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Biotech Medicine

Scientists Make Artificial Protein Mimic Blood 94

Posted by timothy from the this-is-cool-stuff dept.
Al writes "Researchers at the University of Pennsylvania have created a protein that can carry and deliver oxygen — a useful step towards developing artificial blood. This would avoid the problems involved with donor blood — contamination, limited storage, and short supply — and lead to easier and faster blood transfusions on the battlefield and in trauma cases. The Penn researchers used three amino acids to make a four-helix columned protein structure put a smaller structure, called a heme, inside it. The heme is a large flat molecule that has an iron atom at its center, which oxygen binds to. The researchers also made the protein structure flexible, so that it can open to receive the oxygen and close again without letting any water in. They did this by linking together the helical columns with loops to restrict their motions, giving the final structure a candelabra shape."
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Scientists Make Artificial Protein Mimic Blood More

Scientists Make Artificial Protein Mimic Blood

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  • Finally (Score:3, Funny)

    by kandela ( 835710 ) on Tuesday March 31, 2009 @10:23AM (#27402633)
    ... Vampires and Humans can live together in peace.
  • I, for one, welcome the advent of artificial blood. It is my hope that when the robotic overlords take over that they will see me as their brethren, and not as an outdated human. Pumping myself full of artificial blood brings me one step closer to that goal.

  • Various Questions (Score:5, Insightful)

    by D Ninja ( 825055 ) on Tuesday March 31, 2009 @10:36AM (#27402809)

    This sounds extremely cool, and very useful.

    Some questions I would have is:

    1. How much of this 'blood' can a human take before his/her body rejects it (if it ever does)?

    2. How quick and expensive is it to create, say, a liter of blood?

    3. Is there any reason that this blood wouldn't be able to combine with certain blood-types?

    Either way, this is some great research that UPenn is doing. I'm excited to see where this goes.

    • Re:Various Questions (Score:5, Insightful)

      by Vectronic ( 1221470 ) on Tuesday March 31, 2009 @10:43AM (#27402919)

      4. Does this break down into any sort of toxin?
      5. Can kidneys, livers and pancreases deal with this?
      6. How do common diseases or viruses interact with it.

      Personally, I think those would rank #1, 2 and 3... but to each their own.

      • Re:Various Questions (Score:5, Insightful)

        by Cillian ( 1003268 ) on Tuesday March 31, 2009 @11:09AM (#27403303) Homepage
        Well, I'd preface this by pointing out that they aren't yet creating blood, just a single component that mimics a single property of real blood. Proper blood does a whole lot more than just carry oxygen. To copy real blood, the full mixture would need the correct solubility of CO2, some sort of clotting system, and a whole lot more (This is just from GCSE biology, I'm hardly an expert). Although, it could certainly be helpful even if it doesn't do all that - presumably a bunch of crap blood substitute is still better than no blood at all!

        • Re:Various Questions (Score:5, Informative)

          by mikael ( 484 ) on Tuesday March 31, 2009 @12:19PM (#27404243)

          For a blood transfusion, the platelets (for clotting) white blood cells (fighting infections) and plasma (also for clotting) are separated from the red blood cells. Only the red blood cells carry hemoglobin [wikipedia.org], which carries Fe2+ iron ions.

          Just by creating a synthetic red blood cell would eliminate the need for many blood transfusions.

          • Re: (Score:2, Informative)

            by specracer ( 1520289 )
            True, but as Cillian correctly points out, the RBC is substantially more complex than the hemoglobin that gives it its color.

        • Re: (Score:2)

          by sjames ( 1099 )

          Most proposed blood substitutes are just the gas transport part in a carrier liquid that is intended to do little or nothing and cause no trouble.

          Adding in clotting factors and such would make the product vastly more difficult and far more likely to have a fatal (literally) flaw.

          Various use scenarios include at the front line in battle, in an ambulance, and at the scene of a disaster. In all of those cases the hopefully more stable patent then goes to a proper hospital and gets real blood. If only 1 unit is

      • Re:Various Questions (Score:4, Interesting)

        by pete-classic ( 75983 ) <hutnick@gmail.com> on Tuesday March 31, 2009 @11:11AM (#27403325) Homepage Journal

        More to the point, does it induce cardiac infarction, like PolyHeme? (And is the FDA going to foist it on the unconscious without consent, as they did PolyHeme?)

        -Peter

        • >And is the FDA going to foist it on the unconscious without consent, as they did PolyHeme? No.. definitely not. Next time they will say "Raise your hand if you don't want this blood substitute!"

        • Re: (Score:3, Informative)

          by geekoid ( 135745 )

          if they qualify under  50.24 Exception from informed consent requirements for emergency research, The probably. You have read this, right?

          http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr&rgn=div8&view=text&node=21:1.0.1.1.19.2.31.3&idno=21 [gpoaccess.gov]

          • Re:Various Questions (Score:5, Funny)

            by Red Flayer ( 890720 ) on Tuesday March 31, 2009 @12:50PM (#27404709) Journal

            if they qualify under  50.24 Exception from informed consent requirements for emergency research, The probably.

            That's an awesome way to say 'yes'. I think I'm going to use it from now on.

            Wife: Did you take the trash out yet?
            Me: The probably.

            Daughter: Daddy can I have a cookie?
            Me: The probably.

            Wife: Do you want to have another baby?
            Me: The probably.

            At the very least, it will buy me some time while they are confused, which will allow me to either think of a better answer, or escape to another location.

          • Wow. That's one gnarly post. You know Slashdot has a preview function, right?

            Anyway, I don't understand what point you're trying to make. I understand that the FDA authorized Northfield to conduct their research. That's why I said "FDA" in my post.

            Are you suggesting that this makes it okay? Or are you simply offering a historical example to suggest that the same outcome is likely?

            -Peter

            • Wow. That's one gnarly post. You know Slashdot has a preview function, right?

              The probably, it's hard to miss. ;)

              • All you -oids always stick together!

                I didn't want to point out that it's just to the left of the submit button . . . on a page written in a left-to-right language.

                -Peter

      • Re: (Score:1, Informative)

        by Anonymous Coward

        5. Can kidneys, livers and pancreases deal with this?

        You meant to say "spleens" not "pancreases" right? I'm just guessing that you meant to name all three organs that effectively filter blood, and not just two of them and one other random digestive/insulin production organ that happens to be located nearby.

        • That too, the list was about 3 more organs long, but then I noticed that it fucked with the flow of the visual appearance of the list, so I randomly deleted some.

      • When it becomes more efficient at carrying oxygen than blood, will it be banned in all professional sport?
  • Can I start drawing up business plans for my designer blood company? Green, maybe blue? What ever color you want it's up to you!

    Maybe a nice neon pink?

    • Radium. I want mine to glow in the dark.

      But you bring up an interesting point: does artificial blood have types? Rh factor?

      I am not knowledgeable in this area of science, but if these researchers have created something that can cart oxygen around in the bloodstream . . . they'd better start practicing their Swedish for their Nobel prize.

    • Can I start drawing up business plans for my designer blood company? Green, maybe blue? What ever color you want it's up to you!

          Maybe a nice neon pink?

      You'd have a whole bunch of Klingon Language Camp types waiting in line for that one...

  • This is clearly still unreal technology/Technocracy magic.

    Some Vampire/Mage crossover munchkin is trying to change the consensual reality so the paradox stops popping his head open whenever he tries to conjure blood.

    Obviously.

  • Make ER work simpler (Score:5, Informative)

    by Anonymous Monkey ( 795756 ) on Tuesday March 31, 2009 @10:42AM (#27402885)
    This would be a great thing in the ER. Blood type rejection is a major cause of complications and death. If we could develop something as safe as saline solution, that would not be rejected by the body, and would help carry oxygen it would simplify things greatly. It wouldn't even need to carry oxygen as well as blood to be effective. Human blood can be diluted to 10% and still carry enough oxygen, so if this fluid was greater than 5% as effective as blood and the patient had not blead out completely it would be more than enough.

    • Re:Make ER work simpler (Score:5, Informative)

      by chuckymonkey ( 1059244 ) <charles.d.burton ... il.com minus bsd> on Tuesday March 31, 2009 @10:48AM (#27403005) Journal
      It'll also be great on the battlefield. We lost a lot of soldiers just do to the fact that they were being pumped full of saline and by the time they made it to the base their blood looked like pink koolaid.
      • The more I think about this the better it gets. No virus risk (HIV, herpes, hepatitis). No blood type risk. No rejection risk. Not as perishable as real blood. Add in iron and erythropoitien to help regrow the patients own blood and you have a great lifesaving tool.
        • Seriously, blood is a core component for our bodies. Once you can swap it out with something better you get a lot more options. Artificial hearts tend to cause clotting. How about replacing the blood at the same time?

          Along similar lines, I wonder how hard it would be to keep a brain (just the brain) alive on life support. Hook it up to an external interface (not simple, I know) then live virtually forever.

      • I remembered reading about this topic in popular science. Here is the article:

        http://www.popsci.com/scitech/article/2006-11/better-blood [popsci.com]

        Battlefield "first response" was a major topic, as getting oxygen to the brain during the first hours was one of the keys to survival.

        • Wouldn't it make sense to equip soldiers with emergency 'blood banks'? So in case of massive blood loss, the brain and heart close off to form their own little system, leaving the tougher tissues to fend for themselves? It's always annoyed me that my most essential systems are so closely tied in with what should be expendable extremities - it seems like bad design when losing a leg could kill my brain through loss of blood.

          Maybe the whole system just kind of evolved instead of being intelligently designed

    • Re: (Score:2)

      by gambit3 ( 463693 )

      But isn't a bigger issue the LOSS of blood at the scene of an accident rather than blood type rejection?
      Or maybe ambulances could carry this as a "generic" substitute.

      • Re: (Score:1)

        by maxume ( 22995 )

        So you are proposing that accident victims should simply choose to lose less blood?

        I don't think that other phases of emergency care are going to take a successful blood replacement as a license to do less (unless it actually made sense to do so!).

      • Or maybe ambulances could carry this as a "generic" substitute.

        Or your car? How about one where you pour in distilled water and get blood out the other end?

    • Re:Make ER work simpler (Score:5, Informative)

      by quantumghost ( 1052586 ) on Tuesday March 31, 2009 @11:31AM (#27403587) Journal
      While this release is a nice breakthrough, there is still *a lot* of work to replace blood. Many substances have been tried to date and they have failed.

      First transfusions cause immune reactions [that are technically not rejection] but while these may be major events, they are NOT very frequent. Nurses stop transfusions at the slightest reaction. In the past six years I have seen one transfusion reaction and I work at a major urban trauma center.

      Secondly, blood that is transfused is usually near the end of its shelf life and as such you are lucky if 50% of the cells are viable. Within 48 hrs, most (75-80%) of the blood is useless.

      Thirdly, blood itself causes immunesuppresion. Couple this with the SIRS/sepsis response in the body and you are going to have a hard time managing this pt in the long term (this is why patients die weeks to months after surviving the initial trauma (tri-modal mortality - on-scene, early in the ED, and late).

      Fourth, is the ethical issues - not everyone accepts blood - Jehovah's Witnesses classically. (We also happen to be the city's "bloodless surgery" center - but that's a whole other rant).

      The problem with blood replacement is that they also fail in one of these areas. Some substances will cause immune reactions or toxic effects to the body. Hemoglobin and myoglobin (the analogue in the muslces) and their breakdown products are *toxic* to the body...fortunately we have mechanisms to eliminate them safely (most of the time). But what of this protein? Are the breakdown products safe? Does it need to be wrapped in a cell wall to protect the body from it? The article mentions the immune system attacking the molecule, but will the molecule function in physiologic conditions that allow it accept oxygen and release it appropriately? Will it cause other portions of the body to fail? Is the compound stable? How will the body eliminate it?

      As for not needing a substance that transports oxygen efficiently, try again. The human body can only tolerate so much volume. If this substance is only 5% as efficient I need 20x the volume. Not very helpful - I'll stick with blood thank you. And, yes you can survive being bled out to 33 to 50% of your blood volume if you are healthy....but if you are also a trauma patient with injuries, you can tolerate much less blood loss - see above for late trauma mortality. As for the soldiers bleeding out pink koolaid...your medics need to be retrained. The current accepted protocols are not to "flood" the traumas with non-oxygen carrying fluids (crystalloids) but to try to maintain perfusion until surgical control of bleeding can be established.

      And finally, one of the largest hurdles to artificial blood is the ethical concerns. Healthy volunteers may tolerate the substance, but actual "sick" people may not....In 1999 UPenn killed a young relatively healthy volunteer Jesse Gelsinger with their attempt at correcting his ornithine carbamoyltransferase deficiency with their "gene therapy". It wasn't necessarily that the treatment was bad, but due to his illness, he reacted badly to the adenovirus used as a vector. And in the early 1990's Shock Trauma in Baltimore took a huge publicity hit for proposing to use blood substitutes in acutal trauma patients...the problem was that in a trauma patient you cant' get accurate informed consent to an experimental treatment. This ended up becoming a racial issue as the young male African-American population was the largest demographic group "visiting" their facility. Major uproar.

      Now, I for one would love to see a stable, safe, useful blood substitue, they are still a long way off from offering a product I can use on my patients.

  • Interesting and cool... however (Score:5, Interesting)

    by tpjunkie ( 911544 ) on Tuesday March 31, 2009 @10:50AM (#27403039) Journal
    They fail to give any meaningful data on its oxygen dissociation curve against pH, so we have no idea how it will perform as an oxygen transporter at physiological conditions. Also missing is any information on whether histidine groups are present above and below the heme which are quite important for regulating the binding and release of O2. While I am suitably impressed with their engineering of a protein from scratch, I will hold off on kudos for creating something useful until I see some hard data.

    • Missing the point ... (Score:4, Informative)

      by specracer ( 1520289 ) on Tuesday March 31, 2009 @12:22PM (#27404313)
      Not the fault of the Slashdotters, as the MIT Tech Review linked also emphasizes the wrong aspects of this work. If one goes back to the actual paper in Nature, it's immediately apparent that the researchers did not set out to create artificial hemoglobin. Instead, the work is a demonstration of biologically-relevant function occurring in a relatively simple molecule that was *not* explicitly designed for that function. In other words, the protein was designed to ligate a heme and have a hydrophobic core--and that's it. That it behaves much like hemoglobin is coincidental, and that is the point. No design was necessary to incorporate that function. It follows that in nature, life-supporting processes are the natural result of certain molecular properties.

      If this protein could eventually find application as an artificial hemoglobin, that's great, but the point of the work isn't to announce the creation of same, but to highlight the fact that there are many potential solutions to any given biological problem, and that complexity of form is not an inherent requirement for life-sustaining chemistry.
      So, let's answer some "various questions" from above: 1) This has never been put inside a living creature, and it would likely be toxic in its current form. It would probably require significant re-design (changes in surface properties) to become immuno-silent.

      2) While it looks like this is a relatively cheap protein to produce (it's expressed in E. coli per the Nature paper, with nothing exotic added to the media), producing and purifying protein is generally an expensive game. That's one reason why peptide-based cancer treatments are exorbitantly expensive.

      3) Assuming an immuno-silent variant, blood type would be irrelevant.

      4) The components of pretty much any protein are non-toxic, but it's impossible to know a priori if some fragments of such a protein would aggravate the immune system. Probably not, though, provided (again) an immuno-silent design.

      5), 6), etc. .... This protein was created with absolutely no thought to toxicity or viability inside a biological organism. It was designed to test the hypothesis that biological processes can exist in a biologically-relevant framework (a protein, rather than, say, an inorganic metal complex) without being specifically designed-in or optimizing the framework to support said processes.

      Even without a ready-to-use artificial hemoglobin, this work is significant because it implies that evolving biological function is a very simple process, and the solutions nature has found to the problems of biology are not the only possible solutions.
      • A comment on your point 2: in the paper in nature they cite a paper, which has a cite to another paper that has the protein production and purification methods. It seems to be common practice for recombinant hemoproteins to spike the culture media with a heme precursor to crank up it's production. That precursor is listed at $142.50 per gram in my Sigma catalog. The authors may or may not have spiked their culture with it; materials and methods details in Nature papers are extremely brief or like here c

    • They fail to give any meaningful data on its oxygen dissociation curve against pH, so we have no idea how it will perform as an oxygen transporter at physiological conditions.

      Why you gotta be all chemical about it?

      In seriousness, the Dutton lab webpage [upenn.edu], the ones who did it, has a crystal structure image that looks like it does have the histidines in place above and below the heme ring to stabilize the O2, although it's been a while since I had a biochem course. So those could actually be anything and I wouldn't know. Matter of fact, that could be the wrong lab for all I know.

      Anyway, it seems the focus of the lab is non-clinical (predictably.) They may not have mentioned any

    • Re: (Score:1)

      by fain0v ( 257098 )

      http://www.nature.com/nature/journal/v458/n7236/pdf/nature07841.pdf [nature.com]

      If you have access to nature.

      From glancing at the article, this is not a replacement for blood yet, but they are moving in the right direction.

      • Thanks, thats much more enlightening than the linked article. And man oh man, no mention at all of the reversed affinities for O2 and CO in the summary or link, which I think is one of the most incredible things they've discovered here...

  • Can this artificial blood be absorbed through the stomach/intestines into the blood stream? If so these guys will be gazillionares! Forget corn sugar and caffeine, "Drink Bl00d(tm)! Hyper-oxygenated, overly vitamin giga-vitamin-fortified Bl00d(tm)!

    "Ready for a tequila shot, dude?"

    "No, let's do some blood first."

  • Artificial hemoglobin? (Score:3, Informative)

    by clone53421 ( 1310749 ) on Tuesday March 31, 2009 @11:02AM (#27403217) Journal

    Hemoglobin carries oxygen just fine. Why can't they use it?

    Is it too hard to manufacture, too expensive, or ill-suited in some other way for use in an artificial blood?

    TFA didn't answer that question.

    • Re:Artificial hemoglobin? (Score:5, Interesting)

      by ColdWetDog ( 752185 ) * on Tuesday March 31, 2009 @11:21AM (#27403449) Homepage

      Hemoglobin carries oxygen just fine. Why can't they use it?

      Remember, hemoglobin is just one part of the red blood cell - that's the 'thing' that delivers blood to tissues. If you just dump straight hemoglobin in the system, it gets chewed up quickly (like most random proteins) and clobbers the kidneys. (see the interesting wikipedia [wikipedia.org] article for some background. Researchers have tried various 'synthetic' hemoglobins to do just that and so far, they haven't worked well.

      Interestingly, there is a bovine hemoglobin / albumin conjugate that is approved for dogs. So it's possible that some combination of an oxygen carrying protein sans full red blood cell will work, but we haven't got there yet.

      • Thanks, that's quite informative. I was feeling particularly brave and actually clicked through and read TFA to try and find the answer to that question, and must say I was irritated when it wasn't explained at all. Of course I was too lazy to look it up... ;)

      • Re: (Score:2, Informative)

        by wesborgmandvm ( 893569 )
        Interestingly, there is a bovine hemoglobin / albumin conjugate that is approved for dogs. So it's possible that some combination of an oxygen carrying protein sans full red blood cell will work, but we haven't got there yet.

        Actually they are using bovine hemoglobin glutamer for humans in in South Africa for surgical patients http://www.biopure.com/hemopure.php [biopure.com]

    • There are a number of reasons, first is that its actually a tetramer of proteins that must be properly assembled before becoming useful, as the individual alpha and beta subunits are not well suited for useful carriage of Oxygen. Second, and this wasn't really addressed in the article is that the porphyrin ring containing the heme group is built separately from the globin proteins, through a chain of other enzymes, and then inserted into the finished globins. In the article they just had the porphyrin ready

  • further obstacles (Score:1, Insightful)

    by Anonymous Coward

    A great milestone, but a paragraph near then end of the article outlines the obstacles still to be crossed:

    To use the artificial protein in the human body, the researchers will need to make sure that it can hold on to the oxygen long enough to be useful, work in a cellular environment, and be nontoxic. The protein also must not be identified by the immune system as a contaminant to be flushed out through the kidneys, adds James Collman, a professor of chemistry at Stanford University, who makes synthetic hemes that bind to oxygen.

    I would modify one sentence though: "hold on to the oxygen long enough to be useful and no longer"
    What makes carbon monoxide so dangerous is that hemoglobin has more affinity for it than for oxygen. Once CO binds with it it is basically out of commission until the blood cell is reclaimed by the body. If this protein-heme compound has a higher affinity for O2 than hemoglobin, it could "suck" the O2 ou

  • That thing gota heme? (Score:1, Funny)

    by Anonymous Coward

    That thing gota heme?

  • Right now, we are seeing an artificial elevation in Cancer and other diseases. More importantly, these are tied to sharing of blood. We all carry viruses, and this sharing of blood is preferable to dying right then, BUT, a slow death is not much better.

    • Right now, we are seeing an artificial elevation in Cancer and other diseases.

      Artificial? Not sure that is the right word. Remember, we are all mortal (except those lucky enough to get bid by radioactive insects or suffer some equally odd and unlikely fate that comic book writers seem to know all about - oh and vampires...) So anyway, you're going to die of something. We've been slowly pruning the low hanging fruit of early mortality: Bad water, infectious disease, trauma, some heart disease. So that

      • Blood transfusions are safe from what we know. There are MANY virus left to be discovered and figured out. Heck, diseases that we thought were minor are turning out to be wicked. For example, Oral Herpes (cold sores) were considered a nusance while Genital herpes were considered horrible. During the time of reagan, he harped about it, while ignoring the up and coming AIDs. It was only later, than herpes was considered a none issue. Now, both types of herpes has a strong associations with long-term dementia.

        • Re: (Score:2)

          by geekoid ( 135745 )

          Such as...

          Can spread other diseases. Yes, and so?

          "both types of herpes has a strong associations with long-term dementia."
          Link?

          Your coming off as a little.. lets be kind and say 'odd'.

          Could you please be a little more clear as to the point you are speaking to, and the evidence it is based on?

          Are you just bringing up that sometimes diseases can be spread through transfusion?

          • Can spread other diseases. Yes, and so?
            ???? You kidding??? As a one-time MicroBiologists from ages ago (worked at CDC on arthropod-borne disease back in 1980-81; grant ended), I can tell you that science routinely discovers new viruses. Exchanging blood DOES create a risk, just one that is considered acceptable (vs. immediate death).

            "both types of herpes has a strong associations with long-term dementia." Link?
            Are you serious? In this day of Google, you really could not even type in TWO FUCKING WORDS? [google.com]
          • BTW, sorry, If that last post came off sounding like a d**k on my part (the lazy part). I was dealing with my ex over my daughter's school, and realized last night that I had gotten aggressive (with a driving ticket in hand for speeding and other things).

  • I wonder (Score:1)

    by pid ( 40371 )

    When will the "I last longer on synthetic" debate begin...

  • I think some fake blood is exactly what all these fake vampires need. Cranberry juice and V8 gets old after a while.

  • In "The Singularity Is Near", Ray Kurzweil explores some of the implications of artificial oxygen carrying fluid. Assume that it actually works as advertised:

    1. Red blood cells are pretty big for the amount of O2 they carry; the artificial version could be much more efficient per volume.
    2. More efficient == less volume for the same carrying capacity.
    3. Less volume == much less demand on the circulatory system. Imagine distributed, low-volume hearts.

    ...and on and on, in much more detail (and far more convincingl

    • Re: (Score:2)

      by mikael ( 484 )

      Maybe there is a purpose to their large size. Microscope animations of blood traveling through capillaries showed that the red blood cells were just small enough to travel through a single capillary in single file.
      Perhaps they need to be this size in order for blood pressure to keep them moving, otherwise if they were considerably smaller than a capillary, then the water in the blood stream would just stream past them.

  • Are we really to believe that a paragraph on Slashdot or Google News is as bad for Guardian Media Group as would be simply reading their articles straight from their RSS feed [guardian.co.uk]? Make no mistake: a ruling against aggregators is a ruling against RSS!!!
  • Being an avid cyclist I hear about new blood drugs frequently.

    The same hype was used for Hemopure [wikipedia.org] when it first came out, except it had the nasty side effect of kidney failure, or so far as I can tell. Anyone else know definitively why the FDA won't test Hemopure? If this makes it out of the lab, I wonder how long it will be in the wild before they develop a test for it in endurance sports. Personally, I don't think it will. Blood drugs like Hemopure and Erythropoietin have a nasty side effect of dea [guardian.co.uk]

  • I hadn't meant for this to become a Primer on the state of blood and artificial blood products, but considering the importance of the topic... blood is in fact life, and is therefore an issue worth going over thoroughly. The whole synthetic blood discussion is both fascinating and critically important. There simply isn't enough blood available for saving people's lives during disasters and large scale emergencies. That, and blood has a short shelf life so you simply can't build up stocks for the future. Las

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