​

Ke-Hui Cui M.D., Ph.D.

Savannah, Georgia, 31405, U.S.A.

May 3, 2017

Email: khcui72@hereditics.net

​

​

*Comment for "Method behind first successful mitochondrial replacement therapy revealed", ivf.net, April 9,  2017.

​

Creators of first artificial subhuman baby in human history, John Zhang et al. published his paper in Reproductive BioMedicine Online (RBMO) 34: 361-368, 2017. There are many severe problems in the published paper and other MRT related reports.

 

1. All of the news were reported that Zhang’s procedures were performed in Mexico. Thus Zhang’s procedures did not violate U.S. regulations. However, this paper showed most of Zhang’s procedures were performed in U.S. and only embryo transfer was performed in Mexico. This paper confirmed that Zhang and his workers broke U.S. regulations in the U.S. territory. Those original news were falsified in order to escape U.S. government punishment.

 

2. The paper described the stimulation was minimal ovarian stimulation. However, 18 oocytes were collected in the second cycle was belong to hyperstimulation. The author used “minimal ovarian stimulation” in the published paper as his business advertisement, rather than scientifically reported his work.

 

3. Although editors urged the author to describe the oocyte quality in any depth, the author refused to do so. This was one of the reason that all editors of RBMO were unanimous in deciding that the paper should be published for further critical evaluation and open discussion. All of the oocyte retrieval results and fate of oocytes were outlined in the Table 1 of the paper. The paper described: “Because of the overall poor quality of the oocytes, only nine of the 29 harvested oocytes were found to have a polar body (MII) oocytes”. Was it true? Zhang was reckless.  In Table 1, eleven rather than nine of MII oocytes were found. Also, a total of 15 oocytes were described as “degenerate”. What was the reason for so high number of oocytes to be “degenerate”? It was a great issue related to whether the MRT techniques were safe or not. Let us analyze all of the data step by step about Table 1 to confirm the inappropriate report manner.

A. In 29 oocytes, there were three oocytes with germinal vesicle. It meant that the cycle stimulation days were not overdue. Under this condition, the oocyte membrane would be tough and was not possible to be broken down during retrieval.

B. No MI oocytes were reported. If there was any MI oocyte, it would be reported as the case of germinal vesicle to be reported.

C. Although the editors mentioned the possibility of atretic oocytes to be the degenerate ones, the author keep the writing not to be changed. It meant that no atretic oocytes were found.

D. Some trick was hidden in the table1. There were two rows of MII oocytes: one row was “MII (spindle visualized)” and another row was “MII without zona”. They hinted more MII oocytes to be possible in other row. Thus the degenerate row was the focus for everyone to guess whether they were the MII oocytes or not. Without spindle transfer experience, no one could guess them correctly. That was the point for the author to “play” the MII data easily.

E. There were two MII oocytes without zona. It meant the worker’s skill for hand manipulation in deluting oocytes was poor. He was not a very careful worker.

F. After retrieval and oocyte delution, no atretic oocyte and no MI oocyte were found. What were the reason to produce 15 oocytes to be degenerate? If the “degenerate” row was also belong to MII oocytes and some of them were categorized as degenerate by no spindle view, and some of them were degenerated in the courses of spindle aspiration and electrofusion, and also in the later course of embryo death, the editors’ question could be solved. The author avoided to mention any of them for the safety reason. He only put them simply as “degenerate” due to “poor quality of the oocytes”. He showed very nice and very safe results of spindle transfer for FDA to scrutinize, for Human Fertilization and Embryology Authority (HFEA) in U.K. to further support mitochondrial replacement techniques (MRT), and for the world people about his “milestone” work.

G. No document could be shown in the world that a mother with mitochondrial mutant load 23-33% would produce poor oocytes with high degenerate rate. This mother had pregnancy for four times. It confirmed that most of her oocytes were good in quality at the MII stage rather than too poor to have polar body.

H. In spindle transfer, MII oocytes will not be able to be shown 100% spindle view with polscope. If they can be shown 80%, it will be good enough. The author showed it to be 100% successfully.

I. During maternal spindle transfer (MST) or pro-nuclear transfer (PNT) in MRT, chromosomes (spindle or pro-nucleus) of the mother’s eggs (or zygotes) were torn out from mother’s eggs. Microtubules connecting to those chromosomes were also torn, turn to be thin and at last broken down. To use 15 micrometer OD glass needle to aspirate spindle, 80% success rate without cell lyses would be very good. The author and his worker used 20 micrometer OD glass needle to aspirate spindle showed it to be 100% successfully without any cell lyses.

J. When the chromosomes were transferred by electrofusion to enucleated donor’s cytoplasm, 90% success rate would be very good.  The author showed it to be 100% successfully.

K. When embryos showed two pronuclei and grow to blastocyst in IVF, 80% blastocyst rate is very good. The author showed it to be 100% successfully with spindle aspiration and electrofusion reconstructed embryos.

The author used very “poor quality” oocytes, and used poor aspiration needle with poor manipulation skill (above E) performed by the reckless worker for the very traumatic procedures. They reported their result data as 100% successfully in the above procedures of H, I, J and K. It meant that the author had used the worst stuff with most harmful techniques, and he would have produced the best results in the world. It was naïve, impossible and inappropriate. Every embryologist still remembers the 15 “degenerate” oocytes, and knows that oocytes with poor quality will never survive well in severe traumatic manipulation, and they will never develop well in later growth and produce live birth. Put 15 oocytes to be “degenerate” but not “MII oocytes” is out of common sense. Those 15 oocytes were not only (MII) mature oocytes with polar body, but also were manipulated by them in spindle transfer. Their results were degenerated. The author wished to set up his “degenerate” model as a new format for pseudoscienticists to follow in their future subhuman reproduction, to elude safety problem.

 

4. To avoid safety problem, Zhang used another “scientific” technique in his another report paper, which technique may be called “selective data report or part data report”. When he performed PNT in China in 2002 and 2003, total 7 to 10 pregnancies were reported by the news in autumn of 2003, in which five stillbirths happened without any live birth. These data showed very severe safety problem of MRT. U.S. FBI and FDA chased Grifo and Zhang into China and protested to Chinese government. Chinese government – Department of Health immediately banned MRT practice in China in the week of the news report. (That was why Zhang perform frozen embryo transfer in Mexico in 2016). Zhang should report the whole picture of PNT results in China to the public. However, he only reported one pregnancy with twin stillbirth in the 2016 paper after 13 years of the practice in China. The “selective data” report showed much better condition to the public. It was a misleading report. In Zhang’s recent live birth report, the author claimed that only one case of MST was performed. It was forever not possible for the public to know how many cases the author had performed, while “selective data report” existed.

 

5. .Jacques Cohen also used “selective data” to report his MRT health documents. He performed MRT with 5-10% of cytoplasm transfer which was mild damage to the eggs and embryos, because no chromosome transfer was performed. He only selected 13 from 17 cases to report. His incomplete report still showed the MRT babies (produced by only cytoplasm transfer) are suffering from more immune deficiencies and neuropathy problem than usual incident rate of general population. It showed that the three parents’ proteins and genes may be the factors to harm the offspring’s immune system and mental development by embryonic feedback mechanism which has been confirmed in mouse experiments. The results of the quadruplet which did not be reported are very questionable in safety. If four children were suffering from mental retardation, the safety problem would be much severe.

 

6. There was no statistical animal research data to confirm the safety question of MRT in the world. The reason was: It was very obvious that MST and PNT were both very traumatic procedures. The statistical results would only show that they were not safe even use the techniques to produce the first generation babies comparing with a control group. If using the sperm and oocytes from the first MRT generation to produce second generation with MRT techniques, the results would have be much horrible while comparing with the control group. How about the third generation and up to ten generation comparing to the control group? That was why in animal research, people could only use birth case report to show a miracle in MST or PNT. The birth report is to show a life can be produced by the procedures but it is not the statistical results to confirm safety issue. This was the same reason why the cloning sheep Dolly was a case report and there was no statistical data to confirm whether the clone techniques were safe or not. Only the statistics is a scientific method for safety research. A case of birth report is not a reason for scientists to change statistics method to be case birth method to confirm safety. To use live birth report with untrue data or selective data to attract public is not scientific but misleading. It is a corruptive business manner reflects to the field of human reproduction.

 

8. Both electrofusion and virus techniques will harm DNA structures and they are not suitable to be used on human reproduction while germline cells are very vulnerable to anything rather than itself cytoplasm.

 

9. Professor Sir Doug Turnbull and Sir Dr. Winston in U.K. should change their research manner from case report to more scientific statistics, from clinical practice to more basic research, such as Cell Anatomy. Then they can understand that human cell structure should not be changed for the aim to prevent genetic diseases. The unique natural and normal cell structures in human beings are the basic stone for normal genetic materials to be normally inhered to our generation from one million years ago.

 

10. HFEA in the U.K. should suspend the issued licence in Newcastle Fertility Centre about performing MRT with PNT or MST techniques. HFEA should avoid using British people as animal to perform MRT. The basic reason is: MRT with PNT and MST techniques will change the normal cell structures in our human beings to be chaotic cell structures, which will produce severe safety problem. MRT will make human reproduction to be changed into subhuman reproduction. Human species will be changed into subhuman species by the change of germline cell structures.

 

Please also read: “ARTIFICIAL NEW SPECIES – SUBHUMAN BEINGS (Abnormal Cell Anatomy of MRT Subhuman Species)” published on ivf.net 09 April 2017 comment for “Method behind first successful mitochondrial replacement therapy revealed” response on 27 April 2017.

​

​

​

​

​

​

​

​