Biopure was a company doing something similar in the US. They imploded in the early 2000s, but they had created an "oxygen therapeutic" (blood substitute) by isolating hemoglobin based oxygen carrying molecules FROM COW BLOOD!
The fact that they weren't using whole red blood cells meant the product was typeless, room temp stable, and better at perfusing around arterial blockages and into tissue since the molecules were so small.
Unfortunately, the company was kind of a mess. They managed to get licensed for sale in South Africa, and in the US for the veterinary product, but never managed FDA approval. It's a shame. Everyone could see the promise of the product, and it really actually worked, but they just couldn't seem to make the business viable.
Edit: When I say they imploded, I really mean it. They got prosecuted for misleading statements to investors about the state of US clinical trials, and the legal proceedings became farcical.
"On March 11, 2009 [Senior VP] Howard Richman pleaded guilty in U.S. District Court and admitted he had instructed his lawyers to tell a judge he was gravely ill with colon cancer. He also admitted to posing as his doctor in a phone call with his lawyer so that she would tell the judge that his cancer had spread and that he was undergoing chemotherapy."
That guys was sentenced to 3 years in prison. Here's hoping this new blood substitute has a happier outcome!
This class of products is room temperatures stable, and typeless, and it increases oxygen carrying capacity basically immediately. You can imagine how useful that would be for something like a Tour De France team. Keep a half dozen units of fake blood in your team bus. No special equipment. No rigorous temp control. You can give any unit to any one of your athletes without worrying about compatibility. You can administer it on race day, eliminating any chance of being caught in the runup to your event.
Obviously Biopure condemned off-label use of their product for blood doping, but behind closed doors they were super proud that it was seen as effective enough to be called out by name by WADA. No publicity is bad publicity and all that.
What happens to the IP when this happens? If the product works but wasn't supported by the right company how does it not get picked up by someone more competent?
You wait 20 years, then work on it once the patents have expired. This happens to lots of technologies, which aren't properly license while under patent protection, then take off once the protection expires.
Probably the most well known is animated GIFs, which had some popularity in early web pages, but quickly died off, then had a huge upsurge after the patent expired in the 2000's, when anyone could add animated GIF outputs to any program or web service, without licensing.
The controversy around that one was not only that it did not work as well as it could (more patients had heart attacks than with saline), but that it was trialled on trauma patients without their explicit consent - implied consent was used, and people in trial areas could opt-out by requesting a bracelet. Problematic to say the least...
The artificial blood is created by extracting hemoglobin — a protein containing iron that facilitates the transportation of oxygen in red blood cells — from expired donor blood. It is then encased in a protective shell to create stable, virus-free artificial red blood cells. As these artificial cells have no blood type, there is no need for compatibility testing.
Blood-derived synthetic. Still cool, but continues to require a pool of donors.
Apparently their first target is soon-to-expire donor blood erythrocytes — which makes this essentially a (pretty major) scalability improvement in how far existing donor blood goes.
However, that being said: hemoglobin’s just a protein. Recombinant hemoglobin isn’t overly challenging to produce — we do it already. (Currently mostly animal hemoglobin, for vegan meat — but it’s no different to produce human hemoglobin.) We don’t bother with synthesizing human hemoglobin because there’s (until now) no way to go from having a protein to having useful cells serving an erythrocytic function. This research changes that — and so will strongly motivate demand for such production. I would bet money that, 5–10 years out, you’ll be able to buy bags — even drums — of recombinant human hemoglobin from any biopharma supplier.
Yes, I was also surprised that freaking plants have hemoglobin. But apparently, legume plants use it to create the oxygen-depleted environment for nitrogen fixing bacteria to work.
My understanding is a huge issue with blood donation is expiry, and therefore the need for consistent year-round donation - when a disaster occurs there's often a spike in donations but the surplus gets thrown away. A mechanism that can make use of expired blood that works for all blood types and extends the shelf life seems extremely valuable.
“No need for compatibility testing” – I think that’s a really important feature. Not everyone can accept all types of blood. It becomes a real challenge when a person requires constant transfusions and can only accept one specific blood type.
Seems as if the long shelf life vs 42 days for human blood is the biggest advantage. You can use blood about to expire to make this, and it will last 2-5 years more
Interesting to see. There's been some other efforts in this space, from blood products derived to chemically derived (e.g. perflurocarbons, which carry many multiples of what hemoglobin can carry, oxygen-wise).
There's definitely a need for a safe, shelf stable blood substitute.
Though, I'd argue that this isn't artificial blood, it's artificially replacing only the oxygen carrying role of blood -- there's nothing in this product that is producing clotting, fighting disease, managing hormones, fueling cells, etc. Still, excited to see this progress, transfusions are still a risky bet, and having something that can provide at least the O2 capacity in a safer package is very welcome.
You can see my top-level comment for more context, but I've seen other products in this space called "oxygen therapeutics" for exactly this reason. They're not really blood, they're an oxygen delivery system. It seemed like a pedantic distinction when I first heard the term, but I think you make some good points about why the distinction is meaningful.
In your link they have only done tests on rabbits.
In this post they have already done some tests on humans and are now increasing the dosage since March.
> Small-scale studies began in 2022. Three groups of four healthy male volunteers aged 20 to 50 received a single intravenous injection of hemoglobin vesicles — artificial oxygen carriers that mimic the structure of red blood cells — in increasing amounts, up to 100 milliliters. While some participants experienced mild side effects, there were no significant changes in vital signs, including blood pressure. Building on that success, Sakai announced that his team was accelerating the process last July. In March, it started administering between 100 and 400 milliliters of the artificial blood cell solution to volunteers.
> If no side effects are confirmed, the trial will shift to examining the treatment’s efficacy and safety. It aims to put the artificial red blood cells into practical use by around 2030.
The fact that they weren't using whole red blood cells meant the product was typeless, room temp stable, and better at perfusing around arterial blockages and into tissue since the molecules were so small.
Unfortunately, the company was kind of a mess. They managed to get licensed for sale in South Africa, and in the US for the veterinary product, but never managed FDA approval. It's a shame. Everyone could see the promise of the product, and it really actually worked, but they just couldn't seem to make the business viable.
https://en.wikipedia.org/wiki/Biopure
Edit: When I say they imploded, I really mean it. They got prosecuted for misleading statements to investors about the state of US clinical trials, and the legal proceedings became farcical.
"On March 11, 2009 [Senior VP] Howard Richman pleaded guilty in U.S. District Court and admitted he had instructed his lawyers to tell a judge he was gravely ill with colon cancer. He also admitted to posing as his doctor in a phone call with his lawyer so that she would tell the judge that his cancer had spread and that he was undergoing chemotherapy."
That guys was sentenced to 3 years in prison. Here's hoping this new blood substitute has a happier outcome!
https://www.wada-ama.org/en/resources/scientific-research/de...
This class of products is room temperatures stable, and typeless, and it increases oxygen carrying capacity basically immediately. You can imagine how useful that would be for something like a Tour De France team. Keep a half dozen units of fake blood in your team bus. No special equipment. No rigorous temp control. You can give any unit to any one of your athletes without worrying about compatibility. You can administer it on race day, eliminating any chance of being caught in the runup to your event.
Obviously Biopure condemned off-label use of their product for blood doping, but behind closed doors they were super proud that it was seen as effective enough to be called out by name by WADA. No publicity is bad publicity and all that.
Probably the most well known is animated GIFs, which had some popularity in early web pages, but quickly died off, then had a huge upsurge after the patent expired in the 2000's, when anyone could add animated GIF outputs to any program or web service, without licensing.
There was another one in the US called "PolyHeme" which did not go well - https://en.wikipedia.org/?title=PolyHeme
The controversy around that one was not only that it did not work as well as it could (more patients had heart attacks than with saline), but that it was trialled on trauma patients without their explicit consent - implied consent was used, and people in trial areas could opt-out by requesting a bracelet. Problematic to say the least...
However, that being said: hemoglobin’s just a protein. Recombinant hemoglobin isn’t overly challenging to produce — we do it already. (Currently mostly animal hemoglobin, for vegan meat — but it’s no different to produce human hemoglobin.) We don’t bother with synthesizing human hemoglobin because there’s (until now) no way to go from having a protein to having useful cells serving an erythrocytic function. This research changes that — and so will strongly motivate demand for such production. I would bet money that, 5–10 years out, you’ll be able to buy bags — even drums — of recombinant human hemoglobin from any biopharma supplier.
Nope. They're making _plant_ hemoglobin ( https://en.wikipedia.org/wiki/Leghemoglobin ) to stay vegan.
Yes, I was also surprised that freaking plants have hemoglobin. But apparently, legume plants use it to create the oxygen-depleted environment for nitrogen fixing bacteria to work.
I wonder if the recently dead qualify.
There's definitely a need for a safe, shelf stable blood substitute.
Though, I'd argue that this isn't artificial blood, it's artificially replacing only the oxygen carrying role of blood -- there's nothing in this product that is producing clotting, fighting disease, managing hormones, fueling cells, etc. Still, excited to see this progress, transfusions are still a risky bet, and having something that can provide at least the O2 capacity in a safer package is very welcome.
So what's different this time?
(Upon further examination, the 2019 team at the National Defense Medical College also had Dr Hiromi Sakai. So why is this news now?)
In this post they have already done some tests on humans and are now increasing the dosage since March.
> Small-scale studies began in 2022. Three groups of four healthy male volunteers aged 20 to 50 received a single intravenous injection of hemoglobin vesicles — artificial oxygen carriers that mimic the structure of red blood cells — in increasing amounts, up to 100 milliliters. While some participants experienced mild side effects, there were no significant changes in vital signs, including blood pressure. Building on that success, Sakai announced that his team was accelerating the process last July. In March, it started administering between 100 and 400 milliliters of the artificial blood cell solution to volunteers.
> If no side effects are confirmed, the trial will shift to examining the treatment’s efficacy and safety. It aims to put the artificial red blood cells into practical use by around 2030.
more on what I assume is their hemoglobin prep process: https://pubmed.ncbi.nlm.nih.gov/30715862/
and if you want to make your own liposomes, instructions here https://pmc.ncbi.nlm.nih.gov/articles/PMC8234105/