BEIJING — American surgeon Henry Heimlich is best known for inventing a way to rescue choking victims, but a quarter-century ago, he was vilified for promoting a fringe treatment for AIDS and Lyme disease. Called malarial therapy, it involved injecting patients with the malaria-causing parasite, supposedly to stimulate their immune systems.
The U.S. Centers for Disease Control and Prevention issued a report saying the procedure “cannot be justified,” and another critic compared its use to the discredited practice of bleeding patients with leeches. Despite the criticism, Heimlich launched trials of the therapy in HIV patients in Mexico and China in the 1990s. Now, the scientist who led the Chinese study is using malarial therapy again — this time to treat cancer patients. And the still-unproven intervention is being hailed in China as a miracle cure.
Amid the Chinese New Year holiday last month, a prominent Chinese scientist at Guangzhou Medical University announced on state television channel CCTV1 that trials of the immunotherapy had shown promising results, with two cancer patients who “had almost returned to normal.”
An official blog of the Chinese Academy of Sciences (CAS) — a government agency that is leading the project, according to follow-up TV programs — corroborated the results, and the news went viral on social media. That prompted more than 10,000 patients to express interest in enrolling in the next phase of the clinical trial, which will involve 200 patients, according to TV coverage.
China is eager to compete with Western nations and companies pursuing treatments designed to rev up a patient’s immune system to attack tumors. But critics say the malarial therapy trial shows the government-sponsored effort has spawned a feverish medical gold rush to develop and profit from these treatments. Nearly 70 registered immunotherapy clinical trials are underway in China.
“It was utterly inappropriate to make an announcement like this before the work had gone through peer review” and been published in a scientific journal, said Zhai Xiaomei, executive director of the Center for Bioethics at the Chinese Academy of Medical Sciences in Beijing. She said the eminent scientist’s comments on national TV were just the latest of a string of wildly exaggerated claims in China that have stoked excitement about cancer immunotherapies.
The malarial therapy studies promoted on television involve 30 patients with advanced cancers. Zhong Nanshan, a fellow of the Chinese Academy of Engineering and co-principal investigator of the project, told CCTV1 that among 10 patients who had received malarial therapy for at least a year, two — one with lung cancer, the other with prostate cancer — appeared to have no cancer cells remaining at the tumor site. Another five patients with lung cancer had no sign of disease progression.
It wasn’t the first time the team announced the “promising results.” A few days earlier, the lead principal investigator, biologist Chen Xiaoping at the Chinese science academy’s Guangzhou Institutes of Biomedicine and Health, gave a boisterous public speech in Guangzhou at a forum organized by the academy.
In the 23-minute talk, which can be seen on several websites, Chen — Heimlich’s protégé and collaborator on the HIV trials in China in the 1990s — told the audience that the project was sparked by a eureka moment he had when he noted that places with high prevalence of malaria often have a low incidence of cancer. When his team analyzed the global data on malaria incidence and cancer mortality, they found a statistically significant negative correlation.
Ali Salanti, a biologist at the University of Copenhagen in Denmark, called the correlation very weak. For many years, his team has been studying the anti-cancer effects of some malaria proteins, but this is totally different from infecting patients with parasites, he said.
In fact, there’s evidence that the malaria parasite can increase the risk of a type of cancer called Burkitt’s lymphoma. A cancer of white blood cells, it is one of the most common childhood cancers in Africa and occurs in areas where malaria is endemic. In 2015, researchers at Rockefeller University in New York uncovered the mechanism underlying the lymphoma’s link to malaria. In a paper published in Cell, the team showed that the malaria parasite could turn mouse white blood cells into cancer by damaging their DNA.
Even if there is a negative correlation between the prevalence of malaria and cancer, said Wang Liming, a biologist at Zhejiang University in Hangzhou, it’s more likely that in areas with high rates of malaria, a genetic mutation that protects against the illness has been favored by evolution, and that same mutation might also reduce susceptibility to cancer.
Regardless of the correlation, “robust preclinical studies are essential before conducting human trials,” Wang said.
Searching databases of published literature, including Chen’s own website, turned up only one paper that can be regarded as preclinical work directly relevant to the ongoing trials. The study, published in PLOS One in 2011, showed that malarial therapy stimulated the immune system in a mouse model of lung cancer, and resulted in complete tumor regression and prolonged survival in 5 to 10 percent of the animals.
“I don’t think this paper alone can justify the clinical trials,” said Wang.
Other scientists said studies using more complex animal models should have been done to help prove the theory before testing it in people. “Studies in mice may be the first steps to generate hypotheses and early data,” said Jeremy Farrar, director of the London-based research charity, Wellcome Trust. But they are often not relevant to human disease, he added.
Many researchers are also concerned about malarial therapy’s public health implications. China is one of the dozens of countries poised to eradicate malaria by 2020. “It’s extremely disconcerting that they are deliberately infecting patients with malaria parasites,” said Zhai. “Have they analyzed the risk of causing a malaria epidemic?”
In his public talk, Chen said that the infected patients were placed in a closed environment and that the parasite load was controlled “to a safe level” by artemisinin, the anti-malaria drug that earned the Chinese scientist Tu Youyou a Nobel Prize in 2015.
But this has not assured scientists such as Wang. “How can they be sure?” asked Wang. “And it’s still possible that the parasite can become resistant to anti-malarial drugs.”
In an email to STAT, Zhong, an expert on infectious diseases, declined to be interviewed, saying that it’s too early to draw a firm conclusion about the success of malarial therapy for cancer. “I was not aware of Chen’s public talk on the topic,” he wrote. “When CCTV asked me, I did not know they would broadcast my remarks that evening.” Chen did not respond to STAT’s phone calls and emails seeking comment.
China’s clinical trial registry lists three studies testing injections with Plasmodium vivax, one strain of the malaria parasite, for treating advanced cancers, including lung, prostate, liver, breast, and colon cancers. The registry shows that the trials are self-financed and lists CAS Lamvac Biotech, a private company of which Chen is the founder and CEO, as the principal institution running the trials. The trials, according to the registry, were approved by medical ethics committees at the three hospitals that are carrying out the work.
“This does not necessarily mean that the trials can be justified,” said Zhai, adding that the standards of ethics committees in provincial hospitals are often not rigorous. “They don’t always have sound judgment regarding the science or the ethics.”
This weak oversight has contributed to the mushrooming of clinical trials of cancer immunotherapy in China, and may be putting patients at risk of harm. Last September, the country saw the first lawsuit filed over a type of immunotherapy, after a patient with lymphoma died two weeks after participating in a trial of a CAR-T cell therapy, according to Caijing, an independent Chinese-language magazine headquartered in Beijing.
“Patients with terminal cancer and their family are extremely vulnerable,” said Zhai. “We must take all measures to protect them from harboring false hope — or, worse, being exploited.”