Biological Weapons in the Ladybug Wars

"Human activities, particularly international trade,

promote the spread of invasive species that cause

extensive economic losses and negatively affect native

species."

"The harlequin ladybird Harmonia axyridis, introduced

for biological pest control, has become an invader that

is outcompeting indigenous ladybird species in many

countries."

- A. Vilcinskas, K., Stoecker, H. Schmidtberg, C. R. Rohrich,

and H. Vogel, Science, 2013, 340(6134), 862-863.

Harmonia axyridis - the invasive harlequin ladybird.

    In my May 7th post, I discussed a study that revealed an interesting mutualistic relationship between termites and fungi that resulted in the discovery of new compounds, the tyroscherins, that showed some potential use as new antifungals.  Then, in my May 22nd post, we acknowledged that our bodies are, among other things, giant growth vessels for trillions of microbial cohabitants, referred to collectively as the human microbiota.  All of these worlds collide in a recent publication in the journal Science, where Andreas Vilcinskas and co-workers have uncovered a microbe at the crux of an ongoing war that spans multiple continents, is having negative socioeconomic impacts, and could possibly even explain the sometimes funky terroir of wine.  The combatants?  Ladybugs.  Specifically, the invasive central Asian species Harmonia axyridis, AKA the harlequin ladybird, is wreaking havoc on the native European and American ladybug populations.  The study revealed that harlequin ladybirds carry a pathogenic fungal microsporidian closely related to Nosema thompsoni that is functioning as a biological WMD against Coccinella septempunctata, the indigenous ladybird species.  This study reveals yet again that biology we see unfolding at the macroscale (i.e. one ladybug kills another) has, at its core, a microscale explanation. 

    Prior to this study, it was thought that the lethality of the harlequin ladybird towards Coccinella was derived from the exceptionally high levels of harmonine - a foul tasting, stinky, antibacterial, antiparasitic, wine-spoiling alkaloid - in harlequin ladybird hemolymph (ladybug blood).  This study unequivocally showed that this was, in fact, not the case.  Indeed, you could shoot up Coccinella with high concentrations of harmonine, and they'd survive just fine.  However, after identifying the Nosema parasite using microscopy and nucleic acid analysis, the group was able to purify the pathogen from harlequin hemolymph and show that they were the causative agent of sickness and death in the Coccinella victims.  This exposes an entirely new set of questions regarding the biological relationships seen here, and there are several:

1. Nosema kills Coccinella septempunctata (a parasitic relationship).
2. Nosema requires a host, Harmonia axyridis, to survive. 
3. Nosema is not parasitic to Harmonia axyridis.
4. Harmonia axyridis uses Nosema to conquer new territory.

On its face, the paper clearly establishes point #1, as was discussed above.  This raises very interesteing, and perhaps more important, things to consider with respect to points 2-4, and harmonine may be controlling - at least in part - the entire situation.  Harmonine is a known antimicrobial, and it is found in high concentrations in the hemolymph of the harlequin ladybird, but is not present in the hemolymph of the defenseless Coccinella.  It was found in this report that the microsporidia, while living in the harlequin ladybird, were essentially deadbeats - metabolically inactive, non-disease causing cells - that were apparently just along for the ride.  The authors proposed the possibility that the high concentration of harmonine keeps these potential pathogens in check, but were careful to point out that Harmonia axyridis also produces unusually high levels of antimicorbial peptides.  So, to really get to the bottom of Nosema immunity in harlequin ladybirds, more studies will need to be conducted.  Nevertheless, the Harmonia beetles must be employing a system to harbor and control their microsporidian WMDs (points 2 & 3) until they are ready to deliver the deadly payload (point 4) on unsuspecting Coccinella.  The authors think that this system may be a glimpse at a common evolutionary mechanism of successful invasive species: if you amp up your immune system (with compounds like harmonine and antimicrobial peptides), you will be able to resist the new and strange pathogens you are bound to encounter in your new territory, while simultaneously introducing a deadly dose of pathogen to your soon-to-be conquered lands.  In a fascinating perspective piece that served as a lead-in to this article, Stuart Reynolds compares the Harmonia-Coccinella-Nosema relationship to the European-Native American-smallpox scenario that played out horrifically in the 16th century conquest of the Americas.  It may not be a pretty comparison, but it doesn't make it less biologically pertinent. 

An aphid - food for Harmonia

    In a Science and Tech highlight of this article in Chemical and Engineering News, another interesting layer of this story was introduced.  You see, the harlequin ladybird didn't diabolically opt to conquer Europe and the US.  We brought it here on purpose.  It turns out that Harmonia have a voracious appetite for aphids, tiny little insect pests that are notorious for eating, regurgitating on, transmitting diseases to, and otherwise raining hell upon important agricultural crops.  The harlequin ladybird will happily feast upon 100s of the insects a day, far more than the native Coccinella, making them an attractive, all-natural, non-chemical, "pesticide".  (What could possibly go wrong!?  Fast-forward to today...)  Since the Harmonia beetles are now taking over, is there a way to get the population back under control?  The secret may lie in the aphid itself - specifically the aphid gut, where a bacterial symbiont, Staphylococcus sciuri, lives and produces a chemical attractant for the ladybugs, one of which is called farnesene.  The ladybugs smell the farnesene, locate the aphids, and then chow down.  So now that the Harmonia population is out of control, folks are throwing around the idea of using farnesene as bait in ladybug traps!  Why not... what could possibly go wrong...!?

 

    Herein lies a great and complex system of multispecies symbioses.  Nosema is willing to live in the chemically hostile, harmonine laced blood of Harmonia axyridis until they can find a Coccinella septempunctata to infect.  Once the Coccinella die at the hands of Nosema, the harlequins can take over new turf.  Once they do that, they need something to eat, so they follow their noses - via a farnesene signal - to a tasty meal of aphids.  And here is the craziest symbiosis yet.  The symbiont (Staphylococcus sciuri) of the prey (the aphid) attracts the predator (Harmonia).  Essentially, "Hey, come eat my host!"  Like most complex host/microbe relationships, I wouldn't be surprised if there's more here - chemically - than meets the eye.  At any rate, these stories have exposed yet another example of macroscopic biology depending on microscopic biology, which ultimately relies on unique and specialized chemistry.  Am I a biased chemist talking here?  Probably, but it's still cool, isn't it?

- @EJDimise

 

When Politics and Science Collide - The Ongoing Drama at NSF

"The moment you compromise both the merit review

process and the basic research mission of NSF is

the moment you undo everything that has enabled 

NSF to contribute so profoundly to our national

health, prosperity, and welfare."

- Rep. Eddie B. Johnson (D-TX) to Rep. Lamar Smith (R-TX)

Ranking members of the Committee of Science, Space & Technology

    In my May 5 post, I discussed legislation that is currently being considered by the House of Representative's Committee on Science, Space, and Technology that would fundamentally change the way National Science Foundation (NSF) grants would be approved.  The legislation, sponsored by the chairman of the committee, Rep. Lamar Smith (R-TX), would place unprecedented requirements and restrictions on the kinds of research that could be funded by NSF and would add an additional layer of government imposed review in the granting process.  In the same post, I noted how the rule changes would directly clash with the historical vision of the NSF as laid out be Vannevar Bush in the 1940s.  Last month, a discussion draft of the bill, referred to as the "High Quality Research Act" was posted on the web.  Several of the main points highlighted in the draft have resulted in an intense backlash from the scientific community and Democratic legislators (try typing "NSF Lamar Smith" into Google or just follow the link from the quotation at the top of this post).  

    The High Quality Research Act would require the NSF director to certify the following 3 things with regard to any research grant (under Sec.2(a)):

1. it is in the interest of the US regarding, "national health, prosperity, or welfare, and to secure the national defense"
2. it is of high quality and, "answers questions or solves problems that are of the utmost importance to society at large" 
3. it does not duplicate research that is already being funded by any Federal agency     

It's safe to say that the brunt of the controversy stems from point number 1 and the overarching idea that the NSF director will have the depth and breadth of knowledge to certify that all NSF grants meet these criteria.  Point 3 is arguably quite reasonable from the perspective of the legislator, though the current grant review process already tries to address this issue.  Point 2 seems obvious and sounds like the general fluff that precedes most funding announcements.  (Do researchers generally try to address things that are unimportant?)  Perhaps the most foreboding part of the entire 3 page draft was to be found in Sec.2.(e), titled "Implementation By Other Agencies", with the directive that within the first year of implementation of the proposed legislation, "the Director of the Office of Science and Technology Policy, in collaboration with the National Science and Technology Council, shall report... on how the requirements of subsection (a) may be implemented in other Federal science agencies."  So, the legislation would not only add new particulars regarding the motivations for proposed research (does it promote "the interest of the US"?), to be endorsed individually by the head of the NSF, but would seek to extend the new regulations to other scientific funding bodies (e.g NIH, NASA, etc...).

    On the surface, the language may appear more ore less benevolent.  The economic times are hard.  Across government, there is a push to find savings and eliminate "waste, fraud, and abuse".  However, on April 17, the day before the discussion draft of the act was released to the internet, the House Committee on Science, Space, and Technology held a hearing with the acting NSF Director Cora Marrett, the chair of the National Science Board Dan Arvizu, and presidential science advisor John Holdren regarding President Obama's FY 2014 NSF budget request.  Here, the tone from Republicans on the committee reflected how the seemingly straight forward content of this legislation forebodes an unwelcome injection of politics into the process of funding basic scientific research.  With the backdrop of new limits placed on NSF in a spending bill in March, the result of efforts by Sen. Tom Coburn (R-OK) regarding the funding of political science research, which is now limited - by law - to research that promotes the, "national security or the economic interests of the United States", the committee members proceeded to extend similarly narrow logic to any and all NSF grants.  In doing so, they employed the time honored tradition of picking out individual grants with names they thought sounded funny and asking the panel members to please justify why the grants were funded.  A particularly good exchange between John Holdren and committee member Rep. Bill Posey (R-FL) can be viewed via the link embedded in the Holdren quote below:   

"I think it's a dangerous thing for the Congress, 

or anybody else, to be trying to specify in 

detail what kinds of fundamental research the NSF 

should support." - John Holdren, co-chair of

the President's Council of Advisors on Science 

and Technology (PCAST) 

This distills the essence of what makes the current situation so contentious within the scientific community.  Where do lines get drawn?  What research is "worth" funding?  Who gets to decide if a particular project (or discipline) is "in the interest of the US"?  Legislation like the Coburn amendment and the High Quality Research Act set dangerous precedents, allowing political motivations and short-term goals to limit, guide, or restrict the direction of basic research. 

    In more recent developments, acting NSF director Cora Marrett denied a written request from Rep. Smith to make available the, "scientific/technical reviews and the Program Officers Review Analysis" for five grants that were "of interest" and about which he had "concerns".  Rep. Smith was thus seeking the independent reviewer comments and analysis from five NSF grant proposals that he and other committee members, for one reason or another, found questionable.  Director Marrett denied the request based on privacy/confidentiality issues, maintaining that the reviews themselves, in addition to the names of the reviewers, must remain private to fully protect the reviewers and the review process, which she explained in her response to Rep. Smith.  The ScienceInsider blog has posted an inteview with a committee aid regarding the requested information for the five grants.  The aid made clear that the committee didn't want the names of the reviewers, just the content of the reviews themselves.  Additionally, the interview lays bare the fact that the committee had been considering the implementation of an "additional layer of accountability" that would occur as a "next step after" peer review.  The aid was vague on who and what would constitute this "additional layer".  

    If I understand the political zeitgeist, it is that (1) everyone dislikes "big governement" in their own special way, (2) everyone is for government accountability in their own special way, and (3) people like that the US is a bastion of high quality, cutting edge research.  Peer review - the process of "self-policing" of science by scientists - for grants, publications, etc... is a foundational aspect of the scientific enterprise in the US.  Is it perfect?  Absolutely not.  If you're not a scientist, hang out with some and ask them about "that time they were burned by a reviewer".  I promise, they'll have a story to tell you.  Quite possibly they were "burned" justifiably.  But, as in any established system - yes, even those run by scientists - nothing is 100% perfect all the time.  However, the question that seems to be at the heart of the matter here is, "Who is qualified to judge scientific research?"  Congress?  (The answer is "no", by the way).  The peer review system is an imperfect system that is expected to shoulder a massive responsibility - allocating billions of taxpayer dollars.  And yes, there will always be funny sounding research proposals that lawmakers will quote when they need to take a stab at the pointy headed know-it-all lab geeks.  But the reality that lawmakers must grapple with is that foundational, basic research sometimes sounds funny at its outset.  However, some day, that research can turn into things like the internet, or disease vaccines, or unmanned flying military bomber robots.  Injecting politics and politicians ("big government") into research funding decisions ("government accountability") can have the unintentional consequence of making the basic research we conduct in the US narrow and short sighted.  We pride ourselves on being a country that has big visions and accomplishes big things.  If science is guided by the political winds of the moment, then the visions and the accomplishments will cease to be big.  If you prefer a more practical perspective, consider what additional bureaucratic layers and government mandates could do to the current scientific funding quagmire.  One could write volumes (some people actually do...) on how the current scientific research enterprise could be improved.  Scientist will openly acknowledge that there are big parts of the research system that need fixing.  Unfortunately - perhaps not surprisingly - Congress is choosing to focus on the wrong thing during tough times.  Hopefully we won't pay for it as a nation in the short term - FY 2014 funding - and in the long term by ceding the big ideas, big accomplishments, and big talent to our competitors.  

- @EJDimise