A recent headline in The New York Times (December 28) was titled: “Lifelines at risk as bankruptcies stall antibiotics – a health crisis looms: scant profits in fighting drug-resistant bugs sours investors.” This refers to the growing menace of disease-causing germs such as bacteria and fungi, for example, pseudomonas, E.coli, klebsiella, salmonella and TB, which no longer respond to the conventionally used antibiotic drugs. These emerging Multi-Drug- Resistant ( MDR) germs sicken almost 3 million people across the world every year, and the UNO states that if we do not find drugs to fight and kill these MDR-germs quickly enough, the global death toll could soar to 10 million people by 2050.
How did these MDR-bugs come about? Since penicillin and similar antibiotics (erythromycin, floxins) were introduced about 60-70 years ago, we have been using them with success, because each such conventional drug effectively kills millions of germs. Yet a tiny population of them had survived, thanks to some escape routes such as slight change in their genes, leading to pathways that stop the drug from entering their cells or pathways that pump out the entered drug molecules. Such escapees started growing and multiplying into millions over months and years, and became resistant to all the common antibiotics- these are the MDR-germs.
What is needed in this scenario is for scientists and drug firms to do basic, fundamental research into the biology of MDR germs and develop effective drugs to fight and win over them. This often takes a decade or more to bring out the product and make them available in the market. Indeed, it was precisely such an R&D effort that has brought about the discovery and marketing of many drugs against chronic diseases such as diabetes, arthritis, blood disorders and cancer. And the amount of investment for R &D in each one of them has been billions of dollars, and the company expects to gain billions of dollars each year. It is here that the problem lies in the case of investing in drugs against MDR bugs. As Andrew Jacob points out in the above article, major drug firms have shied away from work on MDR-germs, since unlike chronic diseases which are prescribed for long terms (months and years), antibiotic drugs are prescribed for days and at best for weeks, and so no long term profit is made!
Public spirited players
To do research and development and come out with drugs against MDR-germs, too, is no different, and this also requires long-term effort and involves billions of dollars input. And it is here that some private firms have pitched in. Happily enough, they have been getting R&D funds as grants from private foundations and governmental sources. The article describes how the biotech company Achaogen succeeded in obtaining a billion-dollar grant from the US government’s Biomedical Advanced Research and Development Authority (BARDA), spent 15 years of research and development work and came out with the drug called Zemdri, effective against hard-to-treat urinary tract infections. Zemdri was approved by the Food and Drug Administration (FDA) and the WHO. Sadly, Achaogen could not make any sustained profit, the investors were unhappy and the firm went bankrupt. Similarly, the firm called Tetraphase, which obtained a major grant from a nonprofit group and produced the drug Xerava, which is effective against some MDR-bugs, had to cut down its staff and its plans to conduct further R & D efforts since its stock price was plummeting. And so was a third firm, Melinta Therapeutics, which has successfully produced Baxdela, an FDA-approved drug for drug-resistant pneumonia.
It is of interest to note that the firm Achaogen was bought over by CIPLA-USA, which is the US arm of the Indian public-spirited drug company CIPLA. This involved buying all the equipment and the rights to acquire the technology and to make and sell the drug Zemdri across the world.
CIPLA’s move in this area holds out an example for other Indians and firms to enter the field. They may likewise interact with other such firms in the US, acquiring them, or as partners or owners (even set up labs in India), gain the hard-earned technology of making drugs active against MRD-germs, and make these available for use by the needy not only in India but across the world. Note that a recent paper on the mortality burden of MDR-pathogens in India (S. Gandra et al., Clinical Infectious Diseases 2019; 69(4):563-70) which studied 10 hospitals across the country for MDR pathogens and the patient mortality outcomes shows that 13% is the overall rate of death. If this be for hospital-based deaths, we can imagine the millions affected and dying across the towns and villages of India. And surely such a situation would be true in parts of Africa, southeast Asia and other low-income, high-population countries. R&D efforts by Indian scientists will thus be of public health and economic value.
Fortunately, Indian government and its funding agencies are keen in offering grants in this Focal Theme area to researchers in government-operated R&D institutions and universities, as well as to private non-governmental research institutions, and drug companies. Private non-profit foundations in India should also open up their purses (not just the Wellcome Trust of the UK or the Bill and Melinda Gates Foundation of the US).
Many of us in our own country do not realise that India has become the major vaccine provider for children across the world. Just a handful of vaccine-makers across India now provide about 35% of childhood vaccines globally, through their R&D efforts. There is thus no reason why India cannot be a major player in offering good health to the 7 billion people across the world through our efforts in the area of fighting infection by traditional, MDR-type and other emerging disease-causing germs.
dbala@lvpei.org
