Chinese scientists are creating CRISPR babies

A daring effort is under way to create the first children whose DNA has been tailored using gene editing.


When Chinese researchers first edited the genes of a human embryo in a lab dish in 2015, it sparked global outcry and pleas from scientists not to make a baby using the technology, at least for the present.

It was the invention of a powerful gene-editing tool, CRISPR, which is cheap and easy to deploy, that made the birth of humans genetically modified in an in vitro fertilization (IVF) center a theoretical possibility.

Now, it appears it may already be happening.

According to Chinese medical documents posted online this month (here and here), a team at the Southern University of Science and Technology, in Shenzhen, has been recruiting couples in an effort to create the first gene-edited babies. They planned to eliminate a gene called CCR5 in hopes of rendering the offspring resistant to HIV, smallpox, and cholera.

Photo of Jiankui He
He Jiankui leads a team using the gene-editing technology CRISPR in an effort to prevent disease in newborns.


The clinical trial documents describe a study in which CRISPR is employed to modify human embryos before they are transferred into women’s uteruses.

The scientist behind the effort, He Jiankui, did not reply to a list of questions about whether the undertaking had produced a live birth. Reached by telephone, he declined to comment.

However, data submitted as part of the trial listing shows that genetic tests have been carried out on fetuses as late as 24 weeks, or six months. It’s not known if those pregnancies were terminated, carried to term, or are ongoing.

[After this story was published, the Associated Press reported that according to He, one couple in the trial gave birth to twin girls this month, though the agency wasn’t able to confirm his claim independently. He also released a promotional video about his project.]

The birth of the first genetically tailored humans would be a stunning medical achievement, for both He and China. But it will prove controversial, too. Where some see a new form of medicine that eliminates genetic disease, others see a slippery slope to enhancements, designer babies, and a new form of eugenics. The step toward genetically tailored humans was undertaken in secrecy and with the clear ambition of a stunning medical first.

“In this ever more competitive global pursuit of applications for gene editing, we hope to be a stand-out,” He and his team wrote in an ethics statement they submitted last year. They predicted their innovation “will surpass” the invention of in vitro fertilization, whose developer was awarded a Nobel Prize in 2010.

Gene-editing summit

The claim that China has already made genetically altered humans comes just as the world’s leading experts are jetting into Hong Kong for the Second International Summit on Human Genome Editing.

The purpose of the international meeting is to help determine whether humans should begin to genetically modify themselves, and if so, how. That purpose now appears to have been preempted by the actions of He, an elite biologist recruited back to China from the US as part of its “Thousand Talents Plan.”

The technology is ethically charged because changes to an embryo would be inherited by future generations and could eventually affect the entire gene pool. “We have never done anything that will change the genes of the human race, and we have never done anything that will have effects that will go on through the generations,” David Baltimore, a biologist and former president of the California Institute of Technology, who chairs the international summit proceedings, said in a pre-recorded message ahead of the event, which begins Tuesday, November 27.

It appears the organizers of the summit were also kept in the dark about He’s plans.

Regret and concern

The genetic editing of a speck-size human embryo carries significant risks, including the risks of introducing unwanted mutations or yielding a baby whose body is composed of some edited and some unedited cells. Data on the Chinese trial site indicate that one of the fetuses is a “mosaic” of cells that had been edited in different ways.

A gene-editing scientist, Fyodor Urnov, associate director of the Altius Institute for Biomedical Sciences, a nonprofit in Seattle, reviewed the Chinese documents and said that, while incomplete, they do show that “this effort aims to produce a human” with altered genes.

Urnov called the undertaking cause for “regret and concern over the fact that gene editing—a powerful and useful technique—was put to use in a setting where it was unnecessary.” Indeed, studies are already under way to edit the same gene in the bodies of adults with HIV. “It is a hard-to-explain foray into human germ-line genetic engineering that may overshadow in the mind of the public a decade of progress in gene editing of adults and children to treat existing disease,” he says.

Big project

In a scientific presentation in 2017 at Cold Spring Harbor Laboratory, which is posted to YouTube, He described a very large series of preliminary experiments on mice, monkeys, and more than 300 human embryos. One risk of CRISPR is that it can introduce accidental or “off target” mutations. But He claimed he found few or no unwanted changes in the test embryos.

He is also the chairman and founder of a DNA sequencing company called Direct Genomics. A new breed of biotech companies could ultimately reap a windfall should the new methods of conferring health benefits on children be widely employed.

Photo of stage and audience at Human Gene Editing Summit
The first International Summit on Human Gene Editing, held in December 2015 in Washington, DC. The second is taking place in Hong Kong on November 27-29, 2018.


According to the clinical trial plan, genetic measurements would be carried out on embryos and would continue during pregnancy to check on the status of the fetuses. During his 2017 presentation, He acknowledged that if the first CRISPR baby were unhealthy, it could prove a disaster.

“We should do this slow and cautious, since a single case of failure could kill the whole field,” he said.

listing describing the study was posted in November, but other trial documents are dated as early as March of 2017. That was only a month after the National Academy of Sciences in the US gave guarded supportfor gene-edited babies, although only if they could be created safely and under strict oversight.

Currently, using a genetically engineered embryo to establish a pregnancy would be illegal in much of Europe and prohibited in the United States. It is also prohibited in China under a 2003 ministerial guidance to IVF clinics. It is not clear if He got special permission or disregarded the guidance, which may not have the force of law.

Public opinion

In recent weeks, He has begun an active outreach campaign, speaking to ethics advisors, commissioning an opinion poll in China, and hiring an American public-relations professional, Ryan Ferrell.

“My sense is that the groundwork for future self-justification is getting laid,” says Benjamin Hurlbut, a bioethicist from Arizona State University who will attend the Hong Kong summit.

The new opinion poll, which was carried out by Sun Yat-Sen University, found wide support for gene editing among the sampled 4,700 Chinese, including a group of respondents who were HIV positive. More than 60% favored legalizing edited children if the objective was to treat or prevent disease. (Polls by the Pew Research Center have found similar levels support in the US for gene editing.)

He’s choice to edit the gene called CCR5 could prove controversial as well. People without working copies of the gene are believed to be immune or highly resistant to infection by HIV. In order to mimic the same result in embryos, however, He’s team has been using CRISPR to mutate otherwise normal embryos to damage the CCR5 gene.

The attempt to create children protected from HIV also falls into an ethical gray zone between treatment and enhancement. That is because the procedure does not appear to cure any disease or disorder in the embryo, but instead attempts to create a health advantage, much as a vaccine protects against chicken pox.

For the HIV study, doctors and AIDS groups recruited Chinese couples in which the man was HIV positive. The infection has been a growing problem in China.

So far, experts have mostly agreed that gene editing shouldn’t be used to make “designer babies” whose physical looks or personality has been changed.

He appeared to anticipate the concerns his study could provoke. “I support gene editing for the treatment and prevention of disease,” He posted in November to the social media site WeChat, “but not for enhancement or improving I.Q., which is not beneficial to society.”

Still, removing the CCR5 gene to create HIV resistance may not present a particularly strong reason to alter a baby’s heredity. There are easier, less expensive ways to prevent HIV infection. Also, editing embryos during an IVF procedure would be costly, high-tech, and likely to remain inaccessible in many poor regions of the world where HIV is rampant.

A person who knows He said his scientific ambitions appear to be in line with prevailing social attitudes in China, including the idea that the larger communal good transcends individual ethics and even international guidelines.

Behind the Chinese trial also lies some bold thinking about how evolution can be shaped by science. While the natural mutation that disables CCR5 is relatively common in parts of Northern Europe, it is not found in China. The distribution of the genetic trait around the world—in some populations but not in others—highlights how genetic engineering might be used to pick the most useful inventions discovered by evolution over the eons in different locations and bring them together in tomorrow’s children.

Such thinking could, in the future, yield people who have only the luckiest genes and never suffer Alzheimer’s, heart disease, or certain infections.

The text of an academic website that He maintains shows that he sees the technology in the same historic, and transformative, terms. “For billions of years, life progressed according to Darwin’s theory of evolution,” it states. More recently, industrialization has changed the environment in radical ways posing a “great challenge” that humanity can meet with “powerful tools to control evolution.”

It concludes: “By correcting the disease genes … we human[s] can better live in the fast-changing environment.”

Note: This story was updated after publication to include claims by He Jiankui that the trial had produced live births.

Cel- en gentherapie in opkomst maar toepassing kent belemmeringen – ZonMw

De komende jaren komen voor verschillende vormen van kanker en andere ernstige ziekten behandelingen met celtherapie en gentherapie beschikbaar.

Met deze zogenoemde advanced therapy medicinal products (ATMP’s) kunnen bijvoorbeeld afweercellen van de patiënt worden bewerkt om een tumor te herkennen en uit te schakelen. Een andere veelbelovende ontwikkeling is gentherapie voor zeldzame aandoeningen als hemofilie B. Deze ziekte is met gentherapie mogelijk te genezen. Dit blijkt uit een verkenning van de ontwikkelingen van ATMP’s die het RIVM in opdracht van het ministerie van VWS heeft uitgevoerd.

De meeste ATMP’s zijn bedoeld om ernstige, vaak zeldzame aandoeningen te behandelen. Ze kunnen levensverlengend, soms zelfs genezend zijn, of de kwaliteit van leven sterk verbeteren. Ondanks de ontwikkelingen van de afgelopen 20 jaren zijn de hoge verwachtingen nog niet uitgekomen. Wel blijft de techniek hoopgevend en worden er tussen 5 en 10 jaar nieuwe producten verwacht.

Eigenschappen toegevoegd

In algemene zin wordt er bij ATMP’s een (bijvoorbeeld ontbrekende) eigenschap aan cellen toegevoegd die bepaalde processen in het lichaam in gang zet. Zo kunnen bijvoorbeeld kankercellen worden uitgeschakeld of een stollingsfactor worden gemaakt. In Nederland wordt veel onderzoek met ATMP’s bij patiënten gedaan en stijgt het aantal studies met ATMP’s die in een vergevorderde ontwikkelingsfase zijn.


De onderzoekers constateren belemmeringen die een succesvolle behandeling met ATMP’s vooralsnog in de weg staan. Zo zijn ATMP’s moeilijk in te passen in de huidige wetgeving voor markttoelating van geneesmiddelen. Andere belemmerende factoren zijn financiering (de ontwikkeling van ATMP’s is kostbaar)en de maatschappelijke druk om ATMP’s al beschikbaar te maken voor patiënten zonder dat het werkingsmechanisme goed bekend is.

Meer informatie

  • u kunt in het ATMP rapport 2017 meer over toekomstverwachtingen van ATMP’s lezen

Source: Cel- en gentherapie in opkomst maar toepassing kent belemmeringen – ZonMw

Statement from FDA Commissioner Scott Gottlieb, M.D. on agency’s efforts to advance development of gene therapies

Once just a theory, gene therapies are now a therapeutic reality for some patients. These platforms may have the potential to treat and cure some of our most intractable and vexing diseases. The policy framework we construct for how these products should be developed, reviewed by regulators, and reimbursed, will help set the stage for the continued advancement of this new market. Last year, we announced our comprehensive policy framework for regenerative medicine, including a draft guidance that describes the expedited programs, such as the breakthrough therapy designation, and the regenerative medicine advanced therapy (RMAT) designation, that may be available to sponsors of these therapies. Today, we’re unveiling a complementary framework for the development, review and approval of gene therapies.

In the past 12 months, we’ve seen three separate gene therapy products approved by the FDA. This reflects the rapid advancements in this field. An inflection point was reached with the development of vectors that could reliably deliver gene cassettes in vivo, into cells and human tissue. In the future, we expect this field to continue to expand, with the potential approval of new treatments for many debilitating diseases. These therapies hold great promise. Our new steps are aimed at fostering developments in this innovative field.

Gene therapies are being studied in many areas, including genetic disorders, autoimmune diseases, heart disease, cancer and HIV/AIDS. We look forward to working with the academic and research communities to make safe and effective products a reality for more patients. But we know that we still have much to learn about how these products work, how to administer them safely, and whether they will continue to work properly in the body without causing adverse side effects over long periods of time. In contrast to traditional drug review, some of the more challenging questions when it comes to gene therapy relate to product manufacturing and quality, or questions about the durability of response, which often can’t be fully answered in any reasonably sized pre-market trial. For some of these products, we may need to accept some level of uncertainty around these questions at the time of approval. For example, in some cases the long-term durability of the effect won’t be fully understood at the time of approval. Effective tools for reliable post-market follow up, such as required post-market clinical trials, are going to be one key to advancing this field and helping to ensure that our approach fosters safe and innovative treatments.

Even when there may be uncertainty about some questions, we need to make certain we assure patient safety and adequately characterize the potential risks and demonstrated benefits of these products. In part because of the added questions that often surround a new technology like gene therapy, these products are initially being aimed at devastating diseases, many of which lack available therapies, including some diseases that are fatal. In such cases of devastating diseases without available therapies, we’ve traditionally been willing to accept more uncertainty to facilitate timely access to promising therapies. In such cases, drug sponsors are generally required to conduct post-marketing clinical trials, known as phase 4 confirmatory trials, to confirm clinical benefit of the drug. This is the direction Congress gave the FDA by creating vehicles like the accelerated approval pathway.

When it comes to novel technologies like gene therapy, the FDA is steadfastly committed to a regulatory path that maintains the agency’s gold standard for assuring safety and efficacy. As we develop this evidence-based framework, we’re going to have to modernize how we approach certain aspects of these products in order to make sure our approach is tailored to the unique challenges created by these new platforms.

Today, we’re taking a step toward shaping this modern structure for the regulation of gene therapy. The agency is issuing a suite of six scientific guidance documents intended to serve as the building blocks of a modern, comprehensive framework for how we’ll help advance the field of gene therapy while making sure new products meet the FDA’s gold standard for safety and effectiveness.

These policies are part of our efforts to communicate the steps we’re taking to provide clear recommendations to sponsors and researchers, so that we can better support innovation. The documents are being issued in draft form so that we can solicit public input on these new policies. As with all draft guidances, all of the comments we receive will be carefully considered prior to finalizing these documents. We’re committed to working with stakeholders to bring novel treatments to the market while ensuring the safety of patients.

Disease Specific Gene Therapy Guidances

Today we’re issuing three new draft guidance documents on the development of gene therapy products for specific disease categories. These are the first three disease-specific guidances that the agency is issuing for gene therapy products. Our new commitment to develop disease-specific guidance documents reflects the increasing activity in this field, and its growing importance to advancing public health.

Human Gene Therapy for Hemophilia: Gene therapy products for hemophilia are now being developed as single-dose treatments that may enable long-term production of the missing or abnormal coagulation factor in patients. This may reduce or eliminate the need for coagulation factor replacement. To define the proper development pathway for such products, we’re issuing a new draft guidance on gene therapy products that are targeted to the treatment of hemophilia. Once finalized, this new guidance will provide recommendations on the FDA’s current thinking on clinical trial design and preclinical considerations to support the development of these gene therapy products. Among other elements, the draft guidance provides recommendations regarding surrogate endpoints that could be used by sponsors pursuing accelerated approval of gene therapy products that are intended for treatment of hemophilia.

Human Gene Therapy for Retinal Disorders: Another area of fast-paced activity is gene therapy products targeted to the treatment of retinal disorders. The Human Gene Therapy for Retinal Disorders guidance, once finalized, will assist those developing gene therapy products for a wide variety of retinal disorders affecting both adult and pediatric patients. Gene therapy products currently undergoing clinical trials in the United States for retinal disorders are commonly delivered by intravitreal injections (into the fluid portion of the eye), or by subretinal injections (beneath the retina). In some cases, the gene therapy products are encapsulated in a device to be implanted within the eye. This new guidance document will focus on issues that are specific to gene therapies for retinal disorders. The document provides recommendations related to product development, preclinical testing, and clinical trial design for such products.

Human Gene Therapy for Rare Diseases: Rare diseases are those that affect fewer than 200,000 people in the United States. The National Institutes of Health reports that nearly 7,000 rare diseases affect more than 25 million Americans. About 80 percent of rare diseases are caused by a single-gene defect, and about half of all rare diseases affect children. Since most rare diseases have no approved therapies, there is a significant unmet need. The Human Gene Therapy for Rare Diseases guidance, once finalized, will provide recommendations on preclinical, manufacturing and clinical trial design for all phases of the clinical development program for these types of gene therapies. The information is intended to assist sponsors in the design of clinical development programs, where there may be limited study population size, potential feasibility and safety issues, as well as issues relating to the interpretation of effectiveness.

Guidances on Manufacturing Gene Therapies

Today, we’re also providing new and comprehensive updates to three existing guidances that address manufacturing issues related to gene therapy. These updates reflect input from many stakeholders. We encourage additional feedback on these documents during the comment period.

The first draft guidance, Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs), provides sponsors with recommendations on how to provide sufficient CMC information to assure safety, identity, quality, purity and strength/potency of investigational gene therapy products. The guidance applies to human gene therapies and to combination products that contain a human gene therapy in combination with a drug or device. In addition, this guidance is organized to follow the structure of the FDA guidance on the Common Technical Document.

The second draft guidance, Testing of Retroviral Vector-Based Gene Therapy Products for Replication Competent Retrovirus (RCR) during Product Manufacture and Patient Follow-up, provides additional recommendations regarding the proper testing for RCR during the manufacture of retroviral vector-based gene therapy products, as well as during the follow-up monitoring of patients who’ve received retroviral vector-based gene therapy products. Specifically, the draft guidance recommends the identification and amount of material to be tested. The guidance also provides advice on general testing methods.

The third draft guidance, Long Term Follow-Up After Administration of Human Gene Therapy Products, provides recommendations regarding the design of long-term follow-up (LTFU) observational studies for the collection of data on delayed adverse events following administration of a gene therapy product. Because of some of the additional uncertainty intrinsic to a novel platform like gene therapy — including questions related to the durability of the treatment effects as well as the theoretical potential for off-target effects if the genes do not insert correctly — there’s an increased need for robust long term follow-up of patients in the post-market period. This guidance describes product characteristics, patient-related factors, and the preclinical and clinical data that should be considered when assessing the need for LTFU observations and describes the features related to effective post-market follow up.

Once finalized, these draft guidances will replace previous guidances issued by the FDA in April 2008 (CMC) and November 2006 (RCR and LTFU).

The field of gene therapy has progressed rapidly since these guidances were first issued. Therefore, the FDA is updating these guidances to provide sponsors with the agency’s most up-to-date thinking.

Our goal is to help promote safe and effective product development in this field. We’ll continue to work with the product sponsors to help make the development and approval of these innovative gene therapies more efficient, while putting in place the regulatory controls needed to ensure that the resulting therapies are both safe and effective. We’ll also make full use of our expedited programs such as breakthrough therapy designation and regenerative medicine advanced therapy designation whenever possible.

Gene therapy represents one of the most promising opportunities for developing highly effective and even curative treatments for many vexing disorders. Some of these products are almost certainly going to change the contours of medical practice, and the destiny of patients with some debilitating diseases.

Our goal is to help these innovations advance in a framework that assures the safety and effectiveness of these resulting treatments, and continues to build peoples’ confidence in this novel area of medicine.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Source: Press Announcements > Statement from FDA Commissioner Scott Gottlieb, M.D. on agency’s efforts to advance development of gene therapies