Viral Extinction

We conducted the interview via email with Dr. Brown

Email Transcript
Me:

Dear Dr. Brown,

My name is Ben Mackey and I am a first year student at Carleton University. I am part of the “Monsters and Monstrosity” cluster in the ArtsOne program. More specifically, my colleagues and I are part of the “Sociology of the Weird and Apocalyptic" first year seminar.

My classmates and I would like to ask you if you’d be willing to conduct a multi-question interview with us via email or any other form of communication (though I’m sure that doing this via email is convenient for the both of us) to which you’d help us entertain the thought of an apocalyptic scenario based on your profound knowledge in the fields of virology and immunology. We would like you to note that most of us aren’t as fluent as you in these fields of study and that if you agree; the contents of the emails will most likely be posted on the cluster web page (http://monstrosity.ca). We considered you for this interview mostly because of your important and interesting research and we would be grateful if you would participate in this interview.

Thanks for the time,

Ben Mackey and classmates

Dr. Brown:

Dear Ben,

You raise a very interesting topic/scenario; my imagination of the worst case infectious apocalyptic scenario. I can respond with ideas and concepts with as little jargon as possible.

Fire away. I am juggling things these days, so hopefully the scope will not be too large or onerous.

Regards,

Sent: Monday, March 25, 2013 12:32 PM

Me:

To start off and to get the ball rolling, are there viral diseases that can alter someone’s personality? Can it be contagious? If such a disease doesn't already exist, is there the possibility of one ever existing?

Dr. Brown:

Ben,

Yes good example is HIV that cause neurologic diseases at later times in infection; here is a discussion of some of them in this article:

"Psychiatric Complications in Human Immunodeficiency Virus Infection"

Rabies is a classic in foxes and dogs (as well as other animals including humans)  with dumb or furious clinical outcomes, where the animal l bites everything and everyone around including other animals that get infected from thr saliva, so the natural history involves virus entering the body at the bite and moving to the brain in nerves and affecting behavior to lead to spread via infected saliva through biting behavior.

Another one is Borna disease virus recently discovered in horses in Germany that has a link with animal and human psychosis (schizophrenia).

Experimentally infected mice become frenetic, run round the cages and hang upside down, and exhibit bizarre behaviors such as hyper sexualized where males continuously masturbate.

An interesting parasite is Toxoplasma gondii (causes Toxoplasmosis) that normally infected rats which makes then lose fear of cats (they become attracted to cat urine) where they are eaten to infect the cat and compete their lifecycle with shedding of eggs in feces to initiate another round of infection through rats. 1/3 of humans are infected with this parasite (from our cats) but it cannot mature in us and just sits dormant on our brains. (This story is changing with HIV infection in Africa that allows the parasite to grow an cause fatal infections in humans with psychotic symptoms). There is statistical data that humans become risk takers and are more likely to be in accidents, take drugs or engage in promiscuous sex. So not a virus in this case, but an infectious parasite.

The parasites have abilities to modify animal, insect or human behavior in rather grand ways but you asked about viruses and so I won’t give any more parasite stories.



Infection of pregnant mice with several viruses that induce strong inflammation is known to result in fearful and inhibited behavior of the resulting mice.

There are subtle things, like influenza infection that results in mental depression that contributes to the malaise associated with the aches and pains, and anorexia that will weaken your defenses.

These are some things that come to mind but I just got this on Google that lays out a broader tapestry to work from as well:

"The Role of Infections in Mental Illness"

Regards,

Prof. Brown

Sent: Tuesday, March 26, 2013 10:07 AM

Me:

While HIV is treatable to reduce the symptoms and there are vaccines that prevent the manifestation of rabies, is it possible these viruses might evolve or mutate to a stronger virus that's difficult to treat?

Dr. Brown:

Ben,

There is much to response to but will send a short note:

For one thing there is no vaccine for HIV; so far none of them worked (it remains the Holy Grail of vaccinology), and some made the vaccinees more infectable—called immune enhancement where infection with a virus makes you more likely to get serious disease or infected with a related virus. The classic story for this is Dengue fever (aka bone break fever because is feels like someone is breaking your bones for 2 weeks). Dengue is on the march globally hardly anybody dies unless you have been previously infected with one of the 4 serotypes (ie immunologically classified groups) and the other infection is caused by a different serotypes will result in  Dengue Hemorrhagic fever with "renal syndrome" ie Dengue with attitude.

Regarding HIV we have highly active anitretroviral therapy (HAART) which are combinations of usually 3 drugs which effectively treat the virus infection to prevent disease. Use of any one drug is ineffective because the virus easily generates mutations that can escape the drug but HIV cannot make viruses with 3 mutations at once and is killed. This does not kill all the virus in your body (because HIV inserts its genome (its set of genes) into your genome and can go dormant (to hide) and unfortunately many people often go on to have mental dysfunction (a common sequella of late stage AIDS) even though AIDS is kept at bay by HAART.

Viruses especially virus with genes made out of RNA (the most prevalent lifestyle for viruses on the planet; flu, HIV, measles, mumps, rabies, polio, to name a few) make a lot of mutations usually a bit less that about one mutation in every virus is normal. Viruses can keep more or less the same coding without mutation because the ones that have none tend to be maintained in a constant environment but there are always mutants around in a virus populations. This is called the quasispecies which is a mutant cloud that defines all virus populations.

In general drug treatment drives the evolution of resistance in viruses (and other microbes). The usual pattern is that the resistant virus is initially hanging on by it fingernails and so it able to replicate and spread with drug but is not unusually aggressive. But continued evolution in the face of drug especially under conditions of high infection will drive increased virulence (conditions of high density of hosts with high dose transmission always does the trick).

So in general Microbes will evolve resistance which often weakens them a bit and then more mutations must occur to restore normal growth. There are examples where resistance gives more disease right away a seen in bird flu for turkeys (where a mutation (a change in a gene letter code)  lets the virus dodge a killer antibody but the same mutation makes it infect more tissue).



Another thing microbes and viruses can do is if you keep kicking them with drugs continuously (easies to do in a laboratory). The viruses that are not killed can sometimes be “hypermutators” where mutations have occurred in the gene copying machinery to make viruses more mutable so they can evolve faster against drugs (or any negative stimulus). The super mutators are always the best growers with drugs present but they are poor growers when the drug isn’t present because most of the mutations make the bug weak (ie loss of function).

In fact some drugs used to treat viruses, such as ribavirin cause so many mutations that the virus is driven to mutational extinction due to so many mutations that they are driven over the threshold for survival.

I recall that you said you may mount these on a website.

Feel free to correct typos and grammar to improve readability.

Earl

Sent: Wednesday, March 27, 2013 8:42 AM

Me:

Is there a possibility of a virus being capable of wiping out large populations (almost in an apocalyptic way)? Has the impact of virus ever been underestimated in regards to its effects on a population?

Dr. Brown:

Ben,

Highly virulent viruses can almost wipe out densely packed populations but the are often isolated individuals that survive.

They can repopulate, then you are not extinct.

The earliest recording of devastating plagues, often had practitioners and lay people fearing the end of humanity, have often killed 1/3 - to - at most ½ of the  population; such as when 10M killed in the Plague of Athens. This happened at the end of the Peloponnesian wars, as many epidemics have in nature because of the fact that the large concentrated populations living  under limiting conditions of food and shelter often became prey to highly virulent outbreaks of disease introduced from the environment or foreigners.

Napoleon's armies were decimated by tick born typhus in the winter of his assault on Russia. Napoleon's armies were again defeated by yellow fever (epidemic of black vomit because for the color of vomited coagulated blood) when he sought to invade the Americas.

For the world’s worst pathogens ie with mortality approaching 100%, then you may be left with resistant hosts if enough exist to allow the rare resistant host to survive (population less than 100,000’s could be completely killed). When HPAI H5N1 infected commercial poultry operations in Nigeria a few year back they misdiagnosed it as fowl cholera and applied antibiotics which were useless against H5N1 virus. A few birds remained in chicken houses of 5-10,000 birds that probably included chickens with some mutation that made them more resistant.

A similar thing happened with the great Australian rabbit eradication program/experiment where they infected the out-of-control European rabbit population with Argentinean rabbit pox that is near 100 % fatal. (It however it doesn’t kill Argentinean rabbit that have been selected to be resistant due to the presence of that virus (it is a rabbit version of Smallpox).

So they released the virus into Australian rabbits and it killed >99.9 of the rabbits however the surviving  rabbits were the one that were more resistant and they repopulated the land with resistant rabbits to again eat the grass down to the dirt.

So life is very resistant, and species can survive epidemics but you must first undergo the firestorm and lose most of the population ie be hard hit from resistant organism to be selected.

One of the worst episodes of introduction virulent organisms was the transfer of European diseases to NA natives who were 90-95% killed in the process. They had not had the opportunity to gradually develop resistance to influenza, measles, smallpox, typhoid, typhus, whooping cough, tuberculosis, cholera, diphtheria, chickenpox etc and so had higher mortalities.

It also goes the other way such as for Napoleon or others explorers who were all killed when visiting jungle or tropical habits where they had not been selected for immunity and resistance by their forbearers. The natives where immune but the Europeans were killed, so fair is fair. The lessen being is you don’t want to be the first in your tribe to catch a new disease.

So yes some infections can kill groups but it is tough to kill very large populations, to the point of extermination.

Regards,

Prof. Brown

Sent: Thursday, March 28, 2013 12:52 PM

Me:

If such an event were to occur with a 100% mortality rate, what factors would researchers have to consider when developing a vaccine within a short amount of time?

Dr. Brown:

Ben,

Been busy with media contacts about the virulent H7N9 infections in China and other stuff.

To develop a vaccine you need to first identify the infectious agent, which can be a challenge.

Today we often do deep sequencing of a tissue sample from an infected person and identify all the genes that result and run them (millions) against those in Genbank to identify candidates. Any infections organism then becomes a candidate (you usually find many so difficult to know what is the disease causer unless it sticks out like a sore thumb) but you then have to satisfy Koch’s postulates to confirm that the infections agent is the cause. Must isolate organism and it must be present in all infected persons. You must culture orgasm and  grow as a pure culture in lab. Then you must infect human/animals to regenerate the disease. You must then reisolate the pathogen again and confirm that it is present. If these are all positive then  the new agent is proven as causing the disease. (Can be tricky ie multiple organisms causing the disease in combination sometimes.)

Once isolated you must grow it to make microbes which could be killed and used to vaccinate or you can express cloned genes from the organism using recombinant technology to make proteins for a vaccine however you would have to know or determine that the antigens (protein) will stimulate an immune response that would kill or neutralize the toxicity of the pathogen (we currently vaccinate against tetanus and diphtheria by injecting formalin inactivated toxins of these bacteria so we don’t actually kill the organism but we stop the organism from causing disease and limit its ability to grow.

The most routine way of making vaccines is grow them up and inject inactive bacteria/virus, but many bacteria and viruses cannot be cultured in the lab; oops a problem. Ie until 4 yr ago we couldn’t grow HCV (and their still isn’t a vaccine; the HCV evolves to quickly and escapes the immune response (it also hides itself inside a coat that looks like antibodies and so the immune system has a difficult time recognizing it as foreign) ). We can grow HIV but it is difficult (also no vaccine). Most of the bacteria in our intestines can’t be grown So the problem of culturing is big. However if you grow it in something like chicken cells or chicken embryos you then have to purify it and then kill it with something like formaldehyde then clean up the material and inject it into animals to see if it works and then humans see if it works.

The approach works for influenza and polio but doesn’t work for RSV or measles, in both of the later cases the vaccine made the infections worse due to immune enhancement (see earlier communication) or an imbalanced immune response to infection that leads to greater damage.

Another type of  vaccine is live virus that is attenuated (doesn’t cause disease) ie related virus from another animal or the pathogen after having been adapted to another host which makes it les virulent for the original human host (it can genetically revert to virulence so have to be safe).

The other issue if this thing kills 100 % it would kill your lab workers unless you work under level 4 conditions — not conducive to manufacturing.

The alternative to vaccines is making antibodies en in animals or taking them from survivors and injecting their antibodies to cure those that are infected—called passive immunization.

So many challenges:  pretty well all the experimental vaccines they made for SARS induced greater disease in challenge infection testing compared to the animals that were no vaccinated ie immune enhancement.

We still don’ have a vaccine for HIV after all these years so you can want a  vaccine but some of them are hard to makes.

Regards,

Earl

Sent: Tuesday, April 02, 2013 9:53 AM

Me:

I personally believe that the media often exaggerates their coverage of certain things. Do you believe that the media over-exaggerates their coverage on viruses like the H1N1 virus? Or do you believe that the media’s cause for concern was justified?

I've also been busy and I understand that you don't have much time. This is the last question. Thank you for participating in this interview.

Dr. Brown:

Ben,

The media has to get your attention to read/view them so they often exaggerate the lead statements.

This I consistent with “if it bleeds it leads."

New outbreaks are tricky to gauge by everyone involved. For one thing we are in a new era of infectious diseases, some call it the post-infectious disease era or the age of emerging infectious disease because we have conquered our infectious diseases.

Gross generalizations are being  made here, and a myopic view of th advances made in the western developed worlds. However, infection diseases remains the number one cause of death for those under 10 y of age globally.

We also don't know how many new viruses have the ability to infect large numbers of victims before we get them under control. Most people are complacent now, just make a vaccine or dose with antibiotics and don’t bother me about it. For some is all a conspiracy of the pharmaceutical companies to drive their bottom line.

Yes I think that the media is sensationalist with infections but the researchers promote this hype because is makes their work more important and fundable (this was the basis for the overreaction to the H5N1 gain-of-function research). Also scientists are chasing a limited research pool of dollars so anything that gives them an edge is fair game. Scientists are also people who are driven by vain-glory, lucre and sex. Reputation is so important in science making it now more like a star system than a meritocracy. I am getting a bit far afield here but I think you can see how this mix of components can be incendiary when superimposed on the next outbreak.

Case in point, we have a few people dying of viral pneumonia in china due to a novel subtype of influenza, H7N9, that has never been seen in humans before; it appears to be a situation of spillover of avian influenza from poultry from the wet-markets (see my interview with CTV on this topic for more details.) However we haven't observed many pandemic in their genesis and therefore don't know how to read such events.

We do know however that the first steps in established a new infection in a new host is gaining the ability to infect it. This is occurring in H7N9 but this virus currently remains a zoonosis and is not a human pathogen that spreads among people.

There has been some hype at this point but there are not many scientists who are promoting hyperbole because there has been backlash against overstating concerns in the recent past.

Regards,

Earl

Analysis
Our main goal for the emails between Dr. Brown and our group was to explore the possibility of a mass viral extinction of the human race. We also wanted to find out the ideal characteristics of this virus and how it would be medically combatted.

Our beginning question was more aimed at the personality altering aspect of a global pandemic and meant to touch on the viability of a zombie or “feral” outbreak much like our described story for the final group project. Though there are types of personality altering diseases such as rabies and HIV, we concluded it would seem unlikely that any virus would affect a human brain to act in a different in a major way. By a “major way” it is meant that no virus would ever cause someone to mutate their personality into a flesh seeking zombie and peel the flesh off their neighbour. Though the diseases described would cause slight agitation and a whole list of other brain functions such as appetite and vision impairment it is unlikely for someone to undergo a change so immense without killing the host.

He brings up a case of mice infected with an abnormal parasite called Toxoplasma gondii that normally infected rats which makes then lose fear of cats. This is transmitted from the cats to humans in various ways and affects their personality in a minor way. “There is statistical data that humans become risk takers and are more likely to be in accidents, take drugs or engage in promiscuous sex”. Dr. Brown adds that this is not a virus but a parasite.

We began to wonder about the treatment part of the whole zombie scenario where a cure becomes the main objective of people in media. In some movies (Resident evil) the doctors try so hard to combat the virus that they end up mutating it into something more potent. Dr. Brown explained that in HIV some of the vaccines made the host more infectable. The host ends up usually becoming hyper-sensitive to similar diseases and altogether ends up becoming a kind of vacuum for other diseases. In separate cases, when trying to treat a disease with a drug sometimes the drug will end up forcing a mutation itself.



In a later question we ask him how in a short period of time one would combat such a deadly virus. The hardest part would be to find the infected host. Once finding who become susceptible to the virus we would need to grow the organism which can be even harder. To work on this deadly virus one would need to work under “Biosafety level 4”.

We decided to jump back to our original idea of the extinction of the human race. The idea that a population will be completely wiped out is unlikely, as there will be people who are immune to the virus. He brings up a case about the Plague in Athens and a tick born typhus in Napoleons armies which killed mass amount of people. He goes on saying that there will always be, in worst case scenario, a few hundred thousand people left on the planet that will survive and repopulate.

The last question was just a personal inquiry on how Dr. Brown thinks the media portrays deadly diseases and basically the over exaggeration that they place on it to make the viewers interested and watching.