Peng Mei News (www.thepaper.cn) reported that the treatment of advanced cancer is not the first application of clinical trials of Plasmodium chenxiaoping (Plasmodium vivax), a specialist in pathogenic biology. In fact, more than 20 years ago, Chen Xiaoping used Plasmodium to treat AIDS patients. The title of his 1998 Ph.D. thesis was "The interaction and relationship between Plasmodium and HIV: I. Phase I study of malaria therapy for HIV infection II. Clinical responses of HIV/AIDS patients to interfering with vivax malaria, changes in T cell subsets and CD4 cell apoptosis".
Chen Xiaoping called this treatment "malaria therapy" in his paper. His doctoral tutor is Professor Chen Guanjin, who is engaged in parasitology at Zhongshan Medical University. The Guidance Group for the doctoral dissertation also includes John L. Fahey, a professor at UCLA and Henry J. Heimlich, a professor at Heimlich Institute in Cincinnati.
According to the doctoral dissertation, 19 cases of research have proved that malaria therapy is safe in the treatment of HIV/AIDS. Future studies include the establishment of animal models of SIV and malaria co-infection, the expansion of clinical trials, and the declaration of phase II clinical trials in 100 cases of control group.
It is noteworthy that five years after Dr. Chen Xiaoping graduated, their research in the United States triggered waves, and led Fahey et al. to be investigated by UCLA at the end of 2002, and to reopen the investigation in early 2003. In a report in March 2003, the New York Times said, "Some medical experts have severely condemned human trials in China, which in the United States are unthinkable."
Chen Xiaoping's "malaria treatment" for AIDS 20 years ago has not become the mainstream. Twenty years later, he tried to use the same method to see better outcomes in patients with advanced cancer, and he also carried aggressive immunotherapy.
19 cases of "malaria treatment" AIDS, "provable safety"
By injecting malaria and inducing persistent fever, this treatment, popularly known as "fighting with poison" was "carried forward" by an Austrian doctor in the early 20th century.
At that time, penicillin had not been found, doctors had no way to deal with the common sexually transmitted disease syphilis, and patients with advanced syphilis would lead to neurosyphilis, typical manifestations and paralytic dementia, so it is difficult for patients to avoid the outcome of death. In 1917, Julius Wagner-Jauregg, an Austrian doctor, manufactured an artificial malaria infection by injecting blood directly from patients infected with malaria, and found that malaria had an unexpected effect on advanced syphilis.
Although its mechanism of action is not clear, the 1927 Nobel Prize in Medicine awarded the Austrian for "discovering the therapeutic value of malaria in the treatment of paralytic dementia".
Chen Xiaoping tried to emulate Wagner-Jauregg. In his doctoral dissertation, he mentioned that HIV/AIDS, which is now widely prevalent in the world, was classified as "incurable disease" just like neurosyphilis in that year. With the approval of the higher authorities, Chen Xiaoping began to try the first phase of malaria therapy for HIV/AIDS infection in Guangzhou.
Eight male patients, aged 23, 40, 34, 29, 27, 31, 33 and 31, were selected for the first phase of the study. Every HIV-positive patient received intravenous injection of 10 milliliters of whole blood (10 million to 16 million malaria parasites) from the current patient of vivax malaria to induce artificial vivax malaria. Malaria was discontinued (cured) with chloroquine after 10-20 times of high fever malaria array. Patients were not treated with any anti-HIV or anti-AIDS drugs during the treatment and follow-up period.
It is noteworthy that Chen Xiaoping also mentioned a detail in his paper. His team at that time initially proposed malaria therapy for HIV/AIDS in 1992, which was opposed by many American and Chinese doctors. Reasons or many data indicate that malaria infection stimulates the immune system to produce a variety of immune factors, and the increase of many of these factors is unfavorable for HIV patients and AIDS patients, such as promoting HIV replication.
Chen Xiaoping, however, put forward a hypothesis that all these harmful factors did increase significantly during the onset of malaria (based on previous knowledge of malaria), but they quickly returned to baseline levels before malaria treatment or even lower after malaria was discontinued (cured) due to the feedback mechanism of the immune system.
Based on Chen Xiaoping's hypothesis, "the Academic Committee and the higher authorities formally approved us to carry out Phase I research."
In addition to the first phase of the study, 10 men and 1 woman participated in another experiment to explore whether the direct effect of malaria infection or the secondary response or feedback mechanism after the discontinuation of malaria played a role. Similarly, HIV-positive patients and AIDS patients received intravenous injection of 10 milliliters of whole blood (about 10 million malaria parasites) to induce artificial vivax malaria. Malaria was discontinued (cured) with chloroquine after 10 times of high fever malaria array.
The final conclusion of Dr. Chen Xiaoping's thesis is that 19 cases of HIV/AIDS patients with artificial infection of Plasmodium vivax (as in the treatment of cancer) preliminarily confirmed: First, malaria therapy for HIV/AIDS is safe. Secondly, it may improve the immunological indicators of HIV/AIDS patients but not kill HIV.
It is worth noting that Chen Xiaoping's clinical trials at that time were not carried out under the condition that basic research was basically clear, but more to verify a hypothesis. "It will be confirmed or overturned in further immunological, virological and molecular biology studies and clinical observations," he said.
In addition, when he wrote his doctoral dissertation, he applied for 100 Phase II clinical studies (set up as control group) and said, "The sponsors of Phase I research have approved the funding of Phase II clinical studies at the end of the Phase II study and when the results are similar or the same as those of the Phase I study."
Peng Mei News noted that Chen Xiaoping's research team is still conducting AIDS-related research, but all of them are basic research. In December 2014, the team also published results in Retrovirology, a retroviral journal. In the study of the relationship between malaria and AIDS, a rhesus monkey model co-infected with simian immunodeficiency virus (SIV) and malaria parasite was established to simulate the co-infection of human immunodeficiency virus (HIV) and malaria parasite.
Chen Xiaoping told the media at that time that some HIV-positive patients might gain some virological benefits if they were infected with malaria at the same time on the premise of receiving antiviral treatment. However, it is also reminded that, as research is still under way, it is not advocated to encourage AIDS patients to intentionally infect malaria.
U.S. partners surveyed by the school
So who is the sponsor?
Chen Xiaoping's doctoral dissertation also has corresponding clues. Heimlich "gave most of the funding and other assistance for this research," Fahey "provided me with all the funding and guidance and assistance for my experimental research at UCLA free of charge," and Dr. Najib Aziz, Dr. Pari Nishanian and Ms. Hripi Nishanian of UCLA "did it on my own." Punctuality gives a lot of convenience and help.
Xiao Bingquan, then stationmaster of Guangzhou Health and Epidemic Prevention Station, played a key role in the research. In his thanks, Chen Xiaoping said, "Finally, special thanks should be given to Professor Xiao Bingquan, the director of Guangzhou Health and Epidemic Prevention Station, because this topic has been passed in many demonstration meetings, and Professor Xiao's efforts and support play a key role."
According to the comprehensive time line, Chen Xiaoping and Heimlich had reached their cooperation intention in 1992 at the latest.
It is noteworthy that the study, which was opposed by many Chinese and American doctors at the beginning of the proposal, triggered another wave in the United States five years after Dr. Chen Xiaoping graduated.
In an article published in the Cincinnati Enquirer in February 2003, Heimlic described his work in China and mentioned that Fahey of the University of California, Los Angeles, was involved. According to a report in the New York Times in March 2013, Chen Xiaoping's research was conducted in China at Heimlich's request and lasted from 1993 to 1996.
Henry J. Heimlich
Heimlic, who died in December 2016, was the inventor of Heimlich Maneuver. In 1974, Heimlic, 54 years old, used a method of flushing foreign bodies out of the lungs by using residual gases to form airflow for emergency treatment of airway obstruction such as foreign body sticking throat. In 1985, the United States Department of Public Health called the "Heimlick first aid method" the best first aid method, and it is also the standard method of rescuing foreign body patients in trachea all over the world.
However, Heimlic is also a highly controversial person, and one of the controversial points is the treatment of malaria. He believes that inducing malaria fever can stimulate the immune system to fight AIDS, Lyme disease and cancer. In the early 1990s, he held a fundraising party in Hollywood, raising tens of thousands of dollars from movie stars and brokers to treat malaria and AIDS.
The Centers for Disease Control and Prevention (CDC) opposes malaria treatment, and some medical experts have severely criticized him for conducting human trials in China. Noting that Heimlic encourages the use of malaria to treat AIDS and Lyme disease, officials of the United States Centers for Disease Control and Prevention issued a memorandum in April 1993 calling this practice "unreasonable". Reports at the time mentioned that such an experiment was unthinkable in the United States.
Referring to the previous study he funded in China, Heimlic said on February 21, 2003 that when he last contacted his Chinese colleagues in 2001, one person died of a disease unrelated to AIDS and the others were still alive.
But the scientific community does not agree with the results. Dr Peter Lurie, a former AIDS researcher, said it was "insufficient to explain anything" and that Heimlic's use of human subjects to test his theoretical hypothesis was "intolerable". Dr Mark Siegler, then director of the Center for Clinical Medical Ethics at the University of Chicago Hospital, said: "Fifty years ago, the United States injected patients with a dangerous disease to fight another disease, but now this practice will not be tolerated."
Several well-known AIDS researchers said Heimlic's hypothesis had no scientific significance. It is also worth mentioning that many Africans suffer from both AIDS and malaria. "There is no reason to believe that malaria suppresses HIV."
In April 2003, the University of California, Los Angeles, after launching two investigations, confirmed that a researcher had violated federal regulations and participated in a controversial medical study. The researcher, Fahey, was indirectly involved in experiments conducted in China.
The University of California, Los Angeles Institutional Review Committee reviews medical experiments involving humans. A statement issued by the committee said Fahey was not directly involved in the controversial experiment, but assessed data and biological samples brought by a Chinese scientist without the necessary permission of the review committee. The survey also found that Aziz, another researcher surveyed by the university, did not violate the regulation "to work under Dr. Fahey's jurisdiction".
In a subsequent statement, Fahey said he "regretted the misunderstanding caused by the incident". He said he indirectly participated in the so-called malaria treatment research in 1997, when he was training Chinese scientist Chen Xiaoping at the University of California, Los Angeles. Chen Xiaoping spent three months as a visiting scholar. At that time, Chen Xiaoping was testing serum collected from Chinese AIDS patients who had received malaria treatment several years ago.
The University of California, Los Angeles, also reiterated at the time that "no research has ever been approved on the treatment of HIV-related malaria".
However, during Fahey's investigation at the University of California, Los Angeles, Heimlic also announced that he was working with doctors to start human trials of the treatment in five African countries. "I don't know if Fahey followed the right procedure in his work at UCLA, which is between Fahey and UCLA," he said.
Chen Xiaoping's official resume shows that after graduating from the clinical medicine major of Guangdong Medical University in 1980, he worked as an infectious physician and assistant for 5 years in the Affiliated Hospital of Guangdong Medical University. From 1985 to 1988, he received a master's degree in infectious diseases from Zhongshan Medical University, and from 1995 to 1998, he received a doctoral degree in Etiological Biology from Zhongshan Medical University. He was a visiting scholar at the University of California Medical School in 1997.
Chen Xiaoping participated in the University of California, Los Angeles/National Institutes of Health Fogarty International Training and Research Program on AIDS in 1997, which provides AIDS control training for visiting scholars from developing countries.