Mimicking the cells that carry hemoglobin as a blood substitute | Hacker News Reader

Mimicking the cells that carry hemoglobin as a blood substitute

science.org

117 pointsrbanffy58 comments

Reminds me of something I read in one of the Kurzweil books years ago: having nano-blood delivering enough oxygen to stay underwater for 8 hours. Things like that.

The (funny to me) idea that also came from that was that we can remove our digestive systems, because "eating mainly for nutrients" turns into "eating just for enjoyment", and we have a tray in our stomachs that we tap out to empty the chewed food.

At that point, why not just let Neuralink tickle the right brain regions - seems more sensible than literally stuffing food into your mouth. Also seems closer to being achievable than nano blood.

Heroin just doesn't have the same experience as a meal.

Same reason we might choose to have sex instead of masturbate. Masturbating may be faster and easier. But sex is fun and you can do it with friends.

Nano specifics aside, we can already feed people intravenously. We do not yet know how to electrically trick the brain in any meaningful and safe way.

I might also be crossing the streams on partially remembered text, but I believe the nano component of the blood was about engineered hemoglobin that was a more effective oxygen carrier, not glucose.

There was a story here a few months ago from a guy who has severe Crohn's disease, with his gut fused to some other organ I can't recall in a way that prevented eating at all. He was able to survive via a direct infusion of nutrients into his blood, but the viscosity of the subtance would make it far too painful to inject by any normal IV route, so he needed a catheter inserted straight into his vena cava. And though this provided all the sustenance his body required for energy, because hunger hormones are produced in the gut, not eating will leave you perpetually hungry even if you actually have all the energy you need. The very existence of obesity should probably make it obvious this is possible, but removing our digestive systems may have unintended consequences. The way this guy described his experiences sounded like a pretty miserable existence.

I knew it had to into a major vein, but I didn't know about the hunger issue with TPN.

Yeah i mean realistically just the port to “a tray in our stomachs” sounds like a nightmare. How do you make a port big enough to take the tray out? How do you prevent it from always getting infected? What do you do with the core muscles where the tray port goes? How do you clean the pouch where the tray resides? How will you make the tray-escophagus interface leak proof? What if someone with the tray in their stomach wants to do sports, or is in an accident? When they are shocked around will the tray mechanism tear their flesh and organs? Will the tray accomodate body shape changes during a pregnancy? Or changes due to old age? How will people know that their tray is full? Will they just start choking? How big the tray has to be to accomodate a family meal, but also be small enough to not feel as a burden during everyday activities?

The truth is that our body is marvelously complex, and dynamically adjusts to many challenges. It does this so seamlesly that we don’t even notice. That is why people come up with ridiculous ideas like this because they are not consciously aware of how amazing their body is at taking care of the job of keeping them alive.

The closest to this tray idea in reality is an ileostomy. And while it is better than dying, it has many risks and negative consequences. The idea that otherwise healthy individuals would willingly under go such a modification to their bodies is ludicrous.

Look up colostomy bags. It’s not a lifestyle I think many people would choose on a whim

Not sure why you think someone mentioning an ileostomy would be unfamiliar with colostomy bags.

Oh, i think Rumudiez meant it as a general recommendation to everyone who might be interested to learn more. Not specifically to me. Or at least that makes the most sense so i choose that interpretation.

But yeah, there is a lot of stories about patients with bad outcomes with colostomy bags. It sure beats dying of course. As a general rule of thumb: every time you cut into a human there is a high chance of things going wrong. The more you are changing after you cut into them the more likely and more severe the sideffects will be. (Very rough approximation of course.)

This is something i constantly think about cyborgs. They are a a staple of scifis, and usually portraied as stronger and faster than regular humans. But every cyborg with lets say a cybernetic arm would be medically an amputee. Every amputee can tell you that stumps suck. They get infected, or get pressure sores, or their skin gets irritated, etc etc unless you are treating them just right, and even then sometimes they hurt when you did everything right. How would you even grow metal and muscle/skin together without the meat constantly pulling away and getting infected? That is the real scifi not the brain-computer interface.

Iirc serotonin is also found in the gut.

Serotonin is found all over the body: Blood, digestive system, skin, bones, lungs.

It doesn't migrate all over, though. Serotonin in the gut doesn't go into your brain like many people assume.

There has been research suggesting that the vagus nerve might carry serotonin from the gut to the brain:

https://www.psychologytoday.com/us/blog/the-athletes-way/201...

I'd note that this is a five year old article and I haven't heard of any followups. And the article itself may be misinterpreting the underlying actual research, which suggests that it's more about SSRIs:

https://www.nature.com/articles/s41598-019-50807-8

Still, I thought it was worth mentioning.

In recent years the gut-brain axis [1] has been solidified as both real, causal, and critical. So just removing your gut would probably have severe consequences beyond just the more straight forward ones.

[1] - https://en.wikipedia.org/wiki/Gut%E2%80%93brain_axis

The whole concept sounds a bit wooish, and the Wiki article doesn't read like you'd expect it from a description of "real, casual, and critical" concept in medicine. Is there any other real set of factors that would make this particular "axis" special, vs. a pair or triple of any other organs that happen to be spaced far apart in the body?

I'm not sure how you get that conclusion or questions from the article:

---

Chemicals released by the gut microbiome can influence brain development, starting from birth. A review from 2015 states that the gut microbiome influences the central nervous system by "regulating brain chemistry and influencing neuro-endocrine systems associated with stress response, anxiety and memory function".[4] The gut, sometimes referred to as the "second brain", may use the same type of neural network as the CNS, suggesting why it could have a role in brain function and mental health.[5]

---

"can", "may", "suggesting" - those are words used when you want to claim something on a hunch, or otherwise without solid evidence in favor.

It's because it's a very new field. Few people would have ever thought diseases of the 'mind' could be related to the gut biome, so people are still actively researching exactly what is causing what. It's not because there's any question of whether this is an issue at all.

This is also an extremely important discovery, but it will have profound implications on modern health and diets. Everything from glyphosate to fake sugars has been argued to be harmless because we thought that they were largely inert. In reality they are having substantial impacts on the gut biome - the potential implications of this cannot be overstated, and so shooting wild and fast would be poorly advised.

The guts role in mental health is well established. There are literally hundreds of studies on this. Here's a summary - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10384867/

This is basically how refined sugar makes you obese. It goes straight into your blood.

Without grain mills to prechew the food into fine dust particles aka flour, it would be practically impossible to overdose on sugar.

Anyone that has done a water fast for several days can vouch that you are not perpetually hungry. On a long fast the stomach basically shuts down. Hunger pangs do occur, but they subside after an hour or so. In my experience, three or four days or so into the fast the hunger pangs no longer occur unless you start thinking of eating. I've read that once fat reserves become exhausted then hunger pangs come back with an vengeance, as this is true starvation.

Just this morning I was wondering if one could cure their hypertension by getting an artificial heart to circulate their blood more efficiently.

I mean sure you could also treat with weight loss and regular exercise, but it's a fun thought experiment.

Hypertension is not caused by the heart pumping too well, so this would not work for the purpose of curing hypertension. But if you could invent a durable heart replacement therapy, you'd save a lot of lives.

See, ECMO. Although it can save one's life where perfusion is otherwise inadequate, it is extremely difficult to initiate and maintain.

If the pressures in a system are too high (mechanical or biological) the pump is usually not the culprit.

It's not just the food it's flushing out.

An earlier class of candidate blood substitutes tried to replace hemoglobin with oxygen-bearing chemicals called perfluorocarbons, widely used in refrigerants and fire extinguishers. One was even approved by the U.S. Food and Drug Administration (FDA) in 1989 for use in surgeries. But the complexities of making and administering it, along with various side effects, undermined that product, which was ultimately withdrawn.

I was old enough to remember reading about this in the news when it was still news:

https://en.wikipedia.org/wiki/Blood_substitute#Perfluorocarb...

I am very familiar with the company KaloCyte that developed Erythromer. Great technology, great people, good non-dilutive funding, and they are pursuing a Series A.

Another solution; from "Scientists Find a Surprising Way to Transform A and B Blood Types Into Universal Blood" (2024) https://singularityhub.com/2024/04/29/scientists-find-a-surp... :

> Let’s Talk ABO+: When tested in clinical trials, converted blood has raised safety concerns. Even when removing A or B antigens completely from donated blood, small hints from earlier studies found an immune mismatch between the transformed donor blood and the recipient. In other words, the engineered O blood sometimes still triggered an immune response.

How does it compare with xenotransfusion from genetically modified pigs?

https://en.wikipedia.org/wiki/Xenotransfusion#Ethical_argume...

I guess the extended shelf life and more compatibility might be some of the pros of synthetic blood.

In terms of logistics, you wouldn’t need to raise genetically modified pigs. You could potentially scale production on demand and it doesn’t require the environmental footprint of livestock.

“An earlier class of candidate blood substitutes tried to replace hemoglobin with oxygen-bearing chemicals called perfluorocarbons…”

Great idea back then in the 80s the forever blood.

A friend of mine did work in this space back in 90s and early 2000s ("Synthetic Blood International", later renamed to "Oxygen Biotherapeutics", now "Tenax Therapeutics") based on work done by Dr. Leland Clark[0]. It sounded like really interesting stuff-- very sci-fi. They were using a fluorocarbon[1]. It made me think of The Abyss.

They had a ton of interest from the Department of Defense.

Edit:

Oh, holy crap. I didn't realize Dr. Clark actually did the "rat breathing liquid"[2] thing for real! (It sounds cruel, to be sure...)

(Also, Dr. Clark had some serious Isaac Asimov sideburns going on...)

[0] https://en.wikipedia.org/wiki/Leland_Clark

[1] https://patents.google.com/patent/US4289499A/en

[2] https://cen.acs.org/articles/83/i13/LELAND-CLARK.html

This is exactly the kind of bets the government should make. However I was expecting it to be a research project not a startup. If they already have a product what do they need the funding for? I mean, they already know if it works or not.

Running clinical trials is expensive, I imagine.

The article says they've only done testing in animals so far.

There is a huge cost associated with moving from a proof of concept to a commercially viable product. People often severely underestimate the effort involved in this.

This is another company making the same product, they call it OxyBridge https://virtechbio.com/

I have a very very limited understanding of biology because I never took anything other than a highschool class.

Is hemoglobin critical just because of its ability to deliver oxygen to cells? If so could a synthetic replacement for hemoglobin be developed that could replace to function of hemoglobin in the human body? Or is this a issue of chemical structure where our body would reject non hemoglobin molecular structures attempting to deliver oxygen?

Also not a biologist, but the the body actively rejects all things it considers foreign.

Consider that we have A, B, O, and AB with both positive and negative variants as the most common blood types.

Unless you're O+, you will reject the blood causing a massive immune response.

Having the something that works like blood, the body won't reject, and has a shelf life longer than actual blood is hard.

AB+ is the universal recipient of red blood cells, O- is the universal donor. It is reverse for plasma.

The blood rejection is reaction between blood plasma (with cells produced by your immune system) and red blood cells.

And in addition, and TFA alludes to this, each time a person receives a transfusion there is a chance that their immune system will generate antibodies to it. That might not impact the transfusion at the time, but can make the recipient much harder to match for in the future.

My partner has had severe anemia, and because of a prior transfusion went from being an easy match (A+) to a being a 1 in a thousand match. The last time she needed blood it took 12 hours to locate and transport suitable blood.

If you read the literature on survival rates for people with very low hemoglobin level, it's all based on post operative recovery (or otherwise) of Jehovah Witnesses

Mechanically, all hemoglobin does is take up an oxygen molecule when in an oxygen rich environment, and releases it in a CO2 rich environment. CO2 just dissolves into the bulk fluid of the blood and diffuses out in the lungs, it is not carried by hemoglobin. However, hemoglobin can bind to CO carbon monoxide, and it can't let go of it. The hemoglobin molecule is effectively dead and useless.

If you had a molecule which functions in a similar way, it'd probably work in blood. The real trick is getting it to release the oxygen in the presence of CO2.

Immune response is a different matter that I don't know enough about to weigh in on. I'd assume there's ways around it. Possibly immunosuppressor drugs for the (hopefully) short time you're on the synthetic blood.

It needs to collect and release CO2 and O2 at the correct times and pressures. It needs to not be poisonous or toxic. It needs to not be quickly processed by the liver or kidneys, but processed enough that it doesn’t build up and become toxic. It needs to be evenly distributable via blood. It needs to not get into places where it shouldn’t be. It needs to not stick to things like artery walls. It needs to not cause an immune or inflammatory response. It needs to not cause you to clot or bleed out. And it needs to do all this and more in disparate parts of the body in varying chemical environments.

The list of requirements is very long. Out body evolved alongside hemoglobin and finding a replacement that fits the bill perfectly is very difficult.

Also hemoglobin appears in other places. Free oxygen is actually toxic in large amounts and will oxidize random things. Hemoglobin is used as an antioxidant to collect excess oxygen.

Oxygen has very low solubility in water, which decreases with temperature. Haemoglobin binds iron atoms, which bind oxygen molecules, allowing storage of oxygen by the protein. IIRC, this increases the oxygen carrying capacity of blood approximately 60 to 70 times.

I did the math and unless I made a mistake, this $46M is a smaller 'bet' by percentage of income than my yearly $6 bet on the lottery.

I’m very confident that if you could sell your blood on the free market and avoid donation scamming centers, which literally are taking your blood for free (time compensation) and sell it, partly to the Pharma industry for profit, the problem of not enough blood would be solved quickly.

But blood counts as organs and organ trade is prohibited.

Actually, selling blood is legal in the US under the same law that legalises selling plasma. But hospitals won't use sold blood to inject into patients because even if it goes through testing for diseases, they consider it too high a risk.

https://www.statnews.com/2016/01/22/paid-plasma-not-blood/

Ohh that’s good to know thanks. Here in Germany and probably Europe it’s not allowed not even the plasma part.

We will need this to rinse all the PFAS out of our blood circulations.

Is that related to what that Humacyte company was doing? I remember seeing it show up in the various politician stock trade trackers that follow Pelosi, Tuberville, etc.

> Allan Doctor, a bespectacled 61-year-old physician-researcher at the University of Maryland (UMD) School of Medicine

Not at all the point, but I get way too much enjoyment out of the fact that this person is Dr. Doctor. I hope he occasionally insists that people call him that and then quietly hums the song by the Thompson Twins.

Nominative determinism strikes again.

In college the course on Maxwell's equations was taught by Dr. Lord. Every time I walked in to class I thought "Let there be light"

Reminiscent of a Doctor Strange scene:

https://youtu.be/ewFg5wUvkGI?si=bxKgLot0iqwYpLx3

When I was a little boy, the librarian at our small local branch was named Virginia Read.

In the late 70's and early 80's, there were two doctors who shared an office in San Luis Obispo, CA. Their names were Dr. Herten and Dr. Payne.

Was reading yesterday about pioneering female ad-exec Mary Wells Lawrence.

When she was passed up for a promotion, she started her own agency, whose treasurer was "Richard Rich".

I still can't get my head around the fact that one can earn a doctorate in nursing.

Therefore: Dr. Nurse Doctor

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