Originally posted April 18, 2013

“If it bleeds, we can kill it” – Major Dutch Schaefer
(This post is an entry in See Arr Oh‘s Chemistry at the Movies Blog Carnival)

When Dutch and his band of military mercenaries went stalking the Predator in the jungles of South America, they had no idea what they were going up against. Bio-adaptive camouflage. Laser-based weaponry. Infrared vision. These guys were screwed. Not even Apollo Creed or Jesse “The Body” Ventura had any hope of surviving!

So, yeah. This alien is pretty bad-ass. But probably my favorite anatomical feature (ahem) of this thing is its blood. The Predator has this really cool luminescent blood. Being that I’m a nerd (check), that I really enjoy sci-fi (check … really, people, I’m just a statistic), and that I’m a bioinorganic chemist (that means that I study metals in biology, and, specifically, that I study metals in proteins, and, more specifically, that I study hemoglobin and myoglobin, which are the proteins that give the red color to blood and muscles/meat). In fact, one of my primary research goals is to study how proteins like hemoglobin and myoglobin affect the chemistry (gas storage storage capacity, reactivity) of the metal complex that it contains. In the lab, that means that I replace the heme in hemoglobin and myoglobin with non-biological metal complexes and see what happens! So, when it comes to alien blood in the movies, I tend to geek out and try to figure out how that blood might “naturally” occur. The fun part about this is that, while our understanding of biology is limited to how it works on Earth, there are nearly limitless possibilities for how biology might work on another planet.

Blooooooooood

Before we get too much into speculating on alien blood, I thought that a little primer blood and the cardiovascular system might be worthwhile. The main function of these, carrying oxygen to the rest of the body, is one of the reasons why our blood is red. (Actually distributing molecular/cellular nutrients, energy, and defense throughout the body IS the purpose of the cardiovascular system.) But, back to blood and oxygen. For humans (and animals and insects and many bacteria, fungi, and protists) we use the energy stored in the O₂ bonds to supply the energy we need to be active and maintain life. Many of you should be familiar with the chemical reaction depicting respiration:
C₆H₁₂O₆ + 6O₂ –> 6CO₂ + 6H₂O + Energy
In this reaction, oxygen is a critical component, along with glucose, for supplying energy to our bodies. As with many things in Nature, life isn’t this simple as this reaction. This seemingly simple chemical equation is the sum of many different biological and chemical processes that occur. But, the point still stands, oxygen is necessary for our life because life found a way to propagate and evolve through exploiting energy stored in oxygen. To do this, Nature had had come up with a means for storing oxygen, transporting it, and extracting its energy. Nature does this, here on Earth, through the use of metal complexes that are associated with proteins.

In terms of oxygen storage and transport, the proteins myoglobin and hemoglobin are used. Each of these proteins contains a heme complex (shown in the picture below on the upper right). Heme is a compound that is made up of a porphyrin (protoporphyrin IX to be precise) that contains a central iron ion. Heme is attached to these proteins (either hemoglobin or myoglobin) through an interaction between the iron and a one of the protein’s histidine amino acids. Heme on it’s own is purple’ish in color and is clumps up in solid form when you try to put it into water. However, when it is in hemoglobin or myoglobin, and an oxygen is bound to the iron, it is reddish in color and the protein keeps it soluble in water.

So why does (our) Nature use these hemes anyway? Turns out that heme are probably a second-thought or one-off when it comes to evolution. It is likely that they are the not-so-distant chemical (and evolutionary) cousins of another molecule that Nature found useful, chlorophyll. Chlorophyll, shown in the image above on the upper left, is used in photosynthesis. The light that chlorophyll absorbs ultimately leads to the electron removal and energy required for plants (and algae and cyanobacteria) to convert water and carbon dioxide into O₂ and glucose (the opposite of the chemical reaction shown above). If you take a closer look at the structures of chlorophyll and heme (bottom of the above image), you will see that their structures have some very important similarities. In fact, in their basic architectures, they differ by only one double bond (and two hydrogens), as highlighted in red.

Current estimates put the accumulation of atmospheric O₂ at around 2.4 billion years ago, indicating the probability that biosynthesis of chlorophyll was occurring at or prior to that time. (ref) The genes for hemoglobin started appearing roughly 600 million years after that (by best estimates). (ref) And, in what should be obvious from looking at their chemical structures, heme and chlorophyll do share a common biosynthetic pathway. (ref) Nature evolved chlorophyll, which helped produce O₂, and then used that same biosynthetic pathway to create heme for the purpose of utilizing that O₂. Nature uses one basic molecular framework in order to produce and exploit O₂. Pretty cool.

So, we have red blood because Nature started making O₂ with chlorophyll. There is no reason why any other planet would constrain evolution to selecting for chlorophyll and heme biosynthesis. It happened on Earth because of the available materials (magnesium and iron) as well as some primitive biosynthetic pathway. If other species on some distant planet have similar circulatory systems, there is no reason why they would have to have the same kind of blood as we have! This is a bug in our Earth-designed life.

Back to the Movies!

OK. More Fi and less Sci. I hear ya.

Predator

Getting back to our friend, The Predator … The Predator has glowing (luminescent) blood. Actually, in some scenes, it’s blood is shown as black. Let’s think about what is going on here. Luminescence occurs when energy (maybe in the form of heat maybe in the form of light) is absorbed by a molecule and then re-emitted as light. (This is the process that goes on in glow sticks. When you “crack” a glow stick, it initiates a chemical reaction, which puts out energy. This energy is absorbed by another fluorescent molecule inside of the glow stick, which, in turn, converts the energy into the fluorescent light that we see.) In the case of The Predator, one of two things may be happening. In scenario one, his body produces heat, which is absorbed by some molecule in his blood and emitted from that molecule as light. In scenario two, his blood only glows when exposed to energy in the form of light. The question is: Why do we only see his blood when he is bleeding? Why can’t we see it glowing through his body? If the blood is only luminescent upon absorption of light, that could explain it. If, however, their blood was luminescent due to an energy transfer process, then, perhaps, the luminescent light might not pass through their skin. (Our own tissue, by the way, will absorb most visible light.)

What kinds of molecules might be involved in this process? These glowing molecules could be organic compounds (i.e. no metals) or they could have inorganic (i.e. have metals). We know that the predator’s blood is highly luminescent. That is, you can REALLY see it. Therefore, it must have a very high concentration of luminescent compound in it. So, either The Predator relies on a high concentration of an organic molecule, that happens to be luminescent, or the metal complex that it requires to carry oxygen also happens to be luminescent. (Because I’m writing this post, I’m going to speculate that it’s got a metal in it!) Zinc porphyrins happen to be luminescent. But, their glowing is diminished by the presence of oxygen. Other luminescent metals compounds include those of iridium (ref) and ruthenium (ref) So, perhaps The Predator comes from a planet formed in the aftermath of a supernova, which would be necessary for large scale production of either of these two metals. (Like I said … I enjoy this a little too much).

Vulcan Blood

This awesome image was blatantly stolen from “micathemineral” who wrote a great post on the biology of Vulcan blood.

In Star Trek lore, Vulcans (Spock is a Vulcan) have green blood. Actually, it is green when it is oxygenated and rust-colored when it is not carrying oxygen. Also, it is copper-based. So … how the heck would this happen? Turns out that we have copper-based blood here on Earth too. The hemocyanin proteins are the oxygen carrying proteins in many shellfish. There are no special molecular appendages (like heme) in these proteins. The copper atoms (there are two in hemocyanin) are kept in close proximity to one another through their interaction with six histidine amino acids. These proteins are colorless when there is no oxygen bound and blue when they are carrying oxygen. (A twitter discussion of Vulcan blood, started by Biochem Belle was the original inspiration to write this post. And in the discussion, we talked about the comparison between Vulcan blood and shellfish blood). Now, just because the copper-based hemocyanin proteins are blue does not mean that all copper-based oxygen storage proteins would be blue as well. By slightly changing the protein architecture, you can greatly affect the physical and chemical properties of that protein. In thisstudy, Yi Lu performed single mutations on a copper protein. These single mutations dramatically changed the redox properties (i.e. the energy required to change the charge on the copper ion) as well as the color of the protein. So, I can imagine that specific mutations to a hemocyanin-type protein could produce dramatic changes in color. In fact, I would imagine that tuning the color from blue to green would be relatively easy! (Famous last words) As an example of how this might be possible, the Tolman Group at Minnesota synthesized a compound containing three copper atoms with two bridging sulfur atoms (see image below). This molecule is dark green in color.

(Image modified from JACS)

Alien

The aliens in Alien and Aliens have very acidic blood. If these creatures use H⁺ gradients in order to store electrochemical energy, like a battery, that could make a lot of sense. (We do this at a much smaller scale in our mitochondria.)

Avatar

The Na’vi of James Cameron’s imagination have red blood. They also breath an atmosphere that is similar to Earth’s. The main difference is that their atmosphere has a very high content of carbon dioxide, xenon, and H₂S. The humans who go to Pandora can’t breath the air because that level of CO₂ is toxic. And the H₂ would reek to high heaven. So, all indications are that the Na’vi have an O₂ storage system similar to what we terrestrial creatures have.

The blood’s run out

See what I mean … I enjoy this stuff …
tl;dr

There really is a world of possibility out there for protein color (and blood color). And, part of my research is to expand on the types of metal complexes we normally associate as being protein. I guess you could say I’m trying to make up my own alien blood in the lab (if you like that sort of thing). So (a request), if you’ve got some cool metal compounds, and you are interested in what they might look like (and react like) while inside of a protein, send them my way. We’ll do some unnatural things with Nature!