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Nobel viruses

Nobel viruses

RSV public domain crop.jpg

Listen to this story in episode 003 - Hunting Huntington's, Nobel viruses and spidergoats

It may sound strange, but a chicken virus has won three Nobel prizes. Obviously, not by putting on a teeny tiny lab coat and safety specs, but the Rous sarcoma virus, which causes cancer in chickens, has been the starting point for startling discoveries that have changed our understanding of genetics, molecular biology, cancer and more. In fact, viruses have played a key part in at least 16 Nobels over the past century. Not bad work for tiny bags of genes loitering on the edge of life.

In its simplest form, a virus is a piece of genetic material – either DNA or RNA – encapsulated in a protein coat and small enough to evade detection using a normal light microscope. Unlike bacteria and other bigger organisms, viruses can’t replicate on their own, instead relying on hijacking the replication machinery of living cells. Despite this limitation, they get absolutely everywhere. From bacteria and amoeba viruses to viruses infecting every species of plants and animals – where there’s life, there’s viruses.

Most people probably think of viruses as the agents responsible for some of the most widespread and serious diseases we know of, including smallpox, HIV, measles, Ebola and influenza. We also now know that some viruses can trigger cells to run out of control and form tumours, such as the Rous sarcoma virus in chickens, breast tumour viruses that affect mice, and feline leukaemia virus, which causes blood cancer in cats.

Other viruses merely significantly increase the risk that cells will run out of control, such as the human papillomavirus (HPV), which is strongly linked to cervical cancer and several other forms. And on the more mundane side, viruses are responsible for illnesses like the common cold and stomach upsets.

But rather than thinking of viruses as a pain in the posterior, geneticists have a lot to thank viruses for. Since the discovery of the first virus in the 1880s – tobacco mosaic virus or TMV, a rod-shaped virus that causes mottling on the leaves of tobacco plants – studying these tiny particles has shed light on many of the fundamental processes in biology.

Just take the example of the Rous sarcoma virus, RSV, which was discovered in 1911 by US research Peyton Rous, who noticed that injecting a cell-free extract of mashed up chicken tumour into healthy birds could induce tumours to form. In 1975, David Baltimore, Renato Dulbecco, and Howard Temin won a Nobel Prize for discovering that RSV and other similar viruses could turn their RNA-based genome back into DNA and insert themselves into the host’s genome – an act known as reverse transcription.

As well as smashing the established wisdom that information couldn’t flow from RNA back to DNA, the discovery of retroviruses like RSV, along with others such as HIV that came along later, rewrote our understanding of how viruses can interact with the genome. What’s more, discovering and purifying the reverse transcriptase enzyme revolutionised molecular biology, enabling researchers to turn any piece of RNA back into more stable and easily manipulated DNA.

Another RSV-based Nobel went to Michael Bishop and Harold Varmus in 1989. While using the latest fancy DNA mapping and sequencing technique, they were confused to see that healthy chicken cells appeared to contain the same genes as RSV, without being infected by the virus. This led Bishop and Varmus to discover oncogenes: normal genes inside cells that are usually responsible for controlling cell growth and proliferation. If these genes become mutated and overactive, then a cell will grow out of control into a cancer. This is the fundamental genetic basis for tumour formation, and utterly transformed our understanding of how cancers grow.

And Nobel number three for RSV is Peyton Rous himself, who eventually got a Nobel Prize in 1966 at the grand old age of 87, more than five decades after publishing his initial findings.

Other viruses have enabled us to see inside the black box of genetics in different ways. Researchers studying viruses have used their relatively simple, repeating structures to develop powerful techniques like crystallography. French scientists Francois Jacob, Jacques Monod and Andre Lwoff won a Nobel in 1965 for figuring out how genes are switched on and off, using little more than powerful logic and a bunch of viruses that infect bacteria, known as bacteriophages.

And in 1952, Alfred Hershey and Martha Chase used viruses to prove DNA is the genetic instructions, with a little help from a kitchen blender. Sadly, as a mere lab technician, Chase wasn’t able to receive a share of Hershey’s 1969 Nobel, despite doing virtually all the practical work.

Of course, there’s plenty of benefit in studying viruses themselves, and not only in order to develop vaccines and treatments for viral diseases. Viruses are the mainstay of gene therapy, due to their ability to sneak into cells and deliver a genetic payload, and they’re often used as a way to deliver gene editing tools like CRISPR into cells. And researchers are investigating whether bacteriophage viruses could be a useful way to get around the problem of antibiotic resistance.

Finally, the weird and wonderful world of viruses shows us what is possible in biology. In 2003, scientists were shocked to discover a simply enormous virus that infects amoebas, as big as some bacteria and large enough to be seen with a normal light microscope. This viral freak of nature, known as mimivirus, has now been joined by other giant viruses (well, giant in viral terms), which have unusually complex genomes and many genes that have previously only been associated with cellular organisms. And I have no doubt that the viral world has many more secrets waiting to be discovered.

Further reading and references:

Mimivirus: leading the way in the discovery of giant viruses of amoebae - Philippe Colson et al, Nature Reviews Microbiology

Hershey and Chase’s experiments

Nobel prizes and the emerging virus concept – Errling Norby, Archives of Virology

Dr Rous’ prize-winning chicken – Welkin Johnson  

The story of Peyton Rous and Chicken cancer – Jessica Wapner, PLoS Blogs

100 years of Rous Sarcoma Virus – Robin Weiss and Peter Vogt

The origins of viruses – David Wessner, Nature Education

Photo: Density testing of Rous Sarcoma Virus, via Wikimedia commons, public domain

Hunting for Huntington's

Hunting for Huntington's