The Dangers of Hubris on Human Health
The Dangers of Hubris on Human Health
The Dangers of Hubris on Human Health
Humanity has always been under constant threat from infectious disease. Globally, we are getting better at monitoring signs of a health-related crisis and alerting each other – there are far fewer deaths from pandemics today than a century ago. And modern medicine is consistently meeting new diseases with new treatements, as shown by the progress on HIV since the 1980s. But have such modern medical successes bred a sense of hubris, excessive confidence that science will always come to the rescue?
Challenges to human health never cease to evolve. Vaccines and antibiotics have helped us to survive leading causes of death from bygone eras, but we face rising rates of chronic illnesses such as heart disease, cancers and diabetes. Although recent pandemics, such as SARS, avian flu and swine flu, have been contained, they also show how easily deadly viruses can mutate and hop from other species to us.1 For all our successes, we are never far from the edge of catastrophe, as new biological mutations will eventually overcome a prior human innovation.
While viruses may capture more headlines, arguably the greatest risk of hubris to human health comes in the form of antibiotic-resistant bacteria. We live in a bacterial world where we will never be able to stay ahead of the mutation curve. A test of our resilience is how far behind the curve we allow ourselves to fall.
Our survey respondents connected this global risk to others including vulnerability to pandemics, failure of the international IP regime, rising rates of chronic disease and unforeseen consequences of new life science technology. Like storm systems colliding in unpredictable ways, the unexpected interactions of these risks could overwhelm our health systems in the coming decade and unpredictably damage our social and economic systems. See Figure 15
Many people take for granted that antibiotics will always be available when we need them, but soon this may no longer be the case. Every dose of antibiotics gives an advantage for those small numbers in a bacterial population that are resistant to the drug. The more a particular antibiotic is used, the more quickly bacteria resistant to that antibiotic will be selected and increase in numbers. Until now, leaders have been able to turn a blind eye to this problem, as new antibiotics have always emerged to replace older, increasingly ineffective ones. This is changing.
A post-antibiotic era means, in effect, an end to modern medicine as we know it. Things as common as strep throat or a child’s scratched knee could once again kill.²
2. Chan, M. “Antimicrobial Resistance in the European Union and the World”. World Health Organization, http://www.who.int/dg/speeches/2012/amr_20120314/en/index.html, 2012.
Although several new compounds for fighting bacteria are in development, experts caution that we are decades behind in comparison with the historical rate at which we have discovered and developed new antibiotics. More worryingly, none of the drugs currently in the development pipeline would be effective against certain killer bacteria, which have newly emerging resistance to our strongest antibiotics (carbapenems) and fatality rates of up to 50%.3 As shown by the death of six patients – from 18 infected – at the US National Institutes of Health in 2011, antibiotic-resistant infections can kill, even at the world’s most advanced medical centres.4
While predicting the spread of bacteria is notoriously difficult and complicated by a general lack of good global data, troubling projections are emerging in regions where many efforts have been made to better monitor the situation. Figure 16 shows the most recent data for two resistant pathogens, as well as the trends between 2008 and 2011. A well-known antibiotic-resistant bacteria – meticillin-resistant Staphylococcus aureus, better known as MRSA – is stabilizing and possibly decreasing, but not as sharply as had previously been projected.5 For K. pneumoniae, there is a widespread increasing trend.ix
As a consequence, experts are starting to take seriously a scenario in which all antibiotics are rendered ineffective for treating even common infections.
The Costs of Antibiotic-Resistant Bacteria
The spread of antibiotic-resistant bacteria has implications for everyone. The impacts on human health are likely to be highest in poorer countries, as the spread of pathogens is facilitated by poor hygiene, polluted water supplies, overcrowding in urban areas, civil conflicts and concentrations of people who are immuno-compromised due to malnutrition or HIV.6But even in the highest-income countries, few people go through life without needing antibiotics.
The numbers of lives now being lost due to antibiotic-resistant infections may seem small in comparison to heart disease and cancer – for example, currently just under 100,000 Americans, 80,000 Chinese and 25,000 Europeans a year die from hospital-acquired antibiotic-resistant infections.789 However, experts believe these figures from only a few years ago may be worse today. The Global Risks report covers a 10-year time horizon, over which timescale it is far from unrealistic to project a significant spread of antibiotic-resistant bacteria with high mortality rates.10
It is important to remember that antibiotics are not used only to treat infections. They also, by guarding against infection, make possible medical procedures such as heart surgery, organ transplantation, the survival of pre-term babies, and aggressive immune-modulating therapy for auto-immune diseases such as rheumatoid arthritis, as well as for cancers of the blood, bone marrow and lymph nodes. With demographic and lifestyle trends such as ageing populations, changes in diet and declining rates of physical activity, we can expect rising rates of chronic diseases which are currently treated through surgery that would be impossible without effective antibiotics.
On top of destabilizing our health systems, there are profound cost implications for economic systems and for the stability of social systems. The annual cost to the US health care system of antibiotic-resistant infections is already estimated at between US$ 21 billion to US$ 34 billion.11 Elsewhere, losses to GDP have already been estimated at 0.4% to 1.6%.12 The consequences of a pandemic spread of antibiotic-resistant bacteria could also include shortages of food due to untreatable infections in livestock, and as leaders seek to slow the spread of pathogens, restrictions on trade in foodstuffs, and even on travel and migration.13 Figure 17x provides a global snapshot of the costs, impacts and burden of antibiotic-resistant bacteria across the globe.
Why Antibiotics Are Overused
If we want to minimize the rate at which antibiotics become obsolete, we should use them as sparingly as possible. However, a combination of misaligned incentives and lack of information has led antibiotics to be used where they are not truly needed.
Even in systems which restrict the use of antibiotics by making them available by prescription only, doctors can come under pressure from patients who mistakenly believe antibiotics kill viruses – for example, in a pan-European survey, more than 50% of French respondents expected an antibiotic for an influenza-like illness.14 Diagnostic methods that are inadequate to distinguish bacterial from viral infection or to specify the kind of bacterial infection, allied with fear of medical malpractice lawsuits, also mean that doctors tend to prescribe a cocktail of whatever antibiotics are available in the hope that one will be effective, especially in cases of severe infection. This imprecision promotes further spread of resistance in bacteria.
Some medical systems incorporate perverse incentives for antibiotics to be overprescribed. In China, for example, drug sales form a significant part of hospitals’ income and, until 2010, physicians’ pay was linked to profits from the sale of prescription drugs. One study found that 98% of patients in a Beijing children’s hospital were given antibiotics for a common cold.15 Figures from 2009 suggest that 74% of all hospital admissions in China will receive antibiotics to treat their illness or as a preventive measure.16
In many medical systems, antibiotics are not prescription-only. They can be purchased over the counter in pharmacies or in local marketplaces, and inappropriate self-medication is furthering the spread of antibiotic-resistant bacteria. In India, for example, pharmacy sales of strong antibiotics which should be a last line of defence increased nearly sixfold from 2005 to 2010.17 Unfortunately, there is no easy answer to the question of how to prevent excess use of antibiotics without unfairly restricting access to antibiotics in cases of genuine need. A national task force in India recommended the end of over-the-counter sales of antibiotics, but India’s Health Minister responded with concern that such a move would effectively deny access to antibiotics to patients in rural areas where there are no physicians to prescribe the drug.1819 Inadequate and unreliable access to a full range of antibiotics in low- to middle-income countries is also part of the problem. The spread of resistance in these areas is further facilitated by illicit trade in counterfeit drugs of substandard quality.
Meanwhile, antibiotics are over-used around the world in livestock and fish farming (e.g. as growth promoters). Resistant bacteria can be transferred to humans through contact with livestock, through the food chain, and through wastewater from these operations, as well as wastewater from hospitals and pharmaceutical plants.2021 One study found 45 kg of ciprofloxacin (an antibiotic commonly used to treat bladder and sinus infections) – the equivalent of 45,000 doses – leaking daily from factories into a nearby river.2223 Environmental contamination like this has led to an antibiotic-resistant bacteria being detected as far afield as Antarctica.2425
Why the Development of New Antibiotics Has Slowed
Until recently, as older antibiotics have become less useful due to the spread of resistant bacteria, new antibiotics have come along to take their place. But the drug development pipeline for new antibiotics has been drying out. New antibiotics have come to market in recent years, but any sense of progress this provides is false. Our newest antibiotics are the result of scientific discoveries that happened decades ago. A timeline26) of dates of discovery of distinct classes of antibiotics (as opposed to dates of market introduction) illustrates that there have been no (as yet) successful discoveries of new classes of antibiotics since 1987 (Figure 18).27 There are several competing and overlapping explanations why.
Firstly, drugs to treat chronic illnesses such as diabetes and hypertension increasingly offer a greater potential return on investment for pharmaceutical companies. Unlike with antibiotics, resistance is not an issue with these drugs. They have the potential to rapidly achieve wide market penetration, whereas any new antibiotic is likely to be kept as a last-resort treatment, which will be used only for a few weeks even in that setting, resulting in low sales for companies.28xi
Interestingly, respondents to the Global Risks Perception Survey connected antibiotic-resistant bacteria to failure of the international intellectual property regime. This global risk is defined in the survey as “the loss of the international intellectual property regime as an effective system for stimulating innovation and investment” – that is, going beyond the mechanisms of protecting IP to encompass the idea that the ultimate purpose of the IP system is to stimulate worthwhile innovation. The connection highlights a global market failure to incentivize front-end investment in antibiotic development through the promise of longer-term commercial reward, a failure which also applies to drugs to fight malaria and vaccines for pandemic influenza.29
Secondly, regulatory burdens have also impeded development of new antibiotics.30 Many smaller pharmaceutical companies cannot afford the cost of meeting complex requirements for clinical trials, and these burdens risk compromising the development of many promising new agents.31
Thirdly, an increasing amount of effort has been invested in exploring the potential of new life science technologies such as genomics, nano-scale engineering and synthetic biology, without yet yielding new approaches in the treatment of bacterial disease. One unintended consequence of this has been to divert researchers’ attention from the traditional approach of discovering natural compounds to kill bacteria, which may be getting harder.3233
Hubris on health not only means taking for granted that the technologies we have will continue to work, but also assuming that bigger and better scientific breakthroughs are just around the corner. There is no guarantee that putative alternatives to antibiotics will be developed before existing antibiotics become ineffective.
What Can Be Done?
Numerous reports, workshops and conferences have proposed policies and strategies to address the spread of antibiotic-resistant bacteria. The World Health Organization (WHO) launched a global strategy for containment of antimicrobial resistance in 2001.34 However, a hubristic assumption that the medical industry would continue to find solutions has contributed to decision-makers regarding the issue as a relatively low priority. The challenge is complicated by the fact that antibiotic-resistant bacteria do not respect borders, so there are limits on what can be done without strong international and multistakeholder collaboration. An effective response to the pandemic spread of antibiotic-resistant bacteria would involve tackling failures of markets and global governance.
To address market failure, incentives have been suggested to encourage pharmaceutical companies to develop more new antibiotics.35 For example, through advance purchase commitments, governments or philanthropists can promise to purchase a given amount of a new drug that meets stated criteria of effectiveness. This incentivizes private companies to develop new antibiotics, while enabling the sales and marketing of those new antibiotics to be restricted in the public interest.xii
Public-private partnerships have also shown promise in incentivizing the development of new antibiotics. One example is part of the Innovative Medicines Initiative (IMI), a €2 billion initiative of the EU Commission and the European Federation of Pharmaceutical Industries and Associations, which earmarks funds for antibiotics discovery and development.36 The IMI acts as a neutral third party that supports collaborative research projects and builds networks between experts from industry and academia.
There is also potential to use public or philanthropic funding to incentivize academic collaboration with pharmaceutical industry researchers, and more inter-company collaboration as well. Breakthroughs in antibiotic innovation will require pooling and sharing of knowledge among academia, private companies and government regulators.37 Companies and foundations such as GlaxoSmithKline (GSK) and the Bill and Melinda Gates Foundation are pioneering an “open-lab” approach to research which refutes the idea that secrecy and patented monopolies are the bedrock of innovation. GSK has opened its Tres Cantos research facilities to outside academic, government and biotech scientists in order to collaborate on finding antibiotics, and the Bill and Melinda Gates Foundation has “organized a tuberculosis Drug Accelerator program that brings together research teams from Abbott Laboratories, AstraZeneca, Bayer, Eli Lilly, GlaxoSmithKline, Merck and Sanofi with scientists from four academic and government institutions”.38
International efforts would be required to address licensing and regulatory barriers to the development of new antibiotics, such as lack of clarity and stability within the regulatory framework and lack of harmonization in processes of clinical trials between countries.39
Similarly, international collaboration would be required to facilitate improvements in data gathering, to enable more accurate and continuous monitoring of the global spread of antibiotic-resistant bacteria.40 Experience from Europe over the past decade shows that if data on antibiotic use and resistance is publicly available, and national coordinated policies on prevention and control of antibiotic-resistant bacteria are implemented and enforced, significant reduction in antibiotic use can be achieved in human medicine.41
More efforts, however, will be needed to slow the use of antibiotics in agriculture, aquaculture and animal husbandry. Research is needed to understand how Nordic countries have made significant progress – part of the answer may be small herd sizes – and to assess what works in awareness-raising campaigns, such as the Pew Charitable Trusts Campaign on Human Health and Industrial Farming.xiii Figure 1943 shows that the amount of antibiotics used to raise animals for food-production is still high, even in highly regulated markets like Europe.42
As new antibiotics become available, international collaboration will be required to limit their use to cases of need. This implies considering access to antibiotics as a development aid issue for low- to middle-income countries, and finding international mechanisms to promote collaboration on governance issues. There are opportunities to learn from each others’ experience in controlling antibiotic use through aligning financial incentives in the health system to tackle over-prescription, through educational interventions to tackle the problem of unnecessary self-medication, and through improving technologies to diagnose the existence and nature of bacterial infectionsxiv and antibiotic stewardship.44
The late Nobel Laureate Elinor Ostrom has compared the issue of antibiotic-resistant bacteria to that of climate change, “in the sense that both phenomena involve non-renewable global resources, both are caused by human activity and are intrinsically linked to our behaviour. The problem can only be addressed through international cooperation”.65 A cause for optimism is that, unlike with climate change, we know what actions are required. The challenge is to create the will and mechanisms to take them.45
Questions for Stakeholders
- How can the threat of antibiotic-resistant bacteria be addressed, considering that it crosses both national and species borders? How can we build visibility and political momentum to the levels currently surrounding climate change and pandemics?
- How do we re-establish antibiotic discovery, research and development given the higher return on investment on R&D of drugs for chronic diseases? What incentives are feasible? What can facilitate the work of academia and small and medium enterprises on antibiotics?
- How do we preserve current antibiotics until new agents are available? How can we align incentives to tackle overuse of antibiotics in farming of livestock and fish? What incentives work best in health financing systems? How can international organizations be supported to take on a global leadership role to preserve the utility of current antibiotics?
Bringing Space Down to Earth
Damage to space-based infrastructure is one of the more esoteric global risks on which our experts are surveyed annually. Members of the World Economic Forum’s Global Agenda Council on Space Security believe that lack of broad awareness of the importance of satellites explains why this risk consistently ranks at the bottom of the global risk landscape. Few people appreciate how much we depend on satellites to support our most critical infrastructure and to live modern and mobile lives:
- The daily operations of telephony and Internet networks, financial markets, the banking industry, data centres and energy networks all rely on precise timing information conveyed by satellite.
- The €300 billion global TV industry would not be possible without satellites.46 Nor would accurate weather predictions, estimated to equal €60 billion in socio-economic benefits a year in the EU alone.47
- Rescuers in emergency situations depend on satellites for communication, when mobile networks are overloaded. Peacekeeping and military missions also rely on secure satellite communications.
Satellites are at risk of three main “black swan” events which are captured in our global risk landscape: being targeted in a conflict between states; a strong geomagnetic storm; and collisions with space debris. These low-likelihood but high-impact risks are, however, not those that keep satellite operators awake at night. They worry far more about near-term risks on Earth. As society becomes increasingly dependent on invisible signals from space, the unforeseen long-term consequences of shortsighted management of the spectrum – the term for radio waves which satellites use to communicate – threaten essential satellite services. The desire to share scarce spectrum resources to deliver new-age digital services is taking regulators by storm, while invisible yet crucial services are squeezed into silence.
These global risks are not only physical risks to satellites but also are risks which would greatly weaken our ability to respond and prevent some of the most likely and high-impact global risks in the landscape.
- Rising greenhouse gas emissions and Climate change adaptation: Satellite imaging, data and communications can be used to provide early warning systems for extreme weather events and to monitor floods, desertification, and rising sea levels and temperatures in real time.
- Food and water crises: Satellite imagery allows food supplies to be tracked and the availability and quality of arable land and potable water resources to be assessed, as well as the locations and density of the populations that rely on them. Satellite communications allow effective and secure food distribution, as well as tracking for the personal safety of aid workers who distribute it.
- Severe income disparity: Connecting the world via satellite broadband has fundamental and far-reaching effects on individual lives, whether by enabling universal primary education in the most remote areas, bringing healthcare and telemedicine to those who might otherwise die because their homes are too far away from healthcare facilities, or making critical solutions such as micro-finance possible in areas where no other communications infrastructure exists.
- Critical Systems Failure: With virtually every network infrastructure using satellite for its timing reference – whether telephony, Internet, financial markets or banking, from data centres to energy networks – risks to satellite infrastructure could result in a global communications meltdown.
- Land and waterway use mismanagement: Governments have started to use satellite images in near real-time to monitor activities such as forest clearing in the Amazon rainforest and to identify illegal logging.
- Diffusion of weapons of mass destruction and Failure of diplomatic conflict resolution: Satellites play a critical role in the control of weapons of mass destruction by monitoring disarmament agreements. They can provide irreplaceable means for improving transparency and measures for building confidence.
Through their ability to see and speak to all corners of the world, land, air and sea, satellites are enablers that strengthen our resilience to a wide range of global risks. Broader awareness of this fact is needed to ensure that our critical space-based infrastructure is managed sustainably and that we do not underestimate the potential impacts if these critical systems fail. See Figure 20
Figure 16: Percentage of Bloodstream Infections Showing Multi-Drug Resistance, EU/EEA, 2011 and Trends for 2008
Source: European Centre for Disease Prevention and Control, EARS-Net, 2012
Source: World Economic Forum
49 Prakongsai, P., Dhammalikitkul, V., Sampradit, N. et al. “Prevention and Control of Antimicrobial Resistance in Thailand”. Presentation at side event on antimicrobial resistance, the 65th World Health Assembly, 2012.
50 Ham, Y.-S., Kobori, H., Kang, J.-H. et al. Distribution of Antibiotic Resistance in Urban Watershed in Japan. In Environmental Pollution, 2012, 162(0): 98-103.
51 Li, Y., Xu, J., Wang, F. et al. Overprescribing in China, Driven by Financial Incentives, Results in Very High Use of Antibiotics, Injections, and Corticosteroids. In Health Affairs (Millwood), 2012, 31(5):1075-82.
52 Zhang, R., Eggleston, K., Rotimi, V. et al., Antibiotic Resistance as a Global Threat: Evidence from China, Kuwait and the United States. In Globalization and Health, 2006, 2(1): 6.
53 Bhattacharya, D., Sugunan, AP, Bhattacharjee, H. et al. Antimicrobial Resistance in Shigella-rapid Increase & Widening of Spectrum in Andaman Islands, India. In The Indian Journal of Medical Research, 2012, 135(3): 365.
54 Hoa, P.T.P., Managaki, S., Nakada, N. et al. Antibiotic Contamination and Occurrence of Antibiotic-resistant Bacteria in Aquatic Environments of Northern Vietnam. In Science of the Total Environment, 2011, 409(15): 2894-2901.
55 “Burden of Antibiotic Resistance”. Action on Antibiotic Resistance (ReAct), http://www.reactgroup.org/uploads/publications/react-publications/ReAct-facts-burden-of-antibiotic-resistance-May-2012.pdf, 2012.
56 Spellberg, B., Blaser, M., Guidos, R. J., et al. Combating Antimicrobial Resistance: Policy Recommendations to Save Lives. In Clinical Infectious Diseases: an Official Publication of the Infectious Diseases Society of America, 2011, 52:S397-428.
57 “Antimicrobial resistance” Fact Sheet 194. World Health Organization, http://www.who.int/mediacentre/factsheets/fs194/en/, 2012.
58 Rossi, F. The Challenges of Antimicrobial Resistance in Brazil. In Clinical Infectious Diseases, 2011, 52(9):1138-1143.
59 White, A.R. Effective antibacterials: at what cost? The Economics of Antibacterial Resistance and its Control. In Journal of Antimicrobial Chemotherapy, 2011, 66(9):1948-53.
60 Frigo, N., Unemo, M., Kubanova, A. et al. P1-S1.42 Russian Gonococcal Antimicrobial Susceptibility Programme (RU-GASP) – Resistance Levels in 2010 and Trends During 2005–2010. In Sexually Transmitted Infections, 2011, 87 (Suppl 1):A116-A117.
61 Stratchounski, L.S., Andreeva, I. V., Ratchina, S. A.et al. The Inventory of Antibiotics in Russian Home Medicine Cabinets. In Clinical Infectious Diseases, 2003, 37(4):498-505.
62 Ogbolu, D.O., Daini, O.A., Ogunledun, A. et al. High Levels of Multidrug Resistance in Clinical Isolates of Gram-negative Pathogens from Nigeria. In International Journal of Antimicrobial Agents, 2011, 37(1) 62-66.
63 Borer, A., Saidel‐Odes, L., Riesenberg, K., et al. Attributable Mortality Rate for Carbapenem-resistant Klebsiella Pneumoniae Bacteremia. In Infection Control and Hospital Epidemiology, 2009, 30:972-6.
64 Hernández, J., Stedt, J., Bonnedahl, J., et al. Human-associated Extended-spectrum Beta-lactamase in the Antarctic. In Applied and Environmental Microbiology, 2012, 78:2056-8.
Source: World Economic Forum, adapted from Silver, L.L. Challenges of Antibacterial Discovery.
In Clinical Microbiology Reviews, 2011, 24:71-109.
Source: Adapted from Sales of Veterinary Antimicrobial Agents in 19 EU/EEA Countries in 2010. 2012. European Medicines Agency.