More than 30 years ago, two pictures in the epidemiology class gave him a flash of inspiration, "It seems that where there is more malaria, the mortality rate of tumors is low." This is the source of Chen Xiaoping's self-described research on "malaria parasite treatment of cancer" by Chen Xiaoping, a researcher at the Guangzhou Institute of Biomedicine and Health of the Chinese Academy of Sciences.
Chen Xiaoping
On January 28, the official microblog of the Chinese Academy of Sciences released a message, and in a public speech at the Self Forum of the Chinese Academy of Sciences, Chen Xiaoping introduced his research work: the use of malaria parasites to successfully treat patients with advanced cancer. Chen Xiaoping said that the team found that tumor mortality and malaria incidence showed a negative correlation, malaria parasite is helpful in the treatment of cancer, the current clinical trial found that 10 patients, 5 people have obvious treatment effect, of which 2 may be cured. The Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University is organized for the approval of the ethics defense.
Although there are only a few dozen treatment cases and have not yet been officially published in academic journals in the form of papers, "Cure Cancer" still arouses great concern among the public, and it has been half a month since the video was released, but the news is still on the Internet.
On February 12, the surging news (www.thepaper.cn) saw in the ward on the 24th floor of the First Affiliated Hospital of Guangzhou Medical University that someone was responsible for organizing the collection of advanced lung cancer patients in clinical trials, and the patients who filled out the form here came from all over the country. Willing patients enter a WeChat group, and the number of people in the group has reached more than 100 people. The person in charge of the site asked the patient's family who had filled out the form to wait for the next day's phone notification.
According to the families of patients at the scene, the cost of treatment is 10,000-20,000. Chen Xiaoping's team and the clinician of the First Affiliated Hospital of Guangzhou Medical University were not in the performance field, and the staff member responsible for organizing the scene was a staff member who claimed to be surnamed Tong of Guangzhou Zhongke Lanhua Biotechnology Co., Ltd.
The Paper's reporters Deng Yafei and Zheng Chaoyuan took photos
It is worth noting that this cancer treatment strategy, which is popularly known as "attacking poison with poison", returns to the essence of science and is actually the tumor immunotherapy that has been popular in recent years. The so-called tumor immunotherapy, that is, by stimulating the patient's own immune system to attack tumor cells. After direct surgical resection, chemotherapy, radiation therapy and other means have failed, immunotherapy is often seen by cancer patients as the last glimmer of light.
The 2018 Nobel Prize in Physiology or Medicine was spent on immunotherapy. The awards of James Allison and Tasuku Honjo have made the therapy a leading example of the current field of medicine.
In response to Chen Xiaoping's first disclosure of "curative effect" in his speech, some voices said that the malaria parasite "made a great contribution", and some people in the industry believe that there are still many doubts, at least they should be cautious to publish papers formally through peer review. Another collaborator of the project, Academician Zhong Nanshan, chief physician of the Department of Respiratory Medicine of the First Affiliated Hospital of Guangzhou Medical University, responded on February 7 that the therapy is still being experimented with and has not yet reached the stage of being approved for conditional medication. "There seems to be some signs now, but it's too early to draw conclusions."
Is the malaria parasite an "assist" or a "killer" to cancer?
In 1880, the Frenchman Charles Louis alphonse laveran discovered the malaria parasite, which was the first time that protozoa could cause disease in humans. In 1897, British physician Sir Ronald Ross discovered the path of transmission of the parasite: through the Mosquito. The two were awarded the Nobel Prize in Physiology or Medicine in 1907 and 1902, respectively, for their research.
Malaria parasites are single-celled protozoa, and human diseases caused by malaria parasite infection are medically called malaria, commonly known as "pendulum". Malaria requires treatment with drugs such as artemisinin to cure it, and Chinese scientist Tu Youyou won the 2015 Nobel Prize in Physiology or Medicine for discovering artemisinin.
What is the relationship between malaria parasites and cancer?
According to Chen Xiaoping, when he was a graduate student in infectious diseases at Sun Yat-sen Medical University, in an epidemiology class, the teacher hung up a map of the global prevalence of malaria, which showed that malaria was mainly concentrated in tropical areas such as Africa, where mosquitoes are dense. A few weeks later, in the tumor epidemiology class, the teacher hung up another tumor map. Chen Xiaoping had a flash of inspiration in his mind, and he vaguely felt that "where there is more malaria, the mortality rate of tumors is low."
Will cancer patients get better if they get malaria? This was the entry point for Chen Xiaoping to try to treat cancer after that.
However, whether malaria and cancer are negatively correlated is currently different.
According to the surging news (www.thepaper.cn), as early as 1996, Chen Xiaopingren published a paper in the Chinese Journal of Preventive Medicine, entitled "The Relationship between Malaria and Tumors". In this paper, Chen Xiaoping mentioned that the study of the relationship between malaria and tumors is one of the major topics in medicine and biology, which deserves the great attention of the medical community. However, the article does not involve specific studies or experiments, but only a simple comprehensive analysis of the epidemiological and clinical trial research data that have been previously used by the two.
In 2017, Chen Xiaoping collaborated with Boston University in the United States and McGill University in Canada to publish a research paper "Worldwide malaria incidence and cancer mortality are inversely associated" at infect agent cancer. The objective of the study was to assess a possible link between malaria incidence and human cancer mortality.
The paper compared the mortality rates of 30 cancers in 56 countries worldwide and the incidence of malaria in those countries between 1955 and 2008, with age-corrected data and exclusion of mixed factors such as national income levels, life expectancy and geographical location. The findings suggest that malaria incidence is negatively correlated with global cancer mortality, in particular malaria incidence is inversely associated with colorectal and cancers (men and women), (colon cancers men and women), lung cancers (men), stomach cancers (men) and breast cancers (women).
The team believes that the activation of the entire immune system and the suppression of tumor angiogenesis by malaria parasite infection may partly explain why endemic malaria may reduce cancer mortality at the population level.
However, just after Chen Xiaoping announced the "efficacy" of malaria parasites in the treatment of cancer, Wang Liming, a professor at the Institute of Life Sciences of Zhejiang University and a well-known popular science writer, wrote on his certified Weibo that the 2008 global malaria incidence and global tumor mortality distribution map used by Chen Xiaoping in his speech was incorrect, and posted the global cancer mortality rate (age correction data from the University of Washington Institute of Health Indicators and Evaluation ihme) that he found, and the two were very different.
Wang Liming also particularly emphasized two important factors that must be taken into account. First, in malaria-endemic areas, the use of antimalarial drugs, such as quinine and artemisinin, is naturally more widespread. There has been speculation that these two drugs may have anti-cancer effects in themselves, and there are some related studies. Therefore, the weak negative correlation observed by Chen Xiaoping may not be the result of the high incidence of malaria, but the use of antimalarial drugs. Second, malaria has been well-researched to significantly increase the incidence of certain cancers, and considering this, malaria and cancer mortality rates, even if there is a weak negative correlation, need to be used with great caution.
Scientists have indeed confirmed that malaria parasite infection increases tumor risk. In August 2015, Davide Robbiani and colleagues at Rockefeller University in the United States unveiled a mystery that had been around for more than 50 years in the top academic journal Cell: the link between malaria and Burkitt lymphoma. Burkitt lymphoma is a common childhood cancer with an incidence nearly 10 times the average in equatorial Africa, where malaria is also endemic. The researchers confirmed in mice that in the long-term fight against Plasmodium falciparum, B-cell DNA becomes susceptible to carcinogenic mutations.
The safety and efficacy behind "attacking poison with poison"
In addition to the relationship between malaria and tumors, how should Chen Xiaoping's team balance the safety of therapy with the possible efficacy?
Similar cases can be started 200 years ago. Doctors at the time noticed something unusual: bacterial infections sometimes relieved or even eliminated cancer. Since then, the question of whether bacteria can affect tumors has been lingering in people's minds.
American doctor Willian Coley eventually became the first person to eat crabs. In the late 1880s, by injecting patients with a combination of various live and dead bacteria, Coley found a mixture known as "coley toxin." This mixture can cause most tumors to subside, sometimes even eliminating them altogether. Until 1963, this method was still used in the clinical treatment of sarcoma.
However, due to the unclear mechanism behind it, "coley toxin" was gradually abandoned after the emergence of radiotherapy, chemotherapy and other means. But after immunotherapy gradually occupied a position on the scientific stage, Coley was hailed as the "father of cancer immunotherapy".
Like Coley's method 100 years ago, Chen Xiaoping used malaria parasites and bacteria, which infect cancer patients with pathogens, triggering an immune response in the human system, using the tumor patient's own immune system that wakes up from a "deep sleep" to kill tumor cells.
Chen Xiaoping said in his speech that after 14 years of research, the research team found the mechanism behind the phenomenon. In September 2011, Chen Xiaoping and Zhong Nanshan, as co-corresponding authors, published a paper in the journal Plos one in the United States: In vivo experiments, it was confirmed that malaria parasite infection can significantly inhibit the growth and metastasis of lung cancer (lewis lung cancer) in mice, and significantly prolong the survival time of tumor-bearing mice.
In 2017, Chen Xiaoping's team also published a paper in the journal Oncogenesis explaining the mechanism behind it. Chen Xiaoping also mentioned in his speech that in mice, for example, after cancer mice are infected with plasmodium, their immune cells, such as nk cells and T cells, will be activated, and these immune cells will kill tumor cells after activation. At the same time, the cells in the tumor tissue that inhibit the anti-tumor immune response are also inhibited by the malaria parasite infection, thus liberating the immunosuppressive microenvironment in the tumor tissue and promoting T cells to enter the tumor, thereby effectively killing the tumor cells.
The research team mentioned in the paper at the time that the research has positive application prospects, that is, malaria parasite infection may be used for immunotherapy for lung cancer, and may also be used as a new vector carrying tumor antigens to develop new and effective therapeutic lung cancer vaccines.
Compared with Chen Xiaoping, Zhong Nanshan seems to be more cautious in facing the public. According to Zhong Nanshan, the experiment has been carried out for nearly 4 years, and it has been used for other treatment methods without effect, and the disease is in the treatment of terminally ill patients. Zhong Nanshan said that nearly 30 cases have been clinically studied, and 10 cases have been observed for one year, of which 5 cases have a more obvious effect, these patients mainly have lung cancer, there are also a small number of prostate cancer, bowel cancer patients.
Zhong Nanshan said that there are still many unknowns in the study, there is not enough evidence and a sufficient number of cases to confirm the effectiveness of the method, and individual cases are not enough to explain the problem. "There seems to be some signs now, but it's too early to draw conclusions." He also said that infection with the malaria parasite can cause patients to develop various symptoms such as periodic fever, and many problems still exist. "The fever is too high to be controlled, and after infection with the malaria parasite, the patient should be specially protected to prevent the mosquito from infecting the malaria after the mosquito bites the patient."
A chief physician of the Department of Respiratory Medicine in Shanghai mentioned in an interview with the surging news (www.thepaper.cn) that "the prospects for the treatment of lung cancer by malaria parasites are still uncertain, and the efficacy, safety and prevention and control of infectious diseases must be taken into account." The chief physician said, "This therapy should currently be a small preclinical attempt, and the effect has yet to be verified." ”
Wang Liming believes that more than 100 years after the birth of Colley toxin, scientists should dig deeper into the mechanism behind this and find out what immune cells the malaria parasite activates in the human body, how to activate, which part of the activation is meaningful and which part of the activation is non-specific and needs to be avoided, and finally guide us to develop effective and safe new drugs. Instead of simply and crudely imitating Dr. Coley more than 100 years ago, the toxin was directly injected into the human body.