Chinese researcher claims first gene-edited babies
By MARILYNN MARCHIONE
AP Chief Medical Writer
Monday, November 26
HONG KONG (AP) — A Chinese researcher claims that he helped make the world’s first genetically edited babies — twin girls born this month whose DNA he said he altered with a powerful new tool capable of rewriting the very blueprint of life.
If true, it would be a profound leap of science and ethics.
A U.S. scientist said he took part in the work in China, but this kind of gene editing is banned in the United States because the DNA changes can pass to future generations and it risks harming other genes.
Many mainstream scientists think it’s too unsafe to try, and some denounced the Chinese report as human experimentation.
The researcher, He Jiankui of Shenzhen, said he altered embryos for seven couples during fertility treatments, with one pregnancy resulting thus far. He said his goal was not to cure or prevent an inherited disease, but to try to bestow a trait that few people naturally have — an ability to resist possible future infection with HIV, the AIDS virus.
He said the parents involved declined to be identified or interviewed, and he would not say where they live or where the work was done.
There is no independent confirmation of He’s claim, and it has not been published in a journal, where it would be vetted by other experts. He revealed it Monday in Hong Kong to one of the organizers of an international conference on gene editing that is set to begin Tuesday, and earlier in exclusive interviews with The Associated Press.
“I feel a strong responsibility that it’s not just to make a first, but also make it an example,” He told the AP. “Society will decide what to do next” in terms of allowing or forbidding such science.
Some scientists were astounded to hear of the claim and strongly condemned it.
It’s “unconscionable … an experiment on human beings that is not morally or ethically defensible,” said Dr. Kiran Musunuru, a University of Pennsylvania gene editing expert and editor of a genetics journal.
“This is far too premature,” said Dr. Eric Topol, who heads the Scripps Research Translational Institute in California. “We’re dealing with the operating instructions of a human being. It’s a big deal.”
However, one famed geneticist, Harvard University’s George Church, defended attempting gene editing for HIV, which he called “a major and growing public health threat.”
“I think this is justifiable,” Church said of that goal.
In recent years scientists have discovered a relatively easy way to edit genes, the strands of DNA that govern the body. The tool, called CRISPR-cas9, makes it possible to operate on DNA to supply a needed gene or disable one that’s causing problems.
It’s only recently been tried in adults to treat deadly diseases, and the changes are confined to that person. Editing sperm, eggs or embryos is different — the changes can be inherited. In the U.S., it’s not allowed except for lab research. China outlaws human cloning but not specifically gene editing.
He Jiankui (HEH JEE’-an-qway), who goes by “JK,” studied at Rice and Stanford universities in the U.S. before returning to his homeland to open a lab at Southern University of Science and Technology of China in Shenzhen, where he also has two genetics companies. The university said He’s work “seriously violated academic ethics and standards” and planned to investigate. A spokesman for He confirmed that he has been on leave from teaching since early this year, but he remains on the faculty and has a lab at the school.
The U.S. scientist who worked with him on this project after He returned to China was physics and bioengineering professor Michael Deem, who was his adviser at Rice in Houston. Deem also holds what he called “a small stake” in — and is on the scientific advisory boards of — He’s two companies.
The Chinese researcher said he practiced editing mice, monkey and human embryos in the lab for several years and has applied for patents on his methods.
He said he chose embryo gene editing for HIV because these infections are a big problem in China. He sought to disable a gene called CCR5 that forms a protein doorway that allows HIV, the virus that causes AIDS, to enter a cell.
All of the men in the project had HIV and all of the women did not, but the gene editing was not aimed at preventing the small risk of transmission, He said. The fathers had their infections deeply suppressed by standard HIV medicines and there are simple ways to keep them from infecting offspring that do not involve altering genes.
Instead, the appeal was to offer couples affected by HIV a chance to have a child that might be protected from a similar fate.
He recruited couples through a Beijing-based AIDS advocacy group called Baihualin. Its leader, known by the pseudonym “Bai Hua,” told the AP that it’s not uncommon for people with HIV to lose jobs or have trouble getting medical care if their infections are revealed.
Here is how He described the work:
The gene editing occurred during IVF, or lab dish fertilization. First, sperm was “washed” to separate it from semen, the fluid where HIV can lurk. A single sperm was placed into a single egg to create an embryo. Then the gene editing tool was added.
When the embryos were 3 to 5 days old, a few cells were removed and checked for editing. Couples could choose whether to use edited or unedited embryos for pregnancy attempts. In all, 16 of 22 embryos were edited, and 11 embryos were used in six implant attempts before the twin pregnancy was achieved, He said.
Tests suggest that one twin had both copies of the intended gene altered and the other twin had just one altered, with no evidence of harm to other genes, He said. People with one copy of the gene can still get HIV, although some very limited research suggests their health might decline more slowly once they do.
Several scientists reviewed materials that He provided to the AP and said tests so far are insufficient to say the editing worked or to rule out harm.
They also noted evidence that the editing was incomplete and that at least one twin appears to be a patchwork of cells with various changes.
“It’s almost like not editing at all” if only some of certain cells were altered, because HIV infection can still occur, Church said.
Church and Musunuru questioned the decision to allow one of the embryos to be used in a pregnancy attempt, because the Chinese researchers said they knew in advance that both copies of the intended gene had not been altered.
“In that child, there really was almost nothing to be gained in terms of protection against HIV and yet you’re exposing that child to all the unknown safety risks,” Musunuru said.
The use of that embryo suggests that the researchers’ “main emphasis was on testing editing rather than avoiding this disease,” Church said.
Even if editing worked perfectly, people without normal CCR5 genes face higher risks of getting certain other viruses, such as West Nile, and of dying from the flu. Since there are many ways to prevent HIV infection and it’s very treatable if it occurs, those other medical risks are a concern, Musunuru said.
There also are questions about the way He said he proceeded. He gave official notice of his work long after he said he started it — on Nov. 8, on a Chinese registry of clinical trials.
It’s unclear whether participants fully understood the purpose and potential risks and benefits. For example, consent forms called the project an “AIDS vaccine development” program.
The Rice scientist, Deem, said he was present in China when potential participants gave their consent and that he “absolutely” thinks they were able to understand the risks.
Deem said he worked with He on vaccine research at Rice and considers the gene editing similar to a vaccine.
“That might be a layman’s way of describing it,” he said.
Both men are physics experts with no experience running human clinical trials.
The Chinese scientist, He, said he personally made the goals clear and told participants that embryo gene editing has never been tried before and carries risks. He said he also would provide insurance coverage for any children conceived through the project and plans medical follow-up until the children are 18 and longer if they agree once they’re adults.
Further pregnancy attempts are on hold until the safety of this one is analyzed and experts in the field weigh in, but participants were not told in advance that they might not have a chance to try what they signed up for once a “first” was achieved, He acknowledged. Free fertility treatment was part of the deal they were offered.
He sought and received approval for his project from Shenzhen Harmonicare Women’s and Children’s Hospital, which is not one of the four hospitals that He said provided embryos for his research or the pregnancy attempts.
Some staff at some of the other hospitals were kept in the dark about the nature of the research, which He and Deem said was done to keep some participants’ HIV infection from being disclosed.
“We think this is ethical,” said Lin Zhitong, a Harmonicare administrator who heads the ethics panel.
Any medical staff who handled samples that might contain HIV were aware, He said. An embryologist in He’s lab, Qin Jinzhou, confirmed to the AP that he did sperm washing and injected the gene editing tool in some of the pregnancy attempts.
The study participants are not ethicists, He said, but “are as much authorities on what is correct and what is wrong because it’s their life on the line.”
“I believe this is going to help the families and their children,” He said. If it causes unwanted side effects or harm, “I would feel the same pain as they do and it’s going to be my own responsibility.”
AP science writer Christina Larson, video journalist Emily Wang and researcher Fu Ting contributed to this report from Beijing and Shenzhen, China.
This Associated Press series was produced in partnership with the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content.
Meet the Organization You’ve Never Heard of That Decides Whether or Not You Get the Drugs You Need
By Michael Graham
If you’re suffering from a rare, debilitating disease like MS, or cystic fibrosis, or some forms of cancer, and you need a boutique biologic to save your life, Dr. Steve Pearson has a message for you:
Some drugs are just too expensive, which means some lives are not worth saving.
This is the fundamental premise behind Dr. Pearson’s Institute for Clinical and Economic Review, or ICER — a nonprofit, medical review board he founded after working with the United Kingdom’s National Institute for Health and Care Excellence, or NICE. Though there are thousands of British patients who’ve been denied health care deemed too expensive by NICE and many believe it’s anything but.
If you watched in horror over the summer when the parents of 23-month-old Alfie Evans were denied permission by the U.K. government to take their dying infant to another country for care, the premise of health care regulation and government control that made that story possible begins with NICE.
Billing itself as “an independent and non-partisan research organization that objectively evaluates the clinical and economic value of prescription drugs, medical tests, and other health care and health care delivery innovations,” Dr. Pearson and his ICER team merely make recommendations about drugs and drug prices. They issue a finding on what price they would deem “fair” for a new prescription drug heading to the market, and — using a “Quality of Life Years” evaluation similar to NICE — ICER rules on whether insurance companies should cover an available drug treatment.
America doesn’t have a nationalized health care system like the United Kingdom’s — yet. And ICER is a private nonprofit, not a government agency. So does it really matter what its rulings are? To the millions of Americans who have CVS/Caremark prescription drug coverage as part of their insurance — absolutely. In August, CVS announced it would allow health plans and insurers using Caremark to refuse to cover drugs that don’t pass ICER review.
“Specifically, the pharmacy benefit manager set a threshold of $100,000 per QALY, or quality-of-life years, a benchmark that measures both the quantity and quality of life generated by providing a treatment or some other health care intervention,” reports the life science journal STAT.
In other words, a think tank’s opinions about the “quality of life value” of a new and expensive biologic to treat rheumatoid arthritis will determine whether a sick woman who would benefit from this new drug treatment will be covered by her insurance. And not just any think tank, but one led by an advocate of U.K.-style health care rationing, with a governing board featuring representatives of the health insurance industry. In addition to receiving funding from major insurers like Blue Cross of California, Kaiser Permanente, Partners Healthcare, Aetna, Anthem and UnitedHealth, ICER’s governing board includes:
—Peter Long, PhD, president and CEO, Blue Shield of California Foundation
—Murray Ross, PhD (Chair), vice president and director, Kaiser Institute for Health Policy, Kaiser Permanente
—Lewis Sandy, MD, executive vice president of clinical advancement, UnitedHealth Group
Not to mention Carmella Bocchino, a senior adviser at America’s Health Insurance Plans, the largest health-insurance lobbying organization.
Another person who worked for AHIP: Dr. Steve Pearson, founder of ICER.
Another reason for ICER’s influence is more than $19 million in funding from hedge fund billionaire John Arnold and the Laura and John Arnold Foundation. This money has allowed ICER to extend its review process to all newly approved drugs and is part of what Arnold sees as data-driven, statistical-analysis based giving. Others call it “Moneyball philanthropy.” The focus is on providing numbers and data to improve the quality and efficiency of giving, rather than giving to meet immediate needs.
Arnold recently penned an op-ed defending the role of pharmacy benefit managers — “PBM’s” as they’re known in the health care industry — in controlling drug costs. Drug manufacturers argue that PBMs are driving down prices but are keeping the savings or sharing them with the insurance companies they represent.
Tension between drug manufacturers (who like high prices) and insurance companies (who don’t like paying them) is natural. In a free-market system, it’s healthy. But for a pharmacy benefit manager like CVS to remove treatments from insurance coverage using analysis from an insurer-friendly oversight board isn’t exactly a level playing field. And patient advocates are crying foul.
“If I thought ICER wanted to be one part of the drug review process, I wouldn’t be so upset,” Terry Wilcox of Patients Rising told InsideSources. “But Steve Pearson’s endgame is for ICER to become NICE. He’s even got the cute acronym like NICE. He is a true believer in the NICE approach and it’s what he’s working for here.”
Americans have been reluctant to support rationing in the name of controlling costs, but Pearson isn’t shy about expressing support for the U.K. model. “I appreciate the British system’s honesty about the challenge, and their willingness to talk about trade-offs,” Pearson told PharmEx.com. “NICE has a strong reputation in the science and procedures. NICE has stood the test of time.”
Pearson wrote more extensively about the need for these “trade-offs” in an article for The Hastings Center Report in 2014 about so-called “orphan drugs” and rare diseases titled “Which Orphans Will Find a Home? The Rule of Rescue in Resource Allocation for Rare Diseases.”
In it, he and his co-author Emily A. Largent argue that to avoid denying resources for the health care system as a whole, it’s necessary to restrain “society’s desire to help those weakest among us, and … ensure that an undue burden is not placed on others for the sake of a few.”
Largent has previously written in defense of health care rationing, writing that “some rationing is both ethically defensible and necessary.” While she would prefer this rationing be done at the “top-down, organizational level,” she bemoans the “current political barriers” to top-down rationing and distributing of care.
Is it any surprise, therefore, that patient advocates are uncomfortable with ICER and its increasing influence over our health care system?
“The problem with the people behind ICER is that they believe all these new medicines are going to destroy our economy and bankrupt America and we have to find a way to limit access,” says Robert Goldberg, co-founder and vice president of the Center for Medicine in the Public Interest. “And that premise is simply wrong.”
Goldberg and other critics of the ICER approach point out that many of the newer drugs, while expensive, often save money for the health care system by keeping patients out of hospitals or preventing their diseases from reaching the point of requiring expensive critical care.
In addition, the Wall Street Journal reports that the new Trump administration’s lighter-regulation, fast-track approach to getting new drugs on the market has saved Americans $26 billion already. About nine in 10 prescriptions in the United States are already cheaper generics (compared with about half in most European countries) and — the White House reports — “as of August 2018 the relative price of prescription drugs was lower than in December 2016.”
The premise that America faces a crisis of expensive biologics to treat relatively rare or difficult to treat diseases like rheumatoid arthritis, ALS or blood cancers simply doesn’t match the available data. Even the most passionate patient advocates support cost-benefit analysis — as long as the final analysis is about the patient’s care.
“This is where I agree with ICER. Nobody wants to pay for a drug that doesn’t work or that people don’t need. But there’s a difference in tactics. ICER relies on randomized clinical testing and that means you end up working the averages. I was recently talking to a company that has an injection, immunoglobulin, that helps people with weak immune systems. Under the ICER approach, the conclusion would be ‘this drug isn’t effective, don’t cover it. That’s one approach. But I’d rather figure out who the people are who it does work for and get the drug to them, so they can be healthier.”
“As a society, we can’t just sit back and say there are sick people we can’t afford to treat. We need to be looking for ways to make those treatments affordable,” Goldberg said.
ABOUT THE WRITER
Michael Graham is political editor of NH Journal. He’s also a CBS News contributor. You can reach him at firstname.lastname@example.org. He wrote this for InsideSources.com.
Preventing infant deaths: The ABCs of safe baby sleep
November 20, 2018
Chancellor’s Professor of Medicine, Liberal Arts, and Philanthropy, Indiana University
Richard Gunderman does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
Indiana University provides funding as a member of The Conversation US.
Just last week, I read an X-ray study of an infant who died while sleeping with a parent. I am a pediatric radiologist, and in cases where an infant has died unexpectedly, we often obtain X-ray images to make sure that the infant does not have skeletal fractures or other signs of injury that might suggest that he or she was the victim of child abuse. Most of the time we find no such evidence.
Yet every infant death is heart-wrenching, above all for the parents who wake up to discover their infant limp and lifeless.
Each year, about 3,600 U.S. children under the age of 1 year die suddenly and unexpectedly. Such deaths are especially common in babies between 1 and 4 months of age, perhaps because younger infants are less capable of repositioning themselves and crying out for help. For reasons that are unclear, such deaths are also slightly more common among boys than girls.
While all infant deaths are not preventable, many are. A 2010 investigation of hundreds of deaths in North Carolina showed that as many as two-thirds may have been attributable to ill-advised sleep practices, such as the use of unsafe bedding and sleeping with adults. Many are thought to be due to suffocation, when the baby’s airway becomes blocked or when a larger person rolls over and prevents the baby’s chest from expanding during breathing.
The ABCs of safe sleep
Efforts to prevent such deaths have led the American Academy of Pediatrics to formulate a policy on safe infant sleep, key points of which can be summarized as the ABCs of safe sleep:
A – Alone. This does not mean that babies should be put to bed in a room separate from parents. It does, however, mean that infants should not sleep in the same bed. The reason for this is that parents may move during sleep in ways that interfere with babies’ breathing or even crush them. Inadvertently dozing off while breastfeeding or cuddling an infant is just as hazardous as intentionally co-sleeping.
B – Back. Babies should always be put to sleep on their backs. There is nothing wrong with placing healthy babies on their tummies to play, but on the back appears to be the safest position for sleeping. One possible explanation is the fact that babies lying on their bellies are more likely to rebreathe the air they exhale, causing blood levels of carbon dioxide to rise as oxygen falls. This recommendation applies throughout the first year, but it is especially important in the first six months after birth.
The American Academy of Pediatrics policy on safe sleep explicitly contradicts the outdated view that back-sleeping increases the risk of choking. While it is true that many infants experience gastroesophageal reflux, familiar to parents as “spitting up,” healthy babies protect themselves against aspiration. Parents should also avoid raising the head of the crib. It doesn’t reduce the risk of reflux and can cause babies to slide into a dangerous position.
C – Crib. Cribs and bassinets that meet current safety standards are the safest places for babies to sleep, while chairs and sofas should be avoided. A firm surface prevents the baby’s face from becoming caught in a fold or indentation. Likewise, the crib should be empty of loose bedding, pillows, bumpers and toys, any one of which could cause entrapment and suffocation. Too many coverings can also increase the risk that a baby will overheat, an important consideration because temperature regulation is not fully developed in infants.
Of course, there are other steps parents can take to ensure that their babies sleep safely. One is to prevent exposure to cigarette smoke, which appears to increase the risk of sudden infant death. Unsurprisingly, parental intoxication and illicit drug use also appear to place babies at greater risk. Another key factor is making sure that others who care for the baby, such as family members and daycare workers, understand the importance of adhering to the ABCs of safe sleep.
It is important to avoid stigmatizing parents who have lost an infant. In many cases, like the baby whose X-rays I read, we never know for sure what caused the death. Yet there are simple steps every parent can take to enhance the safety of sleeping infants, and it all begins with education. My colleagues and I hope that by educating parents about the ABCs of safe sleep, we may be able to prevent hundreds – perhaps even thousands – of infant deaths every year.