Genetic hackers
How Young Biotechnologists Want to Make Billions on Life Editing
A system called CRISPR has become one of the most relevant technologies in biology. Startups focused on its use have become the focus of investors' attention
Michelle Tinder, Ellie Kincaid, Forbes, 05/16/2019
Translated by Natalia Balabantseva
When Rachel Haurwitz (photo from the website cariboubio.com – VM) started writing her PhD thesis in biology at the University of California, Berkeley, biochemist Jennifer Dudna suggested that she investigate a part of the bacterial immune system. Haurwitz studied how microbes store fragments of virus genes and recognize them in order to repel attacks in the future. Haurwitz herself calls this project esoteric.
Now – no esotericism. A system called CRISPR has become one of the most relevant technologies in biology. It is able to give scientists control over the "building blocks of life itself" and bring big profits to investors. When CRISPR was first described in 1987, it was not directly related to human health. However, Dudna and her colleagues have found a way to turn the system into a gene editing tool. In 2011, Haurwitz and Dudna participated in the creation of Caribou Biosciences. Haurwitz, who was not even 30 at the time, became the CEO of the company the following year.
Haurwitz is not the only young entrepreneur who is interested in gene editing. Dudna and her colleagues at Stanford founded Mammoth Biosciences, which raised $23 million from investors such as Apple CEO Tim Cook. In 2015, in Cambridge, Massachusetts, 29-year-old Luhan Yang founded eGenesis with her mentor, Harvard geneticist George Church, to use CRISPR in human pig organ transplantation. Omar Abudaye and Jonathan Gutenberg, who are not even 30 years old, founded Sherlock Biosciences.
Criminal viruses
CRISPR is short for "short palindromic repeats regularly arranged in groups." Bacteria store fragments of viral DNA in their genomes, as if they were photographs of criminals. These markers are used to identify the virus, just as the human immune system uses control fragments of the polio virus obtained from the vaccine.
If the virus matches the saved "criminal photo", CRISPR-related enzymes break down the virus's death-bearing DNA into harmless parts. Dudna, along with other scientists, figured out how to use these enzymes to cut DNA at specific points in order to change genes. Thus, CRISPR promises to simplify the expensive and malfunctioning process of DNA rewriting, opening up new ways to treat diseases caused by genetic mutations, creating cheaper diagnostic tests and cells that kill cancer.
Eight years after launching in Berkeley, Caribou has raised $41 million and entered into licensing deals (which can bring hundreds of millions of dollars) with DuPont Pioneer, Novartis and others.
Business from the candidate's
Haurwitz grew up in Austin, Texas, and received a bachelor's degree in biology from Harvard. She didn't have a clear plan when she went to the University of California, Berkeley, but she thought she might one day become a patent attorney.
The more exciting her PhD turned out to be, the more plans changed. Haurwitz and Dudna have been discussing for a long time how they could use CRISPR to change genomes and treat diseases. If you program the CRISPR system to cut the gene that needs to be changed, then it is theoretically possible to use it to change the genetic program to either correct the "flaws" that cause the disease, or disrupt the production of unwanted protein.
Caribou originated from the idea of adapting CRISPR technology for DNA editing (it can be used in drug development, agriculture, basic biological research). The founders of Caribou did not want to leave academia and were "crazy enough to allow a 26-year-old girl who had never worked for a company in her life to take on the role of president and CEO," says Haurwitz.
Caribou then obtained an exclusive license for some CRISPR patents held by the University of California System and the University of Vienna. Haurwitz offered to finance the startup to venture investors, but almost no one showed interest in the project.
However, the following year, scientific papers appeared that increased interest in CRISPR. Money from investors soon followed. Editas Medicine, created by Feng Zhang of Sherlock Biosciences, has raised $43 million to apply this technology in therapy. The next was Intellia Therapeutics, founded by Caribou, which raised $15 million in 2014. And the company CRISPR Therapeutics, created by one of the pioneers of technology Emmanuel Charpentier, raised $ 89 million. All three companies went public in 2016, and now their total market value is $3.8 billion.
Meanwhile, Haurwitz began to receive calls from breeding and pharmaceutical companies. In 2015, DuPont invested $11 million in the company, the following year Caribou raised another $30 million. Genus (a firm working in the field of animal genetics) paid Caribou for the exclusive right to use its patented technology to work with the genes of pigs and other livestock. Jackson Laboratory pays Caribou to use CRISPR to create new populations of mice on which human diseases are modeled.
Soon Haurwitz will have to look for capital again. The fact is that Caribou develops drugs – it is expensive, but potentially more profitable. The first priority is to improve existing cancer treatment methods. CRISPR, according to Haurwitz, can be used to edit the DNA of immune cells from healthy donors so that these cells can be transferred to any cancer patient. The company plans to start human trials next year.
In addition, Caribou is developing a program in another "hot" area: it is a microbiome, or a set of bacteria that inhabit all parts of the human body, especially the intestines. This time, investors know what CRISPR is, and Haurwitz has already attracted some of them to her side. "She is one of the few people I have met in my life who can switch from business topics to scientific topics in an instant," says Ambar Bhattacharya, Caribou investor at Maverick Ventures.
Ethics issues
The field in which Caribou operates is characterized not only by competition, but also by conflicts in the field of intellectual property. Overlapping patent applications from the University of California and the Broad Institute have been filed for the underlying technology, which includes the Cas9 enzyme used to make a cut in DNA. The lawsuit between the institutions was decided in favor of the Broad Institute, but the U.S. Patent Office granted patents to both.
Those who own this technology will make a huge profit. Caribou can conduct trials related to a specific gene, but if other companies want to conduct trials related to other genes, they may have to turn to Caribou, says Jacob Sherkow, a professor at New York Law School. "They will have to pay handsomely."
In addition to legal battles, the new field of research may cause a mixed public reaction. In November, Chinese scientist He Jiankui announced that he had used CRISPR to edit the genomes of human embryos – twin girls - thereby prompting the public to increase pressure on scientists to develop rules for using the new technology. According to Haurwitz, Caribou's licensing agreements include a section prohibiting the use of the development on human embryos.
It is necessary to study the scientific side of embryo gene editing, and then discuss how to use such opportunities responsibly, says Dudna. "Are there real unresolved medical problems that require such changes, or not? I think that's the question."
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