Under the guidance of the National Health Commission, the "Expert Consensus on Clinical Trials of Chinese Xenotransplantation" released by the China Organ Transplant Development Foundation on the evening of the 6th made it clear that for xenotransplantation, it should be based on the attitude of "encouraging research and prudent development", scientifically evaluating research progress and soberly recognizing the risks associated with it.
This stems from a big debate about how far heterogeneous organ transplantation can go from animal experiments to clinical success, and whether it can effectively alleviate the shortage of human organ supplies.
In January this year, an unprecedented operation was completed at the University of Maryland Medical Center in the United States, which attracted the close attention and heated discussion of many authoritative experts in the global medical community.
Why is this surgery so special?
The patient undergoing surgery, David Bennett, 57, suffered from a terminal heart attack and was disqualified from receiving a routine human organ transplant.
Reluctant to give up, Bennett pinned his hopes on a special source of organs, the genetically modified pig heart.
Under the "compassionate use" provisions of the FDA (U.S. Food and Drug Administration), Bennett underwent surgery on Jan. 7 after receiving a "special license."
On January 7, 2022, the University of Maryland Medical Center team underwent a heart transplant. Image credit: University of Maryland
Xenotransplantation has never been officially approved in the United States.
According to the University of Maryland Medical Center, in the weeks after the operation, Bennett's transplanted heart functioned well and showed no signs of rejection. He lived with his family and received physical therapy to help restore his strength.
David Bennett ( right ) undergoing a swine heart transplant , preoperatively with Bartley Griffiths , a professor of surgery at the University of Maryland Medical Center , left. Image credit: University of Maryland
Unfortunately, about two months after the transplant, Bennett tragically died, the cause of death has not yet been officially announced.
Behind the big discussion caused by this operation, global problems such as severe shortage of donors and high cost of organ transplants have been highlighted.
Jeff Huang
Chinese organ donation and transplantation
Chairman of the Committee
· In recent years, China has become the world's second largest transplant country, after the United States.
· The average annual number of new organ failure patients in the two transplant countries in China and the United States is about 300,000 and 120,000, respectively, but only less than 20,000 and 40,000 organ transplants can be obtained, respectively, while China's organ donation rate per million population (PMP) ranks low in the world, less than 1/10 of Spain, which has the highest PMP.
The huge gap between supply and demand has left hundreds of thousands of patients with organ failure waiting to die in waiting for a donor.
Number of human organ transplants in mainland China from 2015 to 2020.
Source: Report on the Development of Organ Transplantation in China
Voluntary organ donation rate per million people on the mainland from 2015 to 2020. Source: Report on the Development of Organ Transplantation in China
Xenotransplantation seems to let people see the dawn of solving the problem of shortage of human organs.
The "Economic Reference News" reporter learned that at present, many teams in the mainland are engaged in heterogeneous organ transplant research, and the production capacity of gene editing technology and gene editing pigs is close to the international advanced level.
Among them, about 20 medical institutions or biotechnology companies have conducted xenotransplantation experiments in pig-monkey models. As an organ donor, gene-edited pig breeding has formed a certain industrial scale, attracting a large amount of capital influx.
As a medical experimental exploration, xenotransplantation research is necessary. But the medical team's so-called "success" of the experiment does not mean that humans will soon be able to perform xenotransplantation procedures.
Since the 1960s, the world's key cases of xenotransplantation. Source: Xenotransplantation (published by Shanghai Science and Technology Press)
Relevant departments and authoritative experts said in an exclusive interview with the "Economic Reference Daily" reporter that although xenotransplantation has certain scientific exploration significance, but from animal experiments to clinical success, the road is still very far away, beware of becoming an academic or capital speculation gimmick.
At present, there are three major risks to xenotransplantation:
Risk one: Immune rejection is difficult to avoid completely
The Economic Reference Reporter learned that the pigs used in Bennett's surgery were "knocked out" of three genes that would cause human rejection, as well as a gene to prevent excessive growth of pig heart tissue implanted in humans.
On January 7, 2022, the University of Maryland Medical Center team removed the pig heart from the device stored in vitro. Image credit: University of Maryland
Zhoujiang Bridge
People's Hospital of Wuhan University
Head of the Organ TransplantAtion Section
Organ transplantation engineering is very complex, and the immune rejection disorder of all-species organ transplantation has not yet been fully resolved, let alone xenotransplantation.
Xue Wujun
Xi'an Jiaotong University
Director of the Institute of Organ Transplantation
Cardiac functional compatibility issues of xenotransplantation need to be observed and resolved. At present, it is not clear whether pig heart can fully exert the function of the human heart, including hormone secretion, metabolic balance and so on.
Zhao Hongtao
China Organ Transplant Development Foundation
Chairman
In fact, xenotransplantation, including baboon heart transplantation, has been tried as early as the 1980s and 1990s, but the effect has always been unsatisfactory because the rejection reaction is too severe.
Delayed rejection may occur within weeks, months, or even years after xenotransplantation, and the mechanism of immune rejection of these types is currently unknown. In addition, the genetic modification project does not only knock out the target gene to represent complete resistance to rejection, but also needs to cooperate with a certain immunization program to ensure the success of xenotransplantation.
Risk two: There are major hidden dangers in the biosecurity of cross-species transplantation
On October 20, 2021, the surgical medical team at NYU Langone Medical Center performed a kidney "transplant" operation. Image credit: New York University
Xenotransplantation also faces the risk of cross-species virus infection, and blindly carrying out xenotransplantation clinical trials may cause catastrophic consequences for the spread of unknown viruses and pathogenic microorganisms in animals in humans.
Currently, so-called external physical cleansing methods, such as ultra-clean pig facilities, cannot alter the endogenous potentially pathogenic genes of pigs.
At present, there are 18 kinds of microorganisms known in pigs with "human and non-human" animal transmission. Among them, the most difficult to eliminate is the endogenous retrovirus in pigs, which poses a threat to public health security.
Risk three: social ethics cannot be ignored
Chen Zhonghua
Tongji Hospital affiliated to Huazhong University of Science and Technology
Professor, Transplant Institute
Surgical protocols for xenotransplantation have been proposed for several years and have only been implemented for nearly two years, the most important reason for which is that ethical reviews and standard trials must be carried out with informed consent.
For human heart transplantation, clinical experience can determine that the heart is not a simple biological pump. Recipients will be affected by donors to varying degrees after surgery.
For xenotransplantation, it is bound to bring about changes in epigenetics and even the temperament of the recipient.
In transplant medicine, it is more necessary to strengthen ethical norms and respect for life and human dignity.
There are both medical value and various risks, what to do?
Previously, the CPC Central Committee and the State Council issued the "Opinions on Strengthening the Ethical Governance of Science and Technology", which clarified the ethical principles and governance requirements of science and technology, the governance system of scientific and technological ethics, and the guarantee of the governance system of scientific and technological ethics, and also clarified the boundaries for the ethical governance of science and technology such as xenotransplantation and gene editing.
The relevant person in charge of the Medical Administration Bureau of the National Health Commission
While technological progress, xenotransplantation also involves anthropology, sociology, ethics and other aspects, which will have a huge impact on social ethics.
Therefore, with a high sense of responsibility and the attitude of "encouraging research and prudent development", we should scientifically evaluate the progress of research and clearly recognize the relevant risks.
On June 13, 2020, Liu Jincheng (first from left), director of the Cardiovascular Surgery Department of Xijing Hospital of the Air Force Military Medical University, and team members performed a swine-monkey xenophate heart transplant. Reporter Zhang Yinan photographed Xinhua News Agency
The experts interviewed said that they believe that in the future, the advancement of xenotransplantation technology will find a solution for the shortage of organ transplant donors, but it is not yet the direction of human pragmatic solutions to high-quality transplant medical services.
At this stage, promoting citizen voluntary organ donation is a realistic way to solve the shortage of donors and the reform of organ transplantation.
Source: Economic Reference Newspaper
Editor-in-charge: Guo Yanhui
Proofreader: Huang Chenxi (Intern)
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