Houston, Texas, USA : A scientist in China who claims to have created the world’s first genetically edited babies says a second pregnancy may be underway.
The researcher, He Jiankui of Shenzhen, revealed the possible pregnancy Wednesday while making his first public comments about his controversial work at an international conference in Hong Kong.
He claims to have altered the DNA of twin girls born earlier this month to try to make them resistant to infection with the AIDS virus. Mainstream scientists have condemned the experiment, and universities and government groups are investigating.
The second potential pregnancy is in a very early stage and needs more time to be monitored to see if it will last, He said.
Leading scientists said there are now even more reasons to worry, and more questions than answers, after He’s talk. The leader of the conference called the experiment “irresponsible” and evidence that the scientific community had failed to regulate itself to prevent premature efforts to alter DNA.
Altering DNA before or at the time of conception is highly controversial because the changes can be inherited and might harm other genes. It’s banned in some countries including the United States except for lab research.
He defended his choice of HIV, rather than a fatal inherited disease, as a test case for gene editing, and insisted the girls could benefit from it.
“They need this protection since a vaccine is not available,” He said.
Scientists weren’t buying it.
“This is a truly unacceptable development,” said Jennifer Doudna, a University of California-Berkeley scientist and one of the inventors of the CRISPR gene-editing tool that He said he used. “I’m grateful that he appeared today, but I don’t think that we heard answers. We still need to understand the motivation for this.”
Doudna is paid by the Howard Hughes Medical Institute, which also supports AP’s Health & Science Department.
“I feel more disturbed now,” said David Liu of Harvard and MIT’s Broad Institute, and inventor of a variation of the gene-editing tool. “It’s an appalling example of what not to do about a promising technology that has great potential to benefit society. I hope it never happens again.”
There is no independent confirmation of his claim and he has not yet published in any scientific journal where it would be vetted by experts. At the conference, He failed or refused to answer many questions including who paid for his work, how he ensured that participants understood potential risks and benefits, and why he kept his work secret until after it was done.
After He spoke, David Baltimore, a Nobel laureate from the California Institute of Technology and a leader of the conference, said He’s work “would still be considered irresponsible” because it did not meet criteria many scientists agreed on several years ago before gene editing could be considered.
“I personally don’t think that it was medically necessary. The choice of the diseases that we heard discussions about earlier today are much more pressing” than trying to prevent HIV infection this way, Baltimore said.
The case shows “there has been a failure of self-regulation by the scientific community” and said the conference committee would meet and issue a statement on Thursday about the future of the field, Baltimore said.
Before He’s talk, Dr. George Daley, Harvard Medical School’s dean and one of the conference organizers, warned against a backlash to gene editing because of He’s experiment. Just because the first case may have been a misstep “should in no way, I think, lead us to stick our heads in the sand and not consider the very, very positive aspects that could come forth by a more responsible pathway,” Daley said.
“Scientists who go rogue … it carries a deep, deep cost to the scientific community,” Daley said.
Regulators have been swift to condemn the experiment as unethical and unscientific.
The National Health Commission has ordered local officials in Guangdong province to investigate He’s actions, and his employer, Southern University of Science and Technology of China, is investigating as well.
On Tuesday, Qui Renzong of the Chinese Academy of Social Science criticized the decision to let He speak at the conference, saying the claim “should not be on our agenda” until it has been reviewed by independent experts. Whether He violated reproductive medicine laws in China has been unclear; Qui contends that it did, but said, “the problem is, there’s no penalty.”
He called on the United Nations to convene a meeting to discuss heritable gene editing to promote international agreement on when it might be OK.
Meanwhile, more American scientists said they had contact with He and were aware of or suspected what he was doing.
Dr. Matthew Porteus, a genetics researcher at Stanford University, where He did postdoctoral research, said He told him in February that he intended to try human gene editing. Porteus said he discouraged He and told him “that it was irresponsible, that he could risk the entire field of gene editing by doing this in a cavalier fashion.”
Dr. William Hurlbut, a Stanford ethicist, said he has “spent many hours” talking with He over the last two years about situations where gene editing might be appropriate.
“I knew his early work. I knew where he was heading,” Hurlbut said. When he saw He four or five weeks ago, He did not say he had tried or achieved pregnancy with edited embryos but “I strongly suspected” it, Hurlbut said.
“I disagree with the notion of stepping out of the general consensus of the scientific community,” Hurlbut said. If the science is not considered ready or safe enough, “it’s going to create misunderstanding, discordance and distrust.”
Gene-edited baby trial ‘paused’: China scientist
The Chinese scientist who claims to have created the world’s first genetically-edited babies said Wednesday the trial had been paused, following an international outcry over the highly controversial procedure.
He Jiankui defended his work in front of a packed Hong Kong biomedical conference, saying he had successfully altered the DNA of twin girls born to an HIV-positive father, an apparent medical first.
A total of eight volunteer couples—HIV-positive fathers and HIV-negative mothers—had signed up to the trial, with one dropping out before it was halted.
He said there had been “another potential pregnancy” involving a second couple, but when questioned further agreed it had been a chemical pregnancy—a term referring to a very early miscarriage.
“I must apologise this result was leaked unexpectedly,” He said of the apparent breakthrough “The clinical trial was paused due to the current situation,” he added.
The conference has been upended by the gene-edited baby revelations claims, after university professor He posted a video claiming the twin girls—born a few weeks ago—had had their DNA altered to prevent them from contracting HIV.
The move prompted a heated debate among the scientific community, with many raising concerns over the lack of verified data and the risks of exposing healthy embryos to gene editing.
Editing human embryos can create unintended mutations in other areas—so-called “off-target effects”—which can be carried through to birth, experts warned.
But He took to the stage Wednesday to justify his work, and was bombarded with questions as he told the audience that the parents were aware of the potential dangers when they signed up.
“The volunteers were informed of the risk posed by the existence of one potential off-target and they decided to implant,” he said.
He also said the university where he works had been “unaware of the study’s conduct.”
Southern University of Science and Technology, in the southern Chinese city of Shenzhen, had earlier distanced itself from He, saying he had been on unpaid leave since February and had “seriously violated academic ethics and codes of conduct”.
Organisers of the Second International Summit on Human Genome Editing, which opened Tuesday, also said they had been unaware of He’s work.
Conference moderator Robin Lovell-Badge said He’s trial was a “backward step” for the science industry, but described the babies’ birth as “momentous” nonetheless.
“This is an example of an approach that was not sufficiently careful and cautious and proportionate,” he said.
“Clearly however it is a point in history… These two babies would appear to be the first gene-edited babies. So it is a momentous point in history.”
Summit chair David Baltimore, a Nobel laureate, said there had been “a failure of self-regulation by the scientific community because of a lack of transparency.”
He’s claim would “be considered irresponsible”, Baltimore said.
Bypassed ethical process
He, who was educated at Stanford University, said the twins’ DNA was modified using CRISPR, a technique which allows scientists to remove and replace a strand with pinpoint precision.
Gene editing is a potential fix for heritable diseases but it is extremely controversial because the changes would be passed down to future generations and could eventually affect the entire gene pool.
In many countries the editing of human DNA is tightly controlled.
Qiu Renzong, formerly the vice president of the Chinese Ministry of Health’s ethics committee, told reporters at the conference that lax regulations in China mean that scientists who break the rules often face no punishment, and think of the ministry as being “without teeth”.
China’s National Health Commission ordered an “immediate investigation” into the case, the official Xinhua news agency reported, while the Shenzhen hospital meant to have approved the research programme denied its involvement.
A union of Chinese scientists issued a statement saying it “resolutely opposes so-called scientific researches and biotech applications that violate the spirit of science and ethics,” Xinhua said.
The case has damaged China’s international reputation in the field, said the Chinese Union of Life Science Societies.
This is not the first time Chinese researchers have experimented with human embryo technology.
Last September, scientists at Sun Yat-sen University used an adapted version of gene-editing to correct a disease-causing mutation in human embryos.
There is also a history of fraud within China’s academic community—including a scandal last year that led to the withdrawal of 100 “compromised” academic papers.
A joint statement Monday from a group of 100 scientists in China criticised He Jiankui’s claims and called them a “great blow to the global reputation and development of biomedical research in China”.
Why we are not ready for genetically designed babies
The media is buzzing with the surprise news that a Chinese researcher, Jainkui He, has created the world’s first genome-edited twins. He did this, ostensibly, to provide resistance to HIV, the virus that causes AIDS.
Prof. He, reportedly working with former Rice University supervisor Michael Deem, capitalized on work in 2012 by Jennifer Doudna and Emmanuel Charpentier, who introduced a new and easier way of altering the DNA of human and non-human organisms using CRISPR-Cas9 technology. He also built upon the work of molecluar biologist Feng Zhang, who optimized this genome editing system for use in human cells.
He’s claim moves human germline genome editing from the lab to the delivery room —something other scientists might have been thinking about despite ethical concerns.
The scientific community has expressed widespread condemnation of He’s decision to initiate a pregnancy using genetically modified embryos —as “dangerous, “irresponsible” and “crazy.” What if mistakes are made? How can we be sure this powerful technology will benefit humankind? Are we ready for the consequences of genetically engineering our own evolution?
We argue that we cannot allow individual scientists to decide the fate of the human genome. Heritable human genome editing poses a significant existential threat because changes may persist throughout the human population for generations, with unknown risks.
We must commit to inclusive global dialogue —involving experts and the public —to develop broad societal consensus on what to do with genetic technologies.
Possible mutations or forced sterilization
He announced to the world that he edited the genome of human embryos for seven couples using CRISPR-Cas9 technology. According to He, two of these embryos resulted in a pregnancy, and twin girls (Lulu and Nana, which are pseudonyms) were born.
The goal of the editing was to confer resistance to HIV by modifying the CCR5 gene (the protein doorway by which HIV enters human cells). He claims that these edits have been verified in both twins and this data has been looked over and called “probably accurate” by George Church, a world-renowned Harvard geneticist.
Evidence suggests, however, the procedure was unnecessary, is unlikely to provide benefit and could even cause harm. Although the father of Lulu and Nana was HIV positive, it is unlikely that he would have passed this disease to his children using standard IVF procedures.
The children born of genome editing are genetic mosaics with uncertain resistance to HIV and perhaps decreased resistance to viral diseases like influenza and West Nile. This is because the CCR5 gene that He disabled plays an important role in resistance to these diseases.
As well, there is the possibility of unintended mutations caused by the CRISPR procedure. These health risks cannot be overstated, as the repercussions for these twin girls, in terms of their susceptibility to infectious diseases or cancer will likely be a cause for concern throughout their lives.
Another uncertain consequence for the twins concerns their reproductive health and freedom. As they approach reproductive age will they face the possibility of “forced” sterilization to prevent their edited genes being passed on to future generations?
The Southern University of Science and Technology in Shenzhen, China, where He is employed (currently on leave from February 2018 to January 2021), has distanced itself from the researcher and will form an independent international committee to investigate the widely publicized, controversial research.
Rice University, where Michael Deem is employed, has also said they will investigate.
The Shenzhen HarMoniCare Women’s and Children’s Hospital launched an inquiry into the validity of the ethics documents provided by He documenting research ethics approval.
Importantly, the ethics approval was only uploaded to the Chinese Clinical Trial Database on Nov. 8 as a retrospective registration —likely around the time that the twins were purportedly born.
Designer babies by powerful elites
With the Genetic Genie out of the bottle, we have to ask whether we need any more time to reflect on the ethics?
A just and fair society is one with less disparity and more justice. A predictable consequence of allowing (nay, encouraging) individuals to genetically modify their children will be greater disparity and greater injustice —and not only because of limited access to genome editing technology.
Of significant concern is the inevitable increase in discrimination, stigmatization and marginalization as powerful scientific and corporate elites decide which traits are desirable and which traits are not.
Although He disavows any interest in so-called “designer babies” whose parents have chosen their children’s eye-colour, hair-colour, IQ and so on, we are forced to contemplate such a “eugenic” dystopian future should we continue down this path.
The human genome belongs to all of us. As such, we need to commit to the hard work of making good on the 2015 admonition by the Organizing Committee for the International Summit on Human Gene Editing to work towards “broad societal consensus” on how we should proceed with, or not proceed with, editing it.
In this regard it is heartwarming to have Feng Zhang call for a moratorium on implantation of edited embryos and remind his scientific colleagues that “in 2015, the international research community said it would be irresponsible to proceed with any germline editing without ‘broad societal consensus about the appropriateness of the proposed application.'”
Image : He Jiankui, a Chinese researcher, speaks during the Human Genome Editing Conference in Hong Kong, Wednesday, Nov. 28, 2018. He made his first public comments about his claim to have helped make the world’s first gene-edited babies.