Chinese Scientists Edit DNA in Attempt to Cure Man’s Cancer, HIV

Michelle Fay Cortez September 11, 2019

(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.

Earlier Controversy

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.”

Safety Watch

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.

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