Changing climate

Driving dengue

Chronic diseases

Holistic approach

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Tackling the health toll of climate change

Climate change is not only set to impact ecosystems and weather patterns across the planet, it will also take a toll on human health. While new diseases may be the consequence of this development, the most likely scenario is that patterns of existing infectious and non-communicable conditions will change.

Text by Goran Mijuk, photos by Laura Morton

A researcher retrieves stored cells from the liquid nitrogen storage at the Novartis campus in Emeryville, California.

Table of contents

Changing climate

Driving dengue

Chronic diseases

Holistic approach

Back in 2002, when Novartis decided to set up a research lab in Singapore dedicated to tropical diseases, the idea was not driven by climate change concerns but by the fact that health conditions rife in developing countries, such as malaria and dengue, were generally ignored by the pharmaceuticals industry.

With the foundation of the Novartis Institute for Tropical Diseases, or NITD, the company aimed to fill this research gap. “We felt the need to provide access to healthcare for the millions of patients suffering from diseases that were traditionally neglected,” said Paul Herrling, the company’s first research head, who helped create NITD.

The goal of the institute, which today is headquartered near San Francisco and over the years partnered with private and public institutes, including the Bill and Melinda Gates Foundation and the Medicines for Malaria Venture, was to accelerate research in diseases which were widespread in tropical regions but for which there were limited or no treatment options available.

In the early phase of the institute’s existence, research focused on dengue, malaria and tuberculosis. Later, scientists also looked into other parasitic diseases, such as sleeping sickness, leishmaniasis, cryptosporidiosis and Chagas disease, which helped broaden the research spectrum and deepen its scientific expertise.

Within two decades, NITD, which is led today by Thierry Diagana, has built an arsenal of strong drug candidates in malaria and dengue. These therapies may not only help treat these diseases, but may also be crucial to combat their spread, which is a feared threat due to warming temperatures.

Malaria scientist Eve Chuenchob uses...

Changing climate

According to the 2019 Lancet Countdown report on health and climate change, “a child born today will experience a world that is more than four degrees warmer than the preindustrial average, with climate change impacting human health from infancy and adolescence to adulthood and old age.”

“Across the world,” the researchers wrote in the report, “children are among the worst affected by climate change.” This, as the experts noted, is not only a result of malnutrition and natural catastrophes, but also because children are “most susceptible to diarrheal disease and experience the most severe effects of dengue fever.”

The World Health Organization, for its part, estimates that between 2030 and 2050, climate change could cause around 250’000 additional deaths per year from malnutrition, malaria, diarrhea and heat stress, among other factors.

“There are clear signs that climate change will have a substantial impact on health,” says Jonathan Spector, Head of Global Health at the Novartis Institutes for BioMedical Research. “This includes infectious diseases as well as non-communicable conditions, areas in which Novartis has been active for decades.”

Managing malaria

In the realm of infectious diseases, malaria has long been a focus area of the company. Even before Novartis was created in 1996 through the merger of Ciba-Geigy and Sandoz, one of the predecessor firms worked on chemicals to eradicate the mosquitoes responsible for the spread of malaria and yellow fever. The most important discovery was DDT, for which Paul Hermann Müller received the Nobel Prize in medicine in 1948.

Another major milestone came around the turn of the century with the development of Coartem®, which became the centerpiece of the Novartis Malaria Initiative and turned out to be instrumental in helping global stakeholders including the United Nations and the World Health Organization to control the disease in endemic regions in Africa and Asia.

But despite these achievements, the challenges to eliminate the disease are still huge: More than 200 million people are affected and around 500’000 die from malaria every year – most of them children. And worse: The disease-causing parasite’s ability to adapt to current drugs is increasing resistance risks, while climate change is feared to spread its occurrence. “The Malaria Initiative’s great success gave our research an added impetus from the start,” said Thierry Diagana. “But the key reason for us to push our research was the fact that we were aware early on that resistance to malaria drugs is a reality and that we need to continually work on new treatments. From today’s point of view, climate change, of course, is another factor to accelerate the development of new drugs.”

As part of its research efforts, NITD is currently working on multiple experimental malaria compounds. KAF156 and KAE609 are now being tested in Phase II trials. Furthermore, NITD has discovered INE963, a fast-acting and long-lasting drug candidate against malaria that was the recipient of the Medicine for Malaria Venture’s Project of the Year in 2019. “With these compounds we are optimistic that we can fur-ther contribute to the elimination of this disease,” Diagana said.

...the mosquito machine to test a compound.

Driving dengue

While malaria is set to spread with increasing temperatures, researchers today also believe that another infectious disease, dengue, could affect more people due to climate change patterns. Today, it already causes about a 100 million symptomatic infections each year and kills around 20’000 people.

According to an article published in Nature Microbiology in 2019, the disease, which is “transmitted to humans by Aedes species mosquitoes [that] thrive in tropical and subtropical urban centers around the globe ... will intensify in already endemic areas.” Among the reasons listed by the researchers are “faster viral amplification, increased vector survival, reproduction and biting rate,” which will “ultimately lead to longer transmission seasons and a greater number of human infections, more of which are expected to be severe.”

“Dengue is certainly one of the tropical diseases for which there is growing evidence that climate change could have a strong impact,” says Feng Gu, who leads the dengue drug project at the NITD. “Against this background, our leadership in 2020 decided to continue to support the further development of our preclinical drug candidate in this disease area.”

Currently, Gu and her team are working on a compound known as NITD-688, a pan-serotype dengue inhibitor, which di-rectly binds to the viral NS4B protein that causes the disease.

According to early test results, the compound demonstrates efficacy in both acute and delayed treatment in in vivo models, has favorable pharmacokinetic properties and was well tolerated in preclinical toxicology studies.

“This is a great step towards developing a potential treatment for dengue, which is becoming more prevalent in many parts of the world,” Gu says, noting that in 2019 alone there were major outbreaks in Pakistan, Bangladesh, Nepal, in addition to many countries in Southeast Asia. In the Caribbean and Latin America, cases also hit record highs. “The sheer number of outbreaks shows that disease patterns are changing and that there is an added urgency to develop treatments that can help patients,” Gu explains.

Stephanie Moquin, a post-doc in the Dengue team, works on expressing proteins in a specialized lab at the Novartis research campus in Emeryville.

Chronic diseases

While Novartis remains steadfast to broaden treatments and access for infectious disease, the company is also acutely aware that chronic diseases are on the rise around the globe and affect an ever-growing number of people in industrial and developing countries.

“The consequences of climate change and pollution will lead to an increased need for chronic disease management,” Jonathan Spector says. “A substantial part of our work is inherently already concentrated in this area as we have industry-leading research and development programs focused on a wide range of non-communicable diseases.”

Besides a strong focus on oncology, Novartis has also built research and development franchises in areas such as lung and heart disease, which are set to rise due to increased pollution, especially in urban centers.

According to the Lancet Countdown report, “air pollution – principally driven by fossil fuels, and exacerbated by climate change – [will] damage the heart, lungs, and every other vital organ.” In 2016, “global deaths attributable to ambient fine particulate matter remained at 2.9 million and total global air pollution deaths reached 7 million.”

“There is a clear need for our activities to continue to help rein in chronic diseases, which now constitute the main disease burdens in both industrial nations and developing countries,” Spector says. “We will learn over time how climate change will further impact disease patterns and we need to stay vigilant so we can, to the extent possible, predict where the greatest needs will be and be ready with essential treatments.”

For this reason, both Gu and Spector say that, besides increased scientific and medical research, disease management also needs “to be tackled from a political, economic and healthcare system point of view, including raising disease awareness, providing access to treatments and doing more to curb climate change by reducing pollution.”

Smear test samples...

Holistic approach

Novartis, which has substantially stepped up its environmental efforts in the past two years to curb its CO2 output, its water and plastic use, is also accelerating its already broad access activities for which it launched a so-called sustainability-linked bond worth 1.85 billion euro in September 2020.

Expecting to reach potentially around 24 million additional patients in the next five years with these measures, CEO Vas Narasimhan said the bond was “another important step on our journey to integrate [Environmental, Social and Governance] into the core of our business.”

Through the launch of this innovative financial instrument, Novartis will “measure our progress, hold ourselves accountable, and demonstrate our dedication to making good on our promise to broaden global access to our medicines,” Narasimhan explained.

While the access goals are ambitious, so is the willingness of Novartis to reach them, given the added urgency created through climate change. But the company is ready to put the money where its mouth is: As part of the deal, Novartis will pay investors a higher interest if it fails to reach its targets. This, for the scientists at NITD and their colleagues, will certainly be an added impetus to reach the goals in the interest of patients worldwide.

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