Our government has been keen on promoting cleanliness and good health, and has coined the slogans “Swachh Bharat” ( Swachh for clean; Clean India) and “Swasth Bharat” ( Swasthya for health; Healthy India). Cleanliness leads not just to physical health but mental health as well. That this connection starts at the body, organ, tissue and even at the cellular level was highlighted through the work of Dr. Yoshinori Ohsumi of the Tokyo Institute of Technology, Japan, who was awarded the Nobel Prize in Physiology/Medicine for the year 2016.
While the details of his work (including some of the technical points) on how the living cell cleans up waste material have been well covered in this newspaper on October 3, it is enough to highlight here that Ohsumi teased out and studied the waste disposal apparatus inside the cell that “eats off” metabolic waste material, converting them into the component molecules. That such a waste-digesting bag, called the lysosome, exists in the cell was discovered earlier by Dr. Christian de Duve, who won the Nobel Prize way back in 1974. Ohsumi went further to describe the various steps involved in capturing the waste cargo, making a container to transport them and fusing this container with the lysosome , where enzymes break down the cargo to its component fat molecules or lipids, amino acids, sugars and other small molecules. These are then recycled for the synthesis and renewal of new cells. The cell thus has an efficient waste disposal and recycling machinery-together called the autophagosome (auto - self; phago - eat/devour and some - in the body or the unit).
A few things are noteworthy in this connection. The first is that Ohsumi’s research was carried out using baker’s yeast as the model organism, rather than the human body or its cells. Why did he use the lowly yeast? Because he could work with the ‘normal’ or healthy yeast cells and also with many of its mutants where this process, called autophagy, has been modified ever so lightly or even disrupted. It was a long haul, lasting over two decades. Use of normal and mutant yeast cells was a wonderfully planned approach. Using this method, he could identify a whole set (about 20 of them) of genes, simply called the ATG gene family, study mutant yeasts with errors in one or several genes of the family and tease out the role of each gene (and its product protein) in the various steps involved in autophagy.
It is worth pointing out here that what is true of yeast is pretty much true in human cells. Our cells metabolise and handle waste in much the same way as yeast does. When we eat sugar, metabolise it and generate energy, we use it the same way that yeast does - using the same type of enzymes and making the same energy currency molecules as yeast does. Over evolution, we have preserved our heritage - or as someone said: ‘the more it changes, the more it stays the same’.
Actually, autophagy is a process that helps an organism maintain its internal stability and equilibrium, or what is referred to as homeostasis. What happens when external factors tend to disturb this equilibrium? One such is through infection by pathogenic germs. While autophagy can, and does, handle this by eating the invader up, the immunity of the body can be compromised. Studies are in progress about the process by which autophagy is de-regulated in inflammatory and infectious diseases and how drugs can help restore normalcy.
In some instances, autophagy can be overstressed. The March issue of the journal Experimental Eye Research was dedicated to autophagy in the eye. In one article in that issue, a group from Case Western Reserve University in the U.S. has shown that it is autophagy that protects the retina of our eyes from light-induced damage. Light constantly falls on the retina, where the captured light is converted into the electrical signals that are passed to the brain, helping us see. But when excess light falls on the retina, the cells that receive this light can be damaged, and autophagy might be inadequate. The group suggests that tickling and activating the genes Becklin 1 and ATG7 might be useful in protecting the retina under high-light-stress conditions. Other methods, such as adding new cells into the eye for conditions such as age-related macular degeneration, are also being tried.
A similar situation obtains in the brain, with neurological disorders such as Alzheimer’s disease. In such situations, proteins which should be normally soluble are found to clump together, hampering nerve conduction. Autophagy finds it difficult to dissolve and degrade these protein lumps, and external molecules and drugs are needed to solubilise the clumps and increase autophagic efficiency. This, too, is an active area of research today.
What is the take-away from Dr Ohsumi’s work? That waste must be cleared - not thrown out but broken down into useful starting material and reused; that it is an ancient practice, started over hundreds of million years ago, and a heritage that has been adopted by all organisms with success. And what is good for the individual is good for the community. Swachh Biology and Swasth Biology naturally leads to Swachh Bharat, Swasth Bharat.
D. Balasubramanian
dbala@lvpei.org
