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Scientists Make Artificial Protein Mimic Blood

timothy posted more than 5 years ago | from the this-is-cool-stuff dept.

Biotech 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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Finally (3, Funny)

kandela (835710) | more than 5 years ago | (#27402633)

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

Re:Finally (3, Funny)

Bieeanda (961632) | more than 5 years ago | (#27402671)

Pff. They are like, so late [wikipedia.org] .

Re:Finally (2, Insightful)

fuzzyfuzzyfungus (1223518) | more than 5 years ago | (#27402795)

Or, y'know, a bunch of powerful immortal creatures of darkness no longer have any need to keep us around...

Incidentally this [wikipedia.org] is fun viewing in that vein.

Re:Finally (1)

khellendros1984 (792761) | more than 5 years ago | (#27409143)

But where else would they get new recruits?

Re:Finally (0)

Anonymous Coward | more than 5 years ago | (#27410509)

Or, y'know, a bunch of powerful immortal creatures of darkness no longer have any need to keep us around...

No no this isn't approved for vampire diet. They'll be taking our blood and replacing it with this protein.

Re:Finally (1)

cyberchondriac (456626) | more than 5 years ago | (#27402825)

Depends - will it pass the taste test?

Blood is mostly rusty salt water anyway ..

Re:Finally (1)

Mikkeles (698461) | more than 5 years ago | (#27403237)

Not another bloody mime!

Re:Finally (1)

Chris Mattern (191822) | more than 5 years ago | (#27404659)

Well, maybe. Some of my Ventrue friends say it has a horrible metallic taste and is undrinkable.

Re:Finally (1)

Redfeather (1033680) | more than 5 years ago | (#27409917)

I sked a Toreador, but he laughed at the iron-y.

Re:Finally Very very bloody... (1)

davidsyes (765062) | more than 5 years ago | (#27410383)

Enriching!

Now, what will this mean for athletes, military, other types who get injured and get infused with "proxygen" (blood and java & coded Java) and get told to continue the fight?

Yet another step to cyborg technology. (2, Funny)

TestedDoughnut (1324447) | more than 5 years ago | (#27402701)

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.

Re:Yet another step to cyborg technology. (0)

Anonymous Coward | more than 5 years ago | (#27403373)

Indeed, praise our robot overlords!

Re:Yet another step to cyborg technology. (1)

BiggerIsBetter (682164) | more than 5 years ago | (#27407443)

The hell with that. I'm just thinking I'm one step closer to building my very own Number Eight.

Various Questions (4, Insightful)

D Ninja (825055) | more than 5 years ago | (#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 (4, Insightful)

Vectronic (1221470) | more than 5 years ago | (#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 (4, Insightful)

Cillian (1003268) | more than 5 years ago | (#27403303)

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 (4, Informative)

mikael (484) | more than 5 years ago | (#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 (2, Informative)

specracer (1520289) | more than 5 years ago | (#27404413)

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

Re:Various Questions (1)

sjames (1099) | more than 5 years ago | (#27404829)

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 transfused, that may be fine as-is.

Typically blood substitutes clear the system fairly quickly.

Re:Various Questions (3, Interesting)

pete-classic (75983) | more than 5 years ago | (#27403325)

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

Re:Various Questions (1)

homesnatch (1089609) | more than 5 years ago | (#27403589)

>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:Various Questions (2, Informative)

geekoid (135745) | more than 5 years ago | (#27404309)

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 (4, Funny)

Red Flayer (890720) | more than 5 years ago | (#27404709)

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.

Re:Various Questions (1)

pete-classic (75983) | more than 5 years ago | (#27406493)

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

Re:Various Questions (1)

fractoid (1076465) | more than 5 years ago | (#27411075)

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

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

Re:Various Questions (1)

pete-classic (75983) | more than 5 years ago | (#27412041)

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:Various Questions (1, Informative)

Anonymous Coward | more than 5 years ago | (#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.

Re:Various Questions (1)

Vectronic (1221470) | more than 5 years ago | (#27403655)

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.

Re:Various Questions (0)

tritonman (998572) | more than 5 years ago | (#27403569)

kidneys and liver? What do they matter? I don't think any of the drug manufacturers out there really care about your kidneys or your liver. Any problems with those are just rare side-effects.

Re:Various Questions (1)

dgatwood (11270) | more than 5 years ago | (#27404403)

Can we mod the parent +1, Sad-but-true? These days, I wouldn't be surprised to see a pharmaceutical ad that says, "Side effects are mild and may include internal bleeding, kidney or liver damage, erectile dysfunction, and brain aneurysms...." Half the drugs out there seem to cause some sort of kidney or liver issues in some people---acetaminophen (e.g. Tylenol), NSAIDs (non-steroidal anti-inflammatory drugs, a common type of pain reliever), bisphosphonates (osteoporosis treatment), gadolinium (used in CT scans), Trasylol (clotting drug), propylene glycol (used in LOTS of over-the-counter medicines), etc. The industry long ago crossed the line from "don't care" into outright intentional negligence territory, IMHO.

Re:Various Questions (1)

fractoid (1076465) | more than 5 years ago | (#27411083)

As long as they can supply me with new, synthetic liver and kidney before this faux-blood kills my current ones, I'm all for it.

I like the idea of being able to take my liver in for a tuneup instead of just having to stop drinking for a week every now and then. ;)

Re:Various Questions (1)

JuzzFunky (796384) | more than 5 years ago | (#27412525)

When it becomes more efficient at carrying oxygen than blood, will it be banned in all professional sport?

Re:Various Questions (0)

Anonymous Coward | more than 5 years ago | (#27410615)

More important questions:

1. What kind of storage requirements does this have? (refrigeration? or can I keep it in a first aid kit)
2. What kind of lifespan? (Can I buy once and forget about it? This is important for effective cost)

Giving an IV is a skill that can be trained to non medical people. In the military, every event with any risk of injury (even just standing outside in formation) usually has someone with a first aid bag (not a medic; any profession). They're trained to give an IV with saline if someone gets dehydrated and passes out.

Designer colors? (1)

Hoyty1 (1502645) | more than 5 years ago | (#27402823)

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?

Re:Designer colors? (1)

PolygamousRanchKid (1290638) | more than 5 years ago | (#27403473)

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.

Re:Designer colors? (0)

Anonymous Coward | more than 5 years ago | (#27413209)

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

No. Blood type kinda is a property of your red blood cells but unrelated to their ability to transport oxygen. To make artificial blood with a 'blood type' the scientists would have to specifically add that property to the artificial blood.

Re:Designer colors? (1)

Tetsujin (103070) | more than 5 years ago | (#27405335)

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...

Technocracy (1)

Thanshin (1188877) | more than 5 years ago | (#27402849)

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.

Re:Technocracy (0)

Anonymous Coward | more than 5 years ago | (#27410145)

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.

Wait, what?

Re:Technocracy (1)

Redfeather (1033680) | more than 5 years ago | (#27410279)

I never thought it would happen. But someone out-geeked Slashdot.

Make ER work simpler (4, Informative)

Anonymous Monkey (795756) | more than 5 years ago | (#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 (4, Informative)

chuckymonkey (1059244) | more than 5 years ago | (#27403005)

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.

Re:Make ER work simpler (1)

Anonymous Monkey (795756) | more than 5 years ago | (#27403543)

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.

Sign me up (1)

MichaelSmith (789609) | more than 5 years ago | (#27411163)

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.

Was an article about blood substitutes in popsci (2, Informative)

vecctor (935163) | more than 5 years ago | (#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.

Re:Was an article about blood substitutes in popsc (1)

fractoid (1076465) | more than 5 years ago | (#27411233)

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? :P

Re:Make ER work simpler (1)

gambit3 (463693) | more than 5 years ago | (#27403481)

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:Make ER work simpler (1)

maxume (22995) | more than 5 years ago | (#27403747)

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!).

Re:Make ER work simpler (1)

MichaelSmith (789609) | more than 5 years ago | (#27411251)

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 (5, Informative)

quantumghost (1052586) | more than 5 years ago | (#27403587)

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.

There already IS an artificial blood (0)

Anonymous Coward | more than 5 years ago | (#27410391)

There already is an artificial blood marketed as "OxyGlobin". It's essentially recombinant bovine hemoglobin in an artificial plasma-like fluid. It is free hemoglobin, in the sense that it isn't bound into cells but is freely dissolved (or emulsed, I guess) in the electrolyte solution.

It's used in veterinary medicine and, IIRC, in the military and possibly in Europe. It recently failed to gain FDA approval for human use in the US because of negative side effects. In particular, apparently free hemoglobin tends to deactivate serum nitrogen oxides, which otherwise have a vasodilatory effect. When the nitrogen oxides are deactivated there is a greater risk of heart attack and stroke.

It actually is a great product otherwise, though. It doesn't require refrigeration, has a relatively long shelf-life, is universally compatible with recipients and tends to perfuse better (because the hemoglobin is free it can penetrate in a way that RBCs cannot). Too bad the FDA process pretty has pretty much killed it in the marketplace.

Re:There already IS an artificial blood (1)

quantumghost (1052586) | more than 5 years ago | (#27413665)

Sorry, but I think you missed some of my points. Negative side-effects such as the exposed Fe+2 reducing nictric oxide in a patient are NOT acceptable. We are talking about people who are on the "knifes edge" and the "cure" can't make these people worse!

Also, please read their website. It is NOT artificial blood. It is not recombinant but rather purified bovine hemoglobin.

Directly from their website:

Manufacturing Process
Manufacture of Hemopure and Oxyglobin occurs in four major steps: First, bovine blood is processed to remove plasma and then to remove the hemoglobin protein from red blood cells.

And as such may still carry viral vectors and prions and are potentially susceptable to bacterial contamination.

And before people start knocking the FDA, please be aware that they spare the American public and to a lesser extent the world from over-eager pharaceutal companies.

Interesting and cool... however (4, Interesting)

tpjunkie (911544) | more than 5 years ago | (#27403039)

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 ... (4, Informative)

specracer (1520289) | more than 5 years ago | (#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:Missing the point ... (0)

Anonymous Coward | more than 5 years ago | (#27404763)

look at you goin' back and readin' the actual paper all smart like...

Re:Missing the point ... (0)

Anonymous Coward | more than 5 years ago | (#27405913)

Agreed. Not to mention, there is already blood alternatives that were researched years ago. I have no idea whether they are on the market or not, but the research has been done explicitly to find blood alternatives.

Not a peer reviewed place, but Discover did a story/article about this like 10 years back. The researchers successfully treated a Jehovah's Witness (unless there was another group that doesn't allow blood transfusions too) patient that an ER had referred to them, so they were clearly doing human work, although I don't remember if this was a special case or larger trials.

It's that people continue to give blood (cheap) and hospitals are antiquated in their policies (free blood, little chance of being sued versus using the new stuff). I am surprised, though, that the military hasn't looked into the stuff more. People will continue to give blood, sincet here are many side products that are highly desirable and used for treatments and trauma care, I'm just upset that designed blood altnerative oxygen carriers haven't gained wider acceptance.

Re:Missing the point ... (1)

Bowling Moses (591924) | more than 5 years ago | (#27408155)

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 cite a paper that cites a paper. Anyway, if they did use a heme precursor that adds expense, if they didn't, the proteins produced will have less of the heme which is required for oxygen binding.

As for points 5 &etc., that's critical. A pint or two of blood replacement coursing through your veins triggering an immune response couldn't possibly be good. But yeah you're right, that's not what the authors are really at for this paper. The word "blood" isn't even in the Nature article!

Re:Interesting and cool... however (1)

interkin3tic (1469267) | more than 5 years ago | (#27404857)

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 of that stuff because it was less interesting to them than "holy crap, I've actually made a completely novel protein!" It will be really really interesting to everyone else when it moves into translational / applied clinical research, but from their perspective (and mine too) this is quite remarkable in and of itself, whether or not it will itself be usefull is a close second.

Re:Interesting and cool... however (1)

fain0v (257098) | more than 5 years ago | (#27406725)

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.

Re:Interesting and cool... however (1)

tpjunkie (911544) | more than 5 years ago | (#27407909)

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...

Why? (0)

Anonymous Coward | more than 5 years ago | (#27403117)

Why someone need to invent a protein to replace a 25 year old perftoran?

Choices or Money (0)

Anonymous Coward | more than 5 years ago | (#27403533)

Research into developing new technologies which benefit life tend to be a good thing. Though if this winds up being used where Perftoran works better, then it is because of greed.

Re:Why? (1)

reverseengineer (580922) | more than 5 years ago | (#27406051)

Well, Perftoran and the other perfluorocarbon based oxygen carriers have their own drawbacks, many of which have to do directly with their non-biological nature. In particular, pure perfluorocarbons are not soluble in blood, so they must be formulated as emulsions of tiny PFC globules emulsified by egg phosphatide protein. Even with emulsion, most PFCs are much denser than water, and tend to settle out over time. these globules are too large, the body's immune system will attack them. Perfluorocarbons also cannot be metabolized like proteins. In some respects, this is an advantage over hemoglobin-analogs, which have toxic metabolic wastes, but PFC accumulation could present a serious problem with long-term administration.

Also, storage has proven to be an issue with perfluorocarbon formulations. PFC can be stable several years if kept frozen; it must be thawed before use. While the shelf-life is atractive, the storage requirements make it difficult to use as an emergency blood alternative. There is still a place for PFC-based blood substitutes; indeed, they've proven useful in preserving organs for transplant. Their drawbacks, however, suggest there is also a place for heme-based oxygen carrier therapeutics.

Now how will people blow off Jehovah's Witnesses? (0)

Anonymous Coward | more than 5 years ago | (#27403143)

"You're the people who let your children die because you won't let them have blood transfusions."

With technology like this (to complement some other awesome medicinal advances) the use of blood (which is dangerous and expensive) in medical treatments will be marginalized. Most excellent.

Re:Now how will people blow off Jehovah's Witnesse (1)

Atrox666 (957601) | more than 5 years ago | (#27404491)

I can't be a witness, I didn't even see the accident.

*The* ultimate energy drink! (1)

PolygamousRanchKid (1290638) | more than 5 years ago | (#27403149)

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."

Re:*The* ultimate energy drink! (1)

Thanshin (1188877) | more than 5 years ago | (#27403577)

And we'd finally have cheap real bloody mary.

Artificial hemoglobin? (2, Informative)

clone53421 (1310749) | more than 5 years ago | (#27403217)

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? (4, Interesting)

ColdWetDog (752185) | more than 5 years ago | (#27403449)

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.

Re:Artificial hemoglobin? (1)

clone53421 (1310749) | more than 5 years ago | (#27404317)

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:Artificial hemoglobin? (2, Informative)

wesborgmandvm (893569) | more than 5 years ago | (#27408651)

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]

Re:Artificial hemoglobin? (1)

tpjunkie (911544) | more than 5 years ago | (#27403451)

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 to go. Finally, hemoglobin is a large protein and as such, loose hemoglobin would be rapidly cleared from the blood by the kidneys. In fact, given the large size of Hb as well as the amount needed to carry sufficient oxygen, I could envision kidney damage occurring in some patients receiving large amounts.

cycling (0)

Anonymous Coward | more than 5 years ago | (#27403239)

Sounds like a fantastic doping agent.

further obstacles (1, Insightful)

Anonymous Coward | more than 5 years ago | (#27403269)

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 out of the remaining blood the person has, reducing the effectiveness of the circulatory system as a whole

That thing gota heme? (1, Funny)

Anonymous Coward | more than 5 years ago | (#27403275)

That thing gota heme?

Hopefully, this works (0)

WindBourne (631190) | more than 5 years ago | (#27403295)

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.

Re:Hopefully, this works (1)

ColdWetDog (752185) | more than 5 years ago | (#27403549)

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 'allows' other diseases to take over the grim reaper function. Namely cancer and heart disease (at least in the US).

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.

Huh? Certainly some of the viral disease are blood borne, but modern transfusions are safe, really safe. The major risk is screwing up the typing for antigens. It's not perfect - it's slow and expensive (at least in the US) hence the research for artificial blood products. And of course, you're dying a slow death. The idea is to make it so slow that you're too busy living to notice....

Re:Hopefully, this works (1)

WindBourne (631190) | more than 5 years ago | (#27403667)

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.

In the end, Transfusions HAVE saved lives, but it comes at a costs. And yes, it DOES spread other diseases.

Re:Hopefully, this works (1)

geekoid (135745) | more than 5 years ago | (#27404415)

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?

Re:Hopefully, this works (1)

WindBourne (631190) | more than 5 years ago | (#27406469)

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? Are you really that GD lazy????? I am guessing that you would never have done science back in the 70's/80's, when we really did go to the library for whole days. What are we coming to. [google.com] To be honest, it makes TOTAL sense. Herpes hides in neurons. Once it starts shedding, it kills off the neuron.

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?

Notice the above of where I worked at. Back then, we figured out that AIDs was viral, and even suspected it was a retrovirus (All of the arthropod-borne virus that we worked with were retrovirus, which is why we were brought in to look a bit at AIDs). There was a bunch of early information that NEVER made "the band played on". But, even back in 1981, CDC was calling for "homosexuals" to not give blood because it was thought that it was transferred via blood/sex/etc. Simply put, new viruses come about and then are carried around to be transferred in different fashions. One approach is via air-borne (a sneeze), another is via touch (foods/water/western style toilets/etc), some via fluid exchange (breast milk, urine, sex, and blood). HIV was likely started when a hunter killed an infected monkey and while skinning the monkey, cut himself. That was the original exchange of blood. Now, in humans, HIV can be transmitted via blood exchanges such as needles (druggies or health officials not using cleaned needles) OR wait for it...... BLOOD TRANSFUSIONS. Here in the west, we test for HIV. In fact, MOST parts of the world test for it. But for some, they do not have the money to pay for the whole battery of tests. It costs money for that. In addition, new diseases come along all the time. This is more because we are one of the more dominant species on this planet (in fact, we are the ONLY LARGE SPECIES with any real number save for our domesticated animals). Roughly, we are a target for virus and bacteria. Keep in mind that Genetic Algorithms apply to life. More and more virus and bacteria will target us just due to percentage. And even without that, there are many virus that we have not discovered. Heck, Tagamet was one time the world's most used drug and it was thought that stomach ulcers were genetic. In late 80's, it was "discovered" to be a simple bacteria that had spread via contaminated ppl touching your food.

Look, if an artificial blood could be developed AND made cheaply, it would solve our transmissions of unknown virus. Keep in mind that a virus can be passed on to your children. Personally, I would rather not. In addition, if a blood agent can be made to last for a time ESP without refrigeration, this would allow rural or undeveloped areas to stock this. That is very important.

Re:Hopefully, this works (1)

WindBourne (631190) | more than 5 years ago | (#27416081)

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 (1)

pid (40371) | more than 5 years ago | (#27403537)

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

Fake blood is perfect (1)

sokoban (142301) | more than 5 years ago | (#27404397)

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

Researchers at the University of... (0)

Anonymous Coward | more than 5 years ago | (#27404521)

"Researchers at the University of Transylvania"...

There, fixed for ya!

I wouldn't get too worked up yet (0)

Anonymous Coward | more than 5 years ago | (#27404727)

I wouldn't get too worked up yet. They've shown a proof of concept, but it's got a long road ahead of it before this product would be deemed OK for use. Best of luck to them though. A product like this won't fully substitute ol' fashioned regular blood, but it could certainly buy some time in an emergency situation.

But now comes the hard part: how much product can we make and how cheaply? How does it break down? How does the body rid itself of this product when the time is right? What's the shelf life?

Lots of questions to go, but the concept is good!

Just wondering (0)

Anonymous Coward | more than 5 years ago | (#27404729)

What is wrong with just using ketchup in horror movies. Why would we want real blood?

Finally, we can defeat Gaos! (0)

Anonymous Coward | more than 5 years ago | (#27405255)

All we need now is a giant rotating building and we can trap him until sunrise...

Greater implications (1)

Just Some Guy (3352) | more than 5 years ago | (#27405345)

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 convincingly) than I can muster. Basically, such a thing could utterly revolutionize our idea of what is required to keep a human brain alive, that being the ultimate goal of our project.

Re:Greater implications (1)

mikael (484) | more than 5 years ago | (#27406323)

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.

Re:Greater implications (0)

Anonymous Coward | more than 5 years ago | (#27411881)

Red blood cells are pretty big for the amount of O2 they carry

If I understand correctly, mammal red blood cells are more efficient than those of other tetrapods because they don't have nuclei.

I've always seen the mammal vs dinosaur-reptile competition as our superior blood versus their superior lungs.

I am not a biologist, medical doctor, paleontologist or dinosaur, but I am a mammal.

Syndication in all forms, including RSS (0, Offtopic)

hdon (1104251) | more than 5 years ago | (#27405373)

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!!!

PolyHeme (0)

Anonymous Coward | more than 5 years ago | (#27405451)

What are the differences from PolyHeme? http://en.wikipedia.org/wiki/PolyHeme

which came out a while ago?

Professional Sports Doping? (1)

nloop (665733) | more than 5 years ago | (#27409405)

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 death [guardian.co.uk] . I doubt this one will fair any better despite TFA's claims of safety.

Cutting Edge Technology (1)

Genda (560240) | more than 5 years ago | (#27411469)

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. Lastly, transfusing blood comes with a raft of serious medical problems including distribution, contamination, typing accidents, rejection, allergies, tainting, and a host of unpleasant interactions that can span the gamut from uncomfortable to fatal. all of this underlines the need for a good synthetic blood alternative.

We're on the verge of amazing new products which will make sudden death or injury due to loss of blood or blood flow a problem of the past. Some of the more interesting work is being done in the following areas;

  • Synthetic Heme Containing blood substitutes
    This has been an area of significant research and development. Part of the problem is that the naked HEME molecule is toxic and causes damage to the kidneys (and may also cause problems with the liver and spleen.) As well, until recently, artifical bloods had a serious problem with Nitric Oxide Scavenging [scienceline.org] resulting in constriction of the blood vessels, increased blood pressure, reduced blood flow, and ultimately tissue damage and death. Interesting work is being done on breakthroughs in both oxygen transport and the design of the vesicles which hold the the transport technologies.
  • Perfluorocarbon Emulsions
    You may be familiar with Perfluorocarbons from their use in deep sea diving, As seen in the movie "The Abyss". [answerbag.com] What you may not know is that Perfuorocarbon Emulsions are one of the leading candidates for a new Synthetic Blood Substitute. [google.com] The coolest feature of this product, is that the droplets of perfuorocarbon are nano-scopic. Literally hundreds of time smaller than blood cells. When administered they pass through blood clots as easily as crickets would pass through a highway traffic jam. This means, your heart and brain could continue to receive plenty of life giving oxygen even if a clot stopped the blood flow cold. No more death or long term tissue damage from strokes or heart attacks. If this isn't cool I don't know what is!
  • Respirocytes
    This is more than a little further off in the future. Its a nano machine designed to store oxygen at around 50 atmospheres, and move freely through the blood stream like super small blood cells. You can read volumous writings and illustrations by nanotechnology advocates Ralph Merckle and Ray Kurzweil on this topic. You can also visit the subject at Wikipedia [wikipedia.org] or see a cool video about them at Youtube. [youtube.com] The respirocyte has the same advantages as perfluorocarbon, but will work even if your heart stops. So you have that critical golden hour to get to a hospital with what would certainly otherwise be a fatal condition or injury. Of course by this point, we'd almost certainly have all sorts of other nanotechnology available probably making the whole need for such devices moot. Maybe respirocytes would be the "Po Boy" technology available to those folks who couldn't afford godlike status.

Whatever succeeds in the market place, the future of synthetic blood substitutes is going to save a tremendous number of lives, improve post operative healing, prevent a whole host of diseases involving oxygen transport, and with any luck make death by blood loss or loss of blood flow virtually unknown. Just one more way technology is making things way more interesting!

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