Lab-grown blood given to people in world-first clinical trial
bbc.com
bbc.com
https://www.bristol.ac.uk/news/2022/november/labblood-study....
> "The lab-grown blood cells are all fresh, so the trial team expect them to perform better than a similar transfusion of standard donated red cells, which contains cells of varying ages. Additionally, if manufactured cells last longer in the body, patients who regularly need blood may not need transfusions as often. That would reduce iron overload from frequent blood transfusions, which can lead to serious complications."
They discuss automating the process, but the costs are still likely to be high as you'd need near-clean-room standards of sterility to avoid contamination problems - although that's also a problem with blood donation. Notably, some countries (incl USA, China) allow people to sell their blood, which tends to draw in poor and desperate people who may be more at risk of having transmissible diseases:
https://www.theatlantic.com/business/archive/2018/03/plasma-...
In the long run however, this might become the normal process. Bio-synthetic blood cell production has been talked about for over 20 years, it's cool to see it actually happening. (Synthetic immune system cells are also an interesting possibility, i.e. white blood cells).
The FDA does allows blood donation by paid blood donors. The blood must be labeled as from paid donors, but it is legal.
See https://www.statnews.com/2016/01/22/paid-plasma-not-blood/ for example...
https://www.cnn.com/2018/05/11/health/james-harrison-blood-d...
I just hope that blood donation doesn't go away as a result. There are both ethical and personal benefits - ethical, because it's a visceral experience of doing something good for society that most people can do, and with little effort; personal, because of potential health benefits from donating blood, see e.g. https://jamanetwork.com/journals/jamanetworkopen/fullarticle... .
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[^1]: We still have horses. So there is a chance some people will become recreational vampire-feeders and some people will adopt vampirism as a hobby. Fine, I won't judge.
Not very surprising, that is already a thing.
Like you have a population that must give blood by some means and regularly the various blood banks complain about a shortage and they never seem to be able to put two and two together ...
I think there is not actually regulatory ban. Last I looked into this, it was because of the conflict of interest - the FDA requires blood from donors with hemochromatosis be labeled as such.
And even that requirement can be worked around. See, for example, https://clinicalcenter.nih.gov/blooddonor/donationtypes/hemo.... Background, most centers charge for therapeutic phlebotomy but obviously not for volunteer blood donation. The exception is permissable if the center agrees to allow the patient's blood to be drawn for free, whether or not they would qualify as a blood donor.
The issue with "getting value" from donating is that people sometimes lie in order to be able to get that value. The downstream issues can be very painful - I have personally taken care of patients who got HIV or hepatitis from blood transfusion. I am pretty sure any of them would emphatically agree it is important to ensure the blood supply is as safe as possible.
So it can be done, but it has to be done carefully.
Are people in medical settings dying because of a lack of blood? It seems that unless you're in some exotic blood group you will likely find a compatible donor, and it is not clear as to severity of an imperfect match to rarer groups like the mentioned "Bombay" group.
The donation is to get antibodies.
Antigens are are the stimulus that causes the body to form antibodies.
We give the Rh- mom antibodies so they bind to antigens on the blood from baby; the idea being that "hiding" the antigens from mom's immune system will prevent her from making her own antibodies.
As I understand it, some hospitals offer payment for blood donations but if you want to get paid the most reliable options are probably pharmaceutical companies. By number of donors, both are probably eclipsed by the Red Cross though, which by its nature heavily relies on volunteer work.
What you can see from that is that a "Aufwandsentschädigung" of ~20€ is pretty common.
Pre-COVID the German Red Cross often would have a buffet lunch typically consisting of sandwiches and fruit for donors. Since then they seem to have moved to prepackaged lunches and branded giveaways. But never cash money.
World-changing if it works.
Lab grown blood would make this a bit more convenient, albeit at astronomical cost.
This process filters out stem cells from a blood donation and prevents them from becoming red blood cells long enough to multiply them significantly.
This is just me speaking “out loud”. Today, this would be quite expensive. I can see a future where the technology scales and the richer teams/individuals try this out.
Who is this line for? It's comically certain about this
"Digital will never replace film"
"Landlines will always be the majority of calls"
"Computers are cool, but will never replace typewriters"
People normally don't have a whole lot of stem cells in the peripheral circulation (if they did, they'd have leukemia). For the purpose of stem cell transplantation, the donor is given medications to mobilize stem cells from the bone marrow before collection. I'm sure they're present in very small numbers in the blood, and perhaps they could be cultured in the lab, but even stem cells become exhausted eventually. This is the innovation, probably.
I volunteered for an unstimulated collection when we were validating the process of stem cell collection at my work. I was at the upper limit of normal, but I technically had enough in CD34+ cells in my circulation to do a transplant even without stimulation, and I was in my early 30s at the time.
A single CD34+ cell can probably make a lot of RBCs. (Ok, to be pedantic, I'm not 100 percent sure they are really CD34+ cells, I was taught that CD34+ is a marker for myeloblasts, and the cell population you would probably want are the CD34- hematogones as they are self-replenishing. The article didn't seem to say either way).
oooof.... I knew some blood type was rare, but this is another level.
> Harrison, known as the “Man With the Golden Arm,” has donated blood nearly every week for 60 years. After all those donations, the 81-year-old Australian man “retired” Friday. The occasion marked the end of a monumental chapter. According to the Australian Red Cross Blood Service, he has helped saved the lives of more than 2.4 million Australian babies.
https://www.cnn.com/2018/05/11/health/james-harrison-blood-d...
In the main article, the rare blood type is because the the A, B, AB, 0 and RH+/RH- groups are due to 3 antigens (2^3=8). But there are like 20 or 25 more antigens that your blood may or may not have, so there are like 2^23 or 2^28 blood types. Some are very rare, some combinations are very rare. Most of the time the other 20 antigens don't produce a reaction that is so strong [1], so for most transfusions it's enough to classify using the A, B, and RH.
[1] Why? I'd really like to know why, or if I'm oversimplifying too much.
To answer [1] Why?: it's complicated.
There are more than 35 red blood cell groups (see https://www.science.org.au/curious/people-medicine/blood-typ... for a nice writeup). For each of those blood groups, there is more than one possible configuration of some protein or carbohydrate (something like more than one possible genetic sequence leading to more than one kind of molecule on the surface of the RBCs).
And, even with ABO, there can be infrequent variations that make things more complicated (see https://professionaleducation.blood.ca/en/transfusion/best-p... for more).
For the other blood groups, I think every case the groups were identified because a patient somewhere made an antibody, causing either a transfusion reaction (if not tested ahead of time) or, more likely, a positive (incompatible) reaction on in compatibility testing.
Each of those blood groups will have two or more versions. For example, there is the Kell blood group, which has two primary versions: you can express big K, little k, or both as Kell is a codominant system. Most people are homozygous little k (kk). When you are homozygous little k, you can make antibodies to big K (which is expressed on people who are Kk or KK). So, if you are homozygous little k, you are at risk of making antibodies on exposure to big K. Of course, not everyone is either big K or little k, that would be too simple. There are, I think, more than 20 variants of K out there...
More or less, each of those blood groups can cause antibody formation if you lack an antigen on the surface of those antibodies. In practice, the likelihood of an antigen causing antibody formation varies by antigen (the term there is "antigenic"). Also, the immunologic status of the recipient matters - obviously, someone who is immunosuppressed from an organ transplant may be less likely to form antibodies (that's the point of of the immunosuppression). Conversely, some people are more likely than most to form antibodies.
Also, it appears that the immune system is more likely to form antibodies in other blood groups if a person already has antibodies. In practice, there is a recommendation from NHLBI to match for C, E, and K in patients who are going to be transfused often to try to avoid forming new antibodies.
People 'naturally' form antibodies to A and to B antigens that they lack (I am group O and have both anti-A and anti-B antibodies). This is because they are exposed to those antigens in everyday life (the A and B antigen is found on some gut bacteria). And Rh-D is very immunogenic and clinically significant.
When we test blood prior to transfusion, we attempt to identify what antibodies the patient may have. If they have no unexpected antibodies, just honoring blood and Rh-D type is usually enough. If they have unexpected antibodies, we go through a complicated process to identify blood that lacks those antibodies to try to avoid a transfusion reaction.
(Now to modify that testing point, we know some antibodies are not clinically significant - that is, they do not cause significant transfusion reactions. So, we can, if we have to, give blood that is incompatible for clinically insignificant antibodies. We still try to provide blood negative for those antigens because we wouldn't find out this patient is the first to have a clinically significant version of the antibody. Also, the blood tests as incompatible with clinically insignificant antibodies, and we would prefer to give blood that tests as compatible).
Sorry this is rambling a bit - I have to take my daughter to school. Happy to expand/clarify/etc. when I can get back to it.
Source: I am a practicing physician board certified in "Blood Banking/Transfusion Medicine". My statements in this are still likely inaccurate, but hopefully in a useful way. I am not your lawyer, and I am not your physician.
Nice write up! I'm happy with the answer, but I'd not mind if you decide to expand it. Anyway, I think it would be more useful if you reply to other questions in this thread, but you already have been doing that. I'll upvote your comment, but this is one of the ocasiones when I'd like a x2 upvote.
Edit: If you don't mind a question: What do you [1] do with the people with big K that want to be blood donors? Ask them not to donate[2]? Do you tell them? Label the blood as big K and be more careful?
[1] "You" as the impersonal "you". I could have written "the system" or something more accurate.
[2] I guess they can donate. Otherwise they will be extremely unhappy.
[1,2]: Most people don't have antibodies, so big K+ blood is fine for most people (we worry about avoiding transfusing big-K positive blood into big-K negative people who will be transfused many times, such as somebody with sickle cell disease, it's not really a major issue for most people getting a rare transfusion).
So, K+ people are definitely allowed to donate. Also, there are people who have antibodies to little-k, and so they would actually need big-K homozygous blood.
When we need blood that is big-K negative, such as for a chronically transfused patient or one with antibodies to big-K, we try find units from people whose units were previously identified to be big-K negative. If they don't have any, the donor center can screen blood for them. We then verify compatibility with a crossmatch (reacting plasma from the patient with RBCs from the unit to make sure there is no reaction).
Remember there are lots of other blood types - big-K is one we have to match sometimes. Little-k is another. There are at least 70 altogether, so we can't really even try to match all of them. Even matching C, E, and K is straining the ability of the system to provide special antigen-negative blood.
It will be interesting to see what the long-term applications of lab-grown blood will be. I do worry about rare blood not being as available.
Many counties have laws about paying for blood donations and don’t allow donors to be compensated in any way, so they either need to take on the financial burden of flying to wherever their blood is needed or refusing to take on the financial burden and knowingly allowing someone to die.
It’s not fair to them and while most of these laws prevent darker forms of abuse of vulnerable demographics, they don’t really account for cases like donation of rare blood types.
Is that a real case or hypothetical? If real, I would like to explore further as it does seem rather inappropriate.
In my experience, the blood can be drawn locally and then sent to the recipient. That's also true for bone marrow & peripheral blood stem cell donations.
Source: I am a transfusion medicine physician.
- Some people don't know they need rare blood (because they didn't have the antibody at first, then found they had it later).
- Some people may donate blood to have it available for a need, then a need comes up (either themselves or someone else). At that point, the blood gets used up - what happens when the need is greater than the number of stored units?
- Some people may not be able to donate. We had a patient with something north of 9 antibodies who, due to sickle cell disease wasn't able to donate - (banking blood for long term storage requires freezing, which doesn't work with blood from patients with sickle cell disease).
Interesting. I've been expecting artificial blood for a while but hadn't considered this angle. Athletes and the wealthy with better performance blood!
I think the HN audience understands it at a level of "blood is red cells, white cells, and platelets", but that's really not the whole picture. Blood also has plasma which is composed of gas, nutrients, proteins, ions, and water. We can actually refine blood plasma down to a state where it's basically 100% safe even if someone with "bad blood" donated it.
These 4 different blood components all get seperated at the lab, frozen for storage, and turned into individual products which can be mixed+matched depending on medical need.
Don't get me wrong, growing red cells in a lab is awesome, but I don't see it the same way a lot of comments in this thread do (solving a storage issue, saving a lot of lives, etc).
I think the realistic applications of lab-grown-blood over the next 15 years will be closer to treating rare diseases or possibly rare blood types (some people exist outside the typical A, B, AB, O groupings). I don't see this fixing logistics or supply/demand issues in the next 15 years, especially with how highly regulated the blood supply is in any first world nation.
When given a single transfusion, a patient can usually be given blood based on the ABO and +/- part of the Rh groups alone, but there's more to the Rh system than most people know.
As well as the RHD gene, there's also the RHCE gene. The RHD gene can either be present (D, gives you positive blood) or not present (d, gives you negative blood), but the RHCE gene can give you one of four variations of the C, c, E and e antigens. When the two genes combine, you can have any of the following combinations: Dce, DCe, DcE, DCE, dce, dCe, dcE, dCE (which were given simplified names: Ro, R1, R2, Rz, r, r', r", ry respectively).
When patients have to be given regular blood transfusions, especially on a long-term basis, the blood they receive has to be more precisely matched. That's often why there's always a huge push for black donors - because many black people suffer from sickle cell anaemia, for which the treatment is regular blood transfusions, they need blood that better matches their own.
Just one more example: infants express a different set of hemes that have higher oxygen binding affinity. The switch from fetal to adult heme is being investigated as a potential cause of SIDS.
Obviously, custom tailored stuff is likely to take longer to develop, but it seems feasible.
There are lots of other systems though that add up to make your blood what it is. There's the Rhesus (Rh) system I mentioned before, but the main ones also include the MNS system, the P system, the Lutheran system, the Kell system, the Lewis system, the Duffy system, and the Kidd system. As far as I know, Kell is the third most immunogenic system after ABO and Rhesus.
This is when you need huge amounts of blood, and my guess is that it can be less perfect, when there is simply no other choice to save lives.
An inferior substitute is better than nothing
Maybe I’m parroting an incorrect bar top factoid, but isn’t it usually the case that they need the blood before the disaster? That when events like 9/11 occur and people rush to donate blood, it’s not actually going to do much for the immediate problem?
I mean if this can be scaled up to producing gallons an hour in the field then sure, but we're a ways away from that still.
Do you have a source on this? Given that many blood donation facilities still refuse many “risk groups”, which honestly always carried the stench of politics to me how arbitrarily they are selected, from donating blood?
To answer your direct question, in Toronto there was a doctor who wanted to open a pay-for-plasma clinic like they have in the US. In Canada, blood donations are not paid for which is one of the core reasons the supply is considered to be safer than other first world countries. The regulators shut it down and stopped him, not because of cleaning the plasma from the blood, but for policy reasons.
Back to the point about safe blood... Being a person who is allowed to donate blood is not related to this cleaning process but statistics about risk and also related to costs. So this is part of why there are no plasma clinics in Canada.
The blood donation is tested, but the tests don't catch everything. Really horrible diseases can test negative, which is why the process to donate blood includes an interview to categorize a high risk donor. This is why they don't let you donate blood when you have been living in europe for many years, have tattoos, multiple sexual partners, or had male-with-male sex. A lot of people hear about this and are totally outraged and jump to assumptions that the blood donation system is stuck in some anti-gay-rights 1900s puritan mindset, but that's not what's going on.
People regularly walk into blood donor clinics, lie about their high risk factors because they want to "prove a point", the tests for things like HIV can't always catch it all the time (especially in early stages; stages where there are no symptoms), and one blood donation could actually make it to several other people (like a baby, a motorcycle accident victim, and a surgery patient). It happens regularly enough that your nation's blood supply has a "lookback/traceback" program where they have 10-100 people who sit there all day working on cases and sending letters to people who received bad blood, and it can even come up 5+ years later when someone who donated blood in 2015 just got a diagnosis in 2020, all those people in the "bloodline" get notified, banned from the system, and advised to get tested too.
Doctors depend on multiple layers of checks to keep the blood supply clean, one of them is a statistical layer, one is a testing layer, one is the processing to keep the blood clean/safe, another is policy. Please don't interpret my point about plasma being highly cleanable to mean that all blood components in general can be safely received from the homeless.
You cannot sell whole blood donations though by law, that's all volunteer.
https://www.euractiv.com/section/health-consumers/news/us-bl...
I always cringe when I read sentences like that. "Always"? Really? How could you possibly know that?
Poor expression. (May be completely wrong too for all I know, but I think it's the expression that is rubbing you up the wrong way).