| The Crown (a fiction) 1. Researchers in Viruses Twentieth century is the century of physics. Planck, Einstein, Heisenberg, Schrodinger and many other illustrious names dotted the history of the last hundred years. It is often said that the twenty first century is the century of biology, a century that finally cracks the secret of life. The greatest achievement in twentieth century physics is the understanding of the smallest particles of the nature, the electrons, the protons and the atoms. The greatest achievement in twenty first century biology will be the understanding of the smallest members of the life, the viruses. Jenny has been to New York for more than twenty years now, first as a graduate student and now as a senior researcher in the microbiology program. For many years, she has been working on viruses. Under microscopes, many viruses look like toys, the toys that can be assembled and disassembled. Many biologists do indeed assemble and disassemble them. But not every kind of assembling is equally prized. The ones that gain in function are hotly pursued. Gain in function means the reassembled viruses actually gain certain functions that earlier viruses don’t have. Some viruses originally inhabit on bats. Through genetic engineering, the reassembled viruses may gain the function to inhabit on mice, monkeys, or even humans, the crown achievement many researchers dream of. With the advance of knowledge, creating viruses to inhabit on humans, or infect humans is no more a dream of distant future. This gets people concerned. Regulations become more and more complex. Applications for funding get tighter and tighter scrutiny. With increasing difficulty in funding, many of Jenny’s colleagues drop out the research. Others move to countries where funding is more generous and regulation is less onerous. But Jenny stayed. Being one of the best in her field, she continues to receive large grants on gain of function in viruses. She made rapid progresses. Soon she and her colleagues demonstrated that some viruses living on bats, after some genetic modifications, can inhabit human cells easily. Some researchers celebrate the achievement. Others, however, are less sanguine about the potential implications. They write letters to the journals about the danger of leaking such novel chimeras to the environment. Humans don’t have immunity against these novel viruses. The accidental leaking of such lab made viruses could be disastrous. These letters generate a public outcry. The US federal government abruptly halted all the gain of function research, pending further investigations. Suddenly, Jenny's funding is frozen. She is going to lose her job. She is too old to move on to a new area. Other areas are facing the increasing regulatory burden anyway. But she is not old enough to retire. Her only daughter is still in high school. Some of her PhD classmates are working at McDonald. She wonders if she will end up in the same place. She was in despair. One day, she got an email message from an old classmate from China. He offered her a senior position in Wuhan Institute of Virology. The new salary would be much higher than her current salary. The funding will be generous and steady. Even more enticing, he told Jenny that she will have complete academic freedom on her research. In the states, Jenny has to put up with all the people lecturing her how to do sciences. Seeing no future for her career in the states, Jenny accepted the offer and started packing for China. Jenny has lived in New York for a long time. Now she is leaving. She reflects on her life here and remembers James, her microbiology class teacher. James is passionate about viruses. He is the most brilliant teacher she has ever met. For some time, Jenny had thought to ask James to be her PhD adviser. However, James doesn't run a lab for awhile and he has no funding. In the end, Jenny chose a more active researcher as her adviser. But Jenny always has a fond memory of her microbiology teacher. Jenny sent a message to James, thanking him for the teaching and telling him she is leaving for China. James was very happy to get a message from his former student and invited her for dinner before leaving. James picks a restaurant in downtown. It is Tuesday evening. The restaurant is very quiet, although it is pretty full. James has retired from the university for some time. He is very glad to have a chance to talk to his former student. After the meal, Jenny asked, "Why you stopped active research so early? You are so brilliant. You waste all your talent." James said, "Well, I was very passionate about research when I was young. I hoped to eradicate all harmful bacteria and viruses. That was the dream of my generation. But later I realized most microbes around us are beneficial to us overall. Bacteria help us digest. Many viruses eat bacteria, preventing those bacteria from multiplying exponentially inside humans. The most potent antibiotics are produced by fungi. Penicillin, the most widely used antibiotics, is produced by Penicillium, a type of fungi. If antibiotics kill too many bacteria, fungi will overrun human bodies, for harmful fungi are no more checked by bacteria. Different kinds of microbes, by constraining each other, keep humans healthy most of the time. Jenny said, “But some bacteria indeed do more harm than good.” James said, “We try very hard to eliminate those bacteria or suppress their presence. We are more successful in developing vaccines or treatments against DNA based organisms, which are more stable and easier to target. But RNA viruses mutate very fast. It is more elusive to target the ever changing RNA viruses accurately. Many recent epidemics, such as HIV, influenza, and coronaviruses, are caused by RNA viruses. When we suppress one type of microbes, we celebrate our success. But from the ecological perspective, we merely open a rich ecological niche, human bodies, for new hosts. This is why superbugs flourish in hospitals, where most known microbes are suppressed. When we eliminate one type of bacteria, we make it easier for those weaker and less competitive pathogens to invade us. RNA viruses mutate very often. They make so many mistakes. It is very difficult for them to compete with more stable, more powerful DNA organisms. But when humans eliminate DNA organisms, RNA viruses face less competition. It is we ourselves who make RNA viruses so successful invaders.” Jenny protested, "But overall, the prevalence of infectious diseases is declining over time." James said, "This is true. However, our immune systems are evolved to handle abundant pathogens. When there are not many pathogens around, our immune systems often turn to our own cells. In clean environment, autoimmune diseases become more common. Fetuses are foreign objects. When pathogens are abundant, immune systems focus on more foreign objects, such as bacteria and viruses. But when there are few pathogens around, immune systems turn to fetuses. That could be one reason why fertility rates in modern societies are so low. When we sterilize our environment, we sterilize ourselves." Jenny questioned, “Does that mean all our research are useless?” James said, “Like everything else in civilization, our research reduces pains and gives comfort. Our research insulates us from the vicissitudes of nature. Civilization reduces our danger, and reduces our ability to encounter danger. Nature used to be our playground. Our ancestors hunt, fish and collect wild food. We were the natives of the land. Now we are more and more like invading aliens on this land. We protect ourselves with heavier and heavier armor. We view nature with increasing suspicion. We avoid bears, moose, bacteria and viruses, which have been with us for millions of years. We alienate ourselves from more and more of nature. Our bodies, our immune systems are less and less familiar with nature. In societies where research is heavily funded, population becomes increasingly aging and vulnerable. In societies where research is less funded, population remains youthful and energetic.” Jenny defended, “Even if I don’t continue my research, tens and hundreds of people are waiting to take over my place. You quit research long ago. That doesn’t slow down the pace of research.” James noticed Jenny was depressed. He changed the topic. “You are returning at an opportune time. US is scaling down its ambition in science. Meanwhile, China is scaling up. You are going to have great opportunities.” It was very late when they finished dinner. When Jenny drove back home, she was still pondering what James was saying. I am returning China at an opportune time. I am going to have great opportunities (To be continued)
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