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Scientists Make Artificial Protein Mimic Blood

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."

14 of 94 comments (clear)

  1. Finally by kandela · · Score: 3, Funny

    ... Vampires and Humans can live together in peace.

    --
    Conservation of angular momentum makes the world go round.
    1. Re:Finally by Bieeanda · · Score: 3, Funny

      Pff. They are like, so late.

  2. Various Questions by D+Ninja · · Score: 4, Insightful

    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.

    1. Re:Various Questions by Vectronic · · Score: 4, Insightful

      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.

    2. Re:Various Questions by Cillian · · Score: 4, Insightful

      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!

      --
      -- All your booze are belong to us.
    3. Re:Various Questions by pete-classic · · Score: 3, Interesting

      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

    4. Re:Various Questions by mikael · · Score: 4, Informative

      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, which carries Fe2+ iron ions.

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

      --
      Vintage computer adverts: http://www.vintageadbrowser.com/computers-and-software-ads
    5. Re:Various Questions by Red+Flayer · · Score: 4, Funny

      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.

      --
      "Trolls they were, but filled with the evil will of their master: a fell race..." -- J.R.R. Tolkien on Olog-hai
  3. Make ER work simpler by Anonymous+Monkey · · Score: 4, Informative

    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.

    --
    We are the Borg...
    1. Re:Make ER work simpler by chuckymonkey · · Score: 4, Informative

      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.

      --
      "Some books contain the machinery required to create and sustain universes."-Tycho
    2. Re:Make ER work simpler by quantumghost · · Score: 5, Informative
      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.

  4. Interesting and cool... however by tpjunkie · · Score: 4, Interesting

    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.

  5. Re:Artificial hemoglobin? by ColdWetDog · · Score: 4, Interesting

    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 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.

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    Faster! Faster! Faster would be better!
  6. Missing the point ... by specracer · · Score: 4, Informative

    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.