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

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

July 12, 2017

Email: khcui72@hereditics.net

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*Comment for "Controversial doctor to use MRT technique for over 40s fertility", ivf.net, June 22,  2017.

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Mitochondrial replacement therapy (MRT) is reaching its peak after Dr. John Zhang (the New Hope Fertility Center Clinic in New York City) declared to use MRT for older women to get pregnancy. His theory is to use the maternal spindle transfer process to “rejuvenate” the eggs of older women aged 42 to 47 by the donor’s egg cytoplasm. The human eggs will reconstruct themselves. “Since age doesn't affect the quality of DNA directly, HER IVF replacement techniques may result in a patient oocyte (egg) that is decades younger in age than the patient herself - prolonging natural fertility”. This “invention” is looked very great and successful. However, papers published have confirmed that Zhang’s hypothesis is naive and lack of scientific bases.

 

Chasing back to a paper published by John Zhang, Hui Liu and Jamie Grifo, et al. in 2003 (Hum. Reprod 18: 1903-1907), large scale of mice experiments (483 oocytes) were performed on nuclear transfer and pronuclear transfer (i.e. chromosome transfer). The experiments produced 20 live birth (4.1%). Dr. Grifo concluded several times in news reports that pronuclear transfer was confirmed to be very safe by their plenty experiments, and FDA prohibited them to do the work in US, thus pushed them to do the work overseas. In first group of the experiments in their paper, they produced 86 of 2–cell embryos after chromosome transfer, then they transferred them to foster mice and got six mice pregnancy. One mouse was used for biopsy experiment. The remained five mice “survived to term, but none delivered a live – born pup.” They were all stillborn. How many? No report. If one mice produced six stillborn, five mice would produce 30 stillborn in this group. In second group, 68 reconstructed 2-cell embryos were transferred to foster mice. Eight pups were live birth (12%). In third group, 48 reconstructed 2-cell embryos were transferred, and produced 6 live birth (13%). In fourth group, 37 reconstructed 2-cell embryos were transferred, and produced 6 live birth (16%). How many stillbirth were produced in second, third and fourth groups? Omitted and not reported. They had set up control group for this great scale of experiments. Nevertheless only in their figure 2, they showed the control mouse uterus with significant nice, bigger and shining pregnant bulbs, while the foster mouse uterus with MRT embryos showed smaller reabsorbed bulbs (i.e. miscarriage in human). How about the live birth data of the control group? They (usually more than 30% live birth rate) were too good to be published. How about the stillbirth data of the control group? Not reported. They threw the control data and not published. Luckily, scientists working on mice embryo transfer knows that stillbirth is rare (near 0%) in normal mice, and live birth rate should be trained over 30% before any true experiment. The paper did not calculate the reconstruction failure and non-maturation rate which was up to [(483-311) / 483 =] 35.6%. This reconstruction failure rate was very similar to general reconstruction failure rate: about 33% in nuclear transfer. Obviously, this paper showed chromosome transfer in eggs severely harmed embryo formation and development and influenced live birth in their results. It was not possible to conclude as “safe” and to submit these data for FDA to review. According to their data, people can judge FDA was/is doing in a correct way.

 

The live birth (such as the cloned sheep Dolly) can show a kind of phenomenon, but cannot be used as a confirmation of safety. Also, 20 of live birth from 483 eggs (4.1%) or from 153 embryos (13.1%) in mice cannot be used as a formal confirmation of safety. Safety should be scientifically confirmed by statistical data with control group at the beginning to the end of the experiments.

 

Also in 2003, John Zhang worked in China for human MRT. According to Chairman CanQuan Zhou, (Dept. of OB/GYN) interviewed with reporter of Goat City Evening, they performed 12 MRT cycles, produced 7 pregnancies and 5 stillbirth. No live birth was available. John Zhang only selected one pregnancy and two stillbirth to report in ASRM and 2016 paper (RBO,33: 529-533). Professor GuangLun Zhuang recently complained that MRT is “very difficult to get one pregnancy” (when comparing with normal IVF). That was why in the case which John Zhang reported, five reconstructed embryos were transferred rather than usual two or at most three embryos were transferred as in normal IVF. The fact showed: MRT technique is not safe both in human reproduction and in animal reproduction. In animal research, Prather, et.al. (Biol Reprod. 1989, 41: 414-418) reported: “A total of 56 pronuclear exchange embryos were allowed to go to term, and 7 piglets were born.” That meant: (56 – 7 = 49) stillbirth happened in pig research.

 

Severe stillbirth (many more than 30 in mice, 5 in human and 49 in pig) occurred in mice, human and pig experiments. They were really horrified. People performed this work in China have a kind of guilty feeling and refuse talking about that MRT work anymore. They tried to forget it as earlier as possible. The gross assessment of stillbirth was very remorseful when facing the dark bodies. Were the stillbirth independent events? Grifo guessed that: if the work was performed in US and the pregnancy happened in US, the advanced techniques would lead to live birth. The truth was not as simple as what he thought. When omitted a lot of data, only looking at several live birth, they could confuse themselves by the make-up of the selective data. Now, three independent events (mice, human and pig) combined together. The cover-up problems exposed. It showed at least one systematical problem existing, which both John Zhang and Grifo do not notice and not understand the intrinsic reason until now.

 

The true reason of plenty of miscarriage and stillbirth happened in MRT is that the techniques of chromosome transfer break down the normal cytoskeleton in the eggs or zygotes. It’s not a shame of US government to ban MRT. But it’s a shame of our “scholars” not to read or not to understand basic university science. And it’s a shame of our “scholars” with so cruel heart when seeing so many stillbirth mice bodies and five Chinese stillbirth bodies, they still wish go ahead for large scale of manslaughter with nice word of “rejuvenate” the eggs of older women. When they focus on the cytoplasm, they only focus on hypotheses of molecular biochemical function of the cytoplasm. They neglect and ignore the molecular anatomy function of the cytoplasm. Without normal anatomy structure, our “scholars” could not stand up, could not eat and could not think, also could not survive. Anatomy is the first course in our medical college. No bases, no high-rise building. Focusing biochemical function and ignore anatomy function in cytoplasm is the same as focusing exon function and ignore intron function in DNA research. It is not scientific. Recent research results showed: human genetics or heredity IS not only depend on chromosomes, but also depend on both of INTACT cytoplasm function and intact cytoskeleton. Ignore anyone of them is not scientific. For the aim of increasing biochemical function in cytoplasm (to “rejuvenate” the eggs of older women), to damage cytoskeleton by MRT is not scientific, and it is life threatening. Also, it has been confirmed that cytoplasm was difficult to rejuvenate aging DNA in experiment. John Zhang’s theory “age doesn't affect the quality of DNA directly” is lack of scientific bases according to cancer and Alzheimer’s disease research.

 

In Chapter 16, “The Cytoskeleton” of a book “Molecular Biology of The Cell”, It said: “For cells to function properly, they must organize themselves in space and interact mechanically with each other and with their environment. They have to be correctly shaped, physically robust, and properly structured internally. --- These spatial and mechanical functions depend on a remarkable system of filaments called the cytoskeleton”.

 

“The cytoskeleton’s varied functions depend on the behavior of three families of protein filaments – actin filaments, microtubules, and intermediate filaments. Each type of filament has distinct mechanical properties, dynamics, and biological roles, but all share certain fundamental features. Just as we require our ligaments, bones, and muscles to work together, so all three cytoskeletal filament systems must normally function collectively to give a cell its strength, its shape, and its ability to move.” The egg or zygote cytoskeleton will differentiate into cytoskeleton of muscle cells and neuron cells, etc. as embryo and fetus development.

 

When muscle contract, the “force-generating molecular interaction between myosin filaments and actin thin filaments takes place only when a signal passes to the skeletal muscle from the nerve that stimulates it.” When the actin are damaged, although the muscle is existing there, it could not function as normal human muscle. It would be lack of strength. If it happened in the respiratory muscle, it would lead to respiratory failure.

 

“The heart is the most heavily worked muscle in the body, contracting about 3 billion (3X109) times during the course of a human lifetime. Heart cells express several specific isoforms of cardiac muscle myosin and cardiac muscle actin. Even subtle changes in these cardiac-specific contractile proteins – changes that would not cause any noticeable consequences in other tissues – can cause serious heart disease” “which can also result in early heart failure”. During chromosome transfer and electrical fusion, some actin will be damaged. Thus the MRT babies will have weak heart contracting muscles and they are easily die from heart failure. When heart failure combining with respiratory failure, stillbirth, or sudden death after live birth is easily foreseeable.

 

In nervous system, “Neurons also contain complex cytoskeletal structures.” “Both axons (nerve fiber) and dendrites are filled with bundles of microtubules that are critical to both their structure and their function.” Neuron function mainly is to transfer signals. “After the arm of a …cell is cut off with a needle, the microtubules in the detached cell fragment reorganize so that their minus ends … buried in a new microtubules-organizing center.” Thus the old microtubules separating parts will be difficult to reconnect together at the broken point again. In chromosome transfer, the broken microtubules will be difficult to reconstruct as the original unbroken one. So the neuron is lack of normal structure and functions. Muscles are controlled by neuron signals. When muscles could not get normal nerve signals for breath and heartbeat, human die. Or if the baby survives, the muscle function would be weaker than our normal human beings, because abnormal reconstructed microtubules will transfer lesser signals in the axon of the neuron. Live born does not mean safe and healthy in MRT subhuman beings. The reconstruction rate of cytoskeleton and other cellular organelles of the MRT subhuman beings will be varied from 40%? to 90%? in different items to be tested and in different MRT person. That is how “sub” is originated for the “sub”human beings according to scientific bases. In our human beings, our cytoskeleton is intact, i.e. we are all 100% existing there for over 5 million years and need not to be reconstructed.

 

In Chapter “The Mitochondrion”, it said: “Mitochondria are often associated with the microtubular cytoskeleton, which determines their orientation and distribution in different cell types”. Katayama (Devel Biol 2006, 299: 206-220) reported his experiment results and showed that nuclear transfer destroyed the normal movement of mitochondria to the location near nucleus to supply energy for maintaining normal function of DNA: “The ability to translocate mitochondria to the perinuclear area was lower” in nuclear transfer oocytes than in IVF oocytes. It showed that the reconstructed microtubules functioned worse than the intact microtubules. When the nucleus of the cell is lack of mitochondria energy, aneuploidy will happen. John Zhang’s hypothesis “To use the maternal spindle transfer process to ‘rejuvenate’ the eggs of older women” is failed again according to this reported animal results. His hypothesis is only for business advertisement which is lack of any scientific bases. MRT is only to harm mitochondrial function in the eggs rather than “rejuvenate” the eggs.

 

With above basic theory about Cell Anatomy – Cytoskeleton, it will be much easier to understand the comment:

“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.

 

John Zhang recently registered a new company “Darwin Life” specially offering “Human Egg Reconstitution in vitro fertilization” to perform spindle transfer. He has three reasons for this action.

 

First, he knew that spindle transfer will produce a lot more miscarriage and stillbirth than usual IVF. He had rich stillbirth experience on animal research and human practice in China in 2003. His “New Hope” clinical name is not correspond to the fact of numerous miscarriage and stillbirth. One of Darwin’s theory “Those individuals with heritable traits better suited to the environment will survive” can remind the patients what will happen: i.e. “Those eggs or embryos reconstituted or reconstructed better survive”. “Miscarriage and stillbirth are nothing to do with John Zhang”. “That is natural selection”. Thus John Zhang try to rule out his crime in subhuman reproduction by Darwinism, which subhuman reproduction is absolutely not safe. MRT is not natural selection, but is artificially creating new species of subhuman life and a kind of fascist killing by damage normal cell anatomy.

 

Second, if spindle transfer leads to John Zhang bankruptcy, he wish to use “Darwin Life” to file Chapter 11 or Chapter 13 in U.S. to discharge obligations that he owe to the patients in countless law suits. So he may save his “New Hope” business. John Zhang has foreseen that he will be in high possibility to be sued by the patients and will get bankruptcy very soon after he understood the comment “ARTIFICIAL NEW SPECIES – SUBHUMAN BEINGS (Abnormal Cell Anatomy of MRT Subhuman Species)”. In the consent form he gave the patient, he would never tell the patient that the child which he would produce would be a subhuman being, and the child would have abnormal cell anatomy problems. Registration of “Darwin Life” means John Zhang is very self-distrustful on his spindle transfer work. His previous animal and human work are full of make-up data, which are confusing his justification today: “safe or not safe?”

 

Third, John Zhang is finding A WAY TO STEP DOWN. “To use spindle transfer for old women to get pregnancy” is a way to avoid spindle transfer and get money and pregnancy. Ten years ago, IVF staff had experience that it is easy to get 60% pregnant rate for women over 40 years old. John Zhang wished to use money ($80,000 - $120,000) to motivate IVF centers to follow him for spindle transfer and push down government regulation. This is pure business thinking, and it is nothing related to science. John Zhang is in a new dilemma in this step down.

A. Go on true spindle transfer for older women: the more performance, the more lawsuits. Each of them may cost him one million or up to 3 million dollars. Because MRT person (when grows up) should not marry or sex with human beings to produce offspring to spread out the abnormal cytoskeleton in the world. Abnormal cytoskeleton is a kind of genetic syndromes created by MRT. As MRT going on, it is foreseeable that some new laboratories will be setting up soon for a new kind of medicine - Subhuman Medicine, to diagnose the reconstruction rate of microtubules, actin, mitochondria and Golgi apparatus, etc. Those subhuman children, whose reconstruction rate is not 100% in any of those test items, are qualified to sue the people who make them to be subhuman beings. It shows that MRT will not be a billions-dollar business but billions-dollar lawsuit and billions-dollars of government burden. That is why FDA ban MRT in U.S.

B. Go on normal IVF and collect $100,000 fee with the “reason” of spindle transfer, and it will not last long. One drop of child’s blood DNA can confirm that the child is not three parent genes.

C. Perform any procedures and no pregnancy was reported, and it will not last long too.

D. Perform spindle transfer with the pregnancy to be low. Other centers will show higher pregnancy rate with general IVF techniques. Spindle transfer will be gone too.

E. If charge half million dollars for one real spindle transfer, the income may just cover the law suit fee. Which patient is happy with this kind of investment?

 

On the whole, Safety of MRT is the key issue. Live birth is not the proof of safety. The end of the MRT pseudoscience is coming soon. This is the recent 20-years history of the world war between human reproduction and subhuman reproduction.

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