There is still a long way to go in understanding life

Explore, let human beings live healthy, happy and quality lives

Liu Ying, a professor at Peking University's School of Future Technology, said: "I am very interested in life. I am curious about what is going on inside the human body all the time, and I want to understand ourselves."

Liu Ying specializes in cell biology, studying human metabolism and aging. "Cells are the most basic structural and functional units that make up life. Life is too complex, let's first study the things inside the cell. Study how a cell senses changes in its environment, changes in the levels of energy or nutrients it can use. When we eat a full meal, proteins break down into amino acids, and cells sense these nutrients and cleverly start anabolism, storing up our excess, surplus nutrients. When the cells are hungry, they sense the lack of energy and material in the environment and break down what they have stored to provide energy."

Liu believes it is crucial to study how cells adapt to their surroundings. "Many cancer cells can also continue to grow in an environment with limited nutrients, resulting in excessive cell proliferation and division. So when we do research, we find that some genes are closely related to the development of cancer. In addition, changes in the metabolic state of cells are also closely related to aging. "It's very interesting that people can slow down aging with moderate caloric restriction."

In 1865, Mendel published the hypothesis of the law of inheritance based on the pea hybridization experiment, and genetics was born. Subsequently, genetics and evolution combined to give birth to molecular biology, recombinant DNA technology. In 1990, the Human Genome Research Project was launched. By 2003, scientists had completed the determination of all 3 billion pairs of base sequences of the human genome, and life science was believed to have entered the era of post-genome and proteomics.

It took more than 100 years for human beings to complete the description of the whole face of the genome, which changed our view of life, so that we can rethink what life is, and see a clearer new picture of life.

But human beings are still powerless over "life" in many cases - from cell research to the entire field of life sciences, the understanding of life is still based on limited genetic information. Scientists have crossed the barrier of limited genomes in an attempt to uncover why life behaves in an infinite way of development and differentiation.

"Some time ago, I saw a video where someone said that the science of life is now 90 percent of the way to understanding life." Professor Yang Maojun of the School of Life Sciences at Tsinghua University does not agree: "According to my personal understanding and the law of scientific research, the cognition of life science is still in its infancy and cannot be quantifiable." If I had to quantify it, I'd say less than 1%. Knowledge is like a point, with the accumulation of knowledge, as the point expands into a circle, the more unknown knowledge outside the circle is exposed to, unknown knowledge is infinite, but the knowledge we know is limited, compared with infinite, I really can not define the extent of our understanding of life."

So what can the life sciences do for us? Yang Maojun said that the question should be asked, what do we humans want the life sciences to do for us? "A healthy, happy and quality life, of course. The development of life science in these years is obvious to all. Take the average life expectancy of China's population as an example, it was 35 years old in 1949, 57 years old in 1957, 68 years old in 1981, 75 years old in 2010, and 77.3 years old in 2019. In the past, we often said that life is rare in the past 70 years, and now the elderly over 70 years old are everywhere. This is the most intuitive manifestation of the rapid development of life science in China over the years."

The challenge is that the understanding of how living organisms work is far from sufficient

Scientific research is always exploring the "unknown", but often there are still many "unknowns" in the "known".

In Liu Ying's view, the more research in the field of life science, the more reverence for life, "life is really very subtle, you can't imagine how it can be so smart, so subtle to regulate every step."

But "the more I study, the more I know about life, the more ignorant I find myself," and "some conventional concepts or phenomena have been constantly revised and improved in recent years."

For example, the Warburg effect suggests that cancer cells provide energy and produce lactic acid primarily through glucose degradation (breaking down glucose). But this way of providing energy, it produces very little energy. Because most normal cells get more than 90% of their energy from mitochondria.

Why do cancer cells go through this pathway of sugar degradation? According to Liu Ying, the previous interpretation believed that when cancer cells grow into a large tumor, many cells are crowded together, especially the cells in the middle of the tumor, and cannot access too much oxygen, so there is no way to use mitochondria to provide energy.

"With research in recent years, scientists have gradually found that the tumor will promote the formation of capillaries, oxygen supply is not a lot. The method of sugar degradation was chosen because the metabolites during this period are involved in the synthesis of other biological macromolecules, making their own DNA and proteins. With these substances, cancer cells can divide from one cell into two cells." Liu Ying explained.

"As research continues to deepen, many of the life science phenomena we thought we understood are actually constantly being rewritten. Much remains unknown. Although we study aging, what are the underlying causes of aging? In what ways can we delay aging? At the human level, this is still an open question that needs to be solved. As the population ages, many diseases related to aging, such as neurodegenerative diseases, are also a big social problem." Liu Ying said.

Yang Maojun admitted that the biggest challenge facing the field of life sciences is that our understanding of the internal operating mechanism of living organisms is still far from enough, "For example, the five incurable diseases recognized in the world today: motor neurone disease (ALS), cancer, AIDS, leukemia, rheumatoid disease are listed as the world's five difficult diseases by the World Health Organization." With the development of technology, leukemia can now be cured by cellular immunotherapy or/and bone marrow transplantation, and AIDS can be effectively controlled. I believe that with further research by scientists, other diseases may also make significant progress in the near future."

In terms of disciplinary development, what are the new challenges facing the life sciences profession? Yang Maojun believes that the development of any discipline is nothing more than two dimensions, one is to go deeper and more detailed research, such as molecular level, atomic level and even quantum level research; The other is to extend outward, such as the integration and intersection of life sciences and various disciplines. "The challenge for the life sciences profession is that as we explore the unknown, we face more and more unknowns." Yang Maojun said.

Pioneering, explosive breakthrough in the life sciences

From "Darwinian evolution" breaking the mystery of life, to "cell theory" revealing the commonality of organisms, "Mendel's law" revealing the law of biological genetic change. In 1953, Watson and Crick proposed the famous DNA double helix structure model, which determined the "central law" of life movement and opened up a new era of molecular biology in the 20th century. Every major breakthrough in the field of life science is a milestone.

Liu Ying believes that every technological breakthrough will be correspondingly accompanied by a breakthrough in basic scientific research. "A few decades ago, the resolution of microscope imaging was very low, at most you could only observe the structure inside the cell, and if there was no fluorescent dye, you could not see what was happening inside the cell. However, with the continuous improvement and breakthrough of microscopic technology, now through high-resolution microscopy, you can really see the movement of various organelles inside the cell at all times, and the fusion between cells. As each cell divides, you can even see the whole process of each replication and division of chromosomes."

"With the technological breakthrough, it has really entered a multi-modal, from micro to boundary view to macro, and the overall description and deeper understanding of the phenomenon of life." I think life science in the 21st century will have explosive or leapfrog breakthroughs compared to previous ones."

"As researchers, we have no way to predict how to make a breakthrough, and can only rely on our own little by little to explore." Experiment little by little every day, even trial and error. In the process, we learn lessons, grasp new information, and continuously deepen our understanding of life science issues. It's a process from quantitative change to qualitative change, and when a certain amount of information is accumulated, there may be some breakthrough discoveries."

"Human beings cannot measure the progress of science, but the beauty of science is its uncertainty." Liu Ying said.

In Yang Maojun's view, due to the cross, influence and penetration of various disciplines of natural science and the continuous emergence of various new technologies, the future life science research will continue to be carried out at the micro and macro levels at the same time, and there is a trend of mutual integration. He said: "The future direction is nothing but to make humans understand themselves better, such as brain science; And give us a stronger ability to fight various diseases, such as gene therapy, artificial intelligence applied to drug development and so on."

"There is no doubt that life science will certainly create a new era and make the 21st century truly become the century of life science." Yang Maojun said. "The global outbreak of COVID-19, which has claimed the lives of millions of people, will undoubtedly be an opportunity to raise in-depth research in life sciences to a national strategic level. China's huge investment in life science research in the early stage, such as the 863 program, the national Key research and development program, and the recent establishment of four new national laboratories, have made a good layout of the country's future life science research, the rest needs to be unswervingly continued to push forward."

As a scientific researcher, Yang Maojun's most intuitive feeling is that in recent years, especially after SARS in 2003, the state has significantly increased its support for life science research. "China's basic research and applied research in life sciences have achieved a large number of fruitful results over the years, so it can achieve achievements that attract the attention of the world in the face of the new coronavirus epidemic." From a development perspective, there will still be a variety of diseases in the future that will threaten human life and health. The key to solving and making breakthroughs lies in the active guidance of the state, so that the majority of scientific and technological workers can calm down and do truly meaningful research." Yang Maojun finally said.