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Winning Wonders: Journey towards a better future

Every year, Nobel Prize is awarded by the Nobel foundation for the outstanding discoveries in the field of life sciences and medicine. And there is absolutely no doubt in saying that all these discoveries are ground-breaking. But are you all acquainted with them? Well, here are some of the recent Nobel Prize awarded discoveries to enhance your knowledge.

1. Discovery of Hepatitis C virus

Three laureates were awarded a Nobel prize in the field of Medicine and Physiology in 2020, for the achievement that has granted eminent benefits to humankind. This Nobel Prize is awarded for the discovery of the Hepatitis C virus which is the prime cause of blood-borne hepatitis. It is a major global health problem that causes cirrhosis and liver cancer in people around the world. As a matter of fact, Hepatitis C virus was discovered in 1989 but before that it was called non-A, non-B hepatitis as the virus could not be identified.

Harvey J. Alter, Michael Houghton, and Charles M. Rice made a ground-breaking discovery that led to the identification of a novel virus, Hepatitis C virus. Even though the discovery of Hepatitis A and B virus had been many steps ahead, but a number of cases of blood-borne hepatitis remained unexplained.

The Viral Hepatitis: A,B and C

There are two main forms of hepatitis. One of the forms is an acute disease caused by Hepatitis A virus and it is transmitted by contaminated water or food. The other form is caused either by Hepatitis B virus or Hepatitis C virus. This form of blood-borne hepatitis is often a chronic disease that may progress to cirrhosis and hepatocellular carcinoma. Hepatitis C can be treated and cured. Almost everybody living with HCV can now be cured with a one-pill-a-day aliment in eight-to-twelve weeks.

Here is a brief description about the research:

The systematic studies of transfusion-associated hepatitis by Harvey J. Alter demonstrated that an unknown virus was a common cause of chronic hepatitis when he was studying the occurrence hepatitis in patients who have received blood transfusions. Michael Houghton used an untested strategy to isolate the genome of the new virus that belonged to the Flavivirus family and it was named Hepatitis C virus. Charles M. Rice provided the final evidence which he created using genetic engineering and then experimenting it on the MO (model organism) showed that Hepatitis C virus alone could cause hepatitis.

And now, only because of their contribution, Hepatitis C is curable for the first time in history. Very soon with the help of proper blood tests and vaccines, it’ll be eradicated from almost every part of the world.

The Hepatitis-C Discovery Research

2. Discovery of how cells sense and adapt to oxygen availability

As we all know, cells need oxygen for the production of energy from food. Although we’ve known the importance of oxygen for centuries but how cells adapt to changes in levels of oxygen has been discovered recently.

William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza were awarded Nobel prize in 2019 for the discovery of how cells can sense the changing oxygen availability and adapt to it accordingly. They found out molecular machinery that regulates the activity of genes in response to varying levels of oxygen.

Here is a brief description about the research:

When oxygen levels are low (hypoxia), HIF-1α (hypoxia-inducible factor) is protected from degradation and accumulates in the nucleus, where it associates with ARNT (a gene- aryl hydrocarbon receptor nuclear translocator) and binds to specific DNA sequences (hormone response element) in hypoxia-regulated genes. At normal oxygen levels, HIF-1α is quickly degraded by the proteasome. Oxygen regulates the degradation process by the addition of hydroxyl groups (OH) to HIF-1α. The VHL protein can then recognize and form a complex with HIF-1α leading to its degradation in an oxygen-dependent manner.

This discovered mechanism for oxygen sensing has cardinal importance in physiology, for example for our immune response, metabolism and ability to adapt to exercise. Many pathological processes are also affected positively. This is leading to further studies in development for new drugs that can either inhibit or activate the oxygen-regulated machinery for treatment of anaemia, cancer and other diseases.

The Oxygen Sensing Mechanism

3. Discovery of cancer therapy by inhibition of negative immune regulation

James P. Allison and Tasuku Honjo were awarded the Nobel Prize in 2018 for the discovery of a new cancer therapy which is based on inhibition of negative immune regulation. Their research work is basically on two protein viz. CTLA-4 and PD-1. These proteins are located on T-cells and acting as a blockade, prevent the immune system by attacking tumour cells. The speciality of this therapy is that it doesn’t target tumour cells and it doesn’t involve vaccines or cytokine to turn “on” immune response. Instead, it works by blocking inhibitory pathways to unleash anti-tumour immune response. Let’s see how it works.

Our immune cells protect us from harm by patrolling our blood in search of potential problems and travelling to sites of infection or damage. For example, when our cells are infected with a virus, they need to be destroyed. Infected cells display different molecules on their surface from healthy cells indicating they’re damaged.

Immune cells (T-cells) can recognise these signs of disease and pass on instructions that tell the infected cells to self-destruct. But when it comes to cancer, the situation is lot more complicated. For a tumour to grow, it needs to avoid detection. One way tumours can do this is to produce molecules that can trick the immune system. One of these molecules is PDL-1. It interacts with the immune cell, telling it to ignore cancer.

But now these scientists have discovered anti PD-1 drug which can interfere with this process allowing the immune system to attack cancer.

The Working of PD-1

Allisson’s and Honjo’s discoveries have added a new pillar in cancer therapy that doesn’t target the cancer cells but rather the checkpoints, of the host’s immune system. Until the seminal discoveries by these two laureates, progress into clinical development was modest. But now checkpoint therapy has revolutionized cancer treatment and has fundamentally changed the way we view how cancer can be managed. The ground-breaking discoveries made by the two laureates constitute a total transformation in the fight against cancer.

- written by Anisha Bhamare

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