We are a combination of cells — trillions of them, by the latest estimates. These numerous cells that perform specialised jobs come together to function as a single, coherent unit — the human body. Humans have wondered about the workings of their bodies since ancient times. We are still far from unlocking all the material secrets that make our bodies tick. Yet much progress has been made over the last century. An area where our understanding of the organisation of organisms has taken giant strides is on the code of life, now known to reside largely in a giant molecule called DNA — short for deoxyribonucleic acid.

The first verifiable accounts of functioning microscopes emerged from Europe in the early 17th-century. Once it became possible to peer into the microscopic world, scientists were quick to probe beyond the scope of the naked eye. Did something exist beyond what the human eye could see or was it an empty space not worth worrying about?

Many scientists had made the intuitive assumption that the microscopic domain was packed with surprises, inspite of whether we could see it or not. The microscope helped them find that large organisms were made of numerous tiny compartments — now called cells — which were densely packed in any given tissue. It also led to the observation that different kinds of single cells moved in fluids — be it a pond or blood. For every cell the scientists saw, they could find many more similar looking cells if they looked harder. Could a cell replicate just like humans could give birth to young ones?

It turned out that cells, microscopic compartments filled with who knows what, could indeed replicate and make copies of themselves. These findings opened the doors for the study of single cells, their components and the processes by which they functioned. That was when scientists came face-to-face with the question at the core: How can a cell made of different molecules contain and carry out the instruction to copy itself? Is there a language hidden in the molecules that could be read and followed not only to create a daughter cell but also to pass on the same instructions to the daughter cell and all the cells it would produce in the future?

To understand what must happen for a cell to reproduce itself, let us first imagine the simplest version of a cell. A cell is the combination of many millions of molecules which can somehow replicate the entire pattern. An absurdly simplified version of this scenario would be a single molecule that can replicate itself. How could molecular machines without any guiding ‘brain’, so to speak, make near perfect copies of themselves with ease? This fundamental question gripped the early cell biologists. Could you, if given the blueprint of a car and the manufacturing process, replicate it? You will need raw materials — molecules; the replication process will need — more molecules; and the machinery — even more molecules. So we can re-phrase the question slightly.

Is there a molecule that can make copies of itself when put in a soup containing all necessary components? Do realise that this molecule has to store information on replicating itself as well as for all the machinery that would do the replicating. What follows is a crucial hunch. This must be a rather big molecule if it is to hold so much information.

Ernst Haeckel, a German scientist, had suggested that a sub-compartment inside the cell (now called a nucleus) held the information coding elements responsible for hereditary transmission from cell to cell. Johann Friedrich Miescher, a Swiss biologist, developed methods to isolate pure nuclei from pus cells in discarded surgical bandages. During one such experiment performed around 1869, Miescher used laboratory reagents to obtain a precipitate of a certain substance — a component of the nucleus which on adding the same reagents, behaved very differently from proteins which were, by then, known to be the major component of cells. He called this substance nuclein, and developed methods to isolate large quantities of it for chemical analysis. Other scientists would take this work forward in the years to follow and two major lines of work would emerge — one was to find the precise chemical composition of ‘nuclein’ (now called nucleic acid), and the other to determine whether it was the nuclein or protein that contained the hereditary information of a cell.

The second question was settled by Alfred Hershey and Martha Chase, who produced an elegant experiment showing that it must be nucleic acids that carry hereditary information of a cell. They observed that there were tiny viruses called ‘phages’ which infected bacterial cells.

What followed was an explosion of the number of phages as they somehow hijacked the bacteria to produce more phages. The phages dock onto the surface of the bacterial cells injecting a material — nucleic acids and nucleic acids only — into the bacterial cell. Since this is followed by the bacterial cells beginning to produce full blown phage viruses it must mean that somehow it is this molecule that held the code for a virus’s life. And as would turn out later, for all life on earth.

BLINKSANTANU

Santanu Chakraborty

 

Santanu Chakraborty is a Bengaluru-based engineer, scientist and photographer