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Biotech Medicine

Scientists Make Artificial Protein Mimic Blood 94

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

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

    by Anonymous Monkey ( 795756 ) on Tuesday March 31, 2009 @11:42AM (#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.
  • by chuckymonkey ( 1059244 ) <charles@d@burton.gmail@com> on Tuesday March 31, 2009 @11:48AM (#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.
  • by clone53421 ( 1310749 ) on Tuesday March 31, 2009 @12:02PM (#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:Various Questions (Score:1, Informative)

    by Anonymous Coward on Tuesday March 31, 2009 @12:29PM (#27403555)

    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.

  • by quantumghost ( 1052586 ) on Tuesday March 31, 2009 @12:31PM (#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.

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

    by mikael ( 484 ) on Tuesday March 31, 2009 @01:19PM (#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:Various Questions (Score:3, Informative)

    by geekoid ( 135745 ) <dadinportlandNO@SPAMyahoo.com> on Tuesday March 31, 2009 @01:22PM (#27404309) Homepage Journal

    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]

  • by specracer ( 1520289 ) on Tuesday March 31, 2009 @01:22PM (#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.
  • Re:Various Questions (Score:2, Informative)

    by specracer ( 1520289 ) on Tuesday March 31, 2009 @01:28PM (#27404413)
    True, but as Cillian correctly points out, the RBC is substantially more complex than the hemoglobin that gives it its color.
  • by vecctor ( 935163 ) on Tuesday March 31, 2009 @03:33PM (#27406335)

    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.

  • by wesborgmandvm ( 893569 ) <wesborgman AT gmail DOT com> on Tuesday March 31, 2009 @05:59PM (#27408651) Homepage
    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]

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