Satoshi Omura has long been regarded as preeminent in identifying antibiotics and other useful compounds originating from nature’s microorganisms. His innovative and pioneering research has resulted in the discovery of many new microbes and over 500 novel chemicals, several of which have been developed into widely used medicines in human and veterinary health, as well as in agriculture. These include several leading antibiotics, plus the groundbreaking staurosporine, the forerunner of many of today’s widely used and highly effective anti-cancer compounds, such as Gleevec and ivermectin, a truly extraordinary, exceptionally safe, multipurpose compound; the world’s first “endectocide,” capable of killing a wide variety of organisms inside and outside the body.
The trailblazing nature of his work has recently been recognized through his receipt of the 2014 Gairdner Global Health Award, rapidly followed by sharing the 2015 Nobel Prize in physiology or medicine. It is remarkably uncommon that a biorganic chemist should receive two of the world’s most prestigious prizes in global public health, the accolades being primarily due to the unheralded and unmatched discovery, development, distribution and global impact of the truly astonishing ivermectin. They were also testament to Omura’s pragmatic insight into the need to set up international public-private partnerships (with Merck & Co.) and his unwavering belief that nature’s microorganisms hold the answers to all our health and many other needs. His career-long association with the renowned Kitasato Institute also instilled in him the primary philosophy of the institute’s eponymous founder, namely that the fruits of scientific research should be exploited for the benefit of communities everywhere as quickly as possible.
As Omura constantly searches for novel antimicrobials, ivermectin has now been shown to be effective against, among others, insect disease vectors, bacteria, various parasites, viruses and cancer cells. Yet despite donated ivermectin being used by over 250 million people annually in campaigns to eliminate two of the world’s most devastating and disfiguring tropical diseases, river blindness and elephantiasis, Omura continues to investigate new ivermectin analogues and drug combinations, just in case drug resistance should develop, which could cause the disease elimination efforts to fail. One of ivermectin’s many extraordinary qualities is that, despite decades of monotherapy in people, no ivermectin resistance in humans has been observed, even though such resistance appears swiftly in other animals.
Today, antimicrobial resistance (AMR) is a fast-developing global crisis, recognized as one of the greatest threats to human health. It threatens the effective prevention and treatment of a burgeoning range of infections caused by bacteria, parasites, viruses and fungi. It is a cross-border phenomenon, increasing everywhere, with so-called superbugs flourishing in hospitals and health care centers worldwide. With few new products in development, we are speeding toward a post-antimicrobial era in which “minor” infections will again become fatal. If current trends continue, commonplace interventions, such as organ transplantation, joint replacements and anti-infective chemotherapy will become impossible. This situation heralds the end of modern medicine as we know it. And we need immediate, concerted, universal action to avoid that dire end.
As health and poverty alleviation are fundamental components of sustainable socioeconomic development, improving global health is a major challenge. Accordingly, infectious diseases have been receiving increasing international attention over the past three decades.
AMR was a major agenda item at the G7 summit in Germany (2015), and it will be at this year’s G7 summit in Japan, alongside infectious diseases, dementia, universal health insurance and pandemic preparedness. An Action Plan on Antimicrobial Resistance, adopted by World Health Organization (WHO) Member States in 2015, aims to ensure that prevention and treatment of infectious diseases with safe and effective medicines becomes sustainable in the long term. The plan has five strategic objectives, including improving awareness and understanding of antimicrobial resistance; strengthening surveillance and research; and reducing the incidence of infection. The plan also calls for the optimization of the use of antimicrobial medicines; and ensuring adequate investment in countering antimicrobial resistance.
But can the international community be relied on to follow through on new initiatives? The signs are not encouraging, with the WHO’s 2001 Global Strategy for Containment of Antimicrobial Resistance being virtually ignored as the international community immediately shifted its attention to bioterrorism following that year’s terrorist attacks.
The world would do well to look to Japan for direction, a nation with an enviable track record of being at the forefront of novel and effective health interventions. Omura’s successes at the Kitasato Institute with ivermectin and other compounds reflects the accomplishments of past alumni, Shibasaburo Kitasato (originator of serotherapy) and Sahachiro Hata, who discovered salvarsan for syphilis, the compound becoming the world’s first true chemotherapeutic agent. During the 1950’s and ’60’s, Japan implemented successful health-improvement and disease control programs, involving mass screening and treatment that quickly allowed the population to attain one of the healthiest lifestyles in the world. In a mere 20 years, nationwide, interdisciplinary, mostly community-driven campaigns against parasitic diseases led to the control of ascariasis, trichuriasis, hookworm and other soil-transmitted parasitoses, plus eradication of other major diseases such as malaria, schistosomiasis and elephantiasis.
Japan’s unique overseas development aid philosophy, founded on the basic concept of self help and human security, has exported the unparalleled achievements in disease control and provided support for disease research and control activities internationally. Japan has been a proactive and innovative leader in global health, notably at G7 summits, from the 1998 Hashimoto Initiative, through the Okinawa Infectious Disease Initiative and the subsequent Health & Development Initiative. Japan’s initial proposal in 2000 led to creation of the Global Fund to Fight HIV/AIDS, Malaria and Tuberculosis (GFATM). The nation is also continually promoting capacity building and improved national health infrastructure, as exemplified by the 2008 Health Systems Strengthening initiative.
International commitment has also been substantial for over 20 years, culminating in leaders from governments, industry and global health organizations issuing the London Declaration on Neglected Tropical Diseases (NTDs) in 2012, a turning point in international action to control and eliminate NTDs. Commitment from the international pharmaceutical industry has also been staunch, Merck’s unprecedented drug donation of ivermectin (Mectizan) to tackle river blindness in 1987 being followed by subsequent drug donation programs from several major pharmaceutical manufacturers. Japan’s pharmaceutical companies have also been creative, Sumitomo Chemical Co. not only producing the best anti-malarial, long-lasting insecticidal bednets, but having the foresight to establish a production factory in Tanzania, meaning that local community members gain employment, as well as better health.
The new paradigm of international, multifaceted mobilization for global health was further galvanized by the appearance of the Bill & Melinda Gates Foundation (BMGF) in 2000. The BMGF represented new leadership, creating and expanding multidisciplinary partnerships with NGOs, countries, academia and industry, including the 2013 launch of the Japan-driven Global Health Innovative Technology (GHIT) Fund, based in Tokyo. Inaugurated in 2015, Japan’s Agency for Medical Research and Development (AMED) was created with the goal of facilitating and expediting translation of basic research into practical applications, following the lead of the GHIT Fund.
Integrated measures against HIV/AIDS, malaria and tuberculosis have been highly successful since the GFATM launch, proving that concerted, multi-stakeholder health interventions can conquer intractable diseases. But global health problems are dynamic, forever evolving, so constant vigilance from world leaders, innovative thinkers and visionary scientists will be required to find the much-needed new wonder drugs such as penicillin and ivermectin, safeguard their use, and so protect the long-term health of all global citizens and future generations.
Andy Crump is a visiting professor at Kitasato University and Keio University.