back seat

    As some of you may have noticed the curiosity payoff has been sitting in the back seat of my life for a little while now. I am here, still driving this train, but there is a lot of other stuff vying for my attention. Sometimes when my plate is full my time management goes into overdrive and I am successful at simultaneously working on multiple tasks. Other times I get overwhelmed and spend too much time cleaning the house, purging the closet, and going to the grocery store. All very important activities. But not as important as spinning my wheels on my favorite procrastination activity - doggie spa day.

The resident participants in doggie spa day

    

    When my brain is faced with a to-do list that inspires ADD I try to regain the perspective I settle into when I go backpacking. Hours of hiking allow my brain to indulge in endless peace. When my only task is to put one foot in front of the other, not fall down, and look at striking scenic views every few seconds, my thoughts go into slow motion and I start to see more. Something that seemed blue may start to show hues of green and purple. ?. Maybe? It's a little abstract but stick with me. Several posts ago I wrote about being ‘in the arena’. To me this translated into a message of courage. Being brave enough to put myself on a trajectory toward a goal where there is potential for rewards but also risks, setbacks, and possible failures.

Grand Teton. Photo credit: Jonathan Q. Richmond

    While I was hiking this past September I spent some time doing some slow motion thinking on 'the arena' and saw more hues emerge from my original arena perspective. Two in particular. First, I started thinking about whether it was possible to push yourself too far into the arena. And as soon as I started thinking about that I understood how important it is to identify what my own personal arena is. Everyone has a different arena, and it can change. I think these thoughts were stimulated by my hiking partner/husband’s reading material during our trip. (Backpacking in the fall means early sunsets and a lot of tent time for reading.) He was reading Bolt from the Blue, a story about a climbing team getting hit by lightning on a summit attempt of Grand Teton. The arena of that climbing team was a highly technical rock climbing adventure. An arena we could see for most of our hike, but was very far from our arena on the trail. But, at the same time - to many people we know, including our families - our trail hike was an incomprehensible arena for a vacation. So yes, there is a lot of individual variation when it comes to arenas. (Variation & diversity - the root of all good things.)

    So what is my arena? And, how do I know if I am pushing too far? When I started this blog it took courage to make my writing accessible for everyone to see. Now that I have overcome that hurdle there are new ones. Without sufficient reflection though I often feel like I am running in place. It is important to think back so I don't forget how much courage it took to get past the first hurdle, and how much fun I had while doing it. I am beginning to understand that fun for me means continuing to push past the current comfort zone. And I am grateful for all of the fun that keeps coming my way.

    Next post = pure science. No more updates, reflections, or excuses.

doubling down

    I started this blog to raise my voice about the importance of long-term investment in science and discovery. Today I am doubling down on that goal. Data is our friend. Facts are for everyone. Evidence based decision making is logical. This is not a foray into elitism. On the contrary, it is a fact finding adventure in mutual discovery. Let's play the hashtag game - #factsareforeveryone #dataisourfriend

    I have spent time on this blog talking about why diversity is important to me. In that post I did not mention compassion. Some consider it a buzzword - I consider it essential. For me, one of the first steps toward understanding compassion is to identify and begin to understand my privilege. It is hard. It can be so difficult to see what is most obvious. I work on it every day. And it is not static. It changes. And I try to take the time necessary to recognize those changes.

    The second component of compassion is listening. Another hard task. Especially when I don't like what I am hearing. This is still a work in progress for me.

    One thing I listen to a lot of is podcasts. I live in southern California - I spend a lot of time on the road. And there are so many awesome ones that have helped broaden my perspective. Some of my favorites are Hidden Brain (insights from social science research), Embedded (soul chilling headline backstories), More Perfect (a glimpse into our highest court), Song Exploder (how songs are made), This Week in Evolution (the nerdiest of all nerdy), Beautiful Stories From Anonymous People (talk about learning to listen, this is such a good way to practice), 10% Happier (mainstream conversations about meditation), and of course This American Life and Radiolab. This list clearly exposes me as a huge left of center nerd. I would love to expand my repertoire though, please share your favorites.

Some of my favorite episodes focusing on particularly timely topics:

1. Seriously? (This American Life) - all about the facts

2. Too Sweet, Or Too Shrill? The Double Bind For Women (Hidden Brain)

3. Why Our Brains Weren't Made To Deal With Climate Change (Hidden Brain)

4. The Problem We All Live With, Parts I & II (This American Life) - instrumental for cracking open privilege

    I tried to find a way to end this with some reassuring, but not overly sappy words. Instead, I follow in the foot steps of my mother and seek wisdom from the Dalai Lama:

“The creatures that inhabit this earth - be they human beings or animals - are here to contribute, each in its own particular way, to the beauty and prosperity of the world."
- Dalai Lama XIV (The Dalai Lama's Little Book of Buddhism)

Zika & Wolbachia: Update

    Just a short update on our Wolbachia miniseries from last summer. Remember that question I posed a few months ago -- how effective will Wolbachia-infected mosquitoes be at limiting the spread of human disease? Three months later and we are already closer to getting some answers. Science's Kelly Servick recently reported that two different types of mosquitoes will be released in Brazil to try and prevent the spread of infectious diseases transmitted by the mosquito species Aedes aegypti. The data collected from these releases (in addition to others) will provide the data necessary to continue evaluating the effectiveness of various methods.

    The first release will focus on Wolbachia-infected mosquitoes (previously described here) and is being implemented by the nonprofit organization Eliminate Dengue. These mosquitoes are infected with a strain of Wolbachia that will spread through existing mosquito populations and prevent mosquitoes from transmitting diseases (such as Dengue and Zika). While these releases consist of females (that can bite), the effects of the release are longer lasting because Wolbachia should persist in the resident population of mosquitoes.

    The second release is a genetically modified mosquito developed by the for-profit company Oxitec. These are different from the Wolbachia-infected mosquitoes because their genome has been altered and now contains a modified gene (tTAV: tetracycline-repressible transcriptional activator variant) that kills developing mosquitoes. Males with this gene are released, they mate with females of the resident population, and then the males die. All offspring from these matings contain the modified gene and die before they reach reproductive maturity as adults. Thus, this method is different than the Wolbachia-infected mosquitoes because its goal is to control mosquito populations rather than eliminate their ability to transmit disease. This method may appeal to residents because it reduces mosquito populations and only introduces new males into the population (that cannot bite); however, once the males mate and die a new batch of males must be released. And this can get expensive.

   

  Again, the risks (and expense) associated with these methods needs to be considered in conjunction with the benefits. Preferably from objective third parties. I’ll keep you updated as the story continues to progress.

curiousity on the road

    I have been doing a lot of traveling over the last few weeks so this post comes in the form of pictures (most are courtesy of my husband).

    At the beginning of September we flew to Jackson Hole and spent five days backpacking in Grand Teton National Park, followed by a couple of days driving around Yellowstone.

Alaska Basin (actually outside of the National Park in Caribou-Targhee National Forest)

Me at Sunset Lake, also in Alaska Basin

Behaving like an ectotherm at Marion Lake after our first day of hiking

    We encountered a few more people at Yellowstone, and also a few bison and elk.

My husband's genius photography makes it look like we are the only ones there gazing across the valley

Grand Prismatic Spring, Yellowstone National Park

    Last week a work event brought me to the Duke Lemur Center, a research facility housing 250 lemurs from 21 different species. What an amazing place. Lemurs are very cute and charismatic so I knew it would be a fun experience. It is not a zoo, but tours are available by appointment. We got the VIP tour (it always matters who you are with!), and I was absolutely blown away. It is one of those experiences where you can feel yours eyes and smile widening with each second. The facility, its staff, and the lemurs absolutely amazed me. I was pretty busy asking questions so didn't take a ton of pictures.

Coquerel's Sifaka (Propithecus coquerli) more interested in eating leaves than me

    What a great experience. If you are ever in the Durham area I highly recommend you inquire about making an appointment for a tour of the facility.

getting from here to here

    If you keep up with this blog you know I am intrigued by the process of science and do my best to share a whole story when possible. Not just the brilliant outcomes and success stories, but also the setbacks, failures, and hurdles. To understand the process better I often seek out conversations with researchers to find out what the whole story is. When it comes to stories involving bioinspiration I want to know what comes first, the biology or the engineering? Is there a need that is subsequently filled by biology? Or does biology inspire a solution to a problem we didn’t know we had? If we go back and look at some previous posts there are times when it seems obvious. For instance, with the Velcro® story, it seems George de Mestral started with the biology, the burr, and found a function for the biological mechanism, adhesion. On the other hand, the adhesive needle story clearly started as a surgical need that was fulfilled by biology. Jeff Karp and his team were searching for biological examples of things that attached to animal tissue. Not only do parasites fit this need, there is a large diversity of parasites that have many different ways of attaching to their host (they also study non-parasitic mechanisms of attachment such as porcupine quills). Often times Karp and his colleagues go to the zoo or aquarium for inspiration, but you can’t see internal parasites visiting these venues. For the parasite work they went to the Google and poured over pages and pages of parasite images. I recommend you try it; it could be a moment of enlightenment. Karp kindly referred to his study subjects as ugly critters, I prefer to consider them marvels of evolution. 

A screen shot of the Google search - I started the hard work for you.

    A couple of months ago there was a story in the weekly UC San Diego newsletter that caught my eye. The newsletter often highlights current research being done on campus, and this particular article profiled a research team that developed a robot capable of collecting scientific samples on Mars. It was a cool project that incorporated bioinspiration, undergraduate involvement, and the teeth of sea urchin. The sand substrate on mars is difficult to collect because it is very fine and flows through traditional grasping pinchers. Picking stuff up on Mars could be compared to the arcade game from 1980 where you pay money to use the slippery three-pronged claspers to pluck a a stuffed animal out of the bin. It is difficult. Working with researchers at the Scripps Institute of Oceonography, members of the McKittrick group engineered an effective grasping mechanism inspired by the teeth of the sea urchin, Strongylocentrotus fragilis, which are very strong and have evolved to scrape rock substrates.

The crane game.

    In order to get a better idea of how this process works I emailed the group leader, Dr. Joanna McKittrick, and she accepted my request to come and meet with members of her team and suggested I sit in on one of their weekly group meetings. To get to their building from my office I walked passed the iconic UCSD Geisel Library toward the engineering quad. You know you are in the engineering quad when you see the ‘Fallen Star’ sculpture (a lop-sided house) on top of Jacobs Hall. I arrived at the lab with the intention of gaining insight into the process of bioinspiration, but my interviewing skills were a little rusty. I found it easier to talk about the outcomes of the project and absorb the process. I started out talking to a senior graduate student, Steven Naleway, who was defending his dissertation the following week and has since joined the faculty at the University of Utah’s Department of Mechanical Engineering. I was impressed he was giving me the time of day. A week before I defended my dissertation I was not granting interviews to nosy biologist bloggers. We started out in his office and he walked me through the “process” of bioinspiration starting with biologists, an organism, and an investigation of the structural details of the study subject. Then comes the materials science to mimic the structure, which involves expertise in engineering, physics, and chemistry. This was depicted as a circular process that led to bioinspiration. The reading material on his desk reflected this process - Fishes: A Guide To Their Diversity and Mechanical Behavior of Materials. While we were talking Joanna McKittrick came in followed by her mini dog. Her and Steven discussed a few pieces of business, such as the previous weeks outreach event at a local elementary school, and then she left followed by the dog. She gave me a sidelong glance but was not overly curious about me, or why I was taking up her graduate students time. My conversation with Steven moved down to the lab as more graduate students returned to the shared office and wanted their chairs back.

    The lab was empty of people but filled with what looked to me like a hodge podge of machinery and equipment that I could not deduce the function of. Some pieces looked like they could have been there since 1960, and other items could have arrived yesterday from the manufacturer. As the time for lab meeting approached we walked through the rest of the lab and passed through a small room with a large table covered in inspiration. A shark jaw, an armadillo carapace, and a dried fish on a stand. In this part of the lab it was clear the biology came first. Whether it was finding a useful function for sea urchin teeth, understanding how a woodpecker skull withstands the constant impact of banging its beak into trees, or investigating seahorse armor.

Piranha on a stand. This isn’t the fish in the lab (it wasn’t a piranha), but it looked similar.

     Lab meeting was attended by Joanna, her dog, her Diet Dr. Pepper, five graduate students (one female, five male), and one undergraduate (female). As is customary for these types of events, each person is responsible for defending their productivity from the previous week. The conversation moved around the room as the group members described what they had been up to, what they found out, and what setbacks they encountered. All of the members contributed to a brainstorming session for difficult problems, and then the discussion moved to the next person. Joanna runs a straightforward meeting and balances razor sharp directness with thoughtful suggestions and encouragement – a tried and true method to get #$%$ done. The conversation topics ranged from hydroxyapatites and nanoindentation to 2D freeze casting and how the elementary school kids demonstrated gender specific appeal for the various demos the lab group brought to the elementary school. 

    Integrated into this depiction of “process” for how graduate and undergraduate projects move forward, I should also share the light-hearted elements of camaraderie. For instance, one of the graduate students recently returned from his “Vegas wedding” and everyone offered their congratulations and asked if Elvis was there, and then proceeded to rib him for having an Apple sticker on his Lenovo laptop.

    In the end I learned more about the process of the sea urchin inspired Mars rover from the original article in the UCSD newsletter. Maybe that says more about my interviewing skills than anything else. But hey, I was working my way into the arena and had a great time.

the wo/man in the arena

    President Obama touched on one of the themes of this blog last week at the DNC, and I could not pass up the opportunity to talk about it here.

       “She knows she’s made mistakes, just like I have; just like we all do. That’s what happens when we try. That’s what happens when you’re the kind of citizen Teddy Roosevelt once described – not the timid souls who criticize from the sidelines, but someone ‘who is actually in the arena…who strives valiantly; who errs…[but] who at the best knows in the end the triumph of high achievement.’”

John Muir and Theodore Roosevelt (image source) at Glacier Point in Yosemite in 1903. After spending three days in the wilderness with John Muir, Theodore Roosevelt was convinced to expand Yosemite National Park.

    President Obama’s quote of Teddy Roosevelt (the 26th president of the United States who I admire for putting conservation in the limelight) came from a speech titled “Citizenship In a Republic” Roosevelt gave at the Sorbonne on April 23^rd, 1910:

       “It is not the critic who counts; not the man who points out how the strong man stumbles, or where the doer of deeds could have done them better. The credit belongs to the man who is actually in the arena, whose face is marred by dust and sweat and blood; who strives valiantly; who errs, who comes short again and again, because there is no effort without error and shortcoming; but who does actually strive to do the deeds; who knows great enthusiasms, the great devotions; who spends himself in a worthy cause; who at the best knows in the end the triumph of high achievement, and who at the worst, if he fails, at least fails while daring greatly, so that his place shall never be with those cold and timid souls who neither know victory nor defeat.”

    For me, right now, this quote hums to my bones and fingernails. I think I react so strongly to this message because I know how much effort it takes to be aware of my fear; and to not let mistakes and perceived failures deride my thoughts, behavior, and decisions. Learn from them, yes – berate myself for them, no. It inspires me to sidestep my ego, push myself into the arena, and maintain the strength to stay there. Some days I would rather retreat to a cabin in the woods. But resiliency abounds and cannot be ignored; inspiring, seemingly ego-less individuals that move from one arena to the next with grace and humility. There are many examples I could highlight here but there is one story in particular that I think about often. Yitang (Tom) Zhang is a mathematician that made headlines for solving a very difficult problem in number theory while working as a lecturer at the University of New Hampshire.

    Zhang graduated from Purdue University with a Ph.D. in mathematics in 1991 but was unable to get a tenure-track position. After eight years of making ends meet doing odd jobs, he was given a temporary position teaching calculus at the University of New Hampshire. In academia, these positions are difficult because they offer no permanence or stability, are often seen as ‘less than’, and can be difficult on the ego. But Zhang kept himself in the arena, whether he meant to or not, and received many awards for his break through in number theory, including a MacArthur Fellowship in 2014. In previously published profiles (Unheralded Mathematician Bridges the Prime Gap and The Pursuit of Beauty) Zhang describes himself as shy and is quoted as saying “[m]y life is not always easy.” And it has not been free of mistakes either. In 2007 he posted a paper to an online archive (arxiv.org, a Web site that hosts papers before they are published) that was wrong, which he left up so he could eventually fix it. But one quote in Quanta Magazine stood out to me:

       “Zhang said he feels no resentment about the relative obscurity of his career thus far. ‘My mind is very peaceful. I don’t care so much about the money, or the honor,” he said. “I like to be very quiet and keep working by myself.’”

   Zhang continues his work at UC Santa Barbara where he was offered a full professorship in 2015. I would love to hear who keeps you in the arena - please let me know.

UCSB Campus (Storke Tower)

Zika & Wolbachia III: Wolbachia transmission

    Is Wolbachia going to solve our Zika, dengue, chikungunya, and malaria problems? The short answer is maybe, the long answer is below. I have to be honest; this was a difficult post to write. The topic is technical and I found myself amassing a ridiculously long citation list (a tribute to how much foundational research plays into this story). My usual tack in this blog is to profile one of the citations and highlight how important that research is to the larger puzzle. I did that with the first Wolbachia installment but if I did that with everyone in this story we would end up with a book - which I could be working on. There are many unique and interesting players; I only skimmed the surface of Wolbach, and didn’t even get to Marshall Hertig or the countless others. Regardless of the level of difficulty, I did want to address the potential outcomes we could expect from using Wolbachia-infected mosquitoes to control disease transmission, and address the important question: How effective will Wolbachia-infected mosquitoes be at limiting the spread of human diseases? If you haven’t read the previous two posts in this series (I & II), I recommend you do so.

    It is probably clear by now that scientists are currently relying on decades of Wolbachia research (covering many different types of insects) to get us to this point. In order to take the next step it is necessary to develop experiments testing how Wolbachia will spread through an Aedes aegypti mosquito population once infected individuals are introduced into a disease afflicted area. Interestingly, one of the very intriguing things about Wolbachia that has been extensively studied is its mode of transmission. After years of research, hours of scientific brainpower, and 100+ publications, the true nature of Wolbachia as a genetic manipulator has been revealed. Wolbachia manipulates the reproductive genetics of its host to enable its spread through a population. How does it do this? The mechanisms of manipulation rely on the premise that Wolbachia is vertically transmitted, which means it is passed from parent to offspring. Specifically, Wolbachia is transferred from mother to offspring in the cytoplasm of the egg cell (the cytoplasm is the jelly-like matrix of a cell); Wolbachia cannot be passed from father to offspring in sperm cells. These are the four types of genetic manipulation that can occur in natural populations based on this type vertical transmission:

    1. Cytoplasmic incompatibility: If Wolbachia-infected males mate with uninfected females, or females infected with a different Wolbachia strain, the sperm will die before they can fertilize the egg^1,2. The outcome of cytoplasmic incompatibility = increased Wolbachia infection in the population because infected males can only produce infected offspring.

    2. Parthenogenesis: Females can produce offspring without mating with a male³. The outcome of parthenogenesis = increased number of females in a population spreading Wolbachia.

    3. Feminization of male offspring: Wolbachia infection in embryos causes male offspring to develop into females^4,5. The outcome = increased number of females in a population spreading Wolbachia.

    4. Male killing: Infected male embryos are not viable, leading to populations that are mostly female⁶. The outcome = increased number of females in a population spreading Wolbachia.

Image by Laurent Seroussi profiled by My Modern Met

    Notice a trend? Each of these mechanisms is often specific to a particular type of insect, so it is important to point out that the fruit fly strains of Wolbachia that prevent A. aegypti from spreading disease manipulate the genetics of their host through cytoplasmic incompatibility.

    Our first window into the transmission dynamics of Wolbachia is based on a study done in 1971 by Janice Harumi Yen and Allan Ralph Barr at the UCLA School of Public Health². Decades after S. Burt Wolbach and M. Hertig first discovered Wolbachia, Yen and Barr (studying the same species of mosquito, Culex pipiens) found that Wolbachia infection reduced the ability of certain C. pipiens mosquitoes from producing offspring. Through detailed studies, Yen and Barr found that when sperm were swimming toward the nucleus of the egg, they died after swimming through a field of Wolbachia bacterial cells. Yen and Barr called this phenomenon cytoplasmic incompatibility, a very syllabic phrase that essentially means: the environment of the egg is lethal to the sperm and the egg does not get fertilized. Because the sperm died after swimming through the Wolbachia field, Yen and Barr hypothesized cytoplasmic incompatibility had something to do with the Wolbachia cells present within the egg cell of the mosquito.

    Yen and Barr saw the implications of cytoplasmic incompatibility for controlling mosquito populations, but in a different way than is currently being considered. What we are thinking about here is not a way to control mosquito populations, but a way to release infected mosquitoes and then getting the infection to spread. In this scenario, you want uninfected mosquitoes (that can transmit human diseases) to die, but you want infected mosquitoes (that do not transmit human diseases) to reproduce and spread the Wolbachia infection. The beauty of Wolbachia as a genetic manipulator, especially when it comes to cytoplasmic incompatibility, is that it accomplishes both of these goals.

   

   We are building here. This is the foundation scientists are currently relying on to reduce the spread of Zika and other diseases transmitted by mosquitoes. There may be a voice in the back of your head saying, huh, I wonder if a politician at some point in history spoke out about wasteful spending on insects, their bacteria, or the fruit flies from which the effective Wolbachia strain came from? And the answer is yes, numerous times. Imagine if none of this research had been done.

    Now that we know Wolbachia infection has the inherent ability to spread through a population due to cytoplasmic incompatibility, we can plug this information into mathematical models (!) and make theoretical predictions. Don’t stop reading, we don’t have to get into the mathematics to understand what factors will affect how Wolbachia will spread through a mosquito population after infected individuals are released. The first factor to consider is the number of mosquitoes that currently exist in the target area. Jansen and colleagues⁷ found that the smaller the population of mosquitoes, the fewer infected individuals that need to be released; increasingly larger mosquito populations required the release of more infected adults and eggs. Thus, when planning a release it is important to consider the season, as we know that mosquito populations fluctuate throughout the year. It is also beneficial to have releases coincide with other population control methods (such as some of the biocontrol options talked about in the last post) to reduce population sizes before the release occurs.

    What are the associated risks? With the implementation of any control option there are risks to consider. Risk factors include logistical issues, like not being able to generate enough infected mosquitoes, and public opposition; there are also ecological and economic consequences to consider. Groups of individuals with expertise in different aspects of potential outcomes (biological, economic, and public) were convened to brainstorm and discuss widespread release of Wolbachia-infected mosquitoes⁸. Generally speaking, the risks were calculated as being very low. One of the biggest concerns was that households would reduce efforts to control mosquitoes (eliminate sources of standing water, etc.). Another concern was that dengue would evolve to overcome the resistance of Wolbachia-infected mosquitoes to dengue infection. This type of concern is persistent when dealing with pathogens that can evolve very rapidly (we have talked about this before). There is a reason a new flu vaccine is developed every year – it is called evolution. However, the panel of experts agreed that this risk was relatively low due to the efficiency with which Wolbachia-infected mosquitoes prevent the transmission of dengue.

    With all this in mind, release of Wolbachia-infected mosquitoes was recently done in Australia in dengue-impacted regions with successful results⁹. One month before the release of infected mosquitoes standing water sources (mosquito breeding grounds) were removed from the release sites. Over a period of 9-10 weeks, approximately 150,000 mosquitoes were released at each of two sites in Australia. With each subsequent release, the Wolbachia infection rate increased, and continued to increase up to five weeks after the last release of infected mosquitoes. At this point though, is too early to say how the release affected the transmission of dengue, and scientists are currently evaluating the best way to monitor these effects¹⁰.

    One important thing to note is that much of the research done on Wolbachia-infected mosquitoes was implemented with the goal of reducing the spread of dengue (primarily), not Zika. However, because these two diseases are similar, and transmitted by the same mosquito vector, this research can be applied to the recent Zika outbreak. This is important because it highlights the importance of supporting research during a time of crisis, as well in between crises. Our ability to respond to disease outbreaks is directly related to the research available at the time the outbreak occurs. This is especially pertinent as the number of infectious disease outbreaks is predicted to increase, in part due to climate change.

    Are you still with me? Have I answered the question? It may seem like the way my twenty-something self would have responded to the question of having a boyfriend: it’s complicated. It is complicated, but I think the bottom line is that Wolbachia-infected mosquitoes will be an important aspect of a multi-pronged approach to controlling human diseases vectored by mosquitoes. I think scientists have come a long way with this line of research and it has the potential to have a significant payoff. If you are still yearning for more I will steer you to the Eliminate Dengue website. This is an amazing and well-organized resource with an extensive publication section that provides PDFs of nearly all of the articles associated with the program (also includes current research on Zika).

¹Laven, H (1959) Speciation in mosquitoes: speciation by cytoplasmic isolation in the Culex pipiens-complex. Cold Spring Harbor Symposia on Quantitative Biology 24:166-173.

²Yen JH, Barr, AR (1971) New hypothesis of the cause of cytoplasmic incompatibility in Culex pipiens L. Nature 232:657-658.

³Stouthamer R, Breeuwer JA, Luck RF, Werren JA (1993) Molecular identification of microorganisms associated with parthenogenesis. Nature 361:66-68.

⁴Rousset F, Bouchon D, Pitureau B, Juchault P, Solignac M (1992) Wolbachia endosymbionts responsible for various alterations of sexuality in arthropods. Proceedings: Biological Sciences 250:91-98.

⁵Bouchon D, Rigaud T, Juchault P (1998) Evidence for widespread Wolbachia infection in isopod crustaceans: molecular identification and host feminization. Proceedings of the Royal Society London B 265:1081-1090.

⁶Hurst GDD, Jiggins FM, Hinrich Graf von der Schulenburg J, Bertrand D, West SA, Goriacheva II, Zakharov IA, Werren JH, Stouthamer R, Majerus MEN (1999) Male-killing Wolbachia in two insect species. Proceedings of the Royal Society London B 266:735-740.

⁷Jansen VAA, Turelli M, Godfray HCJ (2008) Stochastic spread of Wolbachia. Proceedings of the Royal Society London B 275:2769-2776.

⁸ Murray JV, Jansen CC, De Barro P (2016) Risk associated with the release of Wolbachia-infected Aedes aegypti mosquitoes into the environment in an effort to control dengue. Frontiers in Public Health 4:43.

⁹Hoffmann AA, Montgomery BL, Popovici J, Iturbe-Ormaetxe I, Johnson PH, Muzzi F, Greenfield M, Durkan M, Leong YS, Dong Y, Cook H, Axford J, Callahan AG, Kenny N, Omodei C, McGraw EA, Ryan PA, Ritchie SA, Turelli M, O’Neill SL (2011) Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature 476:454-457.

¹⁰Lambrechts L, Ferguson NM, Harris E, Holmes EC, McGraw EA, O’Neill SL, Ooi EE, Ritchie SA, Ryan PA, Scott TW, Simmons CP, Weaver SC (2015) Assessing the epidemiological effect of Wolbachia for dengue control. The Lancet Infectious Diseases 15:862-866.

Zika & Wolbachia II: Disease transmission

    I am back. I had some business to take care of, and then of course there was another visit to spend time with my nephew and fulfill my duties as a new aunt. But I am here and excited to resume our conversation about Zika.

    The first part of the Zika and Wolbachia story morphed into a biography of Wolbach, for whom Wolbachia was named. I provided a teaser about recent research that suggests Wolbachia can reduce Zika transmission by mosquitoes. But I didn’t actually talk about Zika at all, and even though it’s only been a short time (~4 weeks) several new Zika stories have come out. Lucky for us, scientists world-wide are ramping up their efforts to understand Zika, and continue research on other diseases like Ebola, which remain important even when not in the spotlight (ideally congress would agree).

Aedes aegypti (Image credit: James Gathany, Center for Disease Control and Prevention Public Health Image Library)

   In 2009, a group of 17 scientists from Australia and Brazil published a study showing that when the mosquito Aedes aegypti is infected with particular strains of Wolbachia, the mosquitoes were less competent disease vectors, and could reduce transmission of diseases such as dengue, chikungunya, and Plasmodium (malaria) (Moreira et al. 2009). Let's put this in perspective, 85 years after Wolbach and Hertig first discovered Wolbachia in a mosquito in Boston (Culex pipiens), and after decades of Wolbachia research resulting in hundreds of publications that have little to do with humans and disease transmission, scientists discovered that Wolbachia could reduce the number of humans contracting deadly viruses. If this is not a solid argument for exploratory research then go fishing. Listen in, and we will see how it works. But first, there are several pieces of information that will help you follow the story: 1) The three main players are mosquitoes, Wolbachia bacteria, and Drosophila fruit flies, 2) There are over 3500 species of mosquitoes and only a handful carry diseases (a.k.a disease vectors), 3) Some mosquito species carry one disease, some carry many diseases, most carry no diseases, 4) The main species of mosquito that carries dengue, chikungunya, and Zika is Aedes aegypti, which is not typically infected with Wolbachia in the wild, and 5) Wolbachia is a genus of bacteria comprising many different types/strains that infect a variety of different insects. The most well-studied strains of Wolbachia are from the model organism Drosophila melanogaster, a fruit fly we will inevitably revisit in future posts.

Drosophila melanogaster: Illustration by Katy Wiedemann (Wiedemann Illustrations)

    Moving on. Methods to reduce the number of humans contracting diseases carried by mosquitoes focus on prevention, either through the development of vaccines or use of bug spray to prevent mosquito bites. The other option is to try and get rid of mosquitoes. Methods of reducing mosquito populations include spraying copious amounts of DDT into houses with growing children, and introducing copepods that eat mosquito larvae.

     

    Between 2000 and 2008, data from several labs coalesced on a different kind of preventive method. By infecting A. aegypti mosquitoes with certain Wolbachia strains isolated from the fruit fly D. melanogaster, the life span of A. aegypti was reduced. From the perspective of limiting disease transmission, this is good because many mosquitoes die before they can transmit disease. At the same time, another group of scientists studying Wolbachia in D. melanogaster found that certain strains were beneficial to D. melanogaster individuals that had harmful insect viruses such as Drosophila C virus, Flock House virus, and Cricket paralysis virus.

    In 2009, Moreira and colleagues put these two things together and hypothesized that Wolbachia infected mosquitoes would be less effective disease vectors. The idea was to test whether A. aegypti mosquitoes infected with Wolbachia from D. melanogaster fruit flies would reduce disease transmission. The answer was yes. The authors showed that A. aegypti with Wolbachia are resistant to several diseases, which prevents the mosquito from being able to pass the diseases onto the next human they bite. The mechanism for how this works remains unclear. The authors suggest it has something to do with how the mosquito immune system reacts to the Wolbachia bacteria, but no direct link was found. The other possibility is that there is competition for resources between the disease and Wolbachia in the cells of the mosquito, and Wolbachia outcompetes the disease. But no conclusive evidence has been presented to support either hypothesis. Regardless of the mechanism, it is clear that Wolbachia infected mosquitoes offer a two-pronged approach for controlling disease transmission: they have a shorter life-span and they show resistance to several different diseases. As a result, non-profit groups such as Eliminate Dengue Program are using this approach to slow the spread of dengue (and other diseases) in multiple locations around the world.

Eliminate Dengue Program

    That was the status of things before the spread of Zika skyrocketed last year, and was declared a Public Heath Emergency of International Concern (PHEIC) on February 1st, 2016. Scientists were quick to react and on June 8^th, 2016, six Brazilian researchers published the results of a study demonstrating the effectiveness of Wolbachia to block two Zika strains currently being transmitted by A. aegypti mosquitoes in Brazil (Dutra et al. 2016). The release of Wolbachia infected mosquito eggs and adults is currently underway in Brazil and scientists are optimistic about the spread of the Wolbachia in Brazilian A. aegypti populations. All of this is very recent but at present it appears to be good news for humans, science, and exploratory research.

   Exactly how Wolbachia spreads in insect populations is an intriguing topic we will investigate next time. It is based on decades of exploratory research covering many different Wolbachia strains in many different types of insects.