Why have I never heard about this biotech breakthrough till now??

On a November evening last year, Jennifer Doudna put on a stylish black evening gown and headed to Hangar One, a building at NASA’s Ames Research Center that was constructed in 1932 to house dirigibles.

Under the looming arches of the hangar, Doudna mingled with celebrities like Benedict Cumberbatch, Cameron Diaz and Jon Hamm before receiving the 2015 Breakthrough Prize in life sciences, an award sponsored by Mark Zuckerberg and other tech billionaires.

Doudna, a biochemist at the University of California, Berkeley, and her collaborator, Emmanuelle Charpentier of the Helmholtz Centre for Infection Research in Germany, each received $3 million for their invention of a potentially revolutionary tool for editing DNA known as CRISPR.

Doudna was not a gray-haired emerita being celebrated for work she did back when dirigibles ruled the sky.

It was only in 2012 that Doudna, Charpentier and their colleagues offered the first demonstration of CRISPR’s potential.

They crafted molecules that could enter a microbe and precisely snip its DNA at a location of the researchers’ choosing.

In January 2013, the scientists went one step further: They cut out a particular piece of DNA in human cells and replaced it with another one.

In the same month, separate teams of scientists at Harvard University and the Broad Institute reported similar success with the gene-editing tool.

A scientific stampede commenced, and in just the past two years, researchers have performed hundreds of experiments on CRISPR. Their results hint that the technique may fundamentally change both medicine and agriculture.

Some scientists have repaired defective DNA in mice, for example, curing them of genetic disorders. Plant scientists have used CRISPR to edit genes in crops, raising hopes that they can engineer a better food supply.

Some researchers are trying to rewrite the genomes of elephants, with the ultimate goal of re-creating a woolly mammoth.

Writing last year in the journal Reproductive Biology and Endocrinology, Motoko Araki and Tetsuya Ishii of Hokkaido University in Japan predicted that doctors will be able to use CRISPR to alter the genes of human embryos "in the immediate future."

Thanks to the speed of CRISPR research, the accolades have come quickly. Last year MIT Technology Review called CRISPR "the biggest biotech discovery of the century."

The Breakthrough Prize is just one of several prominent awards Doudna has won in recent months for her work on CRISPR; National Public Radio recently reported whispers of a possible Nobel in her future.

Even the pharmaceutical industry, which is often slow to embrace new scientific advances, is rushing to get in on the act. New companies developing CRISPR-based medicine are opening their doors.

In January, the pharmaceutical giant Novartis announced that it would be using Doudna’s CRISPR technology for its research into cancer treatments. It plans to edit the genes of immune cells so that they will attack tumors.

But amid all the black-tie galas and patent filings, it’s easy to overlook the most important fact about CRISPR: Nobody actually invented it.

Doudna and other researchers did not pluck the molecules they use for gene editing from thin air. In fact, they stumbled across the CRISPR molecules in nature.

Microbes have been using them to edit their own DNA for millions of years, and today they continue to do so all over the planet, from the bottom of the sea to the recesses of our own bodies.

We’ve barely begun to understand how CRISPR works in the natural world.

Microbes use it as a sophisticated immune system, allowing them to learn to recognize their enemies. Now scientists are discovering that microbes use CRISPR for other jobs as well.

So this is how our microbiomes edit their own DNA too?

Wow!

Some researchers are trying to rewrite the genomes of elephants, with the ultimate goal of re-creating a woolly mammoth.

Writing last year in the journal Reproductive Biology and Endocrinology, Motoko Araki and Tetsuya Ishii of Hokkaido University in Japan predicted that doctors will be able to use CRISPR to alter the genes of human embryos "in the immediate future."

What are we .... wraughting?

Cue Dr. Ian Malcolm from Jurassic Park.

Oh no, Crispr under fire!

http://www.nytimes.com/2015/03/20/science/biologists-call-for-halt-to-gene-editing-technique-in-humans.html

I like this concept of an adaptive immune system.

Doudna and her colleagues thus invented a biological version of find-and-replace — one that could work in virtually any species they chose to work on.

As important as these results were, microbiologists were also grappling with even more profound implications of CRISPR. It showed them that microbes had capabilities no one had imagined before.

Before the discovery of CRISPR, all the defenses that microbes were known to use against viruses were simple, one-size-fits-all strategies. Restriction enzymes, for example, will destroy any piece of unprotected DNA. Scientists refer to this style of defense as innate immunity.

We have innate immunity, too, but on top of that, we also use an entirely different immune system to fight pathogens: one that learns about our enemies.

This so-called adaptive immune system is organized around a special set of immune cells that swallow up pathogens and then present fragments of them, called antigens, to other immune cells. If an immune cell binds tightly to an antigen, the cell multiplies.

The process of division adds some random changes to the cell’s antigen receptor genes. In a few cases, the changes alter the receptor in a way that lets it grab the antigen even more tightly. Immune cells with the improved receptor then multiply even more.

This cycle results in an army of immune cells with receptors that can bind quickly and tightly to a particular type of pathogen, making them into precise assassins. Other immune cells produce antibodies that can also grab onto the antigens and help kill the pathogen.

It takes a few days for the adaptive immune system to learn to recognize the measles virus, for instance, and wipe it out. But once the infection is over, we can hold onto these immunological memories. A few immune cells tailored to measles stay with us for our lifetime, ready to attack again.

CRISPR, microbiologists realized, is also an adaptive immune system. It lets microbes learn the signatures of new viruses and remember them.

And while we need a complex network of different cell types and signals to learn to recognize pathogens, a single-celled microbe has all the equipment necessary to learn the same lesson on its own.

But how did microbes develop these abilities? Ever since microbiologists began discovering CRISPR-Cas systems in different species, Koonin and his colleagues have been reconstructing the systems’ evolution.

It turns out CRISPR can serve other functions like detection of genes and silencing of genes.

To Konstantin Severinov, who holds joint appointments at Rutgers University and the Skolkovo Institute of Science and Technology in Russia, these explanations for CRISPR may turn out to be true, but they barely begin to account for its full mystery.

In fact, Severinov questions whether fighting viruses is the chief function of CRISPR. "The immune function may be a red herring," he said.

Severinov’s doubts stem from his research on the spacers of E. coli. He and other researchers have amassed a database of tens of thousands of E. coli spacers, but only a handful of them match any virus known to infect E. coli.

You can’t blame this dearth on our ignorance of E. coli or its viruses, Severinov argues, because they’ve been the workhorses of molecular biology for a century. "That’s kind of mind-boggling," he said.

It’s possible that the spacers came from viruses, but viruses that disappeared thousands of years ago. The microbes kept holding onto the spacers even when they no longer had to face these enemies. Instead, they used CRISPR for other tasks.

Severinov speculates that a CRISPR sequence might act as a kind of genetic bar code. Bacteria that shared the same bar code could recognize each other as relatives and cooperate, while fighting off unrelated populations of bacteria.

But Severinov wouldn’t be surprised if CRISPR also carries out other jobs. Recent experiments have shown that some bacteria use CRISPR to silence their own genes, instead of seeking out the genes of enemies.

By silencing their genes, the bacteria stop making molecules on their surface that are easily detected by our immune system. Without this CRISPR cloaking system, the bacteria would blow their cover and get killed.

"This is a fairly versatile system that can be used for different things," Severinov said, and the balance of all those things may differ from system to system and from species to species.

If scientists can get a better understanding of how CRISPR works in nature, they may gather more of the raw ingredients for technological innovations.

To create a new way to edit DNA, Doudna and her colleagues exploited the CRISPR-Cas system from a single species of bacteria, Streptococcus pyogenes.

There’s no reason to assume that it’s the best system for that application. At Editas, a company based in Cambridge, Massachusetts, scientists have been investigating the Cas9 enzyme made by another species of bacteria, Staphylococcus aureus.

In January, Editas scientists reported that it’s about as efficient at cutting DNA as Cas9 from Streptococcus pyogenes. But it also has some potential advantages, including its small size, which may make it easier to deliver into cells.

To Koonin, these discoveries are just baby steps into the ocean of CRISPR diversity. Scientists are now working out the structure of distantly related versions of Cas9 that seem to behave very differently from the ones we’re now familiar with. "Who knows whether this thing could become even a better tool?" Koonin said.

And as scientists discover more tasks that CRISPR accomplishes in nature, they may be able to mimic those functions, too. Doudna is curious about using CRISPR as a diagnostic tool, searching cells for cancerous mutations, for example. "It’s seek and detect, not seek and destroy," she said.

Whoa.

I know, right? We live in exciting times!