Nobel Prize in Physiology or Medicine 2015: Avermectin, Artemisinin and the Fight Against Parasites

This note covers the Nobel Prize in Physiology or Medicine 2015: who won it, how two separate lines of research produced novel therapies against roundworm diseases and malaria, how avermectin and artemisinin were discovered, how these drugs work in the body, how the discoveries unfolded over time, why they matter for global health and quick facts for exams.

What was the Nobel Prize in Physiology or Medicine 2015 awarded for?

The prize was split between two separate discoveries. William C. Campbell and Satoshi Ōmura shared one half of the prize "for their discoveries concerning a novel therapy against infections caused by roundworm parasites". Tu Youyou received the other half "for her discoveries concerning a novel therapy against Malaria".

In plain words, this means the prize honoured two unconnected breakthroughs that each turned a soil microbe or a herbal plant into a life-saving medicine.

Campbell and Ōmura's work led to a drug called ivermectin, which kills the larvae of parasitic worms that cause two disabling diseases, river blindness and lymphatic filariasis. Tu Youyou's work led to artemisinin, a drug that kills the single-cell parasite that causes malaria.

Both drugs came from natural sources: one from bacteria living in soil, the other from a plant used in traditional Chinese medicine. The official name of the award is the Nobel Prize in Physiology or Medicine.

Who are the laureates?

William C. Campbell

William C. Campbell was born on 28 June 1930 in Ramelton, Ireland. At the time of the award he was affiliated with Drew University, Madison, NJ, USA, and received one quarter of the prize.

He had earlier worked for decades at the Merck Institute for Therapeutic Research in the United States.

Campbell was the expert in parasite biology who tested Ōmura's bacterial cultures, identified the active compound against parasitic worms, purified it, and helped turn it into the drug used in both animals and humans.

Satoshi Ōmura

Satoshi Ōmura was born on 12 July 1935 in Yamanashi Prefecture, Japan. At the time of the award he was affiliated with Kitasato University, Tokyo, Japan, and also received one quarter of the prize.

He was a Japanese microbiologist skilled at isolating natural products from soil bacteria. Ōmura collected thousands of soil samples, cultured the bacteria they contained, and selected the most promising strains for further study, one of which turned out to produce the drug precursor.

Tu Youyou

Tu Youyou was born on 30 December 1930 in Zhejiang Ningbo, China. At the time of the award she was affiliated with the China Academy of Traditional Chinese Medicine, Beijing, China, and received one half of the prize on her own.

Tu turned to ancient Chinese herbal medicine texts to find a plant-based treatment for malaria, eventually isolating the active antimalarial compound from a plant called sweet wormwood.

What problem were these discoveries trying to solve?

Parasitic diseases have troubled humanity for a very long time and remain, in the words of the Nobel committee's press release, "a major global health problem" that disproportionately affects "the world's poorest populations".

Before the 2015 laureates' work, treatments for many parasitic infections were weak, unsafe or simply did not exist.

The scientific background document notes that while medicine had made great strides against bacterial infections, through antibiotics such as penicillin and streptomycin, there had been limited progress in developing durable therapies for parasitic diseases for a very long time.

Two different groups of parasites were involved. The first group, parasitic worms (helminths), were estimated to affect roughly a third of the world's population, especially across sub-Saharan Africa, South Asia and parts of Central and South America.

Helminths that infect humans are called roundworms or nematodes, and their life cycles are complex, usually needing an insect vector to pass from one person to another.

Among the diseases they cause are river blindness (onchocerciasis), which is spread by a biting blackfly and leads to blindness through chronic inflammation of the cornea, and lymphatic filariasis, spread by mosquitoes, which afflicted more than 100 million people and caused disfiguring chronic swelling, including elephantiasis and scrotal hydrocele.

Adult worms that cause river blindness can live for many years inside a human host, and female worms release huge numbers of tiny larvae called microfilariae that migrate through body tissue, eventually damaging the eyes.

The second parasite is Plasmodium, a single-cell organism spread by mosquitoes that causes malaria. After a mosquito bite, the parasite first multiplies inside liver cells before bursting out to invade red blood cells, producing fever and, in severe cases, brain damage and death.

The press release noted that more than 3.4 billion people were at risk of malaria, with the disease claiming more than 450,000 lives a year, mostly among children.

Earlier malaria treatments such as chloroquine and quinine, and the insecticide DDT, had become less effective as resistance spread among both the parasite and the mosquitoes carrying it, and by the late 1960s efforts to eradicate malaria had failed, with the disease once again on the rise.

How was avermectin discovered and turned into a drug for roundworm diseases?

Satoshi Ōmura focused on a group of soil bacteria called Streptomyces, already known for producing antibacterial substances such as streptomycin.

He developed special methods to culture many strains of these bacteria in the laboratory, something that had previously proved difficult, and screened thousands of cultures, selecting around 50 of the most promising for further testing.

William Campbell then tested extracts from Ōmura's cultures against parasites in laboratory animals. One culture, later identified as a new strain of Streptomyces found in soil in Japan, was remarkably effective at killing worms when mixed into the food of infected mice.

Campbell's team purified the active substance and named it avermectin, which was then chemically modified into a more potent compound called ivermectin.

Ivermectin was tested first in farm and domestic animals, where it proved highly effective against a wide range of parasites, and was then trialled in humans.

It effectively killed the larval stage of the worms causing river blindness, and a single dose could clear microfilariae from the blood of patients infected with the worm that causes lymphatic filariasis.

1. Ōmura collected soil samples across Japan and cultured the Streptomyces bacteria they contained.
2. He screened many thousands of cultures and selected about 50 of the most promising for detailed study.
3. Campbell tested extracts from these cultures against parasites in animals and found one culture that killed worms effectively.
4. The active compound was purified and named avermectin, then chemically modified into the more effective ivermectin.
5. Ivermectin was trialled in humans with river blindness and shown to kill the parasite's larvae with a single dose.

Ivermectin turned out to have several useful properties: it was extraordinarily potent, worked against many kinds of worms in different host species, acted on parasites that had already become resistant to older drugs, and was generally well tolerated, giving doctors a good safety margin.

Because of these qualities, it became possible to treat whole communities with just one or two doses a year, reaching even remote regions where regular medical care was hard to arrange.

How was artemisinin discovered as a treatment for malaria?

Tu Youyou took a different route. Rather than screening microbes, she turned to traditional Chinese herbal medicine to search for a new malaria treatment at a time when conventional drugs were losing their effectiveness and malaria cases were rising again.

Her team screened a large number of herbal remedies in malaria-infected animals, and an extract from the plant Artemisia annua (sweet wormwood) emerged as an interesting candidate, partly because it appeared repeatedly in old recipes for treating fever.

At first the results were inconsistent, with the extract killing anywhere from roughly 12 to 40 percent of parasites in different experiments.

Tu went back to ancient medical literature for clues and found an old description of obtaining "juice" from the plant's leaves using cold water rather than the usual boiling method, since heat appeared to destroy the active ingredient's effectiveness.

Using this improved low-temperature extraction method, she succeeded in isolating the active compound, later named artemisinin, and showed it killed all of the malaria parasites in infected mice and monkeys.

This was followed by clinical tests in which the extract rapidly reduced fever and lowered the number of parasites in the blood of malaria patients, confirming the drug worked in humans as well as animals.

According to the scientific background document, artemisinin represents a new class of antimalarial agent that rapidly kills malaria parasites at an early stage of their development inside red blood cells, which explains why it worked so well even against severe malaria.

Because resistance to artemisinin alone can develop, linked to changes in a parasite protein, the World Health Organization recommended it be used in combination with other antimalarial drugs, known as artemisinin-based combination therapy (ACT), particularly in parts of South Asia where resistance had begun to appear.

How did the discovery unfold?

Why does it matter?

The impact of these two discoveries has been described by the Nobel committee as "immeasurable". Ivermectin is now used in all parts of the world affected by river blindness and lymphatic filariasis.

It is highly effective, has limited side effects, and is distributed freely, with treatment success bringing these two diseases to the verge of eradication according to the press release.

The scientific background document records that, as of 2012, more than 200 million people had received ivermectin, some over periods of up to 25 years, and that global programmes had set targets of eliminating lymphatic filariasis by 2020 and river blindness by 2025.

For malaria, artemisinin-based combination therapy is used throughout malaria-affected regions. The press release states that, when used alongside other antimalarial drugs, artemisinin cuts malaria deaths by over a fifth overall and by over three in ten among children, saving more than 100,000 lives a year in Africa alone.

The scientific background document adds that the overall global death toll from malaria fell by around half in the fifteen years before the prize was awarded.

Open questions remain. The scientific background notes that resistance to artemisinin has emerged in some parts of the world, linked to mutations in a parasite protein, which is why combination therapy rather than artemisinin alone is recommended, especially in South Asia.

The exact way ivermectin works was also not fully understood in every detail at the time, though it was known to affect certain chloride-channel proteins in the nerve and muscle cells of the parasite, giving it a selective action against worms rather than against the human host.

Beyond the direct health benefits, the scientific background document points out that these diseases had long trapped affected communities in cycles of poverty, since chronic illness and disability stopped children from attending school and adults from working, so the drugs' impact reaches well beyond individual patients into the wider wellbeing of entire regions.

How does this connect to what you study?

This prize links directly to topics in school biology such as microorganisms, parasites and the human immune system.

Learning how Streptomyces bacteria naturally produce chemicals that harm other organisms helps explain how many antibiotics and antiparasitic drugs are discovered from nature.

Similarly, the malaria story connects to lessons on vector-borne diseases, since Plasmodium is transmitted by the Anopheles mosquito, a classic example used when studying disease transmission and public health.

The idea of combining traditional knowledge, such as ancient Chinese medical texts, with modern laboratory science is also a useful case study in how old and new methods of enquiry can work together to solve a scientific problem, a theme relevant to discussions of the nature of scientific discovery itself.

How do ivermectin and artemisinin act on the parasites?

The two drugs work in quite different ways, matching the very different biology of the parasites they target.

Ivermectin acts on the nerve and muscle cells of worms and their larvae. It keeps open certain channels in the cell membrane that normally let chloride ions pass through in a controlled way.

By keeping these channels open, ivermectin lets too many chloride ions into the cell, which hyperpolarises it (makes the inside more negatively charged) and leads to paralysis and death of the parasite.

These particular channels exist in roundworms, insects and related creatures but are far less exposed in humans and other mammals, which is one reason ivermectin can kill the parasite at doses that are safe for the person being treated.

Artemisinin works quite differently, attacking the single-cell Plasmodium parasite while it is growing inside a red blood cell.

It destroys the parasite at an early stage of this growth, which helps explain why it is so effective even in severe cases of malaria where the parasite would otherwise multiply rapidly.

A particular parasite protein has been linked to cases where artemisinin resistance has developed, which is one reason doctors now prefer to use it together with other antimalarial drugs rather than on its own.

In both cases, the drugs exploit a biological difference between the parasite and its host, hitting a target that matters enormously to the parasite's survival while leaving the patient's own cells largely unharmed.

This idea, finding a weak point unique to the invader, is a theme that runs through much of the history of successful anti-infective medicine.

Quick facts for exams

The Nobel Prize in Physiology or Medicine 2015 was announced on 5 October 2015 by the Nobel Assembly at Karolinska Institutet. It was divided, with one half jointly to William C.

Campbell and Satoshi Ōmura "for their discoveries concerning a novel therapy against infections caused by roundworm parasites", and the other half to Tu Youyou "for her discoveries concerning a novel therapy against Malaria".

Campbell and Ōmura's work led to the drug ivermectin, used against river blindness and lymphatic filariasis, while Tu Youyou's work led to artemisinin, used against malaria.

The prize amount that year was 8,000,000 Swedish kronor, shared among the three laureates according to their stated shares.

Note: Source. The prize facts in this note are from the Nobel Prize's official site, nobelprize.org.

Glossary

• Parasite — an organism that lives in or on another organism (its host) and feeds on it, often causing disease.
• Helminth — a parasitic worm; a medically important group that causes diseases such as river blindness and lymphatic filariasis.
• River blindness (onchocerciasis) — a disease caused by a parasitic worm, leading to chronic eye inflammation and ultimately blindness.
• Lymphatic filariasis — a disease caused by a parasitic worm that produces chronic swelling, including elephantiasis.
• Malaria — a mosquito-borne disease caused by the single-cell parasite Plasmodium, which invades red blood cells.
• Streptomyces — a group of soil bacteria known for producing substances with antibacterial and antiparasitic activity.
• Avermectin — the compound purified from a Streptomyces culture, found to be effective against parasitic worms.
• Ivermectin — a chemically modified, more effective version of avermectin, used to treat river blindness and lymphatic filariasis.
• Artemisia annua — the plant, also called sweet wormwood, from which the antimalarial compound artemisinin was extracted.
• Artemisinin — the active antimalarial compound isolated from Artemisia annua, effective against the malaria parasite.
• Artemisinin-based combination therapy (ACT) — treatment combining artemisinin with other antimalarial drugs to reduce the risk of resistance.
• Traditional Chinese medicine — a system of medical practice in China that uses herbal remedies developed over centuries, a source Tu Youyou drew upon.

Common errors and misconceptions

• Misconception: All three laureates worked together on the same discovery. Correct: The prize covers two separate, unconnected discoveries; Campbell and Ōmura worked on worm parasites, while Tu Youyou worked independently on malaria.
• Misconception: Ivermectin and artemisinin treat the same disease. Correct: Ivermectin treats diseases caused by parasitic worms, such as river blindness and lymphatic filariasis, while artemisinin treats malaria, caused by a different kind of parasite.
• Misconception: Artemisinin was invented in a modern laboratory from scratch. Correct: Artemisinin is a natural compound extracted from the plant Artemisia annua, identified using clues from ancient Chinese medical texts.
• Misconception: Avermectin and ivermectin are the same substance. Correct: Avermectin is the original compound purified from the bacterial culture; ivermectin is a chemically modified, more effective version of it.
• Misconception: Malaria is caused by a worm. Correct: Malaria is caused by a single-cell parasite called Plasmodium, not by a worm; river blindness and lymphatic filariasis are the worm-caused diseases in this prize.
• Misconception: The prize money was shared equally among the three laureates. Correct: Tu Youyou received one half of the prize on her own, while Campbell and Ōmura each received one quarter.

Exam-style questions with model answers

Q1. In which year was the Nobel Prize in Physiology or Medicine 2015 announced? [1 mark]

1. It was announced on 5 October 2015 by the Nobel Assembly at Karolinska Institutet.

Q2. Name the two drugs associated with this prize. [2 marks]

1. The two drugs are ivermectin, used against roundworm diseases such as river blindness and lymphatic filariasis, and artemisinin, used against malaria.

Q3. Explain how Satoshi Ōmura and William C. Campbell together discovered avermectin and turned it into a usable drug. [4 marks]

1. Satoshi Ōmura collected soil samples across Japan and cultured the Streptomyces bacteria found in them, screening thousands of cultures and selecting around 50 of the most promising for further study. William C. Campbell then tested extracts from these cultures against parasites in animals and found that one extract killed worms very effectively. Campbell purified the active compound and named it avermectin. This was then chemically modified to produce the more potent compound ivermectin, which was tested in humans with river blindness and shown to kill the parasite's larvae with a single dose.

Q4. Describe the problem of parasitic worm diseases that this prize addressed, and why it was considered a major global health issue. [4 marks]

1. Parasitic worms, or helminths, were estimated to affect about a third of the world's population, particularly in sub-Saharan Africa, South Asia, and Central and South America. Two major diseases they caused were river blindness, which leads to blindness through chronic eye inflammation, and lymphatic filariasis, which affected more than 100 million people and caused disfiguring chronic swelling, including elephantiasis. These diseases disproportionately affected the world's poorest populations and, in the committee's words, represented "a huge barrier to improving human health and wellbeing", which is why effective, affordable treatments mattered so much.

Q5. Discuss how Tu Youyou discovered artemisinin and the impact this discovery has had on global health. [6 marks]

1. During the 1960s, with earlier malaria drugs such as chloroquine losing effectiveness and the disease on the rise, Tu Youyou turned to traditional Chinese herbal medicine to search for a new treatment. Her team screened many herbal remedies in malaria-infected animals and found that an extract from the plant Artemisia annua, or sweet wormwood, showed promise, though results were initially inconsistent. Returning to ancient medical literature, Tu found clues pointing to a low-temperature extraction method rather than the usual heating process, and using this approach she successfully isolated the active compound, later named artemisinin, showing it was highly effective against the malaria parasite in both animals and humans. Artemisinin works by rapidly killing malaria parasites at an early stage of their development inside red blood cells. According to the press release, when used alongside other antimalarial drugs it cuts malaria deaths by over a fifth overall and by over three in ten among children, meaning more than 100,000 lives are saved each year in Africa alone. Because resistance to artemisinin alone can develop, the World Health Organization recommends it be used in combination with other antimalarial drugs.

Q6. State the affiliation of each of the three laureates at the time of the award. [3 marks]

1. William C. Campbell was affiliated with Drew University, Madison, NJ, USA. Satoshi Ōmura was affiliated with Kitasato University, Tokyo, Japan. Tu Youyou was affiliated with the China Academy of Traditional Chinese Medicine, Beijing, China.

Q7. What share of the 2015 Physiology or Medicine prize did each laureate receive? [2 marks]

1. William C. Campbell and Satoshi Ōmura each received one quarter of the prize, while Tu Youyou received one half of the prize on her own.

Key takeaways

• The 2015 prize was split between two unconnected discoveries: one on roundworm therapies and one on malaria therapy.
• Campbell and Ōmura's joint work led to avermectin, later improved into ivermectin, from a soil bacterium Streptomyces.
• Ivermectin became highly effective against river blindness and lymphatic filariasis, diseases caused by parasitic worms.
• Tu Youyou isolated artemisinin from the plant Artemisia annua, guided by clues from ancient Chinese medical texts.
• Artemisinin kills the malaria parasite Plasmodium rapidly at an early stage of infection in red blood cells.
• Both drugs have had an immense impact: ivermectin has brought two worm diseases close to eradication, and artemisinin-based therapy has substantially cut malaria deaths.
• The prize was announced on 5 October 2015 by the Nobel Assembly at Karolinska Institutet, with the prize amount set at 8,000,000 Swedish kronor.
• Resistance remains a concern, which is why artemisinin is usually given as part of a combination therapy rather than alone.

Test yourself

What two diseases does ivermectin mainly treat?

Ivermectin mainly treats river blindness and lymphatic filariasis, both caused by parasitic worms transmitted by insects.

From what kind of organism was avermectin first obtained?

Avermectin was first obtained from a culture of Streptomyces, a type of soil bacteria studied by Satoshi Ōmura.

What plant did Tu Youyou study to find a malaria treatment?

Tu Youyou studied Artemisia annua, also called sweet wormwood, used in traditional Chinese herbal medicine recipes for fever.

Where was William C. Campbell affiliated at the time of the award?

William C. Campbell was affiliated with Drew University, Madison, NJ, USA, at the time of the award.

What parasite causes malaria?

Malaria is caused by Plasmodium, a single-cell parasite that invades red blood cells after being spread by mosquitoes.

What share of the prize did Tu Youyou receive?

Tu Youyou received one half of the prize on her own, for her discoveries concerning a novel therapy against malaria.

Why is artemisinin often given in combination with other drugs?

Artemisinin is often combined with other antimalarial drugs because resistance to artemisinin alone has emerged in some regions.

When was the 2015 Nobel Prize in Physiology or Medicine announced?

The 2015 Nobel Prize in Physiology or Medicine was announced on 5 October 2015 by the Nobel Assembly at Karolinska Institutet.