Goodbye Mars, Hello Malaria: Bill Gates’ Imprimatur on Science and the 21st Century

The cover story in the May 14 Science featured not space probes or cancer stem cells but malaria and tuberculosis. This first culminates trends away from classic 20th century research ambitions like a cure for cancer, becoming a spacefaring race and genetically engineering a new post-human species. Instead, as the pages of Science make clear, it’s goodbye Mars, hello malaria. Bill Gates printed out this new agenda, putting his stamp both on it and the new century.

Science both sets and reflects the agenda for American science. In the United States, cancer is the second biggest killer; malaria caused only four deaths in the most recent annual count, all from infections occurring abroad. Although coverage of cancer in Science still overwhelms that of malaria, in 2000 the count of cancer mentions in Science turned down for the first time in the history of the publication. At the same time, malaria coverage tilted up, reflecting a shift from developed to developing world health concerns. (As if in emphasis, last week Nature also ran a malaria cover story.)

Symbolic New Year’s Day 2000 saw the establishment of the Bill and Melinda Gates Foundation. Gates said then of his foundation’s mission: “I think that we could have the goal that every person in the world would have the same type of healthy life that people in the United States have.” His words now seem to have instantly reshaped the trajectory of science.

Source: Science

2000 marked an inflection point for NASA—and a turn in Science toward the terrestrial. Previously, the magazine's affections for space exploration had grown and grown even as the golden age of the 1960s receded. Ironically, coverage reached an apogee at the dawn of the 21st century and began falling back to earth in 2000. President Obama's subsequent cancellation of the Ares program earlier this year scaled back human space exploration to the vanishing point.

Neither are we on a trajectory to create a new, post-human species. In 2001, mentions of malaria in Science exceeded those of genetic engineering for the first time, a predominance that continues.

Can these shifts really be traced to the influence of Gates Foundation? Concerning the new emphasis on malaria, Gates is indisputably causal. The disease began gaining column inches in Science before Gates, from 1980 forward. However, the last decade’s spike to all-time highs not only coincides with Gates’ rhetoric but an enormous funding surge largely orchestrated by the Gates Foundation.

Research agendas are a zero-sum game. Consequently, the rise of malaria and global health automatically de-emphasizes all else. But difficulties specific to cancer, space, and genetic engineering also contributed to their demotion. The war on cancer and the space age are each roughly half a century old and not much nearer to victory or realization. By contrast, exponential advances in DNA sequencing technology seemed to be leading inexorably to a post-human species. However, genetic explanations of both complex diseases and complex traits have been—and might remain—elusive. As the number of genes involved in the relatively straightforward trait of height has grown, the prospects for and coverage of genetic engineering have dropped.

Gates still could have jumped on the spacewagon with fellow software billionaires Paul Allen, a major funder of SETI, or Jeff Bezos (with Blue Origin) and Elon Musk (SpaceX) who continue undeterred towards the spacefaring vision. Even software millionaires like John Carmack (Armadillo Aerospace) can’t help themselves. But Gates isn’t susceptible. In 1997, he praised the (unmanned) Mars Pathfinder mission as “a fine example of small science ... undertaken on a strict budget [with] limited, achievable goals.” He believed space would not be transformative: “Though humanity will do some great things in space in the next 100 years, and there will be enormous benefits, I don't think what goes on in space will fundamentally change the way we live.”

Concerning genetic engineering, Gates contended “It’s all a question of how, not if,” in 1995. He may still believe that, but his energies are going into saving rather than surpassing humans.

The opportunities (and imperatives) presented by global health might be greater than for any alternative research program. But nature yields to science only grudgingly no matter the frontier. Gates’ goal to eradicate malaria will be a multi-decade grind offering frequent parallels with the bogged down, four-decade war on cancer. Already polio eradication is a decade overdue. 

It’s a volitional, pivotal moment. Gates, his full weight on Archimedes’ lever, is moving the world in a new direction altogether different from 20th century imagination and expectation.

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Heavy Lifting: Raising Health Beyond Polio's Reach

Two of the world's kids, Bihar, India. (Photo: kuann)

Bill Gates expanded the campaign to eradicate polio during a frontline visit to India yesterday. The new strategy: lift health beyond polio's reach.

The largest remaining pockets of the disease are the Indian states of Bihar, site of Gates' visit, and neighboring Uttar Pradesh. Over 240 million people live in the region.  Fertility rates are high with more than 500,000 children born monthly in Uttar Pradesh. The new births are accompanied--and perhaps driven by--the highest child mortality rate in India.

Waves of vaccination campaigns have failed to eliminate the disease from the two states. Disconcertingly, even multiple doses of the oral vaccine don't guarantee immunity here, a failure usually explained by widespread unhygienic conditions, undernutrition and illness. By improving broader health conditions, the chain of circumstances favorable to polio could be broken.

The World Health Organization recently began investigating the biology underlying the vaccine failure. Meanwhile, however, Bill Gates signed an agreement with the state of Bihar to "to improve and increase the availability, quality and utilisation of health-care facilities and services," according to the Economic Times.

For all its assets, however, the Gates Foundation cannot fund better health care at Bihar and Uttar Pradesh scale. The memorandum between Bihar and the Foundation might represent a quid pro quo. Polio affects very few, even in India which experienced just 741 cases in 2009. The benefits of eradication accrue to the entire world but India must do the actual work at least to the partial exclusion of more pressing priorities such as child mortality.

A few weeks ago, the Wall Street Journal speculated that Gates might shift away from eradication toward strengthening health systems. Instead Gates added improving health infrastructure to his still-relentless campaign for eradication.

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Related:

Gates Seeks to Close Out Polio in Nigeria (June 7, 2010)

Wall Street Journal: Pulling the plug on polio eradication? (April 26, 2010)

Polio Eradication: Harder Than it Looks (April 14, 2010)

Wall Street Journal: Pulling the plug on polio eradication?

In counterpoint to the New York Timespositive coverage of the war on polio earlier this month, the Wall Street Journal on Friday put forward a case for abandoning the goal of eradication—and not just for polio. The Journal depicts a potentially seismic policy shift as emanating from the de facto leader of global health, Bill Gates.  Such a reversal is unlikely.

Gates got behind polio eradication in 1999 with a $50 million grant he believed would close out the disease. He predicted in 2000 that “If necessary resources and political will are devoted to polio eradication, the world can claim victory over this killer by the end of this year and certify the planet as polio free by the year 2005.” A decade and nearly a billion dollars later, the result is not eradication but oscillation, case numbers rising and falling.

Debate about the wisdom of the eradication policy has ensued. Millions of children die from malaria, for example, compared to which polio’s afflictions, although still horrible, are minute. More suffering could be averted, the argument goes, with a different allocation of global health dollars. The Wall Street Journal urges a move away from disease-specific campaigns and towards strengthening of overall health systems.

Polio might be expensive, but dropping eradication might be more so.  A Lancet study in 2007 concluded that control would be more expensive than eradication. But whatever the optimal policy, it requires funding. Eradication provides a sense of urgency and heroism; a control strategy does not.

Credibility is also at stake for global health advocates and Bill Gates in particular. Gates has backed not only getting rid of polio. In 2007, he and wife Melinda strong-armed a skeptical global health community to embrace malaria eradication. As hoped, tremendous energy and funding were released. A giant vogue for malaria eradication ensued, like Ashton Kutcher’s Twitter-driven campaign for bed nets. At the governmental level, the largest surge in funding commitments to battle malaria came one year after setting eradication as the goal. Arguably to protect these gains, the Gates Foundation doubled-down on polio eradication in 2008. And as the Wall Street Journal points out, Gates personally led the assault, descending in 2009 on the hottest polio spot, Nigeria, where vaccination lagged.

A resurgence of polio that came from consciously letting up on the disease, even if the best policy, would be a public relations disaster. The current trajectory also presents serious problems but far less severe: Eradication is expensive and doesn’t appear to be working. The solution has been continued mass dosing of the polio-vulnerable in the developing world and, for donor nations, a steady drip of good news that, yes, we are at the absolute cusp of eradication. Right now, the news is good in Nigeria and indeterminate in India, the familiar cusp yet again.

Ultimately, polio can be snuffed out by the downward pressure of eradication, the strengthening of health systems and much broader, slower and more costly development—improvements in food, water and sanitation.  In the near term, eradication will remain the strategy, but elusive.

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Related:

Polio Turns Stealthy in India (August 19, 2010)

Heavy Lifting: Raising Health Beyond Polio's Reach (May 13, 2010)

Polio Eradication: Harder Than it Looks (April 14, 2010)

Polio Eradication: Harder Than it Looks

Why it might require a new vaccine

The global campaign to eradicate polio crushed 90% of the disease in the space of a dozen years, by 2000. In the decade since, complete elimination has swung tantalizingly close—and then away again when case counts spiked and outbreaks reappeared in countries recently cleared of the virus. Once again, cases are ebbing and hopes rising. The New York Times recently reported that for four straight months, India has seen no new cases in its two most polio-burdened states. But the real news is the unnoticed opening of a new scientific front in vaccine research, portent of a longer battle.

The polio-free streak in the state of Uttar Pradesh, while encouraging, is actually only two months old and in the state of Bihar just over three. India as a whole did have zero cases in March. But in four of the last ten years, the country has started off with even fewer total polio cases only to see the tide turn. Nationwide, the total cases so far this year, 19, equals the number at this time in 2009. Polio incidence usually rises in May; given reporting delays, by July, the direction of the trend should be clearer.

The Times article cites extraordinary vaccination efforts to explain the new swing toward eradication. Polio vaccination campaigns in India are monumental undertakings, war-sized in scale involving an army of over two million vaccinators going house-to-house and overseen by a supervisor corps numbering greater than 100,000. However, the most enduring reason polio continues in India has not been a failure to vaccinate, but a failure of the vaccine.

If the population covered by campaigns is increasing, so too is the frequency of the campaigns. Vaccinations became monthly in Uttar Pradesh, for example, in 2007 in order to cover more quickly the 500,000 children born there each month.

Although the remarkable vaccination efforts have greatly pushed down polio cases, eradication has remained elusive because eight vaccine doses or even more don’t necessarily confer immunity. In India, the number of polio cases where the individual hasn’t been vaccinated has plummeted toward zero. Instead, increasingly the victims have been vaccinated over and over—to no effect.

In most places in the world—and many places in India—the Sabin oral polio vaccine works after two doses. No one knows what makes it go awry in Uttar Pradesh and Bihar. Those states are highly populous but low in income. Overcrowding and hygiene conditions help infection spread. But the vaccine's inability to elicit immunity is thought to be a product of malnutrition, immune suppression caused by other diseases and possibly genetic factors.

The World Health Organization just closed a call for research proposals to find out why, part of an ongoing large investment in improved vaccines. Critics of the eradication program have vociferated about the oral vaccine for some years. But developing new vaccines or drugs is time consuming, costly and not guaranteed to work, perhaps explaining the reluctance to open a scientific front in the war on polio. Previously, global eradication, while hugely daunting and complicated, came down to logistical execution, will power and funding.

Bruce Aylward, who heads the eradication effort at the World Health Organization, has ample willpower, but worries constantly about finances. He has steadily forecasted the imminent demise of polio for years. To fund the pursuit of eradication, he has learned that when there’s good news, like a favorable turn in case numbers, you cash it in. Aylward told the New York Times: “We’ve never had so many things looking so positive across so many areas.” Concerning a funding shortfall, he hastened to add: “I spend as much time in donor capitals as I do in infected countries.”

Hopefully his efforts will pay off. But if eradication remains unachieved, we will almost certainly be on the verge of it—still.

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Photo credit: Jean-Marc Giboux via quilty2010, Sub-National Immunization Day. Lucknow, Uttar Pradesh

Source, 2nd graphic: AFP Surveillance Bulletin—India Report for the week ending February 6, 2010

Source, 3rd graphic: Paul, Y., Polio eradication in India: Have we reached the dead end?, Vaccine.  2010 Feb 17;28(7):1661-2.

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Related:

Polio Turns Stealthy in India (August 19, 2010)

Heavy Lifting: Raising Health Beyond Polio's Reach (May 13, 2010)

Wall Street Journal: Pulling the plug on polio eradication? (April 26, 2010)

In Burma, the Wrong Kind of Resistance

Drug-resistant malaria may have spread to Burma and, worse, might now be impervious to current first-line drug defenses. Less than a year into the battle to contain resistance, everything that could go wrong may have.

In Southeast Asia, malaria has overrun--twice--the pharmaceutical defenses erected against it, evolving resistance to previously potent anti-malarial drugs and ultimately rendering them useless worldwide. Last year, portents of a third such performance appeared. In cases  along the Thai-Cambodia border, the first-line drug artemisinin began taking longer to completely clear malaria parasites, suggesting that today's champion had lost a step against a strengthening disease. (See Once again, it's 'Apocalypse Now' in Southeast Asia.)

Plans quickly developed to crush this new threat before it spread globally--again. Efforts to eradicate malaria from the affected areas of Cambodia have markedly reduced prevalence of the disease. But preliminary reports now suggest that  parasites in some regions of Burma and Vietnam may also respond poorly to artemisin, meaning the original lines of containment might already be breached.

In the past, drug-defeating strains originated in Southeast Asia and then spread by human carriers to Africa. Worryingly, researchers are currently working to determine whether artemisinin-resistant malaria has arrived in other parts of the world and if there is a connection to Southeast Asia.

On top of news of a faster-than-expected spread, some evidence suggests that artemisinin is getting slower and slower in some cases. If the trend continues, eventually treatment failure will result, meaning complete resistance to artemisinin when there are no new drugs to take its place.

On the other fronts of the war on malaria, a vaccine candidate, called RTS,S, has moved into final clinical trials. However, the protective effects of the vaccine have varied widely, from 40% to 60%, creating a difficult decision on whether to undertake large and costly vaccination campaigns when RTS,S emerges from clinical trials in 2014. The bright spots at present are insecticide-treated bednets. The bednet campaign has raised awareness, money and most importantly actual usage of the nets in malarial regions of the world.