Aids origin ‘was 1920s Kinshasa’


 

Kinshasa in 1955
Kinshasa, pictured in 1955, was at the centre of the pandemic, scientists say

The origin of the Aids pandemic has been traced to the 1920s in the city of Kinshasa, in what is now the Democratic Republic of Congo, scientists say.

An international team of scientists say a “perfect storm” of population growth, sex and railways allowed HIV to spread.

A feat of viral archaeology was used to find the pandemic’s origin, the team report in the journal Science.

They used archived samples of HIV’s genetic code to trace its source, with evidence pointing to 1920s Kinshasa.

Their report says a roaring sex trade, rapid population growth and unsterilised needles used in health clinics probably spread the virus.

Meanwhile Belgium-backed railways had one million people flowing through the city each year, taking the virus to neighbouring regions.

Experts said it was a fascinating insight into the start of the pandemic.

HIV came to global attention in the 1980s and has infected nearly 75 million people.

It has a much longer history in Africa, but where the pandemic started has remained the source of considerable debate.

Family affair

A team at the University of Oxford and the University of Leuven, in Belgium, tried to reconstruct HIV’s “family tree” and find out where its oldest ancestors came from.

The research group analysed mutations in HIV’s genetic code.

“You can see the footprints of history in today’s genomes, it has left a record, a mutation mark in the HIV genome that can’t be eradicated,” Prof Oliver Pybus from the University of Oxford told the BBC.

By reading those mutational marks, the research team rebuilt the family tree and traced its roots.

Chimpanzee

HIV is a mutated version of a chimpanzee virus, known as simian immunodeficiency virus, which probably made the species-jump through contact with infected blood while handling bush meat.

The virus made the jump on multiple occasions. One event led to HIV-1 subgroup O which affects tens of thousands in Cameroon.

Yet only one cross-species jump, HIV-1 subgroup M, went on to infect millions of people across every country in the world.

The answer to why this happened lies in the era of black and white film and the tail-end of the European empires.

In the 1920s, Kinshasa (called Leopoldville until 1966) was part of the Belgian Congo.

Prof Oliver Pybus said: “It was a very large and very rapidly growing area and colonial medical records show there was a high incidence of various sexually transmitted diseases.”

Sex and railways

Large numbers of male labourers were drawn to the city, distorting the gender balance until men outnumbered women two to one, eventually leading to a roaring sex trade.

Prof Pybus added: “There are two aspects of infrastructure that could have helped.

“Public health campaigns to treat people for various infectious diseases with injections seem a plausible route [for spreading the virus].

“The second really interesting aspect is the transport networks that enabled people to move round a huge country.”

Around one million people were using Kinshasa’s railways by the end of the 1940s.

The virus spread, with neighbouring Brazzaville and the mining province, Katanga, rapidly hit.

Those “perfect storm” conditions lasted just a few decades in Kinshasa, but by the time they ended the virus was already starting to spread around the world.

HIV
The human immunodeficiency virus (HIV) attacks the immune system

Prof Jonathan Ball, from the University of Nottingham, told the BBC: “It’s a fascinating insight into the early phases of the HIV-1 pandemic.

“It’s the usual suspects that are most likely to have helped the virus get a foothold in humans – travel, population increases and human practices such as unsafe healthcare interventions and prostitution.

“Perhaps the most contentious suggestion is that the spread of the M-group viruses had more to do with the conditions being right than it had to do with these viruses being better adapted for transmission and growth in humans. I’m sure this suggestion will prompt interesting and lively debate within the field.”

Dr Andrew Freedman, a reader in infectious diseases at Cardiff University, said: “It does seem an interesting study demonstrating very elegantly how HIV spread in the Congo region long before the Aids epidemic was recognised in the early 80s.

“It was already known that HIV in humans arose by cross species transmission from chimpanzees in that region of Africa, but this study maps in great detail the spread of the virus from Kinshasa, it was fascinating to read.”

The element that redefined time


 

Caesium in a vial being held in front of a time station
Caesium centre: a relay station in Colorado where atomic time signals are transmitted across the US
Caesium is the chemical element that has literally redefined time.

All your life you’ll have been told the importance of being on time. Well, thanks to caesium the entire world now keeps time so accurately that it has forced us to reconsider what time really is. It has also introduced a bizarre bug into timekeeping.

Measuring time accurately is actually quite a recent preoccupation. I’m not saying our ancestors didn’t want to know the time, of course they did. For millennia mankind has been creating ingenious devices to gauge the passage of time.

But the truth is that, until about 175 years ago, it was the sun that defined time. Wherever you were, high noon was high noon, and on a clear day a quick glance up into the sky or down at a sundial told you everything you needed to know.

That all began to change with the world’s first railways, here in the UK.

Find out more

In Elementary Business, BBC World Service’s Business Daily goes back to basics and examines key chemical elements – and asks what they mean for businesses and the global economy.

Then the fact that midday in London was 10 minutes before midday in Bristol – because that was how long it took the sun to figuratively sail west across the sky – became an issue, and a very serious one.

It wasn’t just that passengers would miss their trains. Inconsistencies in timekeeping were causing an increasing number of near misses and even train crashes.

In November 1840 the Great Western Railway solved the problem with “Railway Time”. It imposed London time across the whole network, the first occasion time was synchronised between different locations to a single standard.

The move was very controversial. Suddenly, your time of day was to be dictated by the Royal Observatory in faraway Greenwich.

The Dean of Exeter stoutly refused to adjust the Exeter Cathedral clock to meet the demands of the railway company. In Bristol a compromise was found: two minute hands, one showing local time, the other Railway Time.

Bristol clock has two minute hands
This clock in Bristol still has two minute hands 10 minutes apart

Nevertheless Railway Time gradually became the standard across Britain, and the same happened around the world wherever railways were built.

But what does all this have to do with caesium, you are probably asking yourself?

Elementary Business

Various elements

The answer is that whenever you have a network operating over distance, accurate timekeeping is essential for synchronisation. And the faster the speed of travel, the more accurate the timekeeping must be. Hence in the modern world, where information travels at almost the speed of light down wires or through the air, accuracy is more important than ever.

What caesium has done is to raise the standards for the measurement of time exponentially.

I took a trip to the home of accurate timekeeping in Britain. It isn’t Greenwich, but the National Physical Laboratory in the leafy London suburb of Teddington.

The series of off-the-peg glass office buildings located on an upmarket industrial park belie the exotic endeavours that take place within.

The NPL is one of the world’s leading centres for research into the measurement of time and is where the British standards for the seven key scientific units of measurement are kept.

It was here in the 1930s that the physicist Louis Essen developed the first quartz ring clock, the most accurate timepiece of its day, and a precursor of the caesium clock.

Quartz clocks exploit the fact that quartz crystals vibrate at a very high frequency if the right electrical charge is applied to them. This is known as a resonant frequency, everything on earth has one.

It is hitting the resonant frequency of a champagne glass that – allegedly – allows a soprano to shatter it when she hits her top note. It also explains why a suspension bridge at Broughton in Lancashire collapsed in 1831. Troops marching over it inadvertently hit its “resonant frequency”, setting up such a strong vibration the bolts sheared. Ever since, troops have been warned to “break step” when crossing suspension bridges.

A soprano singer
Coming up: The resonant frequency of a champagne glass

To understand how this phenomenon helps you to measure time, think of the pendulum of a grandfather clock. The clock mechanism counts a second each time it swings.

Quartz plays the same role as a pendulum, just a lot quicker: it vibrates at a resonant frequency many thousands of times a second.

And that’s where caesium comes in. It has a far higher resonant frequency even than quartz – 9,192,631,770 Hz, to be precise. This is one reason Essen used the element to make the first of the next generation of clocks – the “atomic” clocks.

Essen’s quartz creation erred just one second in three years. His first atomic clock created at NPL in 1955 was accurate to one second in 1.4 million years.

But why caesium?

1956:  The original caesium resonator which led to the development of the atomic standard time, with J V L Parry (on left) and L Essen, 1956
Louis Essen (right) created the first caesium resonator in 1955

In a lab on the NPL site, chemistry professor Andrea Sella of University College London produces a tin can with a flourish. He opens it up and pulls out a wad of fabric padding. Wrapped inside is a sealed glass ampoule full of a silvery-gold metal.

He warms the ampoule in his hand. The metal gradually melts into liquid.

“Don’t drop it,” he warns when I take the ampoule.

He explains that the careful packaging is necessary because caesium is an alkali metal, from the first column of the periodic table. As such, it is very reactive, even more so than sodium or potassium.

“Drop it into water,” he warns, “and it will release hydrogen and there will be a very loud bang because the hydrogen will explode.”

Being in column one means that caesium has a single electron in its outer shell. That is what makes it so chemically reactive, and it was also the behaviour of this electron that Essen was interested in.

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Caesium: Key facts

Caesium
  • Discovered in 1860 by German scientists Robert Bunsen and Gustav Kirchhoff
  • A silvery metal with a golden cast, it is the most reactive and one of the softest of all metals
  • Melting point of 28.4C means it is a liquid just above room temperature
  • Reacts explosively with water and also spontaneously in air
  • About half as abundant as lead and 70 times as abundant as silver

 

I’m led to a room deep inside the NPL complex protected by a state-of-the-art electronic lock. This is where they keep the machine that sets the standard for the measurement of time in Britain.

It is known as the “caesium fountain” and inside the room I meet the keeper of the fountain, Krzysztof Szymaniec.

Don’t imagine the sort of fountain that plays in the gardens of a palace, this looks like a domestic hot water tank made of stainless steel with all sorts of extra wires and other gubbins attached at the bottom.

It may not be pretty, but it is one of the most accurate clocks on earth.

Caesium fountain

Szymaniec explains it works by using a series of lasers to push a group of caesium atoms so tightly together that they almost stop vibrating, dropping their temperature to a smidgen above absolute zero.

Other lasers launch this atomic “molasses” up into the tank bit of the machine. The atoms fall back under gravity – hence “fountain”.

What the machine does next is tune a beam of microwave radiation into the resonant frequency of the caesium. Just like champagne glasses and bridges, when you hit the right frequency the caesium gets excited, and what happens is that outermost electron jumps into a wider orbit. This is known as a “transition”.

Robert Bunsen
Robert Bunsen co-discovered Caesium in 1860

As the electron moves out into the wider orbit it absorbs energy, and as it jumps back in it releases it in the form of light, fluorescing very slightly. That means you can tell when you’ve hit the sweet spot of 9,192,631,770 Hz. It’s because this transition frequency is so much higher than the resonant frequency of quartz that a caesium clock is so much more accurate.

The caesium fountain at NPL, Szymaniec tells me proudly, is accurate to one second in every 158 million years. That means it would only be a second out if it had started keeping time back in the peak of the Jurassic Period when diplodocus were lumbering around and pterodactyls wheeling in the sky.

But modern technology means these days even more staggeringly accurate clocks are possible.

That’s because caesium was always a compromise element when it came to timekeeping. Louis Essen chose caesium, explains Szymaniec, because the frequency of its transition was at the limit of what the technology of his day could measure.

We now have new ways of measuring time.

At NPL they are experimenting with the elements strontium and ytterbium that operate at far, far higher frequencies – right up in the optical rather than the microwave spectrum.

An ytterbium optimal clock
Optical clocks with strontium or ytterbium, such as this one, are even more accurate than caesium clocks

The frequency of the transition of strontium, for example, is 444,779,044,095,486.71 Hz. A strontium clock developed in the US would only have lost a second since the earth began: it is accurate to a second in five billion years.

The scientists at NPL reckon optical clocks that keep time to within one second in 14 billion years are on the horizon – that’s longer than the universe has been around.

Now, if such insane levels of accuracy seem pointless, then think again. Without the caesium clock, for example, satellite navigation would be impossible. GPS satellites carry synchronised caesium clocks that enable them collectively to triangulate your position and work out where on earth you are.

And the practical applications do not end there. Just ask Leon Lobo – he’s in charge of time “dissemination” at NPL. His job is to tell the time to the UK. For a fee.

NPL has just begun offering businesses standardised timekeeping accurate to the nearest microsecond – a millionth of a second. Mr Lobo is targeting a wide range of clients that all have one thing in common – they need to synchronise a network that operates at speeds far faster than any trains.

Consider for example electricity grids. As wind and solar energy become more widespread, the grid will need to time accurately its reactions to unexpected lulls in the wind or passing clouds. Get that wrong, and you end up with blackouts.

Mr Lobo’s biggest target is the financial markets, which these days are dominated by computers programmed to place thousands of trades per second, transmitted down wires at almost the speed of light.

In this world, the equivalent of a train crash would be ill-timed bets that rack up millions of dollars in losses, and might even briefly sink the market in the process. Unsurprisingly, financial regulators increasingly require a super-accurate timestamp on every transaction.

But the accuracy of caesium clocks has introduced a potentially disastrous glitch into the world’s timekeeping. To understand why, we need to rewind to 1967.

That year, the official international standard second was redefined based on the caesium transition. Yes, caesium has redefined time itself.

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Definition of a second

The duration of 9,192,631,770 periods of the radiation corresponding to the transition between the two hyperfine levels of the ground state of the caesium-133 atom

A diagram of an atom
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It was a momentous decision. Until then, mankind had always defined time (even Railway Time) by reference to the movement of the sun relative to the earth. No more. The sun was dethroned, and caesium took its place – though one wonders how long it will be before strontium or ytterbium knocks caesium off its perch.

The switch to atomic time was for good reason. The rotation of the earth, it turned out, was not such a reliable measure of time. No day or year is exactly the same length.

First off, the earth is very gradually slowing down and thus the average day is getting infinitesimally longer. Then you have to add in the idiosyncrasies of oceanic tides, tectonic drift and the convection of the earth’s mantle, all of which cause minuscule wobbles.

This is a big issue for Felicitas Arias, whose job is to keep time for the entire world. She is the director of time at the International Bureau of Weights and Measures (BIPM) in Paris, which is responsible for ensuring the uniformity of measurements worldwide and maintains the modern time standard, Coordinated Universal Time (UTC).

When UTC was first adopted in the 1960s, long before the advent of GPS, it posed a potential problem for sailors, who still relied on clocks to work out their longitude on the high seas.

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More from the Magazine

Inner workings of a pocket watch

“Who first designed a more accurate timekeeper was once more than a matter of academic interest. In the late 17th Century, clock and watch design was part of national security. Navigation and mapping were both essential for the successful conduct of war – and England was involved in a sequence of wars against the French and the Dutch in this period.”

 

They still exploited a system that the super-accurate clocks of another British pioneer of timekeeping, John Harrison, had first made possible in 1761. They compared the position of the sun or the stars at their particular location, with the time on a clock taken from another fixed location, typically Greenwich. Every four minutes’ difference represented a single degree east or west.

But in order for this technique to continue working, they insisted that UTC remain synchronised with the earth’s wobbly rotation. And that means every now and then an extra “leap second” is inserted. And it is Ms Arias’ job to decide when.

“For a long time leap seconds came every two years,” she tells me. “Then we had seven years without leap seconds. Then they came back every two or two-and-a-half years.”

But every time a leap second needs to be inserted, all the atomic clocks across the world need to be changed.

Most of us wouldn’t notice a second or two every couple of years, but computers do. They might momentarily shut down, which would, apparently, make them vulnerable to cyber-attack. Or they could get out of sync, leading to electronic train crashes.

It hasn’t happened yet but Ms Arias believes the consequences could be disastrous.

“One second in the financial markets can provoke a kind of earthquake,” she warns.

The prospect of City traders losing out on million-dollar deals may not fill you with horror, but she’s worried that as power stations, mobile phone networks and satellite navigation systems are increasingly synched to caesium time they could fail too.

A man stands looking at computer screens at the NYSE
Time is money, especially when it comes to trading at the New York Stock Exchange

That’s why there is a move now to get rid of leap seconds completely and go over to unadulterated atomic time. Most sailors already use satellite navigation, so it might not be such a serious problem for them today as it was in the past. But severing the link between time and the motion of the celestial bodies completely would have some significant consequences.

Because the earth’s spin is slowing, the time on your watch would gradually diverge from the rising and setting of the sun.

“We can predict that in a thousand years we could be one hour out,” she says.

She’s surprisingly relaxed about the prospect. She points out that most of us are already out of sync with solar time.

Due to the earth’s elliptical orbit, the sun can be as much as 16 minutes out of line with mean solar time. Add the distortion of time zones, which average time across huge regions, and the difference is far greater. China, which is almost 5,000km wide, has a single time zone spanning 1h40 of solar time.

The decision of some countries to adjust the clocks twice a year as a “daylight saving” measure exaggerates the issue yet further.

Nevertheless many nations resist the move to end leap seconds. The UK, for example, whose Greenwich Meridian was for centuries the benchmark for global timekeeping, insists that leap seconds are not a serious inconvenience.

And maybe that is a reasonable position given just how slippery the whole concept of time can be.

In 1971 scientists sent three caesium clocks around the world on commercial airliners. When they returned they were compared with caesium clocks that had stayed at home in the United States Naval Observatory.

Two first class seats aboard a TWA jet from London to Washington. One occupied by a caesium beam timepiece accurate to one-millionth of a second used in the USA's space programme. This clock is being returned to America from South Africa and as it must not be allowed to stop it is connected to a power point in the aircraft during the flight. The other seat is occupied by one of the clock's escorts
Five years before the effects of flight were tested scientifically, this caesium clock travelled first class from London to the US – it had to be plugged into a power socket, and strapped in with a seatbelt

The jet-setting clocks were found to be slower by exactly the amount Einstein’s theories of relativity predicted. Thereby proving his hypothesis that the speed at which time passes depends on where you are in the universe and how fast you are moving.

Today, the clocks aboard GPS satellites have to be adjusted to take account of precisely this effect.

And the new generation of insanely accurate optical clocks may make use of relativity to map the gravitation field of the earth, by measuring the minute differences in recorded time caused by the effect of gravity.

But stop and consider the irony here. Caesium clocks have proved that an absolute measure of time is – impossible.

Patients’ app diagnoses ‘not useful’


health app

Treatment suggestions are not always useful, the doctors surveyed said

More patients are going to their GP and telling them what treatment they need based on information from apps and the internet, a survey has suggested.

A third of the UK physicians surveyed said patients would come with suggestions for what prescription they should receive.

Fewer than 5% of doctors felt it was helpful.

Major technology firms such as Apple and Samsung are investing heavily in tech that can monitor a user’s health.

The survey of 330 UK physicians – 300 of them GPs – was carried out by Cello Health Insight, a medical market research firm.

“Doctors have witnessed an explosion in the quantity and quality of information now available to them and their patients via digital media and technology,” said Dan Brilot, the company’s digital director.

“Consumers are increasingly seeking out information (and technological tools such as fitness and health apps) to provide as much information as possible before – and after – consultation.”

Healthier apps

However, doctors were finding technology useful for their own needs. Specifically, Cello’s survey said three-quarters of those surveyed turned to the internet for research on conditions.

Many GPs would also use the internet to share new information with colleagues.

While self-diagnosis was proving troublesome, most of those surveyed did advocate the use of technology for general monitoring.

More than half said apps designed to make sure treatment is taken or administered correctly are useful.

The NHS provides a service that suggests apps for patients that have been checked for accuracy.

The apps could help diabetics keep a check on their blood sugar and patients monitor their own blood pressure.

Polio hits record high in Pakistan


A Pakistani child receives a polio vaccination drops from a health worker in Rawalpindi - 8 April 2014

Pakistan is one of three countries where polio is endemic despite huge investment in vaccination schemes

Pakistan has recorded its highest number of polio cases for 15 years, with health officials blaming the rise on attacks on immunisation teams.

The number of new cases in 2014 so far is 202, exceeding the 199 cases in 2001 but short of the 558 cases in 1999.

Most of the infections are in the north-western tribal region where militants have targeted health teams.

Militants there accuse doctors of being spies and say the vaccinations are part of a Western plot to sterilise Muslims.

Suspicions over the programmes worsened after the US was accused of using a fake vaccination programme during its tracking of al-Qaeda chief Osama Bin Laden in Pakistan in 2011.

Since December 2012, about 60 people, including health workers and police providing security to medical teams, have been killed by Taliban militants targeting polio teams.

The BBC’s Shaimaa Khalil in Islamabad says the rise in cases is hugely embarrassing to Pakistan.

The country has failed to curb the disease despite massive investment on immunisation programmes by the international community, she adds.

Earlier this year, the World Health Organization imposed travel restrictions on the country meaning all Pakistanis must now carry proof of vaccination before travelling abroad.

Pakistan is one of three countries where polio is endemic – the other two being Afghanistan and Nigeria.

Antibiotic Resistance — Problems, Progress, and Prospects.


Two major ways that modern medicine saves lives are through antibiotic treatment of severe infections and the performance of medical and surgical procedures under the protection of antibiotics. Yet we have not kept pace with the ability of many pathogens to develop resistance to antibiotics that are legacies of the golden era of antibiotic discovery, the 1930s to 1960s. We call that period “golden” because success seemed routine then; we call it an “era” because it ended. When industry scientists shifted from making variants of old drugs to pursuing fundamentally new drugs with activity against resistant pathogens, they generally failed. Persistent, costly failure to discover novel antibiotics that would be destined for short-term use even if they survived the regulatory approval process led industry to change its focus to drugs whose long-term use prevents or mitigates noninfectious diseases. As people in wealthier regions run out of effective antibiotics, they come to share the lot of people in poorer regions who can’t afford them to begin with.1

At least some clinical isolates of many pathogenic bacterial species — Mycobacterium tuberculosis, Neisseria gonorrhoeae, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and species of enterobacter, salmonella, and shigella — are now resistant to most antibiotics. The problem seems out of control. Yet there are reasons for optimism: progress has recently been made on 4 of 10 key challenges to ensuring that antibiotics retain an effective role in medicine.2

Recognition. Alexander Fleming and Howard Walter Florey sounded the first warning about antibiotic resistance when they accepted the 1945 Nobel Prize for the discovery of penicillin. Physicians and scientists have expanded and expounded the message ever since, but it has recently begun to resonate with the public, the press, and leaders in business and government.2

In the past decade, various key organizations, including the Infectious Diseases Society of America, the Centers for Disease Control and Prevention, the World Health Organization (WHO), and the World Economic Forum, have made antibiotic resistance the focus of highly visible reports, conferences, and actions. This year, the activity seems to have accelerated. In April, the WHO declared that the problem “threatens the achievements of modern medicine. A post-antibiotic era — in which common infections and minor injuries can kill — is a very real possibility for the 21st century.” In May, the World Health Assembly commissioned the WHO to deliver a global action plan on antimicrobial resistance. In June, the British public voted to dedicate a government-sponsored £10 million Longitude Prize to the best solution to the resistance problem. And in September, the U.S. President’s Council of Advisors on Science and Technology released a report on antibiotic resistance linked to an executive order from President Barack Obama, who directed the National Security Council to work with a governmental task force and a nongovernmental advisory council to develop a national action plan by February 2015. Among other goals, the plan will propose implementation of antibiotic stewardship in health care facilities and the community; development of rapid, point-of-care diagnostics; recruitment of academic and industry partners to increase the pipeline of antibiotics, vaccines, and alternative approaches; and international collaboration for prevention, surveillance, and control of antibiotic resistance.

Partnership. Innovative experiments in public–private partnership are under way for antibiotic-drug discovery. In 2012, the Bill and Melinda Gates Foundation expanded its Tuberculosis Drug Accelerator program to include multiple drug companies, academic institutions, a foundation, and a government laboratory. Participants pool efforts, assays, and compounds, aiming to identify, validate, and inhibit new targets with new drugs. In 2013, the U.S. Biomedical Advanced Research and Development Authority began funding antibiotic research in industry, and the European Commission and the European Federation of Pharmaceutical Industries and Associations launched a partnership for antibiotic discovery.

Return. The retreat of most major pharmaceutical companies from antibiotic research has resulted in little competition in the development of novel antibiotics in a market that is currently worth more than $40 billion annually for drugs that are starting to fail. Several small companies seeking to fill the gap have had new antibiotics approved, and the world’s fourth-largest drug company recently announced its return to the effort. However, major disincentives remain, including the difficulty of conducting large clinical trials to compare drugs in patients with antibiotic-resistant infections.

Prevention. Antibiotics’ growing lack of effectiveness has spurred a resurgence in infection surveillance and control practices; renewed efforts in vaccination; and increased attention to deficiencies in sanitation. Nonetheless, much remains to be learned about how to prevent acquisition and transmission of resistance.

Despite progress on these fronts, securing a long-term ability to treat bacterial infections requires addressing six more daunting challenges.3

Leadership. We believe that sound solutions will require a global organization with the authority, leadership, and resources to oversee collaboration of the health, security, economic, and development sectors; maintain global surveillance of antibiotic resistance; and manage rewards for developing and conserving antibiotics.

Rewards. Unless monetary rewards are delinked from drug sales,4,5 few companies will invest in high-risk programs to develop drugs whose use must be restricted and which will probably ultimately lose their clinical utility. Sales-based compensation has also supported rampant profiteering through drug dilution, substandard manufacture, and counterfeiting, which foster resistance and undermine treatment. Moreover, if rewards derive from price and price reflects value, the prices of new, lifesaving antibiotics will preclude access by the poor. Instead, a new antimicrobial oversight agency could administer a fund that rewards antibiotic developers in proportion to the estimated quality-adjusted life-years saved — creating an incentive to expand medically indicated access by keeping prices close to the cost of production and distribution. At the same time, continuing payouts to originators as long as drugs have clinical utility would minimize the adverse effect of conservation on profitability.

Access. The ideal economic model would enable us to provide access to lifesaving antibiotics to all who need them while restricting overuse that contributes not only to resistance, but perhaps also to epidemic obesity, asthma, and other disorders. A global fund could solicit contributions in proportion to countries’ gross domestic product, but in the short term, equitable access might require wealthier countries to subsidize appropriate antibiotic use in poorer countries.

Conservation through prioritization of medical use. The current practice of applying the most antibiotic tonnage to growth promotion in food animals and plants is incompatible with an expectation that antibiotics will cure life-threatening infections. We believe that governments worldwide should impose restraints like those in force in the European Union, which have not reduced food production.

Conservation through prescription tailored to diagnosis. Ideally, technological advances in point-of-care diagnostics would enable prescribers to avoid dispensing antibiotics for viral infections and fevers of unknown origin. Better diagnostics could allow prescriptions to be tailored narrowly to a pathogen’s susceptibilities. Adoption of such technology would require physician education, suitable reimbursement, and documentation of outcomes.

Conservation through controlled access. In wealthier countries, all health care facilities should institute antibiotic-stewardship programs. In poorer countries, despite the need to expand access to effective antibiotics, there’s also an urgent need to reduce inappropriate use fostered by misaligned financial incentives for providers and by over-the-counter access. Given the ease with which antibiotic resistance spreads, we all share an interest in helping poorer countries build sufficient infrastructure to allow medical personnel to distinguish among pathogens before antibiotics are prescribed.

These issues concern everyone. Military leaders don’t want their personnel devastated by infections associated with wounds or close quarters. Drug-company leaders realize that the public expects their firms to produce life-saving medicines and blames them when they don’t — an attitude shared in countries whose developing economies offer companies their best prospects for growth. But physicians may care about this problem most passionately, for they must tell more and more families that there is no hope. Doctors can act not just individually and medically, but also collectively and civically, to persuade elected officials to respond to expert panels’ recommendations and national leaders’ directives with the legislation, appropriation, regulation, enforcement, and cooperation needed to ensure access to these life-saving drugs.