The Precision Medicine Program, will be a two-step process, with the first step focusing on the prevention, diagnosis, and treatment of cancer; and the second step being a full-scale rollout across a wide range of diseases. So what is the state of precision medicine in medical practice in the U.S. medical community at this stage? In this article, I will focus on the application of genetics in clinical work based on my experience of clinical study and work in the United States. Precision medicine is also in its infancy abroad. Experts are now invited to attend clinical seminars at the individualized treatment centers in their hospitals to get a sense that precision medicine is in a constant state of development. The goal of precision medicine is to provide individualized and precise treatment based on patients’ genetic profile, environment and living habits. Currently, there are numerous disciplines and diseases involved in precision medicine, with molecular genetics diagnosis and chromosome analysis as key tools. From the method/method perspective, genetic testing includes single-gene testing, gene panel (component) and whole-exome sequencing; chromosome analysis includes traditional karyotyping and high-throughput chromosome microarray technology. From the disease perspective, precision medicine penetrates into the prevention, diagnosis and treatment of diseases. Application of Precision Medicine in Common Diseases The maturity of molecular diagnostic technology enables us to prevent, diagnose and treat a large number of diseases (e.g., tumors, diabetes, cardiovascular diseases, autism, etc.) based on the differences in patient genetics. Taking tumors as an example, the advantages of precision medicine are reflected in the molecular cytology diagnosis and individualized treatment of tumors, thus realizing differentiation from person to person and tumor to tumor.In 2014, Mayo Hospital announced the launch of a high-throughput gene sequencing panel for the global market, which detects 50 tumor-related genes and can be applied to a wide range of solid tumors (e.g., lung, breast, colon, and liver cancers), thus enabling clinicians to select effective targeted therapeutic drugs in a timely manner based on tumor gene mutations and individualize treatment for patients. Medical institutions have launched similar genetic testing panels, but the contents of the tests offered by different institutions are slightly different. The advantages of precision medicine are more reflected in the early prevention of diseases. Again taking tumors as an example, for patients with young and/or family history of various types of tumors, genetics specialist assessment and testing, and further tight tumor screening and even preventive surgery can significantly reduce the risk of cancer in patients carrying disease-causing genes. The well-known Hollywood star Angelina Jolie (AngelinaJolie) has been diagnosed with cancer in her family. Angelina Jolie, a well-known Hollywood star who is currently tumor-free, carries a mutation in the disease-causing gene BRCA1, which puts her at 80% and 40% risk of developing breast and ovarian cancer, respectively. While mastectomy and ovariectomy did not completely eliminate her cancer risk, it did reduce it to less than 5 percent. Her example is a classic application of precision medicine in hereditary tumors, where tumor screening and preventive surgery are performed based on the results of genetic mutations. After AngelinaJolie went public with her condition, the number of patients in the United States undergoing BRCA1/2 genetic testing rapidly doubled. However, not all patients are candidates for genetic testing, as only about 5 to 10 percent of cancers are caused by inherited genetic mutations. In clinical practice, if a patient requests genetic testing, he or she is usually referred to a genetics specialist for evaluation by a specialist or genetic counselor. The two most important items in the assessment system are age of onset and family history. Interpretation of genetic test results is complex, and a positive result does not necessarily mean that preventive surgery is needed, as different mutation sites are associated with tumorigenesis, and a significant percentage of patients carry mutations but do not develop cancer. In conclusion, genetic testing is a prudent decision that requires professional evaluation by a physician, while the interpretation of the results and the matching diagnostic and therapeutic options require close multidisciplinary collaboration. In addition to tumors, precision medicine also plays an advantage in the prevention, diagnosis and treatment of other common diseases. A definitive diagnosis from a genetic perspective can help select the most effective treatment options and provide early diagnosis and prevention for their immediate family members. In the case of ruptured thoracic aortic aneurysm, for example, a number of patients have no past medical history, particularly related to thoracic aortic aneurysm formation (e.g., a history of hypertension or smoking), but often have other members of their family who died suddenly of unknown causes at a young age. This group of patients may then be associated with a genetic defect. Several companies in the U.S. market currently offer a panel of genetic tests related to thoracic aortic aneurysms, a genetic diagnosis of the patient that enables physicians to optimize treatment options, and targeted testing for mutated genes and corresponding early aneurysm monitoring and screening for their immediate family members. However, the genes covered by the products of different genetic companies are slightly different, and clinicians need to make appropriate choices based on the patient’s clinical presentation and family history. From the perspective of laboratory examination, medical and biological research is ever-changing, and the rapid translation of the latest research results plays a key role in clinical diagnosis to save the lives of patients and their families. Application of Precision Medicine in Difficult and Rare Diseases and Genetic Diseases Many prestigious medical centers in the United States receive patients with difficult and rare diseases from all over the world. Most of these patients have been to multiple hospitals and have undergone various tests. Whole-exome sequencing is increasingly being used to diagnose these patients. The decision to perform whole-exome sequencing on a patient requires careful discussion by the medical team. Different medical centers have different evaluation criteria. Typically, if a patient agrees to undergo whole-exome sequencing, a genetic counselor will be assigned to explain the genetic concepts, whole-exome sequencing technology, and possible test results to the patient. Currently, there are about 20 clinical laboratories in the United States that offer whole genome sequencing. Most cost around$7,000 and take about 3 to 4 months. Interpretation of genome sequencing results is a complex endeavor that requires discussion and collaboration among a multidisciplinary healthcare team. It is important to mention that despite the increasing maturity of whole-exome sequencing technology, less than 20% of patients with difficult-to-treat diseases can be identified by whole-exome sequencing in clinical practice. It is hoped that with the development of the Precision Medicine Program, we will have a deeper understanding of the huge number of human genes and reveal the causes of more difficult and rare diseases. The development of medical biotechnology has greatly improved the rate of confirming the diagnosis of various types of genetic diseases. Taking chromosomal abnormality diseases as an example, the rapid development of high-throughput chromosome microarray technology in recent years has enabled us to diagnose small segments of chromosome deletions or copy number increases. And this is not possible with traditional karyotyping techniques. Of course, molecular genetics testing, including single-gene testing, gene panel, and whole-exome sequencing techniques, has already made a big difference in the diagnosis of various genetic disorders. Although we are not yet able to repair defective genes or chromosomal abnormalities, with the maturation of pre-implantation genetic screening and diagnostic techniques, it is possible to test fertilized eggs in vitro and implant only those that do not carry disease-causing genes into the uterus to develop into a fetus, thus avoiding the inheritance of disease-causing genes and saving the newborn from disease. This technology is becoming increasingly sophisticated and is successfully used in current obstetric practice. Pharmacogenetics and the legal protection of genetic diagnosis and individualized targeting of medication by health insurance are one of the important elements of precision medicine. In addition to the targeted drug therapy based on different tumor gene variants described earlier, pharmacogenetics is playing a role in clinical drug selection for various diseases. For example, before using allopurinol in Asian patients with high uric acid, testing for the presence of the HLA-B*5801 gene variant was performed to avoid allopurinol-associated severe exfoliative dermatitis. The development of precision medicine programs will greatly facilitate genetics-based drug development and pharmacogenetic testing. It is foreseeable that in the future, we will need to consult patients’ pharmacogenetic information before prescribing and adjust the medication regimen accordingly. A frequently cited concern of patients in clinical practice is cost and possible discrimination due to genetic information. Genetic diagnosis is often costly. Currently, whether or not the cost of genetic testing is reimbursed varies depending on the health insurance company and the patient’s situation. Most health insurance companies require a physician’s certification of medical necessity to perform genetic testing. Under Obamacare, for example, patients who are at high risk for hereditary breast and ovarian cancer are reimbursed 100 percent of the cost of BRCA1/2 genetic testing, while low-risk patients are required to pay a portion, or even all, of the cost of the test. In 2008, President George W. Bush, Jr. signed a law (known as GINA) to protect the American public from potential discrimination by health care providers and employers based on personal genetic information. But this law does not provide protection from discrimination for life insurance, disability insurance, or long-term care insurance. There is no doubt that the Precision Medicine Program will bring about a transformation in the medical community that will change clinical practice. Breakthroughs will be made in the diagnosis and treatment of many diseases. However, this project has only just begun and cannot be accomplished overnight; it will require a great deal of time and financial support. China’s genetic and bioscientific talent pool and mature technology platform, its huge patient population, and its strong research funding all have the ability to be a leader in this ambitious project, which paints the most beautiful picture of the future of medicine. However, it is undeniable that China is also facing many shortcomings and challenges, such as the lack of specialized genetics clinicians, the lack of an electronic medical record system that allows for backtracking and long-term follow-up, and the lack of a mature legal and healthcare insurance policy to support genetics diagnosis and treatment. However, these challenges can be overcome, and we believe that our Chinese colleagues will become one of the major players and leaders in this transformation of the medical world.