Wednesday, April 05, 2006

Dr. Pianka and Ebola

Well it certainly seems like Dr. Pianka has managed to stick his foot firmly in the cow patties and now it's raining cow pats all over him! Everyone and their dog seems to have jumped on this issue and there is quite a large amount of drama going on among blogs, the news media and all sorts of other places.

Firstly, I'll link to this post on the Pandas Thumb that talks about the issue and this one on Pharyngula gives links to various people on the situation. Personally, I recommend reading various accounts for your-self and determining who is merely acting idiotically to blow this whole thing out of proportion. A lot has been said on the issue about what was and wasn't said by Dr. Pianka, with most combatants on the issue never actually hearing Pianka speak at the event. Now as some may realise if you've read my blog for a while, I tend to ignore these examples of spinning brown toilet paper in a bowl drama, as I don't know the full facts and would rather not comment on something I don’t know the full details on. Me being in New Zealand, it's somewhat predictable that I didn’t hear Dr. Pianka speak and I'm not about to pretend I did like some are. I will state that from the general comments I've read, it does seem the whole thing is being blown out of proportion by creationists like Forrest Mims and ID blogs (like Telic thoughts and Uncommon Descent) for propaganda purposes.

In any event, what quite frankly interests me more is the science behind what Dr. Pianka is claiming. Dr. Pianka makes the point that our burgeoning human population is just getting far too high and that eventually, if we don't manage our population numbers, nature (as in, the trees and stuff, not the journal Nature) will do it for us with an incredibly lethal virus. The virus that Pianka seems to think would be a suitable candidate is the Zaire strain of Ebola. Now it's important to bear in mind that Ebloa strains are named after the geographical location they were found in, which should explain the "Zaire" part of the name and have various different lethality rates. Ebola Sudan, for example has a lethality rate of around 60%, while Ebola Zaire has an amazing lethality rate of 90%, which is undoubtably the reason that Dr. Pianka picked it as his prime example killer virus.

This is because Dr. Pianka in his talks claims that the larger the human population becomes, the more susceptible it would be to having it's numbers devastated by such a virus leaving a mere 10% left. A full 90% lethality rate for a virus is a horrific thing to think about for anyone and Ebola itself enjoys a high "fear mythology" among the general public. The problem I see with all this coverage of what Dr. Pianka said/didn't say/what people hope he said is the lack of any critical analysis of this potential super virus plausibly wiping out 90% of humanity. It's almost like nobody wants to discuss the actual science behind the claim and instead focus on trying to make Dr. Pianka say whatever the listener wants people to believe he said.

So is it actually possible? The first thing that’s important to realize is that Ebola isn’t all it’s cracked up to be in the mind of the public. As far as being an infectious disease goes it’s pretty poor. Although the method of transmission of Ebola is still a relative mystery, one idea is that it’s spread from bat guano or some other animal to human transmission vector (infected meat?) to bush workers. It then spreads further when the workers die from traditional funeral practices in Africa where the bowels are ‘cleared’ of material before being the person is buried. From there the Zaire epidemic virus was spread through the reused needles of health care workers to new victims. Once the CDC moved in and put a stop to the traditional funeral practices, cleaned up the use of infected needles and isolated infected individuals the epidemic was halted relatively quickly.

Now, Ebola (a member of the filovirus family) is a horrible virus to actually get and belongs to a little private club of viruses that cause “haemorrhagic fevers”. Essentially these viruses kill by basically ripping apart the blood vessels of the unfortunate host causing huge amounts of internalized bleeding. This internal bleeding is devastating on the patient as it reduced blood pressure (and hence will lead to organ failure eventually), dyspnea and gives victims the classic ‘zombified’ look with the sunken eyes, clinging skin and lack of pallor. Death typically occurs very rapidly, often preceded by a violent amount of spastic convulsing that causes the infected individual to splatter blood all around them. Usually after around one to two weeks after infection as the unfortunate individual finally dies from septic shock or sheer blood loss, although if they are lucky they may simply drown in their own blood first. An even luckier few manage survive, although it doesn’t seem that serum antibodies are involved in this defence*.

Undoubtedly the first reaction to this from our point of view is “how horrible!” but from a viral point of view you should see such a process as “how stupid”. Why stupid you ask? Well, the first thing to do is imagine you are a little Ebola particle and you want to make more little Ebola particles, which is pretty much the only thing that viruses do. You have several very important considerations when you’re a virus:

1) You must be able to get into the host in some manner.

2) You must be sufficiently virulent to overcome the innate immune system. Being destroyed before you’ve done anything isn’t much fun.

3) Then need to be able to find the right cell or cells you replicate in and then be able to actually get inside of them.

4) Even when inside a cell you still need to be able to find where you replicate, such as the cells nucleus or just in the cytoplasm.

5) After all that and you’re happily replicating away you still need to get back out of the cell. Not always as easy as it sounds!

6) Once you’ve finished there you have the additional problem of the host adaptive immune response catching up and you’ve got to deal with that too.

7) You might now think “Surely no more” but nope, you’ve got more to do because what comes in must come out…somehow. You’ve got to have a mechanism for getting to another person or all your little progeny are going nowhere fast.

So you can see that the life of a virus is actually pretty complicated and it’s not as easy as some might think for a virus to do its thing. There is a wealth of problems facing a virus that wants to spread among people and Ebola, like many viruses solves some problems really well but is really bad at other things. What Ebola is bad at despite its gruesome reputation actually make it an amazingly ineffective pathogen for the doomsday world scenario.

To figure out why it’s best to ask the following question: What kind of host are we for Ebola anyway? Well, the answer is fairly simple, we’re a dead end host and for Ebola we’re not something it wants to infect. What I mean by this is when Ebola infects a human being the virus finds that it replicates like mad but it can’t escape. All of the subsequent viral progeny are doomed, the host is usually doomed as well and neither the virus or host wins, much like an audience watching Alien vs. Predator. If this is the case of course, it’s natural to wonder why Ebola is so virulent to the point of being self-destructive in a human. The simple answer is that we’re not the host that Ebola is interested in infecting and it’s evolved to infect another organism.

This is because pathogenic interactions are an example of co-evolutionary warfare between the host and the pathogen. A change in virulence of the pathogen may adversely affect the ability of the virus to spread from one individual to another and on the other hand, a change in the host immune system may force the virus to get around the problem. Ebola is adapted to infect whatever it normally infects in nature (I’ll propose bats for now, but there are other candidates as well) and it’s mechanisms of avoiding immunity and virulence have evolved to combat those of its natural host. As it turns out, when that virus gets into us there are three possibilities that may occur: 1) The virus is immediately annihilated by immune defences or simply can’t replicate. 2) The virus destroys the host or 3) the virus evolves in some way so that it can survive in the new host population.

Ebola is stupid because it does number “2” on the list and because of the sheer rapid destruction of the host that it infects it hasn’t got any time for number “3”. Going back to the seven things a virus needs to do to succeed in a host population, let’s contrast Ebola with another very successful human viral STD, namely Herpes Simplex Viruses (I and II). Recalling those seven points were:

1) You must be able to get into the host in some manner.

2) You must be sufficiently virulent to overcome the innate immune system. Being destroyed before you’ve done anything isn’t much fun.

3) Then need to be able to find the right cell or cells you replicate in and then be able to actually get inside of them.

4) Even when inside a cell you still need to be able to find where you replicate, such as the cells nucleus or just in the cytoplasm.

5) After all that and you’re happily replicating away you still need to get back out of the cell. Not always as easy as it sounds.

6) Once you’ve finished there you have the additional problem of the host adaptive immune response catching up and you’ve got to deal with that too.

7) You might now think “Surely no more” but nope, you’ve got more to do because what comes in must come out…somehow. You’ve got to have a mechanism for getting to another person or all your little progeny are going nowhere fast.

Let’s examine how the two viruses fair on these points against one another:

1) A poorly understood mechanism of transferring between people, but isn’t very efficient as Ebola cannot spread by aerosol transmission and seems to require direct blood or tissue contact.

1) Herpes can spread through direct contact from simply rubbing infected skin on either the lips or genitals.

2) Ebola overwhelms the host innate immune system and rapidly causes infection. I’m not sure on the molecular details of this, but the high infection rate obviously means that Ebola gets past these mechanisms fairly easily.

2) Herpes simplex viruses can interfere with host innate immune defences, such as interfering with the intracellular production of interferon and preventing the cell from going into apoptosis (cellular suicide).

3) Ebola targets receptors that are found on a wide array of cells on the body and can infect nearly any kind of tissue it encounters. To accomplish this trick it tends to degrade the integrity of the epithelia surrounding blood vessels and can escape virtually anywhere in the body.

3) Herpes simplex virus typically targets skin epithelial cells and also cells of the nervous system. It generally only replicates in the skin cells, which is what makes those horrible warts and in the nervous system it tends to hide out.

4) Again, Ebola manages to succeed in this department and can replicate in a wide array of cells.

4) Herpes is somewhat smarter than Ebola here. In its target cells the virus tends to replicate like crazy but in non-target cells the virus integrates itself into the cells nucleus and hides away dormant.

5) Ebola gets out of cells by blasting them apart by producing huge hordes of viruses.

5) Herpes simply sneaks out of nervous cells by tagging along actin filaments and ‘roaming’ down them as if it’s being pulled along a rope. To get between cells it likes to infect it can simply spread using specialized proteins and jump between cellular tight junctions without destroying the original cells.

6) Ebola succeeds better than many pathogens here because it’s so incredibly fast. The adaptive immune system typically takes a week or so to get going, but with the speed of infection and the sheer numbers it just overwhelms the adaptive immunity. This is so prominent a factor that it’s not even thought that adaptive immunity has much of an effect on the success or failure of Ebola to kill its victim.

6) Herpes is very clever in this regard. It rapidly replicates and is very infectious for the periods that it is replicating. In addition to this, herpes can hide in the nervous system, which is ‘immuno-privileged’ where it can’t be touched easily by the immune system. When the individual becomes stressed or otherwise immuno-compromised, it comes back out wanders down the nerves actin filaments and causes a new infection. In this manner it’s no surprise that a flower you give your girlfriend will last for a week, but Herpes will last for life.

7) Ebola fails miserably right on the finish line. It does everything else rather well, but when it comes to getting out of the host it gets a big fat ZERO. Firstly, it kills its host way too quickly to have maximum contact with other individuals to spread more viral particles too. Additionally, signs of an infected individual are fairly obvious due to its distinctive symptoms and infected individuals are effectively bed-ridden (can’t move around). This means they are easily quarantined or spotted by health-authorities. Additionally, its requirement to be spread by direct contact with blood makes it difficult to spread to new individuals as say, skin contact or by aerosol transmission.

7) Now this is how you do things. Herpes can secrete itself onto the surface of epithelial cells and can be spread simply by rubbing ones genitals against the infected genitals of another person. This means Herpes gets around problems like condoms (although condoms do help a bit as well too some degree) and removes any requirement for fluids. It’s also able to make its own open sores if required and once established in a new host is there for life. This is also another massive advantage, as herpes lasts so long it has a persons entire lifetime to spread to another individual. It maximizes the amount of total hosts it can get to and sure enough, Herpes manages to infect millions and probably billions of people world-wide.

Best of all and is the other key to Herpes success is that it causes no overtly obvious symptoms of disease until late into an infectious cycle. The host that doesn’t know about the virus hasn’t got the chance to change their behavior to avoid being infected or spreading the disease further.

So in terms of these two viruses I would rather be Herpes than Ebola. Ebola has the reputation sure, but Herpes at least has a chance of spreading itself to other humans and surviving. There is little point to being a virus if you can’t spread to another human being! So let’s reanalyze the claim that Dr. Pianka makes that Ebola may be a candidate for wiping out 90% of the human population in this world.

Firstly, as I’ve described above, Ebola isn’t going to have hosts that are infected but display sub-clinical infection. Now what I mean by a sub-clinical infection is an individual who has disease, they are directly producing virulent virus, but does not have any outward signs of a fever or any harmful symptoms (see an earlier post I wrote here for more details). This allows the virus to slip under the radar of health authorities and basically avoid detection to infect as many people as it can. As you can imagine, Ebola isn’t anywhere near as subtle as this and infected individuals could be spotted, quarantined and monitored very quickly.

Secondly and working against Ebola again is the fatality rate. It simply kills too many of the people it infects. Ebola would likely run out of hosts well before it managed to infect a wide amount of the human population. For example, if you are a virus as lethal and generally quick off the gun in causing infection as Ebola, you may wipe out the entire population of a village and never get the chance to be taken to the next village, say 20km away. You may think that “well, we’ve got planes and stuff” but bear in mind the claim is that we’re looking at a virus that wipes out 90% of humanity and it has to get to that 90% first. Not everyone lives in cities or areas with easy access by planes or even other forms of transportation!

Thirdly and most definitely what will put a nail in the Ebola as humanities destroyer coffin is the problem with person to person transmission. As I mentioned earlier, the main chance I see of Ebola transferring between people is the large amount of blood, sputum and other fluids discharged around by dying patients as they convulse near death. This mechanism, while horrific is probably not going to be sufficient to transfer from quarantine facilities, hospital staff and even other patients. The reason for this is that containment mechanisms, such as positive pressure sealed rooms, hazard suits and other protective mechanisms can be taken to avoid contact with infected blood. Additionally, even without all of these protective measures, many of the health-care workers and CDC researchers that had contact with Ebola infected patients didn’t manage to acquire an infection.

Lastly and again relating to transmission is this concept of Ebola ‘developing’ the ability to transmit by an aerosol route. With the way Dr. Pianka seems to put across this concept it would seem only a matter of time that Ebola could develop this trick. Nothing could be further from the truth. The first significant development for Ebola to be able to do this would have to be for some form of selective pressure on its natural host. For example, there would have to be selection for either the virus to move from its current means of transmission in its natural host, which could be through an insect vector or by a fecal oral route, to the lungs or mucosal surfaces (like inside your nose). Next, the virus would have to develop a means where it could survive in the outer environment such as dealing with desiccation (drying out) or high amounts of UV light. Finally, even past that point it would have to develop mechanisms of recognizing where it is and binding onto lung tissue.

I’m not one to do the creationist/ID tactic of making up huge numbers purely on whatever I feel will suit the answer I want best, but I would be hesitant to think that Ebola would have a solid selection pressure to alter its natural mode of transmission (it obviously works) to an aerosol method. It could happen, but the mechanism isn’t very likely and as a candidate for the extermination of 90% of the human race it’s not a very good one. There are many other viruses that would be much more capable of such a ‘super-pandemic’ as required by the scenario given by Dr. Pianka, but even then there are considerable problems with a virus killing that many people.

Dr. Pianka may be a fan of Ebola for whatever reason and may genuinely think it’s a good candidate for the downfall of humanity. Unfortunately, this is probably based a lot more on the fearsome reputation of Ebola and less on the actual science of a virus capable of creating such a large scale pandemic.