We have successfully developed vaccines for many viruses and bacteria, and antibiotic and antiviral drugs can often be used to effectively treat infected individuals. But parasite infections pose significant challenges to traditional treatment approaches. This year's Nobel Prize in Medicine has gone to researchers who created treatments for some of humanity's biggest scourges: river blindness, as well as other nematode diseases, and malaria.
The award for development of ivermectin as a nematode treatment is shared by Satoshi Omura and William Campbell. They share the prize with Youyou Tu, who isolated artemisinin and demonstrated its effectiveness against malaria.
The challenge
Treatments for viruses and bacteria are simple in principle. It's possible to design or discover drug molecules that latch on to their proteins, keeping them from functioning normally. Since billions of years of evolution have made these organisms biologically distinct from their human hosts, these chemicals will generally not target the equivalent human proteins. Thus, while the disease-causing organism is killed, the human host is largely unaffected by these drugs. That's the principle behind antibiotics and antivirals.
An alternative approach is to develop a vaccine. This primes the immune system to produce antibodies against the virus or bacterial cell, which allows the immune system to target and destroy these invaders.
Neither of these approaches is especially effective against more complex parasites, such as nematode worms or the malarial parasite. Worms are large, complex organisms, and they can't be attacked effectively by the immune system, leaving vaccines impotent. The malarial parasite could potentially be targeted by a vaccine (and several are undergoing testing), but it's well adapted to the human immune system—its genome encodes thousands of proteins that it constantly shifts among in order to distract the immune system.
Creating drugs that specifically target these organisms is a challenge as well. Worms and the malarial parasite are both on the same major branch of the tree of life as humans, meaning they're much more similar to us than bacteria. Worms are multicellular animals, which places them even closer to us. That's why the drugs honored by this morning's awards have been so significant.
The achievements
In both cases, the drugs were discovered rather than designed. In the case of Youyou Tu, it was in some ways a rediscovery. Tu, currently at the China Academy of Traditional Chinese Medicine, was working at a time when the malarial parasite had evolved resistance to the primary treatment for it, chloroquine. She began a search through an enormous catalog of traditional Chinese medicine for items that were used to treat fevers, a common symptom of malarial infection. Multiple remedies she came up with in her search had a common ingredient: sweet wormwood, or Artemesia annua.
Tu tested extracts of the plant on rodents infected with malaria and found some benefits, but the results were inconsistent. Changing the method of extraction dramatically improved the outcomes (the Nobels suggest the change was inspired by Chinese herbal literature but, as the successful method involved ether, the inspiration must have been indirect).
Tu helped isolate the active ingredient, now called artemisinin, which has since become the main treatment for malaria globally. To limit the evolution of drug resistance, it's meant to be taken as part of a combined therapy with older, less effective drugs. Combined with anti-mosquito campaigns, its impact has been enormous: while global malaria infections are down by a quarter, deaths have been cut in half.
Unfortunately, artemisinin-resistant strains of the parasite have recently been discovered in Southeast Asia. But that does little to diminish the impact that Tu's work has had.
Satoshi Omura wasn't inspired by old medical developments; instead, his work was based on a very recent one: the discovery of penicillin. Penicillin was isolated from mold, and we've since discovered that soil-dwelling microbes are in a constant state of chemical warfare with their neighbors. Many of our most effective antibiotics come from microbes that produce them to kill their competitors in the soil. Omura was a specialist in growing a particular type of bacteria, Streptomyces, grown from various soil samples.
By the 1970s, Omura had a large panel of dozens of strains obtained from the soil of different locations around his native Japan. Recognizing their potential value, the drug company Merck set up an official collaboration that allowed them to test chemicals isolated from Omura's strain. This is where William Campbell, then employed at a Merck research institute, entered the picture. Campbell found that one of Omura's strains (apparently found at a local golf course) was effective in mice infected with a strain of nematodes.
Omura worked with Merck to improve the growth conditions for this strain, while Campbell helped lead efforts to identify the active chemical and then synthesized a more potent version. That was developed as the drug ivermectin, which was shown to be able to completely wipe out immature versions of the parasitic worm with a single dose. It acts by blockading signals that control the worms' muscles, slowly killing them. The slow death turns out to be important, since it keeps the immune system from getting overwhelmed by a sudden influx of debris from the dead worms.
Ivermectin turned out to be effective against a number of horrifying diseases that primarily strike in the developing world. These include river blindness, caused by a worm that can grow up to 50cm long and live for 18 years inside the human body, releasing as many as 1,000 immature worms a day. Lymphatic Filariasis, which can also be treated with ivermectin, blocks lymph nodes, causing various body parts to swell dramatically. A single dose of ivermectin can keep infected individuals free of symptoms for up to a year.
Because of the low treatment requirements and the market in the developing world, there wasn't a major commercial market for ivermectin. But the Nobel organization credits Merck CEO Roy Vagelos for making it freely available for the treatment of these diseases.
While this sort of long slog through isolating natural products isn't as glamorous as some forms of modern drug design, the work of these individuals has had a global impact that most of the people working in biomedicine probably find difficult to comprehend.
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