The antimalarial drug upon which the recent award of the Nobel Prize for Physiology or Medicine is based has a rich history and has been used in Chinese traditional medicine for at least 2000 years. The herb is an annual shrub known scientifically as artemisia annua and called qing hao by the Chinese.
The Chinese identified it as a potential target for a new antimalarial drug through Project 523, a collaboration of academic and industrial institutes. Its need was driven by Chinese and Vietnamese personnel during the Vietnam War who feared malaria. At the time they did not have access to Western antimalarial drugs.
Dr Tu Youyou of the Chinese Academy of Traditional Chinese Medicine was awarded the prize for discovering the drug artemisinin. It is a pure chemical substance shown by the Chinese to be very active in killing the malaria parasite.
The substance, known as qinghaosu but later renamed artemisinin, was isolated from qing hao. Colloquially known as ‘sweet wormwood’ or ‘annual wormwood’, the plant is found in China, Europe, and temperate North America.
Historically it is difficult to gauge the actual input of Youyou into the project. So many groups were involved. It appears it was not her institute in Beijing that first isolated the crystalline artemisinin. This aside, the discovery was to prove of inestimable importance.
Chinese clinicians, including Professor Li Guo-Qiao in Guangdong in southern China, showed that artemisinin was highly effective in curing malaria patients. It was especially helpful for patients infected with strains of the malaria parasite resistant to front line drugs such as chloroquine, pyrimethamine, sulfadoxine among others.
Artemisinin was noted by the Chinese to clear parasites from the blood of the malaria patients more rapidly than any other malarial drug. Chinese chemists then converted artemisinin into new three derivatives which were even more effective than the parent substance in curing malaria patients.
The timing of the Chinese discovery was particularly fortunate. By the late 1970s, malaria had become an increasingly intractable disease to treat. This was because the malaria parasite had become resistant to other front line drugs.
The global mortality rates, that on an annualised basis were greater than any time in history, indicated that containment of the disease was not possible. At this point the World Health Organisation coordinated efforts with the Chinese scientists at first and later to introduce these new drugs into the West.
In the late 1970s and early 1980s, Professor Li Guo-Qiao along with Dr Keith Arnold were the first to combine artemisinin with other malaria drugs such as mefloquine. They did this because artemisinim is an unstable substance due to its unique chemical structure. These so called artemisinin combination therapies or ACTs have now become frontline drugs for treating malaria on a worldwide basis.
In Africa, artemisinin drugs and then artemisinin combination therapies have been enormously important in controlling malaria.
Of all the malaria endemic areas in the tropical world, Africa has proved most intractable. The prevalence of malaria infections and mortality among populations living in these areas are the highest in the world.
In the last 10 years, the incidence of and mortality due to malaria have substantially decreased. It is difficult to obtain reliable statistics for earlier periods in Africa. Globally between 2000 and 2011, there was a 25% decrease in mortality. This includes a 20% decrease in mortality involving children under five.
In Africa, during the same period, there was a 33% decrease in mortality. The figures show that globally, in 2013, 198 million cases of malaria occurred and there were 584 000 deaths. The burden is still the heaviest in Africa, where an estimated 90% of all malaria deaths occur and the majority of these deaths occur in children under five.
The use of mosquito vector control measures has also contributed to the decline in mortality. These measures include insecticide impregnated bed nets, residual indoor spraying and local populations in endemic areas being aware of these controls.
But it is not possible to assess what might have been had the artemisinins not been introduced into Africa. What is clear is that artemisinins have helped enormously in the control of malaria in Africa at large.
It is difficult to compare artemisinin to other technologies. The closest is the introduction of quinine as a pure substance to treat malaria about 150 years before artemisinin was discovered. Quinine was isolated as a crystalline substance from the bark of the cinchona tree in the early 1800s.
When the chemical structure of quinine was established in 1903, many other drugs based on this structure were developed. These include mefloquine and chloroquine, leading to the modern era of chemotherapy in controlling malaria. Now, artemisinin’s unique chemical structure is inspiring the development of newer drugs.
A genuine collaborative effort
Considering the advances that have been made in reducing malaria, the discovery and development of artemisinin is worthy of the Nobel award. In truth, however, it should be seen as an award to all those remarkable groups involved in this collaboration.
Project 523 has to be rated as one of the greatest collaborations of the latter half of the 20th Century. At the time China was in the throes of the Cultural Revolution and did not have access to modern western equipment, instrumentation and techniques.
This is a wonderful Nobel award - as at long last it represents an explicit recognition of the achievements of all those groups in China involved in Project 523. This award is best seen as being presented to Madam Tu Youyou not only in relation to her own substantial inputs, but also on behalf of those groups that carried out the key work leading to the new drug artemisinin and its derivatives. These have saved millions of lives from a devastating disease.