(Bloomberg) — Chinese researchers safely treated a man with leukemia and HIV using gene-edited stem cells, a step forward in a field that was shaken last year when another Chinese scientist used the same technology to create the world’s first genetically-edited babies.
The man’s medical case, published Wednesday in the New England Journal of Medicine, is the first detailed report in a major academic journal of how doctors are using the experimental tool Crispr to manipulate the DNA of a living patient in an effort to cure disease. But even before the earlier controversy in China, there’s been a heavy note of caution in the field about how far and fast to proceed with the technology.
The patient’s dual diseases — HIV and cancer — gave researchers at the Peking University Stem Cell Research Center in Beijing an opening. The man needed a transplant of stem cells to replace the damaged ones that were causing his blood cancer. That procedure also gave them the opportunity to re-engineer a gene called CCR5 in the donor cells to be resistant to HIV.
“This is a green light for the whole field of gene editing,” Carl June, a pioneer in the use of gene therapy to treat cancer and HIV at the University of Pennsylvania, said in an interview. He published a companion piece in the journal.
The work has some parallels to the highly controversial effort by scientist He Jiankui to alter the DNA in two embryos to make the babies resistant to HIV. That effort sparked an international backlash and calls to put a moratorium on using Crispr to create permanent changes in a subject’s DNA, especially in an embryo. The latest effort is a far more incremental but legitimate effort, especially given the imprimatur of one of the world’s foremost academic journals.
The work by Peking University’s Hongkui Deng and colleagues had several key differences from the earlier effort, including the controlled use of gene-editing on only select cells, the patient’s consent and the subsequent publication of the findings.
The experiment had mixed results. Nineteen months after the treatment, the young man’s cancer, an acute lymphoblastic leukemia, is in remission, and the modified cells integrated into his body and remain. The attempt to cure his HIV was a failure: Only about 5% of his infection-fighting lymphocytes are now resistant to HIV, making continued treatment of the virus necessary.
Even so, the results show a key proof of the concept that Crispr-edited cells can be transplanted into a person and persist long-term, Deng said in an emailed response to questions.
“We should all hope that this is a significant and powerful advance in scientific research, for if it can be tested safely and ethically — and it surely can — it could transform medicine,” said Laurie Zoloth, a professor of religion and ethics at the University of Chicago. “The first published paper is quite an historical moment.”
The researchers didn’t detect any adverse events from the gene-editing or signs that the man’s DNA had been damaged. Larger studies where more altered cells persist are needed to confirm the findings, Deng said. Concerns over unknown potential effects of Crispr has been one of the major hurdles standing in the way of more trials moving forward.
“If they had gone the other way, with a lot of off-target hits, that would have been chilling for the technology,” June said.
Data on three patients treated with Crispr-manipulated cells at the University of Pennsylvania, perhaps the first in the U.S., will be presented at the American Society of Hematology meeting in December.
Crispr has been compared to a word-processing system that allows writers to easily cut out extraneous words and correct typos. With DNA, it acts like molecular scissors, precisely trimming specific flaws in genes. Scientists are still trying to determine if tinkering with the genome can create stray errors elsewhere or lead to unexpected harms, such as cancers caused by uncontrolled cell growth.
There’s a biological rationale for targeting HIV in a leukemia patient, in part because of a handful of people cured of HIV who had bone-marrow transplants. Timothy Ray Brown became the first adult ever to be cured of HIV in 2007 after he received a bone marrow transplant to treat his leukemia. The donor cells had a rare mutation in the CCR5 gene, found in about 1 in 20 people, that makes it difficult for HIV to infect cells. Brown was known as the “Berlin patient,” and other researchers have tried to replicate his experience.
Researchers are now planning to try to increase the number of cells that are transformed and can thrive inside of a patient, Deng said. Other diseases with genetic causes, such as sickle cell anemia, muscular dystrophy, cystic fibrosis and cancer are likely to see a surge in interest based on the new results.
“Crispr technology is so flexible it can be used for all types of conditions,” June said. “You can rewrite the genetic code at will.”
But the China study also showed some of Crispr’s limits because only about 5% of the cells were affected, said Zoloth, the University of Chicago professor.
“This thoughtful honesty and modesty in scientific claims are an important part” of the project, Zoloth said. “It is a first step, if tentative, toward engineering naturally occurring constructs in nature in ways that benefit humanity.”
Leaders in the field agreed the safety findings are a critical first step, though they are hoping further refinement of the process will lead to better results. One key issue is that cells that have been altered using gene-editing or other types of technology are “finicky and tricky to transplant,” said Jennifer Doudna, professor of biochemistry and molecular biology at the University of California, Berkeley, who is credited as an inventor of Crispr.
“This plants the flag to say that at least in this one instance, this type of therapy appears safe,” she said. “The next step is showing that there is some efficacy, a therapeutic benefit to doing this.”
While the NEJM report is the first publication about the use of Crispr in humans, other pioneering researchers have been using it for years in China. The first trials started in 2016, when Lu You, a physician at Sichuan University, put gene-edited cells into a lung-cancer patient. Since then, scientists have launched multiple trials and reportedly treated dozens of patients. But little is known about some of those studies, and medical research is not as stringently regulated in China as it is in the West, prompting concerns about their safety and ethics.
“In the next 18 to 24 months, we’ll start to see published results from a number of these ongoing trials,” Doudna said. “That’s where the rubber hits the road. Does it benefit patients? Time will tell.”