Saluting those who heal

Life talks with the recent recipients of the Prince Mahidol Award 2018

From second left, Prof Dr Brian J. Druker, Prof Mary-Claire King, Prof Dr John D. Clemens and Prof Dr Jan R. Holmgren. (Photo by Chanat Katanyu)

Since 1992, the Prince Mahidol Award has been conferred on individuals and institutions for outstanding contributions to medicine and public health.

The award honours HRH Prince Mahidol of Songkla -- the Father of Modern Thai Medicine and Public Health -- for his exemplary contributions to the country's advancement of medicine, public health and human services.

From 49 nominations, Prof Dr Brian J. Druker and Prof Mary-Claire King have been awarded the Prince Mahidol Award 2018 laureates in medicine for their research and contribution to oncology, while Prof Dr John D. Clemens and Prof Dr Jan R. Holmgren jointly received the award in the field of public health for their research and development of an oral cholera vaccine (OCV). HRH Princess Maha Chakri Sirindhorn, as the representative of HM the King, conferred the Prince Mahidol Award on the four laureates at the Chakri Throne Hall last week.

Here, the laureates share their long and unwavering journey to help people overcome cancer and cholera.

Targeted treatment

Last year marked the 20th anniversary of the first clinical trial on Imatinib, which revolutionised the treatment of chronic myeloid leukaemia (CML).

"It's rewarding to see patients who were told that they only had months to live, and are still alive and well after 20 years," said Dr Druker, who was in his 40s when conducting the phase 1 clinical trial of Imatinib.

Beforehand, in the lab, Dr Druker found that from the many compounds tested, one remarkably killed leukaemia cells while not harming normal cells.

However, getting the drug out of the lab to begin the first clinical trial was a five-year crusade for the American oncologist.

"The biggest hurdle was that the pharmaceutical company didn't believe that it was a worthy investment," he said. "I'm not only a researcher; I'm also a doctor. I saw how patients desperately needed an effective medication, and they put faith and trust in me to help them fight the cancer with a targeted therapy."

Ultimately, in mid-1998, Dr Druker started a small clinical study in CML patients who were resistant to or intolerant of treatment with another drug.

Patients responded well to Imatinib -- a first-generation drug that targets genes. The positive results led to more clinical trials, and ultimately the fastest FDA approval for Imatinib in May 2001.

In the same month, the ground-breaking drug was featured on the cover of Time magazine, and hailed as new ammunition in the war against cancer.

"It's basically about understanding what specifically drives the growth of cancer and targeting it, for an effective treatment without side effects. Moreover, it's a pill -- for patients to easily take the drug," said Dr Druker, who is now a professor of medicine and director of the Knight Cancer Institute at Oregon Health & Science University.

Imatinib's efficacy spurred the development of targeted therapies, not only for leukaemia but other types of cancer.

"While not as common as breast or lung cancer, leukaemia is a devastating and lethal disease," he said. "Patients with acute myeloid leukaemia may only live one to two years, those with CML three to five years. It's rewarding to see how they can expect a normal lifespan by taking only a pill."

Relentless research

While pretty obvious today, an inherited predisposition to cancer proposed by Prof Mary-Claire King raised eyebrows back in the mid-1970s.

The relentless Prof King went on to locate the first gene linked to the risk of developing breast and ovarian cancer on chromosome 17, and by coincidence it took her 17 years.

"The research started 45 years ago, and we initially used mathematical tools since we didn't have the genomics technologies available today," recalled King, who is now a professor of medical genetics at the School of Medicine, University of Washington in Seattle.

Transferring to a genetics PhD programme rather than pursuing a doctorate in statistics took her to where she is today. The background in mathematics, however, helped her explain heritable breast cancer and identify the causal gene, which she named BRCA 1 in 1991.

"It's fulfilling for someone coming from mathematics to have an impact on health," expressed Prof King. "Not only mathematically and biologically correct, it actually matters if we can identify women who carry a mutation in the genes."

After BRCA1, the BRCA2 gene was identified as another culprit in causing breast cancer.

Prof King also worked with researchers to develop an affordable genetics test for the screening of the disease. The genetic testing monitors changes in BRCA1 and BRCA2 genes, and is recommended for women, particularly those whose family members have had breast cancer.

The discovery of the BRCA1 gene is depicted in the docudrama Decoding Annie Parker (2013), starring Helen Hunt as Prof King and Samantha Morton as the eponymous protagonist, whose mother and sister succumb to breast cancer, while also falling prey to the malignancy herself. The film shows how breast cancer passes from generation to generation.

Off screen, Prof King has seen encouraging outcomes as women take charge of their health.

"I get to meet women whose children have graduated from high school when they never expected to see their kids pass first grade," she said. "These women were aware of their genetic predisposition and took measures against breast cancer. They saved their own life."

Combating cholera

For decades, Dr Jan R. Holmgren and Dr John D. Clemens dedicated themselves to research on an oral vaccine against cholera -- an acute intestinal infection caused by the ingestion of food or water contaminated with Vibrio cholerae.

Injectable cholera vaccines used until the early 1970s were found to have limited protective effect as well as adverse reactions.

Dr Holmgren was one of the pioneers of a better alternative that resulted in the world's first WHO pre-qualified oral cholera vaccine (OCV). The oral route effectively induces protective antibodies produced on the mucosal surface of intestines.

"Cholera affects so many people, largely those who are the poorest in the world. To see from the very beginning how a concept has materialised to a vaccine applied to public health is very gratifying," said Dr Holmgren, a professor of medical microbiology and immunology, and director at Gothenburg University's Vaccine Research Institute in Sweden.

Developed in the 1980s and internationally licensed in 1991, the first OCV was expensive and difficult to administer, with limited protection. Developing affordable, effective and locally produced options was required to make the vaccine more accessible.

Dr Holmgren was instrumental in this effort by providing technical know-how to Asian manufacturers, in producing vaccines at a lower cost. Two are currently available for mass vaccination campaigns through the Global OCV Stockpile.

A joint recipient of the Prince Mahidol Award 2018 in public health, Dr Clemens played a significant role in vaccine development and evaluation in developing countries, and led the first efficacy trial of an OCV.

The American doctor is currently director of the International Centre for Diarrhoeal Disease Research in Bangladesh. Back in the 1980s, he was a research scientist there, and observed from a trial how OCV provided herd immunity to unvaccinated individuals.

"We evaluated the risk of cholera in people receiving a placebo and found that more of them living in a highly vaccinated neighbourhood were protected, in comparison to those living in an area with a low vaccine coverage," Dr Clemens said.

The combined effect of direct vaccination and indirect herd protection provides good coverage and implies that cholera can be controlled even when not all of the population is vaccinated.

In the future, the two Prince Mahidol Award laureates hope to see the disease being eradicated in many as 20 countries, following the "Ending Cholera: A Roadmap To 2030" strategy launched two years ago by the Global Task Force on Cholera Control.

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