Nobel Prize in Physiology or Medicine: Body, heal thyself!

Photos of James P. Allison and Tasuku Honjo
James P. Allison (left) and Tasuku Honjo (right)
And the 2018 Nobel Prize in Physiology and Medicine goes to:

James P. Allison and Tasuku Honjo!

That link goes to the official announcement. You can also read the Nobel Assembly’s press release (och även på svenska bork bork bork!), or watch the award ceremony from the YouTube include at the end of this post.

The Nobel Prize in Physiology or Medicine 2018 was awarded jointly to James P. Allison and Tasuku Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation.”

or as I’d say:

The Nobel Prize in Physiology or Medicine 2018 was awarded jointly to James P. Allison and Tasuku Honjo “for finding a way to get your own immune system to fight cancer. Sometimes.”

That “sometimes” is important, of course, but their discoveries have led to better immunotherapy drugs, which are right now helping millions of people fight off cancer. These drugs are not a cure, and they don’t work for everyone, but there is no doubt that there are millions of people who would otherwise be dead, but who are alive thanks to Allison and Honjo’s work.

Neither of them set out to save lives in exactly this way. In the early 1990s, they were both basic researchers studying the human immune system – and if you need an argument for why basic research is important, there you go. Allison was at the University of California, Berkeley (he has since moved on to become the Executive Director of the MD Anderson Cancer Center in Houston, Texas), and Honjo was at Kyoto University in Japan. When they started this journey, they had never met, and I’m sure they had no idea they would both someday shake hands with the King of Sweden (watch how it works from the 2016 ceremony; the key handshake is at 31:53).

The immune system is incredibly complicated, and a wonder of human evolution. It is evolved to protect your body from foreign invaders like bacteria and viruses. Given that role, it would be natural to think of the immune system fighting cancer. But cancer cells aren’t invaders – they are your own cells gone rogue and growing uncontrollably. Normally, your immune system doesn’t even know that cancer is something to fight.

Here’s where the details get fuzzy for me, but people who understand this better than I do have come up with analogies that make sense to me, and I’ll pass them on to you.

When you look in detail at the how the cells of the immune system “know” when to attack, it turns out that proteins on the outer surface of the cell play an important role. These proteins “put on the brakes” and tell the cells to back off from fighting other cells. If you can find a way to keep the brakes from clamping down so strongly, you might give the immune system the power it needs to fight off cancer.

Allison studied a protein called CTLA-4, and Honjo studied a protein called PD-1. Their structures are very different, and they work differently – but the end result is the same suppression of the immune system. Interfering with the action of either of these proteins can sometimes result in the immune system attacking cancer cells.

Upper left: Activation of T cells requires that the T-cell receptor binds to structures on other immune cells recognized as ”non-self”. A protein functioning as a T-cell accelerator is also required for T cell activation. CTLA-4 functions as a brake on T cells that inhibits the function of the accelerator.

Lower left: Antibodies (green) against CTLA-4 block the function of the brake leading to activation of T cells and attack on cancer cells.

Upper right: PD-1 is another T-cell brake that inhibits T-cell activation.

Lower right: Antibodies against PD-1 inhibit the function of the brake leading to activation of T cells and highly efficient attack on cancer cells.

See the Nobel assembly press release and additional links for more information.

Suppressing CTLA-4 works better to treat some cancers, and suppressing PD-1 works better to treat some others – but the best results come from both. So it was only right that Allison and Honjo received the prize. Each one gets a medallion, personally handed to them by King Carl XVI Gustaf – and they evenly split the total prize money of 9 million Swedish kronor (about $1 million).

Allison and Honjo would have found out they won a few days before the public announcement. And like most winners, they weren’t there for the announcement; instead, they pick up their prizes at a white tie royal gala on December 10th. But still, imagine you are them, watching the livestream broadcast and hearing these words, first in Swedish:

Nobelförsamlingen vid Karolinska Institutet har idag beslutat att Nobelpriset i fysiologi eller medicin år 2018 skall delas lika mellan

James P. Allison och Tasuku Honjo

för deras upptäckt av cancerbehandling genom hämning av immunförsvarets bromsmekanismer.

and then in English:

The Nobel assembly at the Royal Catherine Institute has today decided to award the 2018 Nobel prize in Physiology or Medicine jointly to

James P. Allison and Tasuku Honjo

for their discovery of cancer therapy by inhibition of negative immune regulation.

But still, they know that they’re not the heroes in this story. Here’s what Honjo told the New York Times:

“When I’m thanked by patients who recover, I truly feel the significance of our research.”

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