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2015年诺贝尔生理医学奖

发布时间:2015年10月09日
The Nobel Assembly at Karolinska Institutet has today decided to award
the 2015 Nobel Prize in Physiology or Medicine
with one half jointly to
William C. Campbell and Satoshi 詍ura
for their discoveries concerning a novel therapy against infections caused by roundworm parasites
and the other half to
Youyou Tu
for her discoveries concerning a novel therapy against Malaria

Diseases caused by parasites have plagued humankind for millennia and constitute a major global health problem. In particular, parasitic diseases affect the world抯 poorest populations and represent a huge barrier to improving human health and wellbeing. This year抯 Nobel Laureates have developed therapies that have revolutionized the treatment of some of the most devastating parasitic diseases.

William C. Campbell and Satoshi 詍ura discovered a new drug, Avermectin, the derivatives of which have radically lowered the incidence of River Blindness and Lymphatic Filariasis, as well as showing efficacy against an expanding number of other parasitic diseases. Youyou Tu discovered Artemisinin, a drug that has significantly reduced the mortality rates for patients suffering from Malaria.

These two discoveries have provided humankind with powerful new means to combat these debilitating diseases that affect hundreds of millions of people annually. The consequences in terms of improved human health and reduced suffering are immeasurable.

Parasites cause devastating diseases
We live in a biologically complex world, which is populated not only by humans and other large animals, but also by a plethora of other organisms, some of which are harmful or deadly to us.
A variety of parasites cause disease. A medically important group are the parasitic worms (helminths), which are estimated to afflict one third of the world抯 population and are particularly prevalent in sub-Saharan Africa, South Asia and Central and South America. River Blindness and Lymphatic Filariasis are two diseases caused by parasitic worms. As the name implies, River Blindness (Onchocerciasis) ultimately leads to blindness, because of chronic inflammation in the cornea. Lymphatic Filariasis, afflicting more than 100 million people, causes chronic swelling and leads to life-long stigmatizing and disabling clinical symptoms, including Elephantiasis (Lymphedema) and Scrotal Hydrocele (Figure 1).
Malaria has been with humankind for as long as we know. It is a mosquito-borne disease caused by single-cell parasites, which invade red blood cells, causing fever, and in severe cases brain damage and death. More than 3.4 billion of the world抯 most vulnerable citizens are at risk of contracting Malaria, and each year it claims more than 450 000 lives, predominantly among children (Figure 1).

From bacteria and plants to novel anti-parasite therapies
After decades of limited progress in developing durable therapies for parasitic diseases, the discoveries by this year抯 Laureates radically changed the situation.
Satoshi 詍ura, a Japanese microbiologist and expert in isolating natural products, focused on a group of bacteria, Streptomyces, which lives in the soil and was known to produce a plethora of agents with antibacterial activities (including Streptomycin discovered by Selman Waksman, Nobel Prize 1952). Equipped with extraordinary skills in developing unique methods for large-scale culturing and characterization of these bacteria, 詍ura isolated new strains of Streptomyces from soil samples and successfully cultured them in the laboratory. From many thousand different cultures, he selected about 50 of the most promising, with the intent that they would be further analyzed for their activity against harmful microorganisms (Figure 2).

William C. Campbell, an expert in parasite biology working in the USA, acquired 詍ura抯 Streptomyces cultures and explored their efficacy. Campbell showed that a component from one of the cultures was remarkably efficient against parasites in domestic and farm animals. The bioactive agent was purified and named Avermectin, which was subsequently chemically modified to a more effective compound called Ivermectin. Ivermectin was later tested in humans with parasitic infections and effectively killed parasite larvae (microfilaria) (Figure 3). Collectively, 詍ura and Campbell抯 contributions led to the discovery of a new class of drugs with extraordinary efficacy against parasitic diseases.

Malaria was traditionally treated by chloroquine or quinine, but with declining success. By the late 1960s, efforts to eradicate Malaria had failed and the disease was on the rise. At that time, Youyou Tu in China turned to traditional herbal medicine to tackle the challenge of developing novel Malaria therapies. From a large-scale screen of herbal remedies in Malaria-infected animals, an extract from the plant Artemisia annua emerged as an interesting candidate. However, the results were inconsistent, so Tu revisited the ancient literature and discovered clues that guided her in her quest to successfully extract the active component from Artemisia annua. Tu was the first to show that this component, later called Artemisinin, was highly effective against the Malaria parasite, both in infected animals and in humans (Figure 4). Artemisinin represents a new class of antimalarial agents that rapidly kill the Malaria parasites at an early stage of their development, which explains its unprecedented potency in the treatment of severe Malaria.

Figure 1: The 2015 Nobel Prize in Physiology or Medicine awards discoveries regarding novel therapies for some of the most devastating parasitic diseases: River Blindness, Lymphatic Filariasis (Elephantiasis) and Malaria. The distribution of these diseases is quite similar and is collectively shown in blue on the world map.

Figure 2: Satoshi 詍ura searched for novel strains of Streptomyces bacteria as a source for new bioactive compounds. He isolated microbes from soil samples in Japan, cultured them in the laboratory (inset to left) and characterized many thousands of Streptomyces cultures. From those, he selected around 50 cultures that appeared most promising, and one of these cultures later turned out to be Streptomyces avermitilis (inset to right), the source of Avermectin.

Figure 3: William C. Campbell discovered that one of 詍ura抯 Streptomyces cultures was very effective in killing off parasites and the active compound, Avermectin, was purified. Avermectin was further modified to Ivermectin, which turned out to be highly effective in both animals and humans against a variety of parasites, including those that cause River Blindness and Lymphatic Filariasis.

Figure 4: Youyou Tu searched ancient literature on herbal medicine in her quest to develop novel malaria therapies. The plant Artemisia annua turned out to be an interesting candidate, and Tu developed a purification procedure, which rendered the active agent, Artemisinin, a drug that is remarkably effective against Malaria.




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