Nobel prize in medicine awarded to hypoxia researchers – as it happened

Prof Bridget Lumb, president of the Physiological Society, has released her thoughts – again stressing how this year’s prize is really a celebration of a fundamental biological mechanism.

“This year’s Nobel prize puts physiology front and centre. It shines a light on the vital research carried out by physiologists,” she said.“Cutting edge physiological research such as this is improving our understanding of how our bodies work and thereby helping keep us healthy.

“Thanks to this research we know much more about how different levels of oxygen impact on physiological processes in our bodies. This has huge implications for everything from recovery from injury and protection from disease, through to improving exercise performance.”

Kaelin’s thoughts on receiving the call have come out – apparently he was speaking to AP.

“I was aware as a scientist that if you get a phone call at 5am with too many digits, it’s sometimes very good news, and my heart started racing. It was all a bit surreal,” he said.

Hellmut Augustin, director of the European Centre for Angioscience, is very excited about today’s prize, saying it has been awarded for the discovery of a very fundamental mechanism of life.

“The hypoxia program controls the expression of hundreds of molecules. Among the more prominently oxygen regulated molecules are the master switch of blood vessel growth VEGF (vascular endothelial growth factor) and the key regulator of erythrocyte [red blood cell] production, erythropoietin,” he said.

“Hypoxia regulation of gene expression governs all kind of biological processes and diseases ranging from the retinopathy of prematurity in newborns, to the growth of blood vessels in tumours to high altitude training of athletes,” he added.

Nobel selfies seem to be a new thing.

More reaction – this time from Dr Alex Greenhough at the University of the West of England who works on cancer biology.

“The work by Ratcliffe, Kaelin and Semenza has been crucial to our understanding of how cells sense and respond to changes in oxygen levels,” he said. “Their work is of huge significance to diseases that feature an impaired blood supply, which includes important solid tumours such as breast, colorectal and pancreatic cancers. Their outstanding work on the fundamental mechanisms of oxygen sensing will pave the way for future therapies that will be able to exploit the disease-specific nature of hypoxia for clinical benefit”

Just in case you feel that Gregg Semenza has been left out of the proceedings on the blog, here is a picture of him post-win.

https://twitter.com/NobelPrize/status/1181159403409612801

Ian Sample has a news story up already on this year’s prize – take a look here. We will be adding further details and reaction to the award as it comes in.

Reaction to this year’s award is coming in. Dr Andrew Murray from the department of physiology, development and neuroscience at the University of Cambridge, said the award was richly deserved and offered the trio his congratulations.

“Oxygen is fundamental to animal life, allowing our mitochondria to extract energy from the food we eat. The work of Kaelin, Ratcliffe and Semenza revealed the elegant mechanisms by which our cells sense oxygen levels and respond to fluctuations, enhancing the delivery of oxygen to the tissues of the body and altering our metabolism,” he said.

“Since the first reports of the hypoxia inducible factors appeared in the early 1990s, we have come to realise the vital role they play in our everyday physiology, in allowing humans to live at high altitude and in countless biomedical scenarios. Hypoxia (a low tissue oxygen content) is a feature of many diseases including heart failure, chronic lung disease and many cancers. The work of these three scientists and their teams has paved the way to a greater understanding of these common, life-threatening conditions and new strategies to treat them.”

Some have noted that, once again, all the winners are male. Only 12 women have been awarded the prize since the awards began. The last woman to win the award was Tu Youyou in 2015.

Sir Peter Ratcliffe appears to be taking the win in his stride.

My colleague Ian Sample previously covered the 2016 Lasker prize: here is his piece on Ratcliffe’s work on how cells adapt to changes in oxygen levels. As Ian notes “The discovery has already led to a raft of experimental anaemia drugs that trick the body into thinking it is at high altitude, causing it to churn out more red blood cells.”

The Crick is rather happy...

On winning the Lasker award for his work that has today been celebrated with a Nobel prize, William Kaelin noted the papers behind the discovery were published more than a decade ago. “Most would be considered quaint, preliminary and barely publishable today,” he wrote. “One — showing that a tumour-suppressor protein was required for oxygen signalling — would today be criticized for failing to include a clear mechanism and animal experiments.”

Today’s win was perhaps not such a huge surprise – in 2016 the trio won the Albert Lasker award for basic medical research. The Lasker awards are sometimes referred to as America’s Nobels, and previous winners often go on to win the Nobel itself.

The impact of the discovery celebrated by this year’s award is wide-ranging, with the body’s response to changing oxygen levels implicated in everything from exercise to foetal development.

It’s also involved in a number of diseases – patients with chronic renal failure produce less EPO, and as a result often suffer from severe anaemia.

In cancer, tumours use the oxygen-regulated system to trigger the development of new blood vessels – an area that is being investigated for new ways to tackle the disease.

This year’s prize is a true physiology award. At its heart is the body’s response to low oxygen conditions. When the body is deprived of oxygen, there is a rise in the hormone erythropoietin (EPO) – this then boosts the production of red blood cells, which carry oxygen around the body.

But how does a drop in oxygen trigger this response? This year’s laureates found the answer.

They found that when oxygen levels drop, levels of a protein complex (dubbed HIF) increase. Under normal oxygen conditions, HIF is rapidly broken down - but under low oxygen conditions it builds up. Crucially this complex binds to segments of DNA near the gene for EPO, regulating the expression of the gene and hence levels of EPO.

The researchers also unpicked how HIF is modified under normal conditions so that it is rapidly broken down inside cells, revealing the key role of oxygen-sensitive enzymes.

Want to know how to win a Nobel prize? Here is a top tip from the lab of William Kaelin, one of this year’s laureates

According to the committee, the mechanism by which cells adapt to oxygen levels is a key reason animals have managed to colonise so many habitats, as it means they can cope with living at different altitudes.

The committee are now taking questions. Apparently all three laureates were contacted by phone, but they didn’t have a phone number for Kaelin so they had to wake up his sister by phone to get hold of it.

The impact of work on how cells adapt to oxygen levels is relevant to everything from pregnancy to altitude sickness to cancer and wound healing.

The committee say that while it has long been known that oxygen is essential to sustain life, the molecular mechanisms that underpin how exactly cells adapt when oxygen supply drops or rises was something of a mystery. Until this year’s laureates set to work. They have unpicked how the activity of genes is regulated in response to varying levels of oxygen.

There we have it: this year’s award is split three ways between researchers who have delved into how cells sense oxygen availability and adapt in response to that. Sir Peter Ratcliffe is based at the Francis Crick Institute in London. Kaelin and Semenza are based at Harvard University and Johns Hopkins University respectively.

And here they are, the committee members have arrived …

I’m really regretting having a huge mug of coffee this morning. This is not the moment for a break...

The fog lifts. Journalists are rustling papers. Hush descends... Any minute now the committee members will walk in and spill the beans on this year’s winners.

As usual the committee has shared an awkward photograph of an official grinning happily while dialling the winners. But if past calls are anything to go by they are more likely to be met – at least at first – with doubt and suspicion than gasps of joy from the unsuspecting recipient.

After a few moments of confusion, the Swedish accent and repeated assurances presumably turns the dream into a reality.

However, not all calls go smoothly.

Physiology or medicine laureate May-Britt Moser said she initially didn’t want to take the call when she was phoned in 2014, as she didn’t recognise the number and was busy. Meanwhile the 2013 literature laureate, Alice Munro, didn’t pick up – and the committee were left talking to her voicemail, and 2010 chemistry laureate Martin Chalfie slept on as his phone rang, missing the call.

For those who like to see the glint of excitement in the committee members’ eyes, you can follow the live video feed of the event here. At the moment it has a foggy filter, presumably to evoke the idea that the winners are currently shrouded in mystery.

What’s the point of the Nobel prizes? Good question. Fortunately my colleagues Ian Sample and Hannah Devlin have delved into the issue for you, looking at cases of misjudged awards, what actually happens at the ceremony, and whether the awards have a diversity problem: as the team point out, more men called John have won Nobels than have Africans.

Why not take a look while we are waiting for today’s event to kick off.

Each Nobel prize is set at nine million Swedish kronor – that’s about £750,000. If there’s more than one winner, they have to split the cash. But the prestige is priceless. And that’s to say nothing of other perks: at the University of California, Berkeley, laureates get their own reserved car parking spaces.

My colleague Ian Sample hit a home run last year with his prediction that Allison would be a winner, which more or less exhausts our team’s luck for backing the right horse for the rest of the century. But there are no shortage of contenders for this year’s prize.

Among them are the scientists behind the gene-editing technique known as Crispr – although this has also been tipped for the chemistry prize.

If Crispr does win, it is a knotty issue as to which of the four key scientists involved in its development would be honoured. Even if the maximum number of awards were given, one of Emmanuelle Charpentier, Jennifer Doudna, George Church and Fang Zheng will be left empty handed.

Another multi-player possibility is optogenetics – a technique which, among other applications, allows researchers to turn neurons on or off using light. Again, it is not obvious who would receive the award as so many have been instrumental in its development. There is also the possibility this could win the chemistry prize.

And what about research into the microbiome – that collection of bacteria, viruses, fungi and more that live on and in our bodies, and have been found to play an important role in our health? Among pioneering the researchers in this area is Jeffrey Gordon at Washington University in St Louis.

Other possibilities include the researchers behind the discovery that particular genes, known as BRCA1 and BRCA2 increase the risk of breast cancer – a finding that became headline news when Angelina Jolie revealed she underwent a double mastectomy after genetic testing showed that she carried the BRCA1 gene. Mary-Claire King at the University of Washington and Mark Skolnick at the University of Utah are among the researchers who pioneered this work.

But it seems less likely that the prize would go to cancer research two years in a row.

What is becoming increasingly clear is the clear-cut divisions of chemistry, physics and physiology or medicine, have become blurred as techniques and understandings from one discipline are harnessed for another and new approaches and fields of research blossom.

Since it was first established in 1901, the Nobel prize in physiology or medicine has been awarded 109 times to 216 scientists.

Last year’s winners were James P Allison and Tasuku Honjo, who shared the prize for their work on cancer treatments which involve harnessing the body’s immune system.

You can read more about their work in this piece by my colleague Hannah Devlin: