IamA researcher interested in parasitic mind control. I use zombie ants as my study system. Want to know more about my research? AMA!

Do we see different types of fungus affecting non-insect animals? If not, is there something about the insect brain that makes it more prone to zombification?

Does this fungus actually control movement systems of the ant or does it act on another part of the brain to simply increase desire to move up? Exciting work!

Thanks very much for your questions! To answer the first one: No, this group of fungi infects insects and spiders and no other animals. However, they infect a whole range of them. You can find many different insects that get infected and among ants we see it across a range of species. These all have their own specialized species of (Ophio)cordyceps fungus though. Other animals do encounter other parasites that can manipulate their brain though! Toxoplasma is a nice example for instance. It takes away the innate fear of cats in rodents and makes them actually attracted to them. There are even researchers that have stated that Toxoplasma might influence human behavior. So, I don't think the insect brain is more prone to zombification. I think, because insect behavior and therefore change of that behavior is easier to study, we can pinpoint a lot better that it is being controlled by a parasite. To answer your second question: we don't know the mechanisms yet. However, I am about to venture in that direction with my work. My microryza crowd funding campaign that is running at the moment is all about unravelling the parasitic genes that might be in play. Have a look at the project's page if your interested in seeing what I am planning https://www.microryza.com/projects/how-does-a-parasite-create-zombie-like-behavior

How "zombie" are the zombie ants? Are they absolutely controlled or do they have some self awareness?

Zombie is the word the media at one point connected with this phenomenon and because people know our study system as such we use it though it is not correct (they are not living dead, they are very much alive when they get manipulated and after that they die). With ant behavior we can't really talk about self awareness, their behavior displays the task they have in the colony which should be seen as one big super organism. The fungus breaks into this pre-programmed behavior and alters it.

So they're more like hacked ants than zombie ants?

Yes! That's a great way of thinking about it!

Have you played The Last of Us?

Yes I did! Loved it!

Do you think it's possible that a zombie like fungus could ever happen in humans? If not something created by nature, in several years when our understanding of biology is further along do you think it could be created by humans? Like a zombie bioterrorism weapon?

The fungi of the genus Ophiocordyceps that our lab study are very species specific and this behavioral manipulation is a result of a tight co-evolution between host and parasite. The manipulated biting is very stereotypical and fine-tuned to the different ecosystems we find this phenomenon in. Within an ecosystem we for instance don't even find all ant species infected, only a specific few. So, I don't think it will just suddenly transmit to humans. The more we learn about parasites and their life cycles in general the more we find that certain species can influence the behavior of their hosts. This is very interesting because however hard the field of neuro medicine for instance tries to treat behavioral diseases in patients, this field is still less successful than certain parasites. I think in the future we could therefore thus learn from the mechanisms these parasites employ to try and develop treatments for these patients.

Do you know much about toxoplasma gondii? I've read that there is a high rate of infection in males who die in motorcycle accidents. The theory goes that it can lead to high risk behavior in humans the same way that infected rats are attracted to cat urine.

Hi! I'm a Graduate student specificially studying Toxoplasma's behavioral modification abilities in mice! I think I'm qualified to answer this.

The data is very, very solid on Toxo's manipulation of rodents to become attracted to cats. This has been well-replicated, although a mechanism is still elusive.

In humans, research has linked Toxoplasma infection to a lot of things. The results of decreased reaction time and personality changes mostly come out of a lab in the Czech Republic, conducted via the "gather a hundred undergrads and make them do things" method, or by screening of army recruits. I'm not very confident in those results, because the experimenters screened for a LOT of things, and the significance of the differences seen was not great. This is the same author who at one point used the phrase "results in X approached significance" in an abstract of his paper.

Toxoplasma has been linked in a number of studies to schizophrenia: many authors describe that schizophrenics are 2 to 3fold more likely to be harboring Toxoplasma than the general population. Whether this is correlative or causative is unclear, however. It could be that lower hygiene and ability to self-care in people afflicted by schizophrenia, as well as elevated risk behavior, could lead to the higher infection rates seen.

If Toxoplasma did have a causative relationship with schizophrenia, you would expect rates of schizophrenia to correlate with rates of Toxoplasma infection from country to country. However, seropositivity of Toxoplasma varies from 10-30% in North America/ Europe, to as high as 80% in Central America. However, incidence of schizophrenia is completely flat worldwide.

The primary hypothesis of Toxoplasma's behavioral manipulation is that the parasite uses parasite-encoded tyrosine hydroxylases, the rate-limiting step in dopamine synthesis in neurons, to modulate neurotransmitter firing in rodents.

However, it was recently (within the last few months) demonstrated that rodents infected with a defective Toxoplasma strain that is incapable of remaining encysted in the host, still causes rodents to demonstrate cat-attraction behavior, many months after no trace of parasite remains in the rat. Which suggests remodelling of the rodent brain at some point during active infection instead.

That's as far as science knows, for now. Once I finish my thesis I'll toss you guys an update!

Sorry to hijack your AMA, but I can't help but love what I do and talking about it.

Go ahead and hijack away! Awesome answer! Did you see there are some more Toxo related questions below? Feel free to answer them! I have a hard time keeping up the pace answering questions as it is, so any expert input is very welcome

"The theory goes that it can lead to high risk behavior in humans"

That is indeed one of the interesting theories. Unfortunately, I don't know any more than the papers that are published about it. It is an intriguing subject which would be a cool AMA for one of the researchers working on this! In and episode of "The Nature of Things" this is briefly discussed, you can find it on YouTube: https://www.youtube.com/watch?v=I3SzH_7QjIA

Do you know the actual physiology of this process? How could these parasites have developed this evolution-wise?

That is a very good question and one we have on our minds as well. We don't know the actual physiology of this process yet. This is something we are working towards though. Until recently, we were only able to study this phenomenon in the field, where it is very hard to get into the questions of "how". Now, we have the system in the lab we are starting to unravel the mechanisms, both from the host and the parasite point of view. My microryza campaign is trying to get funding for the parasite part of this question. To get into your evolution question: we know from work done on different species of Cordyceps and Ophiocordyceps that this group has evolved from fungal plant pathogens. So, at some point in time these fungi switched from plants to insects. Not all of them manipulate behavior though, and some of them switched back to infecting plants. What genes are exactly involved in this switch is something that we however don't know yet

How is this studied in a controlled environment? Do you expose the insects to the parasites and just kinda see what happens?

yes, we recently succeeded in reconstructing it in the lab. All the research that was done before that was done in the field. It is kinda done in the way you are stating here: we infect our insects and look at survival rate and their behavior. Then we freeze the infected ants at different points in time to be able to study their genes.

How'd you get into that field? What kind of equipment do you use?

When I was an undergrad studying biology I got most excited by courses discussing biotechnology, genetics and microbiology. Before I took microbiology, I actually thought fungi were pretty lame but the more I learned about them, the more I got intrigued by the awesome things they can do. I got so intrigued I went on to do a Master's in which I spent 10 months working in a fungal genetics lab and decided I wanted to pursue a PhD in that lab working on fungal complexity. By the end of my PhD I met Dr David Hughes at a conference, who told me he was working on the one group of fungi I was most intrigued by: the zombie-making Ophiocordyceps. He offered me a postdoc position, I accepted, and here we are today. If you ask me, one of the best decisions I have ever made! You can thus already guess from this story my approach is a molecular one. One of the coolest pieces of equipment I am using is a laser capture microscope. This scope is equipped with a UV laser that can cut out biological tissues of interest. I have used it during my PhD to study fungal heterogeneity and am now planning on using it to collect the fungal cells that are surrounding an ant brain to study how it manipulated this brain. I wrote a lab note about it which I posted on my microryza page. It includes a movie showing you how the laser works! https://www.microryza.com/u/jZaOQ

Thanks for doing this AmA.

I've always wondered if there was a way to use these types of fungus for pest control. Do you know of anyone in your field exploring this type of use?

Hi, the answer is YES! People are using insect infecting fungi for pest control. The two genera that are mainly used are called Metarhizium and Beauveria. The sexual states of Beauveria are considered species of Cordyceps. They don't manipulate behavior as far as we know but they have been used as a treatment for a variety of insect pests. One of the research teams working in this field is the Thomas Lab in the Entomology Department at Penn State.

Do you have any creepy and/or weird anecdotes involving your field of study? If so, what was the most bizarre one?

The most creepy one for me was finding an ant that was infected by a phorid fly. This fly lays its eggs inside the head of unfortunate ants. The larva starts eating away everything inside the ant's head and at one point, after manipulating the ant, tries to wiggle it's way out of the empty head, in the process decapitating it. I've seen this happen with my own eyes. Pretty amazing! Here's a Wired blog post on this phenomenon: http://www.wired.com/wiredscience/2013/12/absurd-creature-of-the-week-this-fly-burrows-into-an-ants-brain-then-pops-its-head-off/

It seems like the creators of zombie-based media like World War Z and The Last of Us are taking an increasing interest in portraying the zombie phenotype in a way that is scientifically accurate. How do you feel about the commercial interest in this research? Does it help you and your colleagues reach a wider audience, or do you think it trivializes what you do by painting an oversimplified picture?

I think it is great in the way that it allows us to reach a wider audience. reaching that wider audience is one of the reasons for me to do this AMA and try to crowdsource the funding for one of our projects. I love telling people about what we do. The one downside is however that all this media attention causes some people to not take our research seriously. All most people get to see is the wide spread media attention and they think the hype is all we have got to sell. However, our lab is obviously very serious and passionate about studying behavioral manipulation and we use solid scientific methods to investigate our hypotheses.

What is the end goal of your research?

My main goal is trying to unravel the mechanisms underlying behavioral manipulation. This fundamental question will keep me busy for years to come! Next to that, our lab is also interested in how an infection like this one influences social insect societies, how this has evolved, what species are out there, what the dynamics of this disease are etc. etc. So many awesome questions to ask. From a more applied point of view: We are at the early stages right now, so it's hard to say what we'll find, but hopefully it will lead to the discovery of natural compounds that could be of medicinal value. Cordyceps has been used in Chinese medicine already for decades, indicating that we will indeed find some interesting stuff.

Just want to say as a fellow microbiologist thanks for helping to get people excited about microbiology. I feel like it would be a more popular topic if people knew how incredibly interesting it was.

high five for being a fellow microbiologist! Microbes are incredibly interesting and never fail to amaze me.

How prevalent are zombie ant infestations? What percentage of ant colonies get infected in areas you study?

That is a very interesting question and one that is depending on the ecosystem. I can answer the question for one of the field sites one of the grad students in our lab worked at, collecting an immense amount of data over various months. Her work resulted in the conclusion that all the nests she found were infected. However, these were all from one ant species! Not all species that live in the same area get infected.

You mention open access research methods, and I notice your most recent paper is in PLoS ONE, an open access journal. Where do you think open access journals like PLoS or BMC fit in to the realm of publications along with traditional pay-wall journals? Should all research (particularly federally funded research) be open access, or are these journals more of a niche than evidence of a paradigm shift?

I personally think they are evidence of a paradigm shift and research should be available to all that are interested in learning more about it. When you go on to twitter for instance you'll find that many researchers share this opinion and there is a growing discussion about how research should be published and reviewed. These discussions will eventually lead to some, in my opinion, needed changes.

Is it possible to kill off the fungus after it infects the host without harming the host to a significant degree? Is it possible to "reprogram" the fungus to have it cause other behavior(s) than it normally does?

I am afraid I have to answer these questions by saying: I don't know. It is too early to talk about this unfortunately. Really interesting questions though which I hope we will get to in the future.

Do you think ants and other insects that work as a group are collectively intelligent as a species?

yes. Ant colonies are super organisms in which all individuals have their own task and operate as one. Pretty nifty stuff and too complex to answer in just one simple answer. However, if you are interested in this type of stuff there are some awesome books, blog posts and scientific papers out there about this subject.

I did a paper on ophiocordyceps fungi this past summer, and I couldn't find any research on how the spores manage to enter the ant's bodies. If I recall correctly, spores on the forest floor attach to the exoskeletons/cuticles of foraging ants, but I was wondering how the spore actually begins to create a "zombie ant."

That is a part of the life cycle we don't exactly know for this species. For another fungal insect pathogen named Metarhizium (it's within the same order, that of the Hypocreales) we know that it forms a structure (appressorium) that can penetrate the cuticle by force with the help of some cuticle degrading enzymes of course. We think something similar happens with Ophiocrodyceps. Ones the fungus is inside it grows in a yeast like form and slowly growing bigger and bigger, taking over the host

neuroscientist here. so I already noticed you said we're not yet aware of the exact mechanisms at play, but has anything at least been ruled out? Are there at least any clues pointing at a particular level of explanation?

For example, the much-mentioned toxoplasmosis gondii, i believe, influences behavior in a rather nonspecific way -- IIRC, the antibodies that its presence engenders alter dopamine-related neurotransmission in the nervous system in general. The specific effects on behavior, then, are due to the intrinsic functional specializations of DA in the normal brain, as opposed to a specific targeting of, say, 'risk' or 'fear' circuitry by the parasite itself. In other words, the parasite 'alters behavior' not by targeting the neural bases of these specific behaviors per se, but by producing subtle changes in some large-scale neurotransmitter system which itself happens to have a particular intrinsic functional specialization. The end result, behaviorally speaking, is of course the same -- but the level of explanation, and the degree of mechanistic sophistication is very different from what most people would imagine when they think of something as 'controlling' behavior.

From what little I know of the cordyceps fungus, it causes ants (?) to climb up stalks of plants and stay there until they die / sprout a fungal bloom, no? So, thinking in terms of broad behavior with simple mechanisms, you might expect to find that this behavior could be effectively 'caused' by messing around with some neural system related to a) phototaxis/photosensitivity (trick the ant into climbing up somewhere high by messing with its perception of / desire for light) and b) general activity level (i.e. lock a neural system that cycles through rest/activity cycles into a permanent 'rest' state). If a parasite could find a way to do both of those simultaneously then you'd have an effective recipe for the observed behavior, albeit at a lower level of specificity/sophistication than whole-brain 'hijacking'.

And in fact, there is actually a precedent for linking these two domains of behavior, because we know that -- in vertebrates at least -- brain-wide arousal mechanisms are coupled to the day/night cycle by particular photoreceptors in the eye that specifically detect wavelengths of light unique to sunshine. Now I'm not a comparative evolutionary neuroscientist, so i don't know how neurobiologically plausible this functional connection would be in the case of ant biology -- but this scenario would at least motivate the search for parasitic mechanisms of behavioral control that are normally related to those behaviors in uninfected ants.

Mind you, this is all me just spit-balling here, but despite not knowing much about it specifically, this topic has interested me for some time. So what do you think? do you think these parasitic alterations of behavior are due to sophisticated mechanisms that directly target behavior-relevant aspects of the brain, or do you think there are simpler ways of explaining this behavior?

"but by producing subtle changes in some large-scale neurotransmitter system which itself happens to have a particular intrinsic functional specialization" This is more or less the conclusion of a study that is under review right now. We see substantial changes in the amount of certain neurotransmitters. Next to that we see some other changes as well but we can't put a function to them yet because of databases not being extensive enough at this point in time. I absolutely love your train of thought here. Light is indeed a very important parameter in this system (a study in Thailand showed that the biting behavior is synchronized around solar noon), as are circadian rhythms for ant behavior. So one of my hypotheses that I am working towards is indeed that day/night cycles are involved in all this. Would love it if we could talk more about this! Awesome post and question!

What do you tell people when they ask what you do for a living?

That I am a microbiologist studying parasitic fungi in ants.

You're attempting to crowd fund some research right now. How does that ultimately affect the property rights and accessibility of the research?

For example, work funded by the NIH is legally mandated to be made publicly available via Pubmed. With your crowd funding, do the backers get access to your publications?

Regarding intellectual property, I know that most universities retain ownership of any patents derived from research funded through government agencies. Other times researchers work on contract with private companies, in which case the company retains all rights to anything resulting from the work.

How does funding from many individual donors effect these issues?

The findings of this research will be published in open access journals as much as possible, meaning I will try those journals first, hoping they will accept my publications. The idea of this microryza project is that my backers will also get info on the work that goes on working towards those results. Of course with the current publication system I can't always go into details when I am finding something interesting until the moment I officially publish it. Also, I have to worry about not getting scooped. So, I will update my backers before publication with as much information as I can that doesn't harm an official scientific publication. This fundamental initial exploratory project is not expected to result in any patents at this time. Therefore, I am not too worried about that part.

I think that the Cordyceps fungus is just about the most terrifying thing alive, would you agree?

However i have only seen / heard of it infecting insect species, is the fungus exclusive to insects or has it infected higher organisms?

If not, then could it, given the evolutionary time? - I appreciate this is a very broad question that could just be answered "Yes this could happen to anything", but i would like to know your opinion.

In addition, have you done any work with Rhizocephala? I believe they are barnacles technically, but they are similar to Cordyceps in how they can control other organisms...

I don't thing Cordyceps is terrifying to be honest. It's just a parasite that has a very nifty way of keeping insect numbers in check to keep ecosystems in balance. It has been doing so for quite some time! Fossils were found displaying biting marks in leaves caused by ant mandibles, dating 48 million years ago (you can find the link to the paper on my microryza page at the bottom by clicking on the fossil). This is how long this phenomenon has been around. It is a very species specific interaction as well, so I don't think it will switch to infecting higher organisms any time soon. Too many changes would have to be made in the functioning of this organism.

What are your thoughts on the "hive mind" phenomenon at work on social media sites?

I don't want to say much about this because this is not in line with my work and my expertise. In my humble opinion I think social media are a great way to network, connect and gather and share information. However, we should all take care to not recklessly sharing anything we find on the Internet and don't be afraid to question the stuff we read first.

As an aspiring mycologist I'm stoked to see this AMA.

What is your take on the recent claims that most former medicinal research on Cordyceps sinensis was misidentified? I heard Stamets say in a talk several Chinese scientists withdrew peer reviewed papers after leaning of their misidentification involving endofungi which were symbiotic/parasitic of the cordyceps fungus.

I haven't heard anything since that talk in April 2013 but if anyone knew a Cordyceps spp. researcher would.

Thanks again for doing this!

I haven't heard much about it since either. In my opinion where other studies might have gone wrong is (next to misidentification of course) not studying these fungi in relation to what they actually produce as a reaction to insect tissue. Some studies I read about are done by extracting molecules from fungal structures that might not have been pure cultures and might have had other microorganisms on them as well. That makes it hard to determine what you are actually looking at.

Hello, I think this whole thing is very cool. I'm at currently on a year break from studying zoology at university. I love the kind of research you're doing, and it's why I wanted to study the animal kingdom. How did you get into such an interesting field? What advice do you have for someone who's on a year break because they've no idea what they're doing but want to pursue this kind of thing?

Hi, thanks for your kind words! I got into this field because I happened to bump into the one person at the time working on this mind-control fungus (Dr David Hughes) and decided to just take the leap, move across the world and go work with him. This was quite the risk at the time but I am very happy with my decision. I get to work on the one thing that fascinates me the most! So my advise would be to not be afraid to take a risk once you figured out what you'd like to do. If you want to be a researcher, it's hard to choose the subject you'd want to specialize in but once you made a choice it doesn't necessarily mean you're stuck. I actually changed fields rather drastically when I started working on this. Hope this helps a little? Good luck with your decision and don't be afraid to contact labs that do the research you would be interested in. Most researchers are happy to talk science with people like you who are interested.

What specific physical changes have you seen in zombie ants/insects? Do they tend to move fast/slower, exert energy faster/slower, and does it increase/decrease the amount of force exerted by the ants (for example in their mandibles and carrying capacity)? Thanks for your time!

Very interesting question! We generally observe these ants being rather unstable in their movements when they are within the 48 hours prior to manipulation. They are not easily startled and do not engage in their regular worker ant tasks anymore. If we try to disturb them, they are not impressed at all, might react to it but then carry on with whatever their business was, unlike healthy ants. One of the things we are getting a set up for is measuring the mandible strength, since biting is the end stage of the manipulation. We are collaborating with an expert on these type of measurements in insects so hopefully we'll have some data on this soon.

What is your favorite zombie movie?

That is a tough question but I would have to say the Romero movies. I even got all dressed up as a zombie once to help promote "Land of the Dead" when it got released. So much fun stumbling around the down town area of the city I lived in at the time. I must say I do really like Shaun of the Dead as well

I took a picture of a dead moth with what looked like white roots coming out of it while exploring a cave in the Pacific Northwest. Then I noticed there were a lot of them in this section of the cave. About 12 feet above, closer to the entrance, there were a bunch of unaffected moths. I was wondering a few things. Are the white root structures coming out of the dead moths a parasite? Is it possible that the dead ones release a pheromone that attracts the moths which in turn become infected when they brush up against the parasitic structures? I contacted a parasite expert in Oregon and based off the picture he said it may be a new species. He asked for a sample and hasn't responded since I sent it to him.

PICTURE: http://i.imgur.com/TZSzRqB.png

Amazing story! Yes, it does sound like a moth with a fungal parasite. I did see some in the field when we were in the Amazon 2 years ago. Very beautiful. I like your suggestion that they have aggregated at one spot because of smell/ a volatile chemical. We do see these type of "graveyards" in ants as well. Random spots in the forest with a high density of dead infected ants.

How do you square the crowd funding with your University? Do you know how applicable the fungus would be to pest control? Any plans to study the epigenetics of infection?

The answer to your first question can be found on the microryza faq page. Some fungi are already used for insect pest control (see answer to one of the questions above). Time will tell if this fungus would be a good candidate as well. I am definitely interested in the epigenetics of infection. The heterogeneous gene expression this fungus displays both in time during infection and throughout the host is something I am very much interested in. Epigenetics must play a big role in this

Just for future use, has anything been found to reverse or halt the fungus in your subjects without causing harm? Or is it a lost cause one the take over begins?

In our lab set up not all ants make it to the manipulated stage, some die without being manipulated and some don't die at all. Next to that, just manipulation is not enough for transmission, the right fungal growth has to occur, spores have to be formed and those have to be spread. What we are finding is that this process is very hard to reach and depends on very precise environmental cues which we don't know much about at this stage.

You stated before that it can also infect spiders, can it control these as well? And can the same species of fungi infect multiple species of insect and control them?

To answer your second question first: extensive sampling across the globe and morphological studies of the fungi seen in different ant species indicate that the species of insect that get infected all have their own species of fungus. For the behavior of the spiders we unfortunately don't know enough about their behavior to be able to tell if the ones we find dead and infected were manipulated before they died. We find that most spider species died in their burrows

Love this kinda stuff! Do you also study the effects of bacterial infections? I have read that there is a significant amount of 'behavioral changes' on mice when their bacterial count diminishes. In other words, bacteria affect how they behave, not unlike how fungus affects how ants behave.

Do you have to write your own research grant proposal so you get to do this cool work or are you hired somewhere, with salary?

Interesting stuff! No, I am not looking at the effect of bacteria on all this. We are still very much at the beginning of unravelling this phenomenon so we have to take baby steps. For now I hold a Fellowship that is providing me with the salary to do this awesome work and as a fellow I am part of a lab at Penn State. Of course to sustain our lab we have to write grant proposals or find other ways of funding like my crowd funding project