Crocodile serum to cure HIV?

Reuters have come out with a fascinating article that crocodile serum may yield powerful new 'antibiotics'. Aside from the obvious nitpick, that crocodiles are clearly not microbes, which makes the concept of them providing new antibiotics somewhat odd, there are some extremely unusual claims made by one of the researchers involved.

The first thing that should be noted from the article, is that the majority of the work has been done on the North American Alligator Alligator mississippiensis by Mark Merchant (see below references) and they have found its serum is rather good at killing HIV. Unfortunately, it also happens to be toxic to the cells you are trying to treat too:

Higher serum concentrations (50% serum) reduced cell viability by
60%, while the anti-WNV effect was reduced to 32%. The full potential of the anti-WNV properties of alligator serum are difficult to evaluate due to the toxicity of the serum toward the Vero cells(1). [emphasis mine]

It's a treatment that would not only take out the virus but indiscriminately kill the patients cells in a non-specific manner. In a test tube they've had some wonderful results, but the actual useage of putting this into a treatment you can give to patients, immunocompromised patients at that, is highly suspect. That is probably why they have concluded the piece as follows

However, the crocodile's immune system may be too powerful for humans and may need to be synthesized for human consumption.

May, as we will see, is quite an understatement.

Sometimes you have to wonder why the media ask the wrong people about things, for example I don't see why they didn't continue to query Mark Merchant about this research (who has done the majority of it) and instead where they dug up this Britton fellow.

Initial studies of the crocodile immune system in 1998 found that several proteins (antibodies) in the reptile's blood killed bacteria that were resistant to penicillin, such as Staphylococcus aureus or golden staph, Australian scientist Adam Britton told Reuters on Tuesday

No duh. Antibodies do not function in the same way that antibiotics like penicillin do. Penicillin compromises the bacterial cell wall by inhibiting enzymes called transpeptidases, gradually causing the wall to become structurally unstable and the bacterium to explode from building internal pressure. Antibodies however work differently, they are produced and bind to certain structures on the surface of the organism. Once bound, antibodies function to lyse the cell through complement or to function as an 'eat me' signal for other cells.

The comparison is simply nonsensical. He might as well have compared deaths from heart attacks to deaths by being hit by a large asteroid as being equivalent.

"If you take a test tube of HIV and add crocodile serum it will have a greater effect than human serum. It can kill a much greater number of HIV viral organisms," Britton said from Darwin's Crocodylus Park, a tourism park and research center.

And most other things too, including cells you aren't particularly wanting to destroy. The positive thing of course, is that this can be up to 10x more effective than the human immune system, it's just not as specific. The advantage with using antibiotics made by microbes, is these are pretty specific for targets on other microbes and are generally not going to recognise and react with human 'bits' (some exceptions do exist).

Britton said the crocodile immune system worked differently from the human system by directly attacking bacteria immediately an infection occurred in the body.

Except the human immune system is perfectly capable of doing this and does. Complement, neutrophils and many other aspects of the immune system are immediately around to attack and attempt to destroy invaders right from the outset. It takes specific virulence factors to get around these mechanisms to even begin establishing any meaningful infection to begin with. This is because the innate vertebrate immune system is prepared to fight immediately. If it didn't we'd be in a lot of trouble.

What the difference actually occurs in is that crocodilian serum factors like complement, have a much higher binding affinity than human complement and have a wider range (not as specific). Additionally, I would probably hypothesise that their convertases, the enzymes that make complement proteins turn into lethal killers, are 'simpler' to make and hence destroy the bacterial cells. As Mark Merchant summarises from another paper (2) :

The antibacterial activities occurred relatively quickly in vitro, with significant activity occurring within 5 min of inoculation with E. coli and maximal activity at 20 min. Also, the antimicrobial activity exhibited temperature dependence, with a substantial decrease in activity below 15 degrees C. These data suggest that the antimicrobial properties of alligator serum may be due to an active serum complement system (2)

Both systems have mechanisms for 'immediately' attacking bacteria, it seems clear at the moment that crocodiles are extremely good at doing this (which, given what they encounter in the environment makes perfect sense).

"We may be able to have antibiotics that you take orally, potentially also antibiotics that you could run topically on wounds, say diabetic ulcer wounds; burn patients often have their skin infected and things like that," said Merchant.

Antibiotics are molecules produced by microorganisms like bacteria and fungi, to either kill or restrict the growth of other microorganisms. It's rather bizzaire that Dr. Merchant would describe using crocodile serum as an 'antibiotic', even if I can appreciate what message he was trying to convey, but it's not technically accurate to call it an antibiotic. I wouldn't want to be injecting this stuff into people, because aside from its potential general toxicity, it may also be reacted to by the human immune system and be only very limited in use (one use then it's stuffed effectively). This is because the antibodies in the serum are themselves recognised by the human immune system and will be eliminated the next time they are encountered: reducing their effectiveness.

It has potential, but there are numerous drawbacks to using this as a potential treatment for anything to be overly optimistic right now.

(1) Merchant ME, Pallansch M, Paulman RL, Wells JB, Nalca A and Ptak R (2005). Antiviral activity of serum from the American alligator (Alligator mississippiensis). Antiviral Research, 66(1):35-8.

(2) Merchant ME, Roche C, Elsey RM, Prudhomme J (2003). Antibacterial properties of serum from the American alligator (Alligator mississippiensis). Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 136(3):505-13.