The place where the world is recreated is a sober place. A yellow and beige low-rise building halfway between the University of California, Berkeley, campus and the lively San Francisco Bay. In the building where a bakery used to make Twinkies, America’s popular, cream-filled mini cakes, there are no football tables, biodynamic vegetable patches or whiskey bars made from recycled teak, which are a must-see around Silicon Valley. Instead, bare walls and gray needle felt. It is quiet as a church in the large laboratory rooms, only the huge freezers are humming. Rachel Haurwitz guides us through an open-plan office where scientists are concentrated on their computers. “We built the plane during the flight,” she says as she takes a seat in the conference room, from whose windows she overlooks the hallway.
But Haurwitz doesn’t build airplanes at all – rather plants, animals, people. The 31-year-old is the boss and co-founder of Caribou Biosciences, one of only a handful of start-ups worldwide that hold the rights to CRISPR-Cas9: the innovative genetic technology that makes genetic changes by human hands easier, cheaper and more precise than ever before .
CRISPR is the abbreviation for repetitive sections in the DNA and describes a method that its protagonists believe will completely change our lives. CRISPR aims to make it possible to treat inevitably fatal diseases today. With CRISPR one could also bring the mammoth, which died out thousands of years ago, back to life, exterminate the malaria mosquitoes, breed calves without horns and wheat that hardly needs rain. Researchers are working on all of these goals – or they have already achieved them.
Blessings for some – nightmare for others
For some, CRISPR-Cas9 is the long-awaited breakthrough that will change the world for the better. They hope that, thanks to this technology, cancer and Alzheimer’s can be cured and humanity conquered hunger. For the others, however, a nightmare becomes true: that man now has the “tool of God” with which he can tamper with the genes of man, animal and plant as he likes.
From a biological point of view, CRISPR-Cas9 is a molecular system. It was discovered for the first time in bacteria and works like a pair of scissors: with the help of a molecule, a specific section of the genetic material is targeted in the cell. The Cas9 enzyme cuts the DNA strand apart so that the gene at this point can be replaced by a new sequence. Then the strand closes again – and the gene is either repaired or completely changed.
CRISPR is far superior to all previous genetic engineering. In the pre-CRISPR era, anyone who wanted to breed a red mouse had to invest months of work and thousands of dollars. Today a basic knowledge of molecular biology and $ 200 is enough. For the “Jugend forscht” competition, students at the Albert Schweitzer High School in Erfurt recently switched off a certain gene in the Capsella rubella plant. The herb then sprouted several flowers instead of one.
This genome editing, the editing of genes, still only takes place in the laboratory. But a race has long since begun that is not about fame as a researcher, but about big money. A handful of start-ups like Caribou, but also global corporations like Du-Pont, Bayer and Novartis take part in this race. They are fighting for patent rights, and they all want to commercially exploit the technology that almost no one had heard of six years ago: bringing drugs onto the market or new types of seeds.
“We are convinced that genetic engineering will revolutionize all markets for biotech products. Simply everything from therapeutics to agriculture to industrial biotechnology and basic research, ”says Haurwitz. In 2011, the then 25-year-old was Caribou’s first employee. The cell biologist is currently writing her doctoral thesis with Jennifer Doudna, who, along with the French Emmanuelle Charpentier, is considered to be the discoverer of the CRISPR-Cas9 method – a breakthrough that could bring the two women the Nobel Prize.
“I finished my doctoral thesis pretty quickly and plunged into building up Caribou – a seamless transition from doctoral student to CEO,” says Haurwitz, who wears a relaxed smile with jeans and a cardigan. The company started in the incubator at Berkeley University, in the basement of the building that also houses Doudna’s laboratory. The Californian sun floods through the skylights at the company’s headquarters; scientists only work in neon light in the 1,500 square meter laboratory.
The race for patents and licenses is in full swing
The boss herself can no longer be found in a white coat. The petite woman with porcelain skin and long, brown hair is the polished entrepreneur who negotiates with cooperation partners and investors on an equal footing. Caribou has raised over 40 million dollars – effortlessly. Venture capital investors have given money, as have the pharmaceutical company Novartis and the agricultural giant DuPont. Caribou has also signed an agreement with the seed manufacturer for the mutual use of their CRISPR licenses. The dwarf from California and the giant from the east coast brought together “mutual friends in scientific circles,” says Haurwitz. “We were interested in DuPont’s intellectual property. And vice versa.”
In fact, DuPont Pioneer has announced that it will be bringing CRISPR-modified waxy maize onto the market in five years. First field tests have already been carried out, according to the group. Waxy maize is used to produce high-quality starch products. But because the previous breeds come from a very old variety, the harvest yield is comparatively low. CRISPR will remedy this shortcoming, Pioneer is convinced of that. And then you want to optimize other food crops: immunize soy and wheat against pests or drought.
The agricultural corporations are particularly fascinated by the fact that, unlike other techniques, the intervention using CRISPR does not leave any traces. As long as no foreign varieties are combined, it can hardly be proven whether it is a natural mutation or genetic engineering was at work. The US Department of Agriculture has already decided that Pioneer’s CRISPR corn is not a genetically modified organism – and therefore does not fall under the strict GMO regulation. The Federal Office for Consumer Protection and Food Safety sees it the same way. Now the ECJ was asked about such plant genetic genome editing.
Like traditional breeding, but in turbo mode
Haurwitz is convinced that CRISPR will plow up agriculture. Because of the high requirements and costs, “Biotechnology 1.0” essentially only applied to maize, soy and a few other crops. With CRISPR you can achieve the same results as with traditional breeding, but in turbo mode. For many plants, she believes the development process could be shortened by several years. That would be a “huge gain” for humanity, she thinks. “The world population is growing rapidly and we have to increase food production dramatically.”
But many gene critics are alarmed. Yinong Yang from Pennsylvania State University has already felt the fear of “Frankenfood”. The professor at the Institute for Plant Diseases and Microbiology has succeeded in using CRISPR to switch off a gene that quickly turns white mushrooms brown after cutting. His research project was inspired by the head of the mushroom manufacturer Giorgio Mushroom Company, who donates 100,000 dollars to the university every year. After much public excitement, the mushroom could end up as the first CRISPR product in the supermarket. “We have to optimize the product further,” explains Yang cautiously. “We also have to evaluate public opinion and the business model.”
At least in this respect, “red genetic engineering”, medicine, has it easier. “If a baby would definitely die in five years from a genetic heart disease, then in my opinion it is a real option to try something new,” says Axel Bouchon. Of course, one also wants to ensure “the greatest possible security of the method”.
Bayer wants to bring Crispr from the laboratory to the medicine cabinet
Bouchon is supposed to bring CRISPR from the laboratories to the medicine cabinets for the German Bayer Group. At the beginning of 2015, shortly after Bayer had extensively celebrated its 150th anniversary, the then CEO Marijn Dekkers, his future successor Werner Baumann and Chief Innovation Officer Kemal Malik got together and drafted a master plan: What had to happen in order for the traditional company to remain at the top of the world in the future would play along? The result was the selection of ten “moonshots” that would fundamentally change the world – and Bouchon’s appointment as head of the new Bayer Lifescience Center.
“We said we definitely need DNA editing, preferably CRISPR,” says Bouchon, who is now head of the Leaps innovation initiative. After ten years at Bayer, the doctor of biochemistry moved to the Boston biotech scene, where everything “runs considerably faster”. But then he got fascinated by the “slightly crazy” idea of the Moonshots and came back. Bouchon tried CRISPR-Cas9 for the first time four years ago. “This is just amazing. It’s like a protein robot with a GPS system. Ideally, it finds the flaw in the DNA, cuts it out, reassembles the strands and disappears. “
Healing instead of treating
Bayer’s problem: Anyone can research with CRISPR, but three small start-ups hold the basic patents: Caribou and its spin-off Intellia Therapeutics, which has allied itself with Novartis. Editas, the company of scientist Feng Zhang and his Broad Institute at Harvard and MIT Universities. And CRISPR Therapeutics, where Emmanuelle Charpentier contributed her intellectual property.
Bayer has teamed up with CRISPR Therapeutics – and it wasn’t that the start-up was the petitioner. The Leverkusen company was awarded the contract not because of its investment commitment of 335 million dollars, but because of its experience with molecules. The joint venture aims to conquer three therapeutic areas: blood diseases, blindness and hereditary heart defects. All areas in which doctors are pretty helpless today. “What can you really heal completely today?” Asks Bouchon. “Infectious diseases and a few other diseases.”
All future profits of the joint venture will be shared. Charpentier’s company alone is allowed to use whatever knowledge emerges for other disease areas. What is wasted in the agricultural sector belongs to Bayer. Bouchon is not afraid that the patent disputes, which have already cost the parties 20 million dollars to date, could thwart his plans. “In the past, disputes like this were usually resolved in the end.”
But they are not the only ones who want to capitalize on CRISPR. According to a September 2015 study by the Boston Consulting Group (BCG), genome editing technologies have invested $ 1 billion in genome editing technologies within two years. The University of Pennsylvania has already received the green light for a first human trial. Immune cells are to be removed from cancer patients and these are genetically upgraded so that they attack and destroy cancer cells back in the body. The study is funded by the billionaire Sean Parker, the first president of Facebook. But the Americans could possibly be overtaken by the competition in China, where a similar study is running.
Bouchon knows he won’t be the first. But Bayer wants the big hit: the repair of cells in humans. Because, unlike blood cells, heart or lung cells cannot simply be removed from the body, repaired and reused. “We want to take the next step: give a syringe or an infusion, and that would be done.” What sounds like a long way off, is initially a five-year plan. “We definitely want to have three patient studies running by then,” says Bouchon.
About licenses and bioethical challenges
But isn’t CRISPR too much of a feasibility? The specter of designer babies is already haunting. Because Great Britain has approved an experiment in which the genome of human embryos is changed. In China, too, attempts have been made on – non-viable – embryos.
Bouchon sees no medical need for interventions in the germline – that is, in the genetic make-up that is passed on to the descendants – neither now nor in the future. Because an inherited disease can be repaired in the tissue cells. He still considers the ethical debate to be necessary. With every new technology, its justification, effects, side effects and goals must be discussed. “Otherwise we run the risk of reducing the potential of this technology to craziness like changing a child’s hair color. And forget about the great, positive potential for terminally ill people. “
But even if human design repair is an unlikely vision, it has long been a reality with animals. Caribou has licensed its CRISPR-Cas9 technology to the UK biotech company Genus, the world’s largest cattle breeder. First goal: to give pigs resistance to PRRS, a disease that affects growth and reproduction.
Elsewhere work is being done to make pigs fatter with less food. Brazilian cattle are said to develop stronger muscles and put more meat on the plate. Cashmere goats are said to grow longer fur. The Chinese company BGI has announced that it will sell colorful “micro pigs” the size of a beer mug. In the “American Journal of Bioethics” two very serious authors sketched that CRISPR could also create a kind of dragon.
Caribou has nothing in mind with such “Jurassic Park” gimmicks. At first, the company boss Haurwitz said that the focus was not on products, but on the basic technology. That didn’t detract from the company’s value. There are several offers to buy, she says. “So far, however, there has not been anything that we have taken seriously.” An IPO is also conceivable.
For Haurwitz, the Californian dream should come true. From student to millionaire in just a few years. “CRISPR technology has a great future,” she says soberly.
The article was published in Personal-Financial.com 10/2016. Are you interested in capital? Click here to go to the subscription shop, where you can order the print edition. Our digital edition is available from iTunes and GooglePlay