Nobel Prize History
The Nobel Prize is the most prestigious award in the scientific world. It was created according to Mr. Alfred Nobel’s will to give a prize “to those who, during the preceding year, have conferred the greatest benefit to humankind” in physics, chemistry, physiology or medicine, literature, and peace. A sixth prize would be later on created for economic sciences by the Swedish central bank.
The decision of who to attribute the prize to belongs to multiple Swedish academic institutions.
Legacy Concerns
The decision to create the Nobel Prize came to Alfred Nobel after he read his own obituary, following a mistake by a French newspaper that misunderstood the news of his brother’s death. Titled “The Merchant of Death Is Dead”, the French article hammered Nobel for his invention of smokeless explosives, of which dynamite was the most famous one.
His inventions were very influential in shaping modern warfare, and Nobel purchased a massive iron and steel mill to turn it into a major armaments manufacturer. As he was first a chemist, engineer, and inventor, Nobel realized that he did not want his legacy to be one of a man remembered to have made a fortune over war and the death of others.
Nobel Prize
These days, Nobel’s Fortune is stored in a fund invested to generate income to finance the Nobel Foundation and the gold-plated green gold medal, diploma, and monetary award of 11 million SEK (around $1M) attributed to the winners.
Source: Britannica
Often, the Nobel Prize money is divided between several winners, especially in scientific fields where it is common for 2 or 3 leading figures to contribute together or in parallel to a groundbreaking discovery.
Over the years, the Nobel Prize became THE scientific prize, trying to strike a balance between theoretical and very practical discoveries. It has rewarded achievements that built the foundations of the modern world like radioactivity, antibiotics, X-rays, or PCR, as well as fundamental science like the power source of the sun, the electron charge, atomic structure, or superfluidity.
The Weight Of Parasite-Born Diseases
For a time, modern chemistry and medicine were thought to have mostly solved the problems caused by bacterial infections thanks to antibiotics. We now know that this is not fully the case, as more than a million people worldwide still die from antibiotic-resistant infections.
But compared to the world before the invention of penicillin, we know that very rarely, a small cold or cut could lead to a deadly infection. For this reason, penicillin was recognized by the Nobel Prize of Medicine in 1945.
However, another class of diseases is still very much ravaging human health – Parasitic diseases. Often caused by small multicellular organisms, these are affecting massive sways of the world’s population, especially in tropical areas and poor countries.
For example, Lymphatic Filariasis afflicts more than 100 million people. It causes chronic inflammation and leads to life-long stigmatizing and disabling clinical symptoms, including Elephantiasis (Lymphedema) and Scrotal Hydrocele.
Then there is River Blindness (Onchocerciasis), which is caused by being bitten by a fly carrying the disease. This results in a parasitic worm that affects 15.5 million people.
Another parasite, plasmodium, is the cause of malaria, a disease transmitted through warm-weather mosquito bites. The organism invades red blood cells and causes weakness, fever, and, in severe cases, brain damage and death. Malaria is a threat to 3.4 billion of the world’s most vulnerable citizens, and each year, it claims more than 450,000 lives, mostly children.
Source: Nobel Prize
Finding A Treatment
Because the diseases are caused by complex organisms like worms or single-cell eukaryotes organisms with advanced camouflage mechanisms (like malaria, hiding inside red blood cells), they are difficult to treat with drugs. Molecules like antibiotics, acting directly on the bacteria cell walls, cannot work here. So, more “exotic” molecules had to be explored to find a solution.
All 3 winners of the 2015 Nobel Prize have found novel parasite therapies from molecules produced by plants, with William C. Campbell and Satoshi Ōmura responsible for the joint discovery of avermectin, and Tu Youyou responsible for the discovery of artemisinin.
Source: Nobel Prize
Avermectin would later be improved and form ivermectin, a powerful anti-worm drug used in animal and human health. Artemisinin would create a new class of antimalarial agents, saving many lives.
The Arduous Path To Discovery
All 3 researchers had to pursue a painstakingly slow process to come to their discovery.
Satoshi Ōmura is a Japanese microbiologist and an expert in isolating natural products. He used his skills to analyze in depth the bacteria group Streptomyces, found in soil. Streptomyces are known to produce plenty of compounds toxic to other microorganisms, of which the most famous at the time was streptomycin, a major antibiotic discovered in 1939 (a discovery winning Selman A. Waksman a Nobel Prize in 1952).
Ōmura isolated thousands of Streptomyces cultures, ultimately studying 50 of them in further detail.
This is where William C. Campbell, an expert in parasite biology working in the USA at the Merck Institute for Therapeutic Research, came to help. He discovered that a chemical compound in one of the bacterial cultures was very efficient against parasites on animals. He isolated the molecule and named it avermectin. Avermectin would later be slightly modified into ivermectin, to be even more efficient.
Source: Nobel Prize
On a separate research track, Youyou Tu worked to tackle malaria, looking into traditional Chinese medicine to find new therapies. As malaria used to be treated with chloroquine or quinine, but with declining success, finding an alternative was crucial. As a result of this dire need, the program that found artemisinin was launched and financed by China’s People’s Liberation Army.
She did a large-scale screening of herbal remedies’ efficiency to alleviate malaria infection in animals. An extract from the plant Artemisia annua emerged as a potential candidate.
However, the results were far from conclusive at first due to inconsistent results. By researching ancient literature and traditional practices, Youyou Tu discovered how to produce and extract the active compound more efficiently, leading to a more consistent and demonstrable success rate.
Source: Nobel Prize
She would then be the first to demonstrate the efficiency of the extracted molecule, now called artemisinin, against malaria in both animals and humans in 1972.
Ivermectin
Massive Success
Ivermectin was first commercialized as a veterinary antiparasitic in 1981. It was a massive success for Merck, becoming the bestselling veterinary medicine in the world.
Merck also looked into the drug’s potential use in human medicine, getting it approved in France in 1987. In 1988, Mectizan, the commercial name of ivermectin, entered a donation program financed by Merck to eradicate river blindness.
The program was implemented by the Task Force For Global Health, coordinating the efforts of Merck, the WHO, as well as local public and private actors. It currently reaches 400 million people annually.
35 years later, river blindness has been eradicated in Colombia, Ecuador, Guatemala, and Mexico, and many other countries are on track for complete eradication as well.
This took a long time, as the drug needed to be given to a whole area at least once a year, and the program needed to work for at least 10-15 years, or the lifespan of the adult worm. Only once all the adult worms die and the larvae cannot become reproducing adults can the disease be eradicated from an area.
Ivermectin is also efficient against lymphatic filariasis and other parasitic diseases caused by nematode worms and arthropods. The donation by Merck inspired other similar programs, for example, the donation by GSK of albendazole for contributing to eradicating lymphatic filariasis together with ivermectin.
Covid Controversy
Ivermectin became the center of a massive controversy during the pandemic, with some seeing it as a miracle drug against Covid-19. This led to a rather dramatic press release, notably a famous communication by the FDA on social media:
“You are not a horse. You are not a cow. Seriously, y’all. Stop it.”
The Guardian
Ivermectin, alongside the antimalarial drug hydroxychloroquine, was discussed as an alternative treatment for the COVID-19 virus or to the COVID-19 vaccine. Now that spirits have somewhat calmed down, we can look back.
The warning came as people used ivermectin dosages and formulations designed for animals onto humans, which is hardly good medical practice. This does not change the fact that ivermectin can be used on humans with very positive effects (see the river blindness program). But more than that, its effect on viral infections is dubious at best. And that this is still a potentially dangerous treatment when taking an inappropriate dosage.
So far, the FDA and multiple studies have not seen a positive effect of ivermectin on COVID treatment and consider it mostly inefficient for this application.
Artemisinin
Artemisinin became a standard treatment over time for malaria. While it was discovered in a plant, it can now be currently produced from a precursor molecule synthesized by genetically engineered yeast, making the production process a lot more efficient than direct extraction from the plant.
Production in GMO yeast or GMO plants could help answer the global demand for the molecules, reduce costs, and allow for better control over malaria.
This is especially important as artemisinin is a very efficient malarial drug but also more expensive than the alternative. Considering that most countries and people affected by malaria are relatively poor, this limits the adoption of artemisinin globally.
Despite still not being used to its full potential due to costs and production constraints, artemisinin has already saved up to 1.5 million people in sub-Saharan Africa alone.
Resistance
The molecule is highly recommended by the WHO to be used in combination therapies, in order to limit the risk of the apparition of resistance to the disease. The first case of resistance was reported in 2008 in Cambodia, and later on in the rest of South-East Asia in 2008-2014.
While not dramatic, the growing resistance to the treatment could endanger millions. Luckily, a malaria vaccine might be deployed at scale soon by GSK (see below).
Anti-Parasite Companies
Even if most of the people afflicted by parasite-born diseases are in developing countries, this is still a major business for large pharmaceutical companies.
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1. Merck
As the employer of the co-discoverer of ivermectin, and the force behind the complete eradication of river blindness in many countries, Merck holds a special place in the fight against parasitic diseases.
Anti-parasite treatment is a large part of its $5,6B/year veterinary business (10% of total revenues).
Merck is also a leader in vaccines, which stays the main method to keep at bay most pathogens, especially viruses.
Merck is the #1 spot for non-COVID-19 vaccine sellers. Among its best sellers is the anti-HPV (Human Papillomavirus) vaccine Gardasil, bringing $8.8B in 2023, and explosive revenue growth in the last 3 years.
Source: Merck
The company is also looking to launch a new pneumococcal vaccine with a PDUFA date set for its V116 vaccine in June 2024 and 5 other vaccines in the R&D pipeline.
This includes dengue, a tropical disease that plagues low-income countries.
Source: Merck
Merck has a long history of leadership in the infectious disease segments, from anti-parasite treatments to vaccines and dedicated molecules. A success in large part built upon the technical and commercial achievements of ivermectin.
This makes the company a good pick for investors looking for exposure to this sector.
Especially as many of the countries affected by parasites and tropical diseases are seeing their average income rising quickly (most notably SE-Asia). It should make them a lot more able to finance massive public campaigns for vaccination and disease eradication, and these countries have a lot of goodwill toward Merck thanks to the program to give free ivermectin over the last 35 years.
2. GSK
Most artemisinin production is done in China and India. However, other investable companies listed in the West are active in the fight against malaria and other parasites.
One of them, and by far the largest when it comes to malaria-related patents, is GSK.
Source: Pharmaceutical Technology
GSK has started the roll-out of a new malaria vaccine in Africa in 2024. In clinical trials, this vaccine prevented half of the malaria cases a year after vaccination. If used seasonally, the vaccine even reduces the cases by 75%.
This vaccine uses artificial proteins and virus-like particles to solve the long-lasting problem of traditional vaccines not working against malaria.
A second malaria vaccine (R21/Matrix-M), created by the University of Oxford, was approved and is currently deployed as well. This is just one part of the new generation of vaccines coming into use, which we discussed in our article “The Next Generation Of Vaccines”.
Malaria is only the latest in a series of GSK innovative vaccines. It notably sells an advanced 5-in-1 meningococcal vaccine (for meningitis) that brought $1.6B in revenues in 2023, even though it was accepted for review in the USA only in April 2024, implying much higher revenue for 2024.
Source: GSK
More innovative vaccines are in development, including for:
- Influenza
- Singles
- Meningococcal diseases
- Pneumococcal diseases
- Hepatitis B
- Herpex simplex virus
GSK is also the manufacturer of albendazole, a broad antiworm and anti-parasite molecule. The company has been giving for free 10 billion tablets of the drug since 2000 to fight lymphatic filariasis and soil-transmitted helminths, the two most widespread Neglected Tropical Diseases (NTDs).
GSK is a very large pharmaceutical company with the experience, R&D pipeline, and network to make a real difference in the fight against infectious diseases.
This includes malaria, but also many other diseases, which GSK can help keep at bay either with vaccines or small molecules.