At the height of the Vietnamese war, the common enemy
of soldiers on either side of the battle lines was chloroquine-resistant
malaria. In 1964, the North Vietnamese Government approached the Chinese
leader Mao Tse Tung to find a solution to this deadly scourge. Mao
immediately established a military mission Project 523 with a main aim
to discover a drug for resistant malaria. Youyou Tu was a phytochemist
who was in charge of the project. She and her team combed through
hundreds of old Chinese traditional medicine texts. Around 2000
chemicals extracted from various plants were evaluated. Finally, they
zeroed on to an extract of Artemesia annua L. also called Quinhao
which was found to have excellent antimalarial efficacy in a mouse
model. The details of this research were – for several years – largely
unknown outside China because it was published anonymously in Chinese.
Subsequently, artemesinin has become known worldwide as one of the most
effective drugs against chloroquine-resistant malaria.
Youyou Tu received this year’s Nobel Prize for
medicine. It is especially creditable as she is neither a doctor nor a
PhD nor has ever worked overseas; all considered vital for a Nobel in
medicine. She shares the Nobel Prize with William C Campbell and Satoshi
Omara for the discovery of Avermectin which opened avenues for the
treatment of a range of parasitic diseases. Omara is a Japanese
microbiologist who has isolated several species of the soil bacteria
Streptomyces, and successfully cultured them in the laboratory. From
these, he selected 50 of the most promising streptomyces with good anti
microbial activity. Campbell who was working for Merck in the US took
his streptomyces strain, and found that one of the molecules extracted
from the culture was remarkably effective against parasites of domestic
and farm animals. The molecule was further purified to form ivermectin
which has revolutionized treatment of various parasitic diseases. It has
helped to eradicate river blindness (onchocerciasis) from Africa, and to
significantly control filariasis. (http://www.nobelprize.org/nobel_prizes/medicine/laureates/2015/press.html).
Nobel Prize in Chemistry
The inherent instability of DNA is a double-edged
sword. Damaging lesions can also be mutagenic and change the coding
capacity of the genome, which can lead to devastating diseases,
including cancer, neurodegenerative disorders and biological ageing. On
the other hand, without mutations, Darwinian evolution is unthinkable.
Interestingly, mutagenic chemicals and radiations can also be
therapeutic. For instance, these can be used to treat cancer, by
introducing DNA lesions that halt cell proliferation and stimulate
programmed cell death.
The Nobel Prize in Chemistry 2015 was awarded jointly
to Tomas Lindahl, Paul Modrich and Aziz Sancar for elucidating three
different mechanisms by which errors occur in our DNA and the various
mechanisms of DNA repair. In the 1970’s, Lindahl discovered that DNA
undergoes regular decay and damage. For example, cytosine loses an amino
group to become uracil resulting in a mutation. Subsequently, he
discovered an enzyme system called uracil-DNA glycosylase which corrects
this error. This process was called base excision repair. Aziz Sancar
discovered and cloned the gene for an enzyme called photolyase which is
critical in correcting DNA mutations caused by high doses of UV
exposure. He further went on to identify the exact chemical processes
involved in this nucleotide excision repair. Paul Modrich discovered the
mechanism by which DNA errors during cell division are identified and
repaired. The process is called mismatch repair.
A deeper insight into DNA repair mechanisms will help
us in understanding disease pathogenesis and identify potential
therapies for some apparently incurable diseases. (http://www.nobelprize.org/nobel_prizes/chemi
stry/laureates/2015/advanced-chemistryprize2015.pdf)
The Precision Medicine Initiative
President Obama has unveiled an audacious new
initiative to personalize and improve clinical care to patients. The
basis of this precision medicine initiative is that in prevention and
treatment of disease, individual differences need to be taken into
careful account. This will be possible only if large amounts of very
precise data, entailing millions of patients, are analyzed very
meticulously. The time appears ripe now since it is theoretically
possible to collect and analyze detailed medical, genetic and
physiological data.
Today we have powerful methods for characterizing
patients (such as proteomics, metabolomics, genomics, diverse cellular
assays, and even mobile health technology), and computational tools for
analyzing large sets of data. Americans are also increasingly interested
in being active partners in medical research. Increased connectivity
through mobile devices has simplified the problem.
The plan is to recruit one million participants in the next four
years either individually or through health care providers. Volunteers
signing up to be part of this project would agree to be recontacted,
take a baseline health examination, share their electronic health care
records, and provide a biospecimen. The issues like prevention of misuse
of data and security need further exploration. The plan is imaginative
and grand. Time and patience will certainly yield good results. (Scientific
American, 22 September 2015).