Montgomery and his team perform transplant operations
"This is not a progress in science and technology, but an ethical breakthrough, but it has obvious predictive clinical significance
For the world’s first organ transplant operation in which a pig kidney was implanted into a human body, Chen Zhonghua, a professor at the Institute of Organ Transplantation of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, and editor-in-chief of "Chinese Journal of Organ Transplantation" made the above comments
On October 19, the Montgomery team, professor of transplant surgery at New York University Langone Medical Center, announced that they had successfully transplanted a genetically edited pig kidney to a brain dead person
"The effect is even better than we expected
Many people in the industry believe that this operation is a major milestone in the history of organ transplantation, and it also brings hope to potential xenotransplantation in the future, and is expected to solve the current shortage of donors
However, Chen Zhonghua told China Science Daily that, strictly speaking, this is not a clinical xenotransplantation in the true sense.
Huge gap in organ donors
Huge gap in organ donors Nowadays, organ transplantation has been generally accepted by the society.
"With the promotion and use of effective and safe immunosuppressive agents in the clinic, organ transplantation is becoming more and more popular, especially the number of heart, liver and kidney transplantation is increasing year by year
Unfortunately, there is a huge gap in organ transplantation at home and abroad
According to Huang Jiefu, chairman of the China Organ Transplant Development Foundation, since January 1, 2015, voluntary organ donation by Chinese citizens has become the only legal source of organs for organ transplantation in China
Can xenotransplantation successfully escape hyperacute rejection?
Can xenotransplantation successfully escape hyperacute rejection? "If gene-edited universal sterile animal organs can be transplanted to humans, it will definitely improve the shortage of organ donors
But the difference between humans and pigs is that pigs have one more protease than humans.
"This is also one of the biggest problems facing xenotransplantation-hyperacute rejection
However, the emergence of gene editing technology seems to have brought "sunlight" to xenogeneic organ transplantation
As early as 2003, Revavicor of the United States created the world's first cloned transgenic pig that knocked out α-Gal
.
The pigs used in this operation are pigs whose alpha-Gal genes that can cause immune rejection have been knocked out using genetic technology
.
Xiu Dianrong said that the operation did show that after knocking out α-Gal, hyperacute rejection can be avoided
.
However, the targets that cause hyperacute rejection are not only α-Gal, but also CMAH gene, β4GalNT2 gene and ASGR1 gene
.
"Knockout of all relevant genes may be able to minimize the hyperacute rejection of xenotransplantation
.
"
In addition, the liver has complex functions.
Only in terms of protein synthesis, albumin synthesized by animal liver is not exactly the same as human albumin
.
Therefore, in Xiu Dianrong's view, the real realization of xenotransplantation requires further research
.
Mainly a breakthrough in ethics
Mainly a breakthrough in ethics Chen Zhonghua has reservations about how relevant media call it "the world's first case
.
"
He believes that the results of this experiment have not yet been peer-reviewed and have not yet been published in official medical journals
.
As far as the limited information provided by the media is concerned, it can only be said to be the establishment of a new model higher than the top animal experiment (non-human primate)
.
A reporter from China Science Daily also noticed on the official website of the New York University Langone Medical Center that the operation did not directly transplant the genetically modified pig’s kidney into the human body, but attached it to the subject’s upper thigh and outside the abdomen.
The blood vessel is covered with a protective cover for observation and kidney tissue sampling
.
The researchers removed the subject's ventilator 54 hours later, marking the end of the trial
.
"This model is collectively referred to as in vivo perfusion, and it is infinitely close to in vivo transplantation
.
" Chen Zhonghua said that as early as 2018-2019, he had in-depth discussions with Montgomery on this subclinical model and research at the U.
S.
Transplantation Conference.
, And carried out a detailed notification to the domestic counterparts
.
At the same time, he also made careful deployments in relevant domestic transplant centers
.
"At the end of last year, we have completed careful planning and corresponding preparations
.
"
Chen Zhonghua believes that in terms of medical technology, this kind of surgery is not difficult, and the most important reason why it can only be achieved after 2 to 3 years is the ethical obstacles and the search and collection of standard trials under the premise of informed consent
.
In the United States, brain death is the legal standard for termination of treatment
.
Although China has its own medical standards and norms for the clinical determination of brain death, the popular application still lacks corresponding policies, regulations and legal support
.
Zhang Di, an associate professor at the School of Humanities, Peking Union Medical College, told the China Science Daily that the safety of xenotransplantation still needs to consider the impact of cross-species infection on the health of individuals and populations
.
For example, studies have shown that some viruses and bacterial pathogens carried by animals do not develop disease in carriers, but they may be fatal to humans.
They may also be genetically recombined with human viruses to produce new viruses and cause epidemics and epidemics
.
This will not only affect the individual health of the recipient, but may also threaten the health of the population
.
In addition, cross-species transplantation also involves issues such as human dignity, personality identity, technology accessibility, and animal welfare
.
"Recipients of xenotransplantation may think that they are no longer humans, no longer the previous self, and have become another person or species
.
" Zhang Di said
.
"We can't stay in the laboratory forever"
"We can't stay in the laboratory forever" Of course, organ transplantation is a complicated systematic project.
In addition to the shortage of donors, there are also high costs, acute rejection, side effects of immunosuppressive agents, and infections after immunosuppressant use
.
"Some patients have satisfactory long-term results after organ transplantation, but some patients will have the problem of recurrence of the primary disease
.
In addition, the long-term management and follow-up of patients after transplantation cannot be ignored
.
" Xiu Dianrong said that any technological development is bringing mankind.
At the same time of progress, new problems will arise.
Although it is not yet possible to predict which problems will arise when animal organs are finally applied to the clinic, relevant scientific research should be done in advance and the ethical, legal and social issues caused by technology should be discussed
.
For example, what is the long-term response of animal organs after implantation in the human body, and to what extent the long-term effects of animal genes on the human body
.
"But we can't stay in the laboratory forever, we must always take a step
.
" Chen Zhonghua said that every major advancement in science and technology will inevitably put forward higher requirements on ethics, and the high standards of ethics and morality guide science and technology towards Moving in the right direction, but the ultimate goal is to serve human health
.
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