How can laboratory results benefit clinical medical research? How can clinical research be reoriented and corrected with the help of basic research? This is the challenge in front of many medical researchers. The “Systematic Research on Molecular Mechanism of Deafness and Early Warning of Prevention and Control”, which won the second prize of the 2008 National Science and Technology Progress Award, has provided insights to researchers. The project leader, Professor Han Dongyi, director of the Department of Otolaryngology and Head and Neck Surgery of the PLA General Hospital, said that the achievement of this scientific research is the result of continuous positive interaction between clinical and basic research, which is to find problems from the clinic and solve them from basic research. The clinic should borrow “brains” from the laboratory,” said Han Dongyi, “those engaged in clinical research should be good at borrowing ‘brains’ from basic research. The results of basic research can often break the bottleneck of clinical research. With the support of basic research and multidiscipline, the ideas of clinical research are opened at once.” Since 1996, with the support of 14 projects funded by the National Natural Science Foundation of China (NSFC) and the National 863 Program, Dongyi Han and his research team have been conducting research on deafness from a clinical perspective. Deafness is one of the most common disabling diseases in humans and a common genetic disease. It is the dream of many medical researchers to help deaf patients return to the world of sound. Han Dongyi said that the number of people with hearing disability in China is huge, about 27.8 million, accounting for 34% of the total number of people with disabilities. Hearing disabilities often lead to language disabilities, and countless deaf people live in a silent world, which seriously affects their quality of life and communication, causing them and their families great pain and a heavy financial burden. The researchers initially tried to find a breakthrough in the clinical setting, and the shift in research direction from clinical to molecular mechanisms of deafness came from a serendipitous inspiration, Han said. In 2001, Han attended the World Congress on the Molecular Biology of Deafness in Washington, D.C., where an expert mentioned that “all human diseases are genetically related. This statement suddenly awakened Han Dong Yi: Since diseases are so closely related to genes, molecular biology is the most promising door to success in overcoming neurological deafness. Han Dong Yi explained that deafness is different from other disabilities in that about 60% of newborn deaf children are caused by genetic factors, and about 30,000 deaf children are born in China every year. The other 40 percent are due to environmental factors. For deafness caused by environmental factors, it can be effectively prevented by preventing infections, enhancing perinatal care during pregnancy, and avoiding the application of ototoxic drugs. However, for hereditary deafness, the only way is to go for a definitive diagnosis. It’s a bold vision, but with a lack of evidence, how can the correctness of the vision be verified? Han Dongyi says this requires looking to basic research for answers. To engage in basic research, especially in molecular biology, one must establish one’s own laboratory. Dongyi Han admits that he was under considerable pressure and even took out a loan to set up his department’s molecular biology laboratory. Han told the reporter that after just a few years of development, the lab was able to publish more than ten international high-level papers every year. Behind this report card is the “basic research + clinical application” model that the researchers adhere to, looking for problems from the clinic and solving them from basic research, which has formed a positive situation of interaction between the clinic and the laboratory. Basic research should be the “root” of clinical practice. “No matter how clinical medicine develops, basic research is the ‘root’.” Han Dongyi said that it is now known that many genes are inextricably linked to hearing, and that mutations in one or several of them, or mutations in different loci of a gene, can cause the same performance, which is deafness. However, deafness genes and their mutated loci vary among different races and even among different regions of the same race. The only way to “target” is to “have something”. In order to conduct a genetic diagnosis of deafness in Chinese people, it is necessary to have informative national molecular epidemiological data as a guide, instead of copying foreign data. The first thing Han and his research team did was to establish a systematic network of Chinese deafness genetic resources collection and genetic resources database. They collected and preserved 8,300 Chinese deafness families and cases with multiple genetic patterns and phenotypic characteristics. The accumulation of genetic data allowed the researchers to make several breakthroughs: for the first time in the international arena, they proposed and proved the existence of a new mode of deafness inheritance, namely Y-linked inheritance, enriching the theoretical content of hereditary deafness. The research also succeeded in discovering a new mutation in POU3F4, the causative gene of an X-linked congenital deafness family lineage, which solved the mystery of deafness that has plagued the family for nearly a century; successfully conducted a systematic study on the molecular mechanism of deafness caused by aminoglycosides, and discovered and elucidated for the first time in the international arena a new mutation in mitochondrial 12SrRNA C1494T, which is a new molecular mechanism of deafness caused by hypersensitivity of family members exposed to aminoglycosides He was the first to conduct a nationwide molecular epidemiological survey of deafness and successfully completed the mapping of hotspot mutations of deafness susceptibility genes in China. Since 2004, the Center for Molecular Diagnosis of Deafness of PLA General Hospital has collected DNA samples from 3,564 deaf patients from 28 provinces, autonomous regions and municipalities directly under the central government in China, and the results of the study have verified the initial idea. Dongyi Han and his research team found that 21% of the deaf patients carried the GJB2 gene mutation, 14.5% carried the SLC26A4 gene mutation, and another 3.8% and 0.6% carried the mitochondrial DNA A1555G and C1494T mutations, respectively. This is an important finding that reveals the frequency of common deafness mutations in Chinese deaf people and identifies GJB2, SLC26A4, and mitochondrial genes (A1555G and C1494T mutations) as the three most common genes that cause the majority of hereditary deafness to occur in China, and testing for the above genes can diagnose nearly 80% of hereditary deafness. The researchers identified and demonstrated that mutations in the SLC26A4 gene are the causative agent for patients with vestibular aqueduct enlargement syndrome in the Chinese deaf population, and established a pre-symptomatic genetic test. This series of findings soon benefited the clinic. The Molecular Diagnostic Center for Deafness of the PLA General Hospital has been conducting deafness genetic diagnosis since 2005, and has performed deafness genetic diagnosis for more than 1,500 deaf patients attending outpatient clinics, and has clarified the genetic cause of deafness for more than 500 of these patients. Most satisfying to Han Dong Yi, the Deafness Molecular Diagnosis Center has successfully helped 51 families who had already had a child with hereditary deafness to have a healthy baby for re-birth. This new clinical practice of combining deafness genetic diagnosis with prenatal diagnosis, which diagnoses and prevents deafness, provides new ideas and means for prevention and intervention of hereditary deafness. Han Dong Yi explained that this scientific research result involves many disciplines such as basic, clinical and epidemiological from the design, and many links constitute the complete chain of scientific research output. The traditional basic research and clinical practice are often separated by a series of barriers, which experts describe as “fence walls”. For this phenomenon of disconnection between clinical and basic research, the international community has begun to emphasize the concept of “translational medicine” in recent years, emphasizing research “from the laboratory to the bedside” and translating the results of basic research into therapeutic tools. When evaluating this phenomenon, Han Dong Yi said that basic research should not be conducted behind closed doors at home, researching for the sake of publishing papers or taking up topics, but should be combined with clinical needs to carry out targeted research. The promotion of the concept of translational medicine requires medical researchers to identify and raise problems from clinical work, and then have basic researchers conduct in-depth research, and then quickly transfer the results of basic research to clinical applications. Basic and clinical researchers work closely together in order to improve the overall level of medical care. After the breakthrough in basic research, researchers at PLA General Hospital lent a channel to industrial R&D and successfully developed a genetic diagnosis kit for deafness and promoted its clinical application. 2003 saw the birth of a test kit for mutations from A to G at locus 1555 of the mitochondrial gene, which was validated by the National Center for Biomedical Analysis with an accuracy rate of 100%. The effort to help tens of thousands of deaf patients return to the world of sound has also yielded significant economic and social benefits. Han Dongyi said that in China, 30,000 deaf children are born each year, 40 percent of whom can be prenatally intervened through genetic testing. Based on the minimum cost of 300,000 yuan per person for cochlear implantation and rehabilitation, the prevention of 12,000 new deaf children through genetic testing alone will save the country 3.6 billion yuan annually. Han Dong Yi said that bridging the “wall” between basic and clinical research requires that researchers often change their perspective and that the research process should develop in a more open, patient-centered direction.