Wired Magazine: This genetic technology will reshape life

Release date: 2015-08-28

On August 15th, the US "Connected" magazine recently published a cover article entitled "Simple Gene Editing Technology Will Change the World" by Amy Maxmen. The article introduces a gene editing technology called "Crispr Cas9", which can play an important role in the treatment of AIDS and cancer. It can also produce crops for the next 9 billion people, but it can also bring huge disasters. Like all kinds of monsters that appear in science fiction movies.

The following is the main content of the article (Tencent Technology compiled and organized):

Between the craft buildings of the Asilomar Conference Grounds in California, there are many thorns and jagged pine trees.

This place is a 100-acre sand dune where the Monterey Peninsula is embedded like a hammerhead in the Pacific Ocean. This rugged landscape is striking and designed to inspire people to think about the evolution of the Earth's environment.

There is also a very important mission in this place: In 1975, 140 scientists around the world chose to hold an unprecedented conference here. These scientists are worried about the whims of human "recombinant DNA - the source code for manipulating life."

In the 1950s and 1950s, the three scientists, James Watson, Francis Crick, and Rosalind Franklin, described the DNA for the first time. The gene is a DNA fragment carrying genetic information and is the basis of heredity.

These scientists focused on the Asiloma Conference Center to discuss a question: how to decipher and reorganize biological genes, and how this behavior will affect humans. Transplanting a gene from one living being into another is a godlike force.

If this technology is used wisely, it could save millions of lives. But scientists know that this technology can also get out of hand. They want to know which actions related to this should be banned.

In 1975, research in other fields of science such as physics was greatly limited. For example, almost no one is allowed to study atomic bombs. But biology is different. Biologists are still conducting their research in accordance with the original plan.

But sometimes regulators still get involved. After the promulgation of the Nuremberg Code and the exposure of the Tuskege human experiment, regulators warned biologists not to use technology to do bad things. Scientists hope to establish very open and forward-looking guidelines at the Eslomar Conference.

Biologist David Baltimore

At the end of the meeting, David Baltimore, a biologist at the Massachusetts Institute of Technology, and four other molecular biology families wrote a consensus statement all night. They envisioned ways to prevent potentially dangerous behaviors and explicitly identified clones and dangerous pathogen experiments as restricted areas.

Several participants were also worried about the “family” to modify this crazy idea, but most people think it is unrealistic to consider things that are too far away. Because the design of microbes is already difficult enough, the rules set by scientists involved in the Asiloma meeting seem to be very advanced.

Earlier this year, Baltimore attended another conference at The Carneros Inn in Napa Valley, California, with 17 other researchers. “I have a feeling of deja vu,” Baltimore said. He once again gathered with the world's smartest scientists to talk about the impact of genetic engineering.

However, things have changed. Everyone at the Napa conference can use a gene editing technique called Crispr Cas9. "Crispr" is an abbreviation for "clustered regular interspaced short palindromic repeats", describing the genetic basis of this technique; "Cas9" is the name of a protein, exactly it Make "Crispr" possible.

Aside from the technical details of "Crispr Cas9", it will make genetic transplantation easier and cheaper, and the genes of any organism, whether it be bacteria or humans, can be transplanted. “This is an important moment in the history of biomedical research,” Baltimore said.

This technology was only available for three years. Using this technology, researchers have been able to reverse genetic mutations that cause blindness, prevent cancer cells from multiplying, and protect cells from HIV. Agronomists have developed wheat that is resistant to deadly bacteria such as powdery mildew, suggesting that humans can genetically engineer the main crops that can feed 9 billion people. Bioengineers have used "Crispr" to alter the yeast's DNA so that it can break down plant matter and ethanol excreta, a technology that is expected to end human dependence on oil.

In addition, startups committed to developing "Crispr" technology have also emerged. International pharmaceutical and agribusiness companies have accelerated the development of the “Crispr” technology. The two best universities in the United States are competing for basic patents related to this. Through "Crispr", someone saw a sparkling future world, someone saw the Nobel medal, and someone saw a lot of dollars.

Technology is revolutionary, but like all revolutions, it is also dangerous. The impact of "Crispr" greatly exceeded any discussion at the Eslomar Conference. It finally allows genetics researchers to see what people have been worried about – designing babies, invasive mutants, specific species of biological weapons, and many other things that appear in science fiction. It brings new rules to the practice of life science research. But no one knows what the rules are and does not know who will be the first to break them.

Long history of genetics

Before people know what genes are, humans are already genetic engineers in a sense. By breeding, humans can breed life-characteristic species with new characteristics, such as sweet corn and flat-faced bulldogs. But it takes a long time, and it may not be successful.

In the 1840s, human transformation of species became faster. Scientists x-ray bombarding seeds and insect eggs can cause their genomes to spread like shrapnel, leading to genetic mutations. If a large number of irradiated plants or insects grow up and have the characteristics that scientists hope they have, they become different. This is the origin of red grapefruit and most of the barley used to make beer.

The risk of genetic modification has become smaller. In 2002, molecular biologists learned to use a enzyme called zinc finger nuclease to delete or replace specific genes. A new generation of technology uses a transcription activator-like effector. Nucleases, TALENs) enzymes.

However, this process is costly and extremely complicated. This technique is only applicable to organisms whose visceral molecular structure has been thoroughly clarified by scientists, such as mice or fruit flies. Genetic engineers have been looking for better ways until the emergence of "Crispr Cas9".

However, it was first discovered that “Crispr” was not a genetic engineer, but a basic researcher exploring the mystery of the origin of life. They sequenced the genomes of ancient bacteria such as archaea. In the genetic sequence of these bacteria, microbiologists notice a segment that circulates like a palindrome. Researchers don't know what these clips do, but they know it's weird. Scientists named these fragments of palindrome "Crispr."

In 2005, a microbiologist at a Danish food company called Rodolphe Barrangou found the same palindrome in a bacterium called Streptococcus thermophilus, which the company used to make yogurt and cheese. of.

Barrangou and his colleagues found that the unidentified DNA sequence between these "Crispr" matches the gene fragment of the virus invading S. thermophilus. Like most creatures, bacteria are also attacked by viruses, which are called phage.

Barrangou's team continued its research and hoped to see if this gene fragment played an important role in the defense of bacteria against phage, which acted as an immune memory. They found that if the phage invades a bacterium and the bacterium's Crispr carries a trait, the bacterium will counterattack the virus. Barrangou and his colleagues realized that by choosing Streptococcus thermophilus with Crispr sequences, which are resistant to common dairy viruses, they can save the company some costs.

As researchers sequenced more and more bacteria, they found Crisprs in more bacteria. The same is true for most archaea. Even more peculiar, unlike the typical characteristics of genes, some Crispr sequences are not the ultimate coder of a protein, instead they lead to the appearance of RNA.

This finding points to a new hypothesis. Some researchers are beginning to suspect that Crispr is not the original immune system. As a researcher, Jill Banfield of the University of California at Berkeley found Crispr in a bacterium of 110-degree acidic water in an abandoned iron mine in Shasta County, California.

Fortunately, Banfield was helped by the famous RNA expert Jennifer Doudna during the research. Jennifer Doudna is a biochemist who first revealed the three-dimensional structure of complex RNA molecules. The bacteria from the mine caused Doudna's curiosity, but when she looked closely at their Crispr, she did not see any indication that the bacterial immune system is related to the immune system of plants and animals. However, she believes that such a system may be suitable for diagnostic testing.

The person who asked Doudna to help study the Crispr project was not one of Banfield. In 2011, Doudna attended the American Society for Microbiology conference in Puerto Rico, and a French scientist named Emmanuelle Charpentier asked her for help.

Emmanuelle Charpentier explained that a protein containing Crispr seems unusual. This protein appears to be able to search for specific DNA sequences in the virus and cut them off. Emmanuelle Charpentier hopes that Doudna will help him study how this happens.

After returning, Emmanuelle Charpentier collected a cluster of S. pyogenes and used it for observation and experimentation. Few people are willing to approach S. pyogenes because they can cause pharyngitis and necrotizing fasciitis. But this is the work of Charpentier. It was in this Streptococcus pyogenes that she discovered a mysterious and powerful protein - now known as "Cas9." She sent the sample to Doudna.

Charpentier's team worked with Doudna's team to find that Crispr was able to produce two short-chain RNAs, and Cas9 attached to them. This short-stranded RNA sequence matches the DNA sequence of the virus and can be tracked like GPS.

When the "Crispr Cas9" gene editing technology finally came to the fore, "Cas9" had the magical power: it changed shape, grabbed DNA and cut them precisely.

Doudna's postdoctoral student Martin Jinek combines two RNA sequences into one editable sequence, the "guide RNA." He can make "guide RNA" with any genetic code symbol - not only from viruses, but also from any creature they call a name. In vitro, the combination of Jinek's "guide RNA" and "Cas9" proteins proved to be a programming technique that can cleave DNA.

"I remember I ran to my Berkeley colleagues to tell them about this fantastic result and said it was a very exciting technology in the field of genetic engineering. But I don't think they fully understand it," Doudna said. "They are a little perfunctory, they say 'Oh, yes, this is good'".

On June 28, 2012, Doudna's team published the results of this research in Science. In this paper and earlier patent applications, they believe that their technology can be a tool for genome engineering. This technology is simple and low-cost, and can be operated by an ordinary graduate student.

This discovery quickly caught the attention of researchers. In the 10 years before 2012, more than 200 papers mentioned Crispr. By 2014, this number has risen more than threefold. Doudna and Charpentier recently won the Breakthrough Prize in Life Sciences for a $3 million prize. They are also selected as one of the 100 most influential people in the world selected by Time magazine.

Source: Tencent Technology

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