"I want a healthy baby for so many years" is the common wish of many couples who cannot give birth to healthy children because of various genetic diseases. Can the genetic curse be completely broken? What problems does human reproductive technology face? In this issue, Dr. Huang Hefeng, an academician of China Academy of Sciences, is invited to share the cutting-edge progress of assisted reproductive technology.
Character business card
Huang Hefeng, Academician of China Academy of Sciences, Academician of Developing Countries Academy of Sciences, Honorary Fellow of Royal College of Obstetrics and Gynecology. Engaged in clinical work in obstetrics and gynecology for more than 30 years, specializing in the diagnosis and treatment of reproductive genetics, birth defects, infertility and gynecological endocrine diseases. Won the honorary titles of "Bethune Good Doctor" and "Lin Cup Good Doctor in Obstetrics and Gynecology".
Noninvasive genetic testing to crack the "gene curse"
Moderator: Academician Huang, you are one of the earliest experts in reproductive medicine in China. You have worked in this field for more than 30 years. How much influence will parents' genetic code have on their children's health?
Huang Hefeng: All of us, including the descendants of animals and plants, are inherited from the previous generation, and the genetic code is in the so-called genes. But the genetic code is not copied, and it is also affected by the environment. Therefore, genetic inheritance includes both mutation and environmental impact. In the process of mutation, some genes will have diseases, that is, genetic diseases. Compared with the whole population, the proportion of genetic diseases is not very large, which may be thousands, even hundreds of thousands, hundreds of thousands of rare diseases, but falling into a family is a mountain.
As the name implies, many genetic diseases are directly inherited by parents, and most diseases belong to "recessive inheritance". People have alleles of two chromosomes. When both parents have a pathogenic gene in one gene at the same time and pass it on to the next generation, the next generation will get sick. Therefore, genetic diseases are difficult to prevent, because even if both parents are normal, they may actually carry the disease-causing genes, but they are not sick on the surface.
Now we need to screen out the pathogenic genes through scientific methods before the expectant mother gets pregnant. This technology, called "screening of couples with disease-causing genes before pregnancy", has only been popularized in recent years. If you don't screen, you don't know that there is this pathogenic gene, and you may give birth to a sick child. This is the role of genetic code in health and disease.
Moderator: In our real life, there is another situation. Mom and dad have no pathogenic genes, but the children born have problems. How to avoid this situation?
Huang Hefeng: Mom and Dad have no pathogenic genes, but the pathogenic genes have changed in the process of evolution. We call it "mutation" or "no feature", which belongs to the whole family. If passed down from generation to generation, it will become the first disease in this family. We call it "ancestor", which is the ancestor of this disease.
This situation is difficult to check, and I don't know if I have it until I am pregnant. We all know that pregnancy can be detected by ultrasound and magnetic vibration, but there are also many diseases without structural abnormalities. For example, epilepsy, he has been convulsing since birth, and his mental retardation. It is impossible to examine the uterus with ultrasound. Prenatal diagnosis is necessary, and some diseases, such as Down syndrome, are screened by amniocentesis. Because there are fetal exfoliated cells in amniotic fluid. However, there is a problem. After all, amniocentesis is an invasive operation, and not everyone is willing to do it. So one of the methods we are studying now is to diagnose whether the child will get sick by checking the mother's blood. After all, blood routine is what every pregnant woman should do, and the genes and chromosomes of the fetus are free in the mother's blood. After checking the mother's blood, you can immediately know whether the child has such a disease, and then do amniocentesis to confirm the diagnosis. This technique is called noninvasive prenatal detection of fetal free DNA (NIPT), and is currently used in clinical chromosome diseases.
Besides chromosomal diseases, the next generation NIPT developed by our team Dr. Zhang Jinglan can also be used for noninvasive detection of dominant monogenic genetic diseases during pregnancy. Dominant genetic disease means that as long as the allele of one of mom and dad is mutated, it will get sick. For example, breast cancer, as long as there is one, will get sick. At present, the next generation NIPT technology is under clinical study.
5G and Artificial Intelligence Empowering Reproductive Medicine
Moderator: During your research, have you found any types of diseases, and their heritability is high?
Huang Hefeng: Up to now, more than 10000 single-gene diseases have been found in the world. Because it rarely happens, we call it a rare disease.
We have made a technology, and now there are 83 units in the Red House Village and County Alliance, including Peking Union Medical College Hospital and Zhejiang Maternity Hospital, all of which are very good hospitals. According to our statistics, a * * * made a "carrier screening" for China's population of 1.3 million, and counted the top 1.5 recessive diseases, such as Schilling's deficiency and deafness, and the single-gene diseases of 1.5, including polycystic kidney disease and SMA spinal muscular atrophy.
The Obstetrics and Gynecology Hospital affiliated to Fudan University has built a cloud platform for genetic disease consultation and gene transmission, and analyzed patients' pathogenic genes through cloud computing. For example, I want to see the last patient, which can be achieved by giving the patient remote ultrasound. Cloud platform can gather all over the country, and this new diagnosis and treatment mode is also a good choice when the relative doctors in China are not satisfied, especially when COVID-19 is now normalized.
Moderator: Not long ago, the Obstetrics and Gynecology Hospital affiliated to Fudan University launched the country's first online multi-functional one-stop birth defect prevention and control platform, which helped a Hunan patient to quickly find her relevant information report through the platform. Can you tell us again what kind of operation mode the platform is?
Huang Hefeng: This case is very interesting. The other end of our connection is Hunan Maternal and Child Health Hospital. The situation is a young couple. The woman was only 22 years old, but her pregnancy was terminated at 16 weeks because the child was found to have many cysts on both sides of the kidney, just like blisters and grapes. But strangely, neither father nor mother has this gene, but the fetus has two pathogenic genes, which leads to the disease. Therefore, through the technology of 5G and AI empowerment, we first made a genetic numerical diagnosis of the genetic material of the couple and the fetus, which was uploaded in about 9 minutes. Then, through cloud computing on more than 40 computers, we immediately found out the pathogenic gene PKD 1. For this pathogenic gene, when the patient gives birth to a second child, we are going to be the third generation test-tube baby and shave off the PKD 1 gene.
The cloud platform extends the service radius of top hospitals.
Moderator: How to make this technology more popular and let more hospitals master this technology?
Huang Hefeng: In fact, some of the 83 units we cooperate with have our level, some may not be at the same level, and some are even at the grassroots level. However, it is impossible for any medical institution to establish such top-notch technology, and the other is even more unattainable. Therefore, we hope to have a good diagnosis of polygenic diseases scattered in all corners through alliances at different levels.
The birth defect prevention and control platform can do many things. One is training, such as genetic counseling, detection of genetic data, MDT multidisciplinary counseling. Because there are many kinds of diseases, an obstetrician and gynecologist doesn't know about other diseases, so when consulting, such as hematologists and brain doctors, I feel very relaxed and particularly effective. This platform is actually more targeted, more efficient, more accurate, smarter and more user-friendly. In fact, more than 80 units are also responsible for many, such as Zhejiang Maternal and Child Health Hospital, where the whole of Zhejiang Province is treated. He may come to consult us again, so the Red House Hospital basically brings together some top hospitals in China. Because they are the top hospitals in the province, they can not miss a few families, which is what we also hope to do.
Second, the red house hospital can detect and analyze genes, which the general hospital can't. The birth defect prevention and control platform has a green channel, which is opened through internet hospitals and mobile medical care. Once the patient is found to have a disease, he can quickly go to the hospital for diagnosis or even treatment through the green channel.
Moderator: Academician Huang, we know that medical resources in different regions may be unbalanced. As far as "prenatal and postnatal care" is concerned, how to make the whole country enjoy balanced medical services as much as possible?
Huang Hefeng: The technology of "screening couples with pathogenic genes before pregnancy", especially gene analysis, whole family screening and gene pathogenicity, is very difficult and requires a strong team of doctors. If we want to promote some rare diseases in the whole country, we must think of some new models, such as taking a region as the center, or taking a province as the center, or even making it bigger, such as East China or making it bigger, and setting up several centers throughout the country. Now our country is also doing this, and the Ministry of Science and Technology will build a clinical research center for birth defects and rare diseases throughout the country.
Honglou Hospital is also laid out according to its own technological progress. With the help of the resources of the Obstetrics and Gynecology Hospital affiliated to Fudan University, we have established the Red House Alliance, including more than 80 hospitals. Therefore, I think it is still the same as what the country thinks, because it is impossible to develop high-tech equipment and talents at the grassroots level, because high standards are required.
Through the interpretation of Academician Huang, we know that the development of medicine is increasingly dependent on the collection, analysis and processing of big data. The empowerment of 5G has also broken the barriers of time, space, professional disciplines and personal experience, overcome the limitations of materials and equipment, and extended the service radius of top hospitals and top experts. We also hope that everyone in China can get their own genome sequencing data in the shortest time in the future, which will play a very important role in improving people's health, diagnosing and analyzing diseases, and decoding rare diseases.