In 1928, British scientist Fleming accidentally discovered penicillin while culturing bacteria, which gave rise to the modern antibiotic industry. Since then, surgery has become a routine treatment, organ transplantation has rapidly developed, and chemotherapy, which easily causes immune system decline, has also been used in cancer treatment. Penicillin has become a great revolution in medical history and has helped change the course of medicine.

　　For decades, antibiotics have saved countless lives from once-fatal infections, making significant contributions to the prevention and control of human infectious diseases. However, more than half a century after the first antibiotics revolutionized medicine, these indispensable antibiotics are rapidly losing their effectiveness due to overuse or misuse in human and animal health.

　　The overuse of antibiotics threatens existing treatments, while the development of alternative drugs is relatively slow. Antibiotic resistance is coalescing into a "silent tsunami," and more importantly, people are unaware of it. Even if they are aware, there seems to be nothing they can do.

　　 The "Silent Tsunami" of Antibiotic Resistance

　　Antibiotics are a class of secondary metabolites produced by microorganisms (including bacteria, fungi, and actinomycetes) or higher plants and animals during their life cycle. They have anti-pathogenic or other activities, mainly by interfering with the biochemical processes of cells, thereby inhibiting cell growth and division, and ultimately killing cells.

　　After penicillin paved the way for the antibiotic industry, scientists subsequently discovered more antibiotics that can control bacterial and fungal microbial infections. Among them, the discovery of compounds that inhibit the growth of Mycobacterium tuberculosis by screening microorganisms in soil, and the elucidation of the method for determining the minimum inhibitory concentration (MIC) of antibacterial compounds, laid the foundation for the subsequent development of drugs from soil microorganisms, and also pushed the development of antibiotics into a golden age.

　　However, after the 1960s, researchers found that naturally occurring microbial metabolites in the environment have considerable pharmacological or toxicological defects. Therefore, obtaining new antibiotics from soil has become increasingly difficult. People began to turn to synthesizing new antibiotic molecules in vitro based on the known mechanisms of action of existing antibiotics, but very few new antibiotics were synthesized, only nitrofuran in 1953, quinolones in 1960, and oxazolidinones in 1987.

　　On the other hand, while the development of new antibiotics is lagging, antibiotic resistance is growing wildly. In fact, antibiotic resistance is a natural process. In terms of mechanism, when microorganisms mutate or acquire resistance genes, resistance will occur, causing the microorganisms causing the infection to survive after contact with drugs that usually kill them or stop their growth.

　　Studies of microorganisms in natural environments and permafrost samples have shown that antibiotic resistance genomes are genetically diverse, widely present in all ecosystem environments, and predate the modern antibiotic era by thousands of years. This means that bacteria already had resistant individuals before contact with antibiotics.

　　The use of antibiotics actually helps bacteria to undergo natural selection. The vast majority of ordinary bacteria are killed, while a few resistant bacteria survive and reproduce in large numbers. As a result, the dosage of antibiotics used is increasing, and more and more antibiotics are becoming ineffective.

　　In addition, due to the lack of competing strains, strains that can still survive after contact with specific drugs will grow and spread, leading to the emergence of "superbugs." In recent years, various new "super-resistant bacteria" have been discovered, such as methicillin-resistant Staphylococcus aureus (MRSA) and extremely drug-resistant Mycobacterium tuberculosis, which are difficult to treat with existing drugs.

　　The overuse of antibiotics has accelerated the development and spread of resistance, and people lack new drugs to combat these emerging superbugs. Although comprehensive data are lacking, the World Health Organization (WHO) has listed antibiotic resistance as one of the top ten public health threats facing humanity. Antibiotic resistance is coalescing into a "silent tsunami," laying the groundwork for potential future failures.

　　 The seeds of the resistance crisis have already been sown.

　　According to data from the US Centers for Disease Control and Prevention (CDC), more than 2.8 million antibiotic-resistant cases occur in the United States each year, resulting in more than 35,000 deaths. In India, antibiotic resistance-related neonatal infections cause nearly 60,000 neonatal deaths annually. The United Nations (UN) is concerned that by 2050, 10 million people worldwide will die each year from drug-resistant infections.

　　Antibiotic resistance not only seriously affects human health but also imposes a huge burden and loss on the economy. The US healthcare system alone spends $20 billion annually to address the problem of resistance. British economist O'Neill predicts that by 2050, global antibiotic resistance could accumulate economic losses of $100 trillion. In addition, reports from the World Bank and the UN Food and Agriculture Organization also point out that if the problem of antibiotic resistance is not solved by 2050, global annual GDP will decline by 1.1% to 3.8%, equivalent to the impact of the 2008 financial crisis.

　　A fundamental factor leading to the development of resistance is drug abuse. Economic development has enabled more people to access life-saving drugs, but overuse and unnecessary use often lead to a divergence between the effectiveness of antibiotics and actual medical needs.

　　Patients often request antibiotics and other drugs from physicians without knowing their needs, or even purchase them directly through retail channels. Even if they seek and follow professional medical advice, doctors often prescribe inappropriately, such as using antibiotics to treat viral infections rather than bacterial infections.

　　At the same time, the food chain also contributes to antibiotic resistance. There is now a growing consensus that the unnecessary use of antibiotics in animals and agriculture is a major cause of antibiotic resistance. The agricultural and aquaculture industries clearly need antibiotics, and the correct use of antibiotics can ensure animal health and welfare and food safety.

　　However, most of the antibiotics used globally are not used to treat sick animals, but to prevent infection or simply to promote growth. In livestock farming, not only is the amount of antibiotics used enormous, but they often include drugs that are very important to humans. In the antibiotics defined by the US Food and Drug Administration (FDA) as medically important to humans, 70% (by weight) are used in animals.

　　Despite the growing problem of antibiotic resistance, humanity is losing these drugs far faster than replacement drugs are being developed. Global sales of antibiotics amount to approximately $40 billion annually, but only $4.7 billion comes from patented antibiotics.

　　Since the 1980s, the rate of discovery of new antibiotics has dramatically decreased. Even the few new antibiotics that have been brought to market in the last 20 years are based on scientific breakthroughs from decades ago. Readily available natural antibiotic products are harder to find, and genomic screening techniques, first used in the 1990s, have failed to revolutionize antibiotic discovery.

　　This is closely related to changes in health perspectives in the latter half of the 20th century. The biggest public health challenges, at least in developed countries, were no longer infectious diseases but non-communicable diseases. This view of infectious diseases as a "problem of the past" led to an over-adjustment of research priorities, an excessive focus on non-communicable diseases, and ultimately, neglect of infectious disease research and development.

　　In addition, pharmaceutical companies have gradually abandoned antibiotic research, shifting to areas that may not be easier to research but offer significantly higher commercial returns, such as oncology. Since 2010, the registration rate of new products in oncology has doubled compared to the early 20th century, demonstrating the impact of sustained industry focus on scientifically challenging but commercially lucrative disease areas. However, antibiotics have attracted only a very small and shrinking amount of venture capital.

　　Statistics show that between 2003 and 2013, $38 billion in venture capital was invested in pharmaceutical R&D, but only $1.8 billion went to antibacterial drug research. Despite the increasingly serious problem of drug resistance and growing public awareness, the total investment fell by more than a quarter.

　　Finally, more than half a century after the first antibiotics revolutionized medicine, the overuse of antibiotics threatens existing treatments, while the development of alternative drugs is relatively slow. Antibiotic resistance is coalescing into a "silent tsunami," setting the stage for potential future collapses. Preventing a major outbreak of drug resistance is urgent.