CRISPR-based cures will soon help combat all kinds of disease, from UTIs to leukemia. But terrifying implications of gene editing are abound as well
Nobel Prizes in the sciences are generally awarded after a few decades of meticulous research. Indeed, usually, many years are required for the greatness of a scientific discovery, its contribution to humanity and its positive implications for the realm of science, to be grasped. But in the case of Jennifer Doudna and Emmanuelle Charpentier, the Nobel arrived with record speed: Their groundbreaking study was published in the journal Science in 2012, and last year the Nobel Committee for Chemistry deemed them worthy of the prestigious award.
Anyone who has in recent years visited a laboratory where research is conducted in the life sciences will know the reason for the panel’s decision. The mechanism the two scientists developed – known as CRISPR – is used in almost every experiment in biology, whether it deals with human beings, animals, plants or microorganisms. Since 2012, the number of studies using the technology has doubled every year; by now it has been cited in more than 485,000 scientific articles and in more than 1,000 patents.
What is CRISPR? If DNA is comprised of “letters” (nucleotides), which together form “words” (genes), which constitute the instruction manual for the production of proteins that are responsible for all our bodily actions – what Doudna and Charpentier have offered the world are the function keys for DNA cut-and-paste. That is, using CRISPR technology, scientists can easily cut out whatever specific DNA segment they want, and then allow the genome to repair the missing segment by itself or to replace it with the desired segment.
The two scientists – Doudna from the University of California, Berkeley, and Charpentier, who heads Berlin’s Max Planck Unit for the Science of Pathogens – had already appeared on Time magazine’s list of 100 most influential people in 2016. The press release for the 2020 Nobel Prize in Chemistry stated that they were being given the award for discovering “a tool for rewriting the code of life.” The journal Nature described the result of their research as a discovery that changes the rules of science.
It was obvious from the start that the new technology was bursting with potential – and a decade later it’s also obvious that its immense potential is being realized. “It’s no longer fantasy, but reality,” Doudna, 57, tells Haaretz in the first interview she has given to an Israeli media outlet since being awarded the Nobel. “CRISPR is already curing many diseases. There are numerous clinical experiments that are making use of CRISPR, and soon some of them will become part of the medical possibilities that are available to every person. It is very exciting.”
Indeed, a series of studies in this realm around the world are now entering the final stretch. CRISPR-based cures will soon be available to help combat diseases that affect millions of people everywhere: from urinary tract inflammations, muscular dystrophy, genetic blindness and immune system failure, to AIDS and leukemia.
But curing diseases is only one side of CRISPR. Using the technology of gene editing, scientists have also succeeded in eradicating mosquitoes that spread malaria, dealing with the resistance of certain types of bacteria to antibiotics, diagnosing diseases, creating test kits for COVID, producing an improved type of biological fuel and even advancing the idea of implanting organs from pigs in humans.
And even that is only part of the big picture. “In agriculture, too, a wonderful opportunity exists to use this technology to change one gene or more in plants,” Doudna says. “Changes can be made that will lead to plants’ resistance to aridity, to increase crop yields and to help cope with the challenges of global warming. From the perspective of agriculture, this technology arrived at the right time.”
These opportunities are already being realized by researchers worldwide, including in Israel. CRISPR is making it possible for scientists to transform wildflowers into fruit-yielding plants, to bolster the resistance of field crops to diseases and pests, to grow potatoes that contain more starch, even to help purple flowers morph into white ones. On top of this, local researchers are using the technology to prevent chickens from laying eggs containing male chicks, to breed healthier sheep and to increase the amount of protein in fish.
All of these scientific achievements, some of which were until recently in the realm of science fiction, are opening up more and more paths for research, which are in turn growing ever more ramified. Along the way it turns out that it’s necessary to trod on some of these paths with extreme caution; in some cases it seems that some are actually best left untrod.
“The co-discovery of CRISPR came from curiosity-driven science,” notes Doudna, who is naturally aware of the serious moral issues that have arisen in the wake of the technology, particularly in regard to the possibility of editing the human genome. “Deeper into our team’s research, we realized the amazing programmability of CRISPR and its potential as a genome-editing tool. It was then that I started to consider the ethical implications of the technology more deeply.”
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats – a long name for the sections of DNA in bacteria that protect them against viruses. Doudna and Charpentier succeeded in harnessing the mechanisms used by the pieces of bacteria to enable gene editing of any organism that possesses a genome – i.e., a genetic set of instructions. The two scientists didn’t discover CRISPR itself, but rendered the whole complex genetic system more effective and comprised of just two components: RNA and the Cas9 protein. In their famous 2012 article in Science, they explained how they programmed the DNA cutting mechanism in unicellular bacteria called Streptococcus pyogenes, to make it capable of excising any kind of DNA in the world, and thereby create genuine “genetic scissors.” They also showed how to use RNA to insert a desirable genetic piece in place of the one that was edited out of the DNA.
In one fell swoop their innovation rendered an entire technology simple, cheap and accessible. There are now dozens of biotech companies worldwide that sell CRISPR technology to laboratories. All that’s needed is to determine which genes are to be removed and which are to be inserted in their place; you can even order a CRISPR kit online. The cost ranges from a few hundred to a few thousand dollars, depending on the complexity of the procedure involved.
A simple example of how “CRISPR changed all the rules of science” is a new treatment for two hereditary diseases that are each caused by one flawed gene. The first, thalassemia, which causes a drop in the production of hemoglobin, compels the 280 million people who suffer from the disease to receive blood transfusions throughout their lives. The second, sickle cell anemia, which affects approximately 4.5 million people, causes the red blood vessels to take the shape of a sickle instead of a round platelet, so it becomes difficult for them to carry oxygen to the various parts of the body.
In 2019, the American firm Vertex – one of the world’s 15 leading pharma companies – started to develop CRISPR-based medications for the two diseases. Just two-and-a-half years later, the medications were proved successful in clinical trials and are now in the process of being approved. “The causes of both diseases have been known for decades. With the discovery of tools such as CRISPR gene editing, we now potentially have an opportunity to address diseases at their root cause,” Rob Clark, communications director at Vertex, tells Haaretz.
“These are lifelong diseases that have a significant impact on peoples’ daily lives and consume substantial health-care resources. We are investigating the use of gene-editing technology to see if we can discover and develop a one-time potential treatment” for both diseases, Clark says. He explains that blood is collected from patients, and then, using CRISPR, the genes in the blood stem cells are edited – i.e., the flawed genes are cut away and replaced, “before being reinfused back into the patient as part of a standard bone marrow transplant.”
Deeper into our research, we realized the amazing programmability of CRISPR and its potential as a genome-editing tool. It was then that I started to consider the ethical implications of the technology more deeply.
The 15 participants in the thalassemia clinical trial are now “transfusion independent,” Clark notes, while those who took part in the sickle cell disease trial “are free of vaso-occlusive crises – namely, severe pain events caused by blockages of blood vessels.” He admits that it’s premature to talk about the future cost of such treatments and how accessible they will be, but if the procedures are adopted by public health systems, they could be made available in every hospital in the world. Adds Clark: “It is imperative that the appropriate health-care infrastructure is in place in countries to allow for access to gene-editing technologies.”
CRISPR-based treatments are currently also leading to breakthroughs in cancer medication. Last year findings were published following the first clinical trial in this field that involved CRISPR-based treatment. In the study, which was aimed at inhibiting the development of lung cancer and was conducted at Sichuan University, China, a dozen patients were injected with immune cells that had undergone gene editing, which enabled them to combat cancerous cells. The findings, which were published in the journal Nature Medicine, showed that in 11 of the 12 patients, the altered blood cells were still in evidence two months after the transfusion. The higher their proportion in the blood, the bigger the reduction in cancer cells.
Similar clinical trials were carried out at the University of Pennsylvania on 18 individuals suffering from different types of blood cancer – and the treatment has so far been deemed successful. Closer to home, the Laboratory of Precision NanoMedicine at Tel Aviv University, under the direction of Dan Peer, is also working on developing a cure for certain types of cancer by using gene editing technology. Here the system is different: Prof. Peer carries out gene editing in the cancerous cells themselves – not of the immune system that is geared to fight them. He has for the first time succeeded in halting the development of cancer in cells with the aid of CRISPR, and says clinical trials using his method are set to begin next year.
“It’s complicated to cure cancer by means of CRISPR, because multiple genes cause cancerous tumors. So even if you remove one gene, there are others that might be active,” Peer says. “Even so, we were the first to show that it is possible to execute gene editing of cancerous cells that affect an entire organism – in our case, a mouse. Today we are on the brink of the era of personalized medicine, and this is a key tool in that realm. An important opening has been created in the field of cancer medication.”
The same picture exists with respect to AIDS medicine. Recently an American pharmaceuticals company received FDA authorization to launch clinical trials for CRISPR-based treatment. Here the researchers draw blood from AIDS patients, edit the DNA of their immune system so that the HIV virus will not be able to attack, and then re-infuse the blood in the hope that the edited cells will grow and spread in the body.
Examples of other uses for gene editing abound. Clinical trials are expected to begin soon toward a cure of Duchenne muscular dystrophy, a severe disease that causes premature death. The scientists from Southwestern University, in Georgetown, Texas, who developed the treatment, have already used it successfully in dogs suffering from the disease. Similarly, Intellia Therapeutics, an American company that develops biopharmaceuticals using a CRISPR gene editing system and is proposing a host of creative applications for it, is currently launching clinical trials that focus on three heart and liver diseases that are caused by a genetic defect.
“I believe that in another few years we will be able to cure familiar diseases like diabetes or Parkinson’s,” John Leonard, Intellia’s CEO, tells Haaretz. “In these diseases, the trials are still at the stage of searching for the locations in the DNA which will undergo editing when the time comes.”
People suffering from what’s called severe combined immunodeficiency, or SCID, diseases – those once known as “bubble babies,” because they were compelled to live in an isolation bubble – may also find relief soon thanks to CRISPR technology. Dr. Ayal Hendel, from the Genome Editing and Gene Therapy Laboratory at Bar-Ilan University, and Prof. Raz Somech, director of the Pediatric Immunology Unit of Sheba Medical Center, Tel Hashomer, are co-researching a cure for SCID by means of CRISPR, and are on the brink of clinical trials. “We cut away the flawed gene and replace it with a segment of standard DNA,” Hendel explains, adding that the treatment being developed will be administered by means of a regular bone marrow transplant.
There are also diseases that are less complex but more widespread, that may be treatable by way of CRISPR. One example is inflammation of the urinary tract, which affects more than half the women in the world. Urinary tract infection, caused by harmful bacteria, is usually treated with antibiotics. But the American pharma company Locus Biosciences recently developed a new technology: The company’s scientists manufactured a “cocktail” of three viruses that attack UTI bacteria (bacteriophages) and carried out genetic alterations of certain sections of the viral DNA, as a result of which they then attacked the strains of bacteria responsible for the overwhelming majority of these infections. The clinical trials, conducted last February, were successful and produced no side effects.
Developments of this sort are of significance not only in curing diseases that degrade the quality of life of billions of people around the world, but in helping to counter one of the major medical challenges of our time: the high resistance of bacteria to antibiotics.
CRISPR’s applications in the realm of medicine are not confined to treatment of disease. One of the most talked-about uses of the technology is related to the effort to develop organ transplants for humans from pigs. A significant challenge here is the danger that the recipients will be infected by viruses that originate in swine. Scientists in the labs of the eGenesis company, founded by the well-known geneticist from Harvard Medical School, Prof. George Church, have already succeeded in breeding dozens of pigs that are resistant to those viruses, by genetically altering their DNA with CRISPR technology. In addition, the company is working on solutions to prevent the rejection of the implanted organs.
The technology can also be used to prevent diseases – for example, malaria. Researchers from Imperial College London were able to edit the DNA of malaria-transmitting mosquitoes, to prevent the females from laying eggs. Indeed, the mosquito population that was used in the anti-reproduction experiment became extinct within eight generations. The system of propagating an engineered gene among an entire population is known as “gene drive,” and is executed with extreme caution, out of fear that the alteration will undergo unintended mutation and impart a new and undesirable trait to that population. In the Imperial College malaria study, it emerged that the gene drive transmitted a desired trait (sterility) in 100 percent of the cases. Nevertheless, the tool has not yet been approved for use outside the lab.
We are on the brink of the era of personalized medicine, and this is a key tool in that realm. An important opening has been created in the field of cancer medication.
CRISPR is also rapidly dominating the realm of diagnostics. How does this work? CRISPR identifies the DNA segment of a particular virus or bacterium, excises it and replaces it with a section that lights up or assumes a specific color, in special diagnostic kits. If the test produces the light or color, that means there is an infection of the same bacterium or virus; if the original color remains unchanged, there is no infection. These kits, which are usually cheap and easy to use, are becoming common in hospitals, clinics and also for use at home.
The most familiar example of this are the home kits that test for COVID-19, which work according to the same principle. In Prof. Doudna’s lab in Berkeley, for example, researchers were able to manufacture a swab test for coronavirus detection that provides results in 20 minutes. These kits are not yet being marketed in Israel but have been approved for use by the FDA and will likely be in use worldwide soon.
David (Dudu) Burstein completed his postdoc in Doudna’s lab three years ago and is now a researcher in the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University. At Berkeley, he looked for new CRISPR systems, which originate from viruses that are different from those studied by Doudna and Charpentier.
“The Cas9 protein for cutting DNA, which Jennifer and Emmanuelle discovered, is the most familiar and is considered one of the most efficient enzymes discovered to date,” Dr. Burstein says. “But there are other Cas proteins that possess different traits – some are smaller, for example – which are capable of executing actions that are sometimes more precise.”
Burstein has published two articles about the Cas proteins he’s found, in Nature and in Science. He is currently working with Cas12 proteins in developing viral and bacterial diagnostic kits, in cooperation with Dr. Gur Pines from the Volcani Center, an agricultural research organization in Rishon Letzion, and he is also examining whether it is possible to use CRISPR-based diagnostic kits in space. Eytan Stibbe, who is slated to become the second Israeli astronaut, will take with him to the international space station two such kits and will examine the way they function.
“When you’re in space, you don’t want to have to resort to clumsy instruments that require expertise to operate. The kit we are checking is a small one that offers easy and fast diagnostics for identifying the substances that cause disease. That will make it possible for astronauts to know whether they have an intestinal bacterium, or whether their stomach is just trying to adjust to the lack of gravity,” Burstein says.
The Journal of Food Science chose in 2015 to devote its gala 75th anniversary issue to CRISPR and to the future promise the technology holds for the realm of food. In an article titled “CRISPR-Based Technologies and the Future of Food Science,” Kurt Selle and Rodolphe Barrangou, both of North Carolina State University, note that although the “ongoing CRISPR craze” is focused on the “high potential” for medicine, “CRISPR-based applications are now poised to revolutionize many fields within food science, from farm to fork.”
Researchers of agriculture are especially fond of CRISPR, because it is not considered a technology involving genetic engineering – rather gene editing. In genetic engineering, a stretch of DNA from a foreign organism is inserted into the desired organism – for example, DNA of locust-resistant bacteria is merged with corn DNA. In contrast, in gene editing, DNA of a plant or animal is only cut away, without foreign DNA being inserted in its place.
The first commercial edible product to undergo gene editing came on the market in the United States in 2018. It’s a soybean cooking oil called Calyno, created from beans genetically edited to give them a reduced amount of unhealthy trans fat. According to Wired magazine, Calyxt, the company that manufactures Calyno, “describes its oil as having the heart-healthy fat profile of olive oil without its strong, sometimes grassy flavor.” The product isn’t yet being marketed in supermarkets, being sold only to a few American food chains and restaurants. Still, this marks an important moment in agricultural history – the onset of an era of gene-edited foods that have undergone changes not only to make life easier for farmers but also to make life healthier for consumers.
In Israel, too, which is in the forefront of agricultural research and development, CRISPR has made its debut with a fanfare. Last year a national center for genome editing in agriculture was established: an umbrella organization encompassing about 30 groups of researchers from six different institutions. Its goal, according to Dr. Amir Sherman from the Volcani Center, who is coordinating the organization’s activities, is “to create agricultural products based on genomic editing and to establish scientific infrastructure in this field.” In the meantime, various crops are being examined within this framework, including wheat, barley, apples, squashes, melons, cucumbers, watermelons, peppers, potatoes – as well as fish, sheep and chickens.
“Several research groups are working with fish, so that the length of time they spend in the breeding pond can be shortened to yield the same amount of protein,” Sherman relates. In another project, a group of researchers succeeded in breeding St. Peter’s fish without their typical black stripes, which might prove popular in the Asian market, where there is a preference for reddish fish. As for the sheep project, a system of genomic editing is being developed with the aim of improving the health and reproduction of ewes; researchers are also currently experimenting with CRISPR technology to perform in-vitro fertilization of sheep embryos. The technology is also being used to improve the shelf life of potatoes and to create resistance to disease in squashes and nightshades. Several research groups are developing ornamental plants, such as chrysanthemums, that are not affected by the amount of daylight they’re exposed to. Another group is engaged in creating vines that can be grown in a hothouse.”
Two research groups are working on genomic editing of tomatoes. One, from the Hebrew University of Jerusalem, is aiming to intensify the plant’s red color, while the other, from the Volcani Center, aims to improve the tomato plant’s resistance to disease. That group is led by Maya Bar, head of the laboratory for plant pathology and weed research in the center’s plant protection unit.
“We are working on a number of projects that will make tomatoes more resistant,” Dr. Bar relates. “One project is being carried out in cooperation with Tel Aviv University, where it was discovered by chance that a particular form of gene editing renders tomatoes resistant to fungi, bacteria and also to certain pests, such as moths. This intervention is already in the process of being licensed, in the hope that it can soon be marketed and farmers will be able to buy the new seeds. In another project we actually increased the tomato’s ability to bind with a positive fungus that protects it against diseases and pests, which allows for more efficient biological pest control and reduction of chemical pest control measures. Here we are in the process of registering a patent.”
Gene editing is also taking place in the realm of ornamental plants. Research is underway in Israel to determine whether CRISPR technology can be used to step up the rate of growth and to enhance the pleasant scent of petunias and chrysanthemums. In Japan, too, labs are working intensively in this area. One of them, from the University of Tsubuka, succeeded in editing a gene in the morning glory plant so that its flowers’ petals are white instead of purple.
Work is underway at Tel Aviv University on a CRISPR intervention that sounds quite dramatic, to solve one of the major problems in agriculture: the unnecessary killing of farm animals of the undesirable gender. The scientists involved – Profs. Udi Qimron, Ariel Munitz and Moti Gerlitz, and Dr. Ido Yosef – have used gene editing successfully on mice DNA. They used the process on the Y chromosome found in male mice, so that immediately after fertilization, embryos containing it would not develop. Thus, only an encounter between two X chromosomes can produce a mouse, and it can only be a female.
The researchers are moving on to poultry, specifically to layers of eggs, and to large mammals in the agriculture industry. The egg industry relies solely on female chicks: Male chicks are typically fed into grinders upon hatching. Indeed many millions of live male chicks are disposed of around the world in this horrifying way every year. The dairy industry, for its part, also needs only female calves, so millions of males considered to have no economic value are annually slaughtered at a young age.
Efforts to alter the DNA of animals have achieved their goal in many cases, but have also produced quite a few surprises and unexpected side effects. In one case, researchers in China tried to reduce fat in rabbits – and along the way caused the animals’ tongues to become exceptionally long. When they tried the procedure on pigs, it led to the emergence of an unnecessary vertebra in their spines.
In general, as a Wall Street Journal survey of the subject showed, the larger the animal, the more complications that ensue. When researchers in New Zealand tried to bring about a minor genetic change so as to lighten the pigment of cows’ hides so they would suffer less from the sun’s heat – the newborn calves did not survive. In another case, an American company created a herd of hornless beef cattle. The animals became celebrities and were even featured on magazine covers, but then it turned out that they now carried genes that strengthened their resistance to antibiotics.
These examples provide graphic illustrations of the potential threat posed by CRISPR – and the deep fear that accompanies it. We don’t really know what the far-reaching effects could be of seemingly small genetic changes. In addition, the tool in question is so efficient that almost anything can be done with it, including rather grotesque things. At the end of 2015, for example, Chinese scientists showed that they had succeeded in altering embryos of beagles so that the dogs’ muscle mass would double. The goal was to make them more effective for police and army missions.
Efforts to alter animal DNA have produced surprises. In one case, researchers in China tried to reduce fat in rabbits – and along the way caused the animals’ tongues to become exceptionally long.
The possible dilemmas become especially acute, of course, when we come to editing human DNA. Theoretically, CRISPR technology could be used to influence human traits caused by particular segments of DNA: for example, to help develop certain physiological traits in embryos or to produce enhanced capabilities such as enhanced physical strength, improved stamina after limited hours of sleep or heightened powers of vision.
“It is not out of the question that in the future we will find the genes that cause attention deficit disorder,” Aaron Ciechanover, a Nobel laureate in chemistry from the Technion – Israel Institute of Technology, tells Haaretz. “Would you want to edit out these genes in your next pregnancy? The technology will easily make it possible to have children according to choice: height, talent, hair color, eyes and so forth. It can’t be ruled out that in the future a country that does not adhere to the ethical discipline of the rest of the world – North Korea, for example – will create embryos that are resistant to chemical and biological weapons, and will thus forge a generation of ‘enhanced’ soldiers.”
Scientists and other professionals across the planet are actively weighing in, in the moral debate over the use of CRISPR technology. In fact, Doudna and Charpentier have established an international consortium of scientists, jurists, philosophers and politicians that meets every few years in order to discuss where the red line should lie in gene editing, particularly in human beings. An international conference on the subject is scheduled to be held in London next March.
The topic is being discussed in Israel as well. At a conference on bioethical challenges, organized jointly last month by the Van Leer Jerusalem Institute and Bashaar – Academic Community for Israeli Society, one session was devoted to the topic “Gene editing: Are the good and the bad separable?” The speakers, in English, via a video conference, were Profs. Doudna and Ciechanover.
What ethical boundaries should be set for CRISPR, Ciechanover asked his colleague. “When CRISPR is used to treat or cure a patient who is suffering from a disease like sickle cell disease, that treatment affects only that individual,” Doudna noted. “It’s not a change to DNA that is creating heritable alterations that can be passed to future generations. The difference is in using CRISPR in what’s called the ‘germ line’ – in embryos, eggs or sperm, that create heritable changes to DNA, meaning that those changes are passed on to future generations.” She added that this dilemma surfaced from the outset, and that as early as 2015 a conference was held in California to consider possible germ line editing. “Could it happen? We agreed that yes, it could. Should it happen? We agreed that probably not, right now.”
Ciechanover basically agreed with Doudna about the need to ensure responsible use of CRISPR, though he also noted that “putting limitations [on the use of the technology] might also affect the quality of research. So we should be very careful about what we are doing, because we might obliterate the expansion of knowledge and the acquisition of new knowledge.” Now it was Doudna’s turn to agree that scientific progress should be encouraged, but that it needs to be “responsible progress.”
In many countries, including Israel, the law forbids genetic intervention, human cloning or genetic alteration of reproductive cells. With regard to experiments on embryos, the scientific community agrees that they are permitted only up to 14 days after conception, because after that the embryo’s nervous system starts to develop. Even so, the temptation to carry out human genome editing is great, as Doudna and Charpentier saw in November 2018 at an international conference on gene editing, in Hong Kong. To the astonishment of the participants, He Jiankui, a genome-editing researcher at the Southern University of Science and Technology of China in Shenzhen, announced that he had succeeded, with the use of CRISPR technology, in editing the genome of Chinese twins, Lulu and Nana, so that one of them was born immune to infection by the HIV virus.
Jiankui related that he had disabled the CCR5 gene, which is responsible for producing the protein by means of which HIV penetrated the cell in fertilized eggs of seven sets of parents who had undergone fertility treatments. Lulu and Nana, he said, were the product of the only treatment that had resulted in a successful pregnancy. (Since then it has been discovered that a third infant was born after such experiments, but her fate is unknown.) The global scientific community immediately condemned Jiankui. The authorities in China also grasped the enormity of the drama and placed him on trial, resulting in a three-year prison term.
How could gene editing affect the fate of the twins in question? As Time magazine noted, CRISPR sometimes makes mistakes like a text feature on a computer that creates a completely new word. In other cases, it does not edit out the repaired sections methodically enough, with the result that some of the cell’s genes are edited while others are not. Experts who examined some of the evidence Jiankui presented thought that this was exactly the case with the twins: Not all the cells had undergone editing, so the procedure did not necessarily protect them against HIV. In addition, dispensing with the specific gene could have further consequences, such as making the girls more vulnerable to other diseases, including flu.
And let’s say that the two girls grow up healthy. What will happen when they will want to have children? Would they be given permission to give birth to infants who will inherit a genome that underwent editing?
“We know very little about the fate of those two girls right now,” Doudna said, in reply to a question from Ciechanover about the controversial procedure. “But it’s clear that the announcement sparked an international outcry in which scientists around the world said, ‘This should not be done, this is not right, we should not be using the technology in that fashion, at least not now.’”
Jiankiu is not the first or last person to edit DNA of human embryos, but as far as is known his altered embryos are the only ones to have been implanted in a woman’s womb. The other experiments done on embryos were always for research purposes only.
In fact, the first research study that involved genomic editing in embryos was conducted in China in 2015, when scientists succeeded in editing out the gene that causes thalassemia in embryos. Already then the researchers noted that their results “reveal serious obstacles to the use of the method in medical applications.”
In a 2020 article in the journal Cell, researchers from Columbia University showed what could go wrong in embryo editing. In an experiment conducted solely for research purposes, using exactly the same technique as Jiankui, it turned out that in half the cases the editing caused unintended changes, such as the loss of an entire chromosome. Doudna is well aware of these grim scenarios, as she noted in the conference last month. “There’s a saying that ‘you can’t put the genie back in the bottle’ – you can’t unlearn something once you’ve learned it. So I don’t think it’s realistic to think that we can unlearn how to do germ line editing with CRISPR, for example. But we can certainly encourage responsible use by parties who have access to it around the world.”
The Nobel Prize awarded to Doudna and Charpentier is precedent-setting in another way: It marks the first time women won the prize in a scientific category without sharing it with any male colleagues. In a short video documenting Doudna minutes after it was announced that she was a co-winner, she is told about this precedent and finds it hard to believe. “Really? Never? Never? Never?” she repeats with genuine amazement. Indeed, a look at the list of Nobel laureates in chemistry turns up 178 men, mainly white, and just seven women – one of whom is Israel’s Prof. Ada Yonath.
Doudna, who was born in Washington, D.C., and moved with her family to Hawaii at age 7, says she dreamed of becoming a biologist from a young age. In Hawaii, an exotic locale bursting with nature, she found herself, a curious child, asking many questions about her surroundings. Her father, an English literature teacher at the University of Hawaii, spotted his daughter’s passion and when she was 12 gave her the book “The Double Helix,” written by the discoverer of the structure of the genome, the Nobel laureate James Watson. From there she went on to study chemistry in high school, finished an undergraduate degree in biochemistry and completed her PhD at Harvard Medical School, under the tutelage of yet another Nobel laureate, the geneticist Jack Szostak.
“When I was growing up,” she tells Haaretz, “it was a woman scientist researching cancer who redefined my image of a scientist and inspired me to pursue my passion for chemistry, despite being discouraged from it by many others. We need to celebrate the contributions of women researchers, mathematicians, and engineers.”
Women, she adds, “are consistently making remarkable discoveries that will impact the future of our society. Science is better because of our diversity in background and perspective.”