideas were too new and too hard for editors and referees to accept.
Professor Crossley said he hoped Professor Mojica was awarded a Nobel Prize for the work.
Most scientists in the field agree someone will get a Nobel Prize for CRISPR. As Professor Mojica emphasised, there were a lot of people that came after him, and did arguably just as important work, turning his discovery into a tool.
"I am one in 100 or 1,000. Many people have been involved in CRISPR," he said.
The Spanish microbiologist said he continues to work on CRISPR. "Of course. I love CRISPR."
He said he was looking at other types of CRISPR systems that could one day themselves lead to other powerful gene-editing tools.
But what really motivates him is not technological applications, but seeking knowledge.
"I have to confess that is not my goal. I just want to know."
First posted June 15, 2018 04:58:53