On the end-of-year lists, Ozempic keeps taking top honors for achievements in science. But in our new golden age of medicine, one of the most eye-opening breakthroughs has been in the less glamorous corners of public health.
In late October a large-scale pilot rollout of the malaria vaccine RTS,S in parts of Africa by the World Health Organization was shown to have reduced child mortality in by 13 percent over four years, Science reported. It was so astonishing that mortality reduction in one disease could reshape the prospects of all childhood deaths that the epidemiologist who led the program said she expected gasps in the audience when the news was announced.
The results made RTS,S sound like a miracle drug. But it also looked — immediately — like a missed opportunity. The key breakthrough was made more than three decades ago, and the safety and efficacy of the vaccine were shown in clinical trials that began as far back as 1998, though a few questions about side effects lingered. The W.H.O. did not recommend the use of RTS,S until October 2021. Since then, fewer than two million children have been vaccinated, and only 18 million doses (enough for just 4.5 million children) are expected to be available through 2025. More than 18 million people, most of them young children, have died of malaria in the quarter-century since the vaccine’s 1998 trials.
In the meantime, a new vaccine has come along, perhaps even more impressive. Called R21, it has been shown to reduce symptomatic cases of malaria by 75 percent in the 12 months following completion of a three-dose series. But rollout of the new vaccine has been slow, stymied in part, The Financial Times has reported, by a lack of urgency by the W.H.O., which finally added it to a list of prequalified vaccines in December.
One hundred and twenty million doses of R21, enough to save the lives of more than 200,000 young children, could be delivered over the course of 2024, according to the public-health advocacy group 1Day Africa. But even with prequalification, many fewer doses than that are expected to be delivered right away. In a December status report, 1Day suggested that tens of millions of doses may go unused this year.
These vaccines aren’t perfect, and even a global rollout will not eradicate malaria — a 2015 clinical trial of RTS,S reported a vaccine efficacy of 36.3 percent for clinical disease, although R21 looks more promising. But with diseases of this scale, even limited effectiveness can save huge numbers of lives. More than 600,000 people die of malaria every year; more than half of them are children under the age of 5.
From the promontories of the developed world, it can be easy to believe scientific breakthroughs and drug discoveries mark new eras for medicine almost instantaneously, and to regard poor-world diseases like malaria as eternal features of the global status quo. But every day malaria kills more than 1,000 children, many of whom could be saved at remarkably little cost, with effective vaccines we have already manufactured. A global rollout of R21 could cost just $1 billion, 1Day calculates, making the average cost of saving a child’s life just $4,000. Other estimates are even lower.
This may sound like an argument for effective altruism — that even small-scale philanthropists can fund truly transformational medical interventions in the developing world. But vaccine manufacturing and rollout are more complicated than distributing bed nets. For me, the real lesson is less about finding public-health workarounds than about how much more might be achieved by muscular state action.
In an admirably comprehensive history of the 141-year saga of malaria vaccines published in Works in Progress in September, Saloni Dattani, Rachel Glennerster and Siddhartha Haria draw an alternate road map: By promising to pay for vaccines before they are developed, with what are often called advance market commitments, governments could sharply accelerate drug deployment.
The RTS,S vaccines took so long in trials and pilot studies, they point out, largely because the relevant research had to be funded by philanthropy because there was no potential for real profit. “Why would you allow children to die instead of distributing the vaccine?” asked Adrian Hill, one of the Oxford scientists who developed the R21 vaccine. Ripley Ballou, who helped spearhead the development of RTS,S, gave kind of an answer to Undark last May: “Primarily, this is the problem that you face when you’re trying to develop a vaccine that nobody wants to pay for.” But the solution may be relatively simple, the Works in Progress authors suggest: find a way to pay for it ahead of time. As they point out, a $1.5 billion advance market commitment pledged for pneumococcal vaccines by five countries and the Gates Foundation in 2009 had saved, just a dozen years later, 700,000 lives.
That is not just a lesson for the developing world, though, or a morality tale about the public-health indifference of countries with deep pockets. In the United States, Operation Warp Speed has come to be seen as a similar kind of inspiring, moonshot breakthrough — at least for those still inclined to trust and celebrate the achievement of the Covid-19 vaccines — and a reminder of how much more we might do for public health, even in the wealthy world, should we really commit to it.
In some corners, the success of Operation Warp Speed gets described as an entrepreneurial triumph — the businessman Jared Kushner, gathering a best-and-brightest collection of innovators from biotech and Silicon Valley, and running a no-red-tape operation like a ruthless start-up. But the federal government’s advance market commitments were a major driver of the program’s success: Enough money was guaranteed up front not just for mass vaccination but also for the cost of running expensive clinical trials.
That isn’t the normal playbook for drug development, either domestically or globally. But perhaps we should consider working from it a bit more often.