Scientists Just Made A Stunning Biological Discovery

Sometimes something happens that takes your breath away, in a good way.

Those who read my stuff know I’m not someone who gets carried away by optimism, to say the least.

But a new paper by scientists at Columbia has blown me away.

Researchers have made a discovery, which, if it holds up, has the potential to transform treatments for autoimmune diseases and post-viral illness like long covid and myalgic encephalomyelitis.

Because these scientists say they have found the dial in the brain that controls inflammation and the body’s immune response.

In their own words, they believe they have found “the master regulator.”

The summary of the paper in Nature called it a black-swan type event.

The researchers say “it's a whole layer of biology we haven’t even anticipated.”

So what did they find and how did they find it?

They found that neurons in a part of the brain known as the caudal Nucleus of the Solitary Tract (cNST) fire, or misfire, to produce a balanced or dysregulated immune and inflammatory response.

They found, in their own words, “a new brain circuit.”

A circuit that determines how your body responds to infection. A response that determines if you live, die, or develop a post-viral or autoimmune condition.

Let’s delve in to the detail.

The cNST is the major first stop for information being sent from the body to the brain, information carried to the brain by the vagus nerve, the longest cranial nerve in the body connecting the gut to the brain.

When immune cells somewhere in the body are activated, by infection or injury, the vagus nerve transmits this information to the cNST.

The cNST first processes, then passes on this information to cells throughout the body, telling it how to respond to infection. Should it produce a small amount of inflammation to knock out the invader? A large dose?

To make the discovery, researchers gave mice a bacterial compound that stimulated an immune response in the body of mice and activated neurons in the cNST.

On witnessing the activation, the researchers reckoned that if they blocked the neurons in the cNST from sensing the information being sent by the vagus nerve about the infection, it would affect the immune response.

It did.

Inhibiting the neurons “resulted in a dramatic increase in the pro-inflammatory response, and a concomitant decrease of the anti-inflammatory response.”

The researchers called this a “remarkable” discovery.

Levels of pro-inflammatory cytokines rose to over 300% compared to the levels in mice where the immune response was activated but the cNST neurons weren’t preventing from sensing the information coming from the vagus nerve.

The anti-inflammatory response was also affected, with the anti-inflammatory component of the response 140 times lower. The researchers called it a “profound” reduction.

Stopping the neurons from responding to the signals sent by the vagus nerve created, in words of the researchers, “a run-away, out-of-control inflammatory response.”

They said the results suggest the cNST functions as a “homeostatic neural control of peripheral immune responses.”

The cNST as the control knob for the immune system.

The role of the vagus nerve was also key.

Long postulated as critical to the immune system, blocking the ability of the vagus nerve to transfer information to the cNST meant the neurons didn’t respond to the activation of the immune cells elsewhere in the body.

This confirms the vagus nerve as a critical component of the immune system, in essence the telephone line that enables the body to talk to the brain to tell it to activate an inflammatory response.

Then, rather than suppressing the neurons, they tried artificially activating them to see if it would produce the opposite response – a substantially reduced pro-inflammatory response and a substantially increased anti-inflammatory response.

It did.

“These experiments demonstrate that modulating the activity of these brainstem neurons can bidirectionally regulate peripheral inflammation.”

Bidirectionally? Yep.

“Anti-inflammatory and pro-inflammatory cytokines activate two discrete non-overlapping populations of vagal sensory neurons.”

There are two knobs!

One dials up inflammation, one dials it down.

“One line carries anti-inflammatory signals and….enhances the anti-inflammatory response and helps suppress the pro-inflammatory state. The other responds to pro-inflammatory signals and helps tune down the pro-inflammatory response.”

This makes it easy to visualise how dysregulated immune responses happen and how they can provoke ongoing health issues: you’re infected by a virus or pathogen, the two dials start moving in response to the information sent by the vagus nerve, they start rotating to find the right combination to unlock the sweet spot in the immune response. Up, down, up, down, searching, searching.

Then instead of aligning equally on 5, unlocking an optimal immune response, they get stuck. Stuck in the wrong locations.

One dial is up at 9, one is down at 2.

The immune response has been compromised.

Inflammatory molecules are now being pumped out to the wrong locations. Maybe parts of your body that actually need some inflammation aren’t getting enough.

Things are all out of whack. And they stay out of whack.

Some people’s dials might be a little out of sync, others a long way out of sync.

Hence mild post viral issues or severe post viral issues. Quick onset autoimmune disease, slower onset.

It’s also important to note that the researchers were focused on the innate immune system, not the adaptive immune system. The innate immune system is the body’s first line of defence that goes into action on the initial identification of a pathogen. The adaptive immune system is the body’s targeted response to a pathogen that it has previously encountered and the element of the immune response that provides longer-lasting protection against the worst that pathogens can do.

If the innate immune system doesn’t set the dials in the correct position, after infection or even vaccination, the adaptive immune system can’t function properly to recognise the pathogen when it visits again.

Maybe this is why those with long covid are more prone to reinfections?

Inflammatory dials getting stuck in the wrong place also seem to me like a plausible mechanism for those with vaccine-induced long-covid-type illness. The innate immune system doesn’t line up the dials on 5, doesn’t unlock the intended immune response.

This is also why every infection, especially with a full-body virus like SarsCov2 that can access so many organs, is such a roll of the dice. We have to bank on those dials lining up on the immune sweet spot every single time.

Now, the exciting thing is that once they had made these discoveries, the researchers played around with the dials, with this newly-found neuronal system.

And they restored dysregulated immune balance! (In mice)

For one experiment, they artificially activated the neuronal system in mice then injected them with a lethal dose of the bacterial molecule. Despite this intense immune challenge, 90% of the mice survived.

Other mice were injected with a compound to mimic the inflammatory bowel disease ulcerative colitis. The mice in whom the neuronal system had been artificially activated were all protected against disease development, whereas the control group all progressed to disease.

The scientists took serious steps to validate that what they were concluding was correct, including injecting the mice with a variety of viral compounds to confirm transfer of signals from the vagus nerve to cNST neurons, and even the removal of the vagus nerve in mice (I know…).

Now for the caveats.

The obvious one: the discovery and experiments were undertaken in mice.

Although humans and mice share many of the same genes, they don’t always function similarly in different cells.

And while human brains and mouse brains do have roughly the same number of cell types - around 75, the type of cell that senses serotonin in mice is different from the type of cell that senses serotonin in humans. Microglia, the brain’s immune cells, can also differ in their gene behaviour.

This being said, mouse models have helped develop treatments for numerous diseases, including sickle cell disease, in recent years.

Another caveat: we live in capitalism.

This means that funding for further research can’t be guaranteed, that monopoly control on therapies and treatments is likely, and that inequitable global access due to profiteering is likely, as we’ve seen with the covid vaccines.

But overall, this discovery should blow us away.

It is just a first, preliminary step, the results will need to be replicated and lots more research on other pathways influenced by this new-found brain circuit will need to be undertaken.

Of course we need to know, hopefully sooner rather than later, if the system in humans works as it does in mice.

But in a world devoid of good news, there is no need to downplay this: it’s huge.