Obama Administration Seeks to Fill Multiple Science Leadership Posts with Super-Star Female Nominees

"The extraordinary dedication these individuals bring to their new

roles will greatly serve the American people.  I am grateful they

have agreed to serve in this Administration and I look forward to

working with them in the months and years to come."

- President Barack Obama, White House Press Release (July 31, 2013)

This summer, the turnover of key scientific leadership roles in several federal agencies and Administration offices are coming fast and furious.  One of the vacancies, the Administrator of the Environmental Protection Agency (EPA), has already been filled by the former assistant administrator of EPA's Office of Air and Radiation, Gina McCarthy.  Nominations for three other posts are currently pending Senate approval.  Yale microbiologist Jo Handelsman has been nominated for the Associate Director position in the Office of Science and Technology Policy (OSTP).  Kathryn Sullivan, the first American woman to walk in space, has been nominated to fill the lead role at the National Oceanic and Atmospheric Administration (NOAA).  To replace Subra Suresh, the current National Science Foundation (NSF) leader, Pres. Obama has nominated France Córdova, an astrophysicist and President Emeritus of Purdue University.  All of the nominees are exceptionally impressive and warrant a brief introduction.


Gina McCarthy - EPA Administrator (current)

Gina McCarthy (photo)

After over 4 months of wrangling (nomination submitted by Pres. Obama on Monday, March 4), the Senate voted on Thursday, July 18 to confirm Gina McCarthy to the post of EPA Administrator in a 59 to 40 vote.  All Senate Democrats, with the exception of Sen. Joe Manchin (D-WV), voted to confirm McCarthy.  Six Republicans voted to confirm the nomination as well; Sen. Lamar Alexander (TN), Sen. Bob Corker (TN), Sen. Kelly Ayotte (NH), Sen. Susan Collins (ME), Sen. Jeff Flake (AZ), and Sen. John McCain (AZ).  Sen. Roger Wicker (MS) did not vote.  A lengthy filibuster that blocked an up-or-down vote was broken in a 69-31 vote only after the Senate Democratic leadership threatened rule changes that would have diminished the rights of the minority to filibuster executive branch nominees.

McCarthy faced fierce opposition that stemmed from Republican fears that she would be a staunch and forceful advocate for limiting greenhouse gas emissions.  Democrats countered that she had successfully worked with conservative leaders in the past, a prime example being her service as the Undersecretary of Policy in the Massachusetts Executive Office of Environmental Affairs under Republican Gov. Mitt Romney.  Environmental advocacy groups quickly applauded her confirmation (see NRDC, Union of Concerned Scientists for examples).

Moving forward, McCarthy will make climate change a top priority of the EPA.  In a speech at Harvard Law School on Tuesday, July 30, she emphasized the environmental and economic impacts of global climate change.


Jo Handelsman - Associate Director OSTP (nominee)

Dr. Handelsman and Pres. Obama (photo)

On Wednesday, July 31, the White House put forward its nomination of Prof. Jo Handelsman, a Yale microbiologist, to step in as Associate Director of the Office of Science and Technology Policy, replacing physicist and Nobel recipient Carl Weiman.  Prof. Handelsman has been a Howard Hughes Medical Institute professor since 2002.  Once confirmed (and it is assumed she will be confirmed), she would like to follow in the footsteps of Weiman as a leader and advocate for STEM education.  She was the recipient of the 2013 Graduate Microbiology Teaching Award from the American Society of Microbiology.  She has also published multiple books on teaching and mentoring.  In 2011, Prof. Handelsman was the recipient of one of only 11 Presidential Awards for Excellence in Science, Mathematics, and Engineering Mentoring in recognition of her leadership and accomplishments in mentoring science students.

Prof. Handelsman's research at Yale focuses on understanding microbial communities, with an emphasis on the genetic factors that contribute to community stability and dynamics.  She is particularly interested in the gut microbiota of insects and the microbial community structures that exist in soil environments.  Readers of this blog know that these are big, complicated, and important research areas with implications for human heath, agriculture, and environmental stability and well-being!  Prof. Handelsman and colleagues have recently published a review article that lays out the current state of knowledge on microbial community stability.


Kathryn Sullivan - Head of NOAA (nominee)

Kathryn Sullivan (photo)

On Thursday, August 1, Pres. Obama nominated Dr. Kathryn Sullivan to replace Jane Lubchenco as the Undersecretary of Commerce for Oceans and Atmosphere (i.e. head of NOAA).  Sullivan has had a storied career thus far, with the obvious highlight of being the first American woman to walk in space on October 5, 1984.  Not to be outdone, she was a member of the shuttle crew that took off on April 24, 1990, that deployed the Hubble space telescope.  Dr. Sullivan has also served important leadership roles on Earth.  She has served as the assistant secretary at the Department of Commerce (which oversees NOAA) since 2011 and was the chief scientist at NOAA from 1993 to 1996.  Dr. Sullivan has also been engaged in academic research and has served administrative and leadership roles at various STEM related associations (see John Glenn School of Public Affairs, Center of Science and Industry).

NOAA is a fairly hefty federal entity with a multi-billion dollar annual budget (NOAA FY2014 budget request was $5.4 billion).  In tough fiscal times, Dr. Sullivan will have her hands full.  She will have to continue to grapple with the effects of sequestration while simultaneously navigating the political currents attempting to direct NOAA's emphasis toward weather forecasting over climate change research. 


France Córdova - National Science Foundation Director (nominee)

France Córdova (photo)

On the same day that Pres. Obama nominated Jo Handelsman for the OSTP post, the White House also requested that Dr. France Córdova follow Subra Suresh as the Director of the NSF.  Córdova has an exceptionally impressive resume and is expected to be approved for the post without much of a fuss.  She is trained as an astrophysicist and has served as president of two major research universities; the University of California Riverside and Purdue University, where she served as the first female president.  From 1993 to 1996, Córdova worked as the first female chief scientist at NASA.  She has conducted research at Los Alamos National Laboratory, served as head of the Astronomy and Astrophysics Department at Penn State, was chair of the Board of Reagents at the Smithsonian, and has been a member of the National Science Board.  (For more details, see an interview conducted by the AAAS or a brief digest by Scientific American).

France Córdova's long, successful history of research excellence clearly shows that she's got the scientific chops to handle the NSF directorship, hands down.  What sets her apart from many past directors is her extensive administrative experience and her knowledge and familiarity with Washington.  The NSF, like other federal agencies, is feeling the pinch of the sequester.  Add to that a FY2014 budget request of $7.6 billion with no budget resolution from Congress leading into the August recess, talk of government shutdowns, and scientists everywhere grappling for research funding, and it is clear that Dr. Córdova will have her work as a scientist and administrator cut out for her.  She remarked to the AAAS that, "every time I’ve had a leadership position there have been big budget concerns" but that she's, "not worried about navigating budget constraints. It’s part of every job." 

As readers of this blog know, the NSF has been forced to play politics this year.  Republicans on the House of Representatives Committee on Science, Space, and Technology, chaired by Rep. Lamar Smith (R-TX), have been critical of the NSF grant review process (see my May 28 post).  This behavior by cost-cutting politicians is in many ways not shocking (but yes, still disappointing), given the difficult fiscal times.  As the funding battles in Congress are not likely to go away any time soon (the 2014 mid-terms are coming up!), we can be sure that France Córdova will end up carrying the fight for peer review forward just as her predecessors have done. 


As of the publication of this post, only Gina McCarthy has been approved by the Senate, with the other three nominees awaiting a vote.  As Congress is out of town for a while, political and scientific followers will have to keep their eyes and ears peeled when Congress reconvenes for the fall session.  I'll follow up here as things progress.  Let's hope Prof. Handelsman, Dr. Sullivan, and Dr. Córdova won't have to wait as long as Director McCarthy did for the Senate to get around to an up-or-down vote.

- @EJDimise

Akkermansia muciniphila, the Weight Loss Bug

"These results provide a rationale for the development of a 

treatment that uses this human mucus colonizer [A. muciniphila]

for the prevention or treatment of obesity and its associated

metabolic disorders."

- A. Everard et. al., Proc. Natl. Acad. Sci. USA, 2013, 110(22), 9066-9071

Looking over my recent posts, it appears that I've been focusing on all of the reasons why we should be afraid of bacteria.  They're in your food, and they're antibiotic resistant.  Tuberculosis is a world wide scourge.  Killer MRSA strains are lurking everywhere, and they're practically invincible.  Be afraid, be very afraid!  And to think that a few days ago, I complained about the news media always trying to scare the hell out of everyone.  Back in my July 3rd post, I promised I'd discuss something that would make us all feel a little bit better about the bugs we live with, and today, I'm finally going to make good on that promise.

I'd like to introduce you to a bug named Akkermansia muciniphila (IJSEM, 2004, 54(5), 1469-1476).  A. muciniphila is a rod shaped bug.  It's so intolerant of oxygen that it dies if it encounters any.  It secretes a sticky layer of molecular goo all over the surface of its cells.  It survives by eating mucus (yum!).  Oh, and by the way, it's living in your intestine.  Well, according to a report that came out in May in the journal Proceedings of the National Academy of Sciences of the USA (A. Everard et. al., 2013, 110(22), 9066-9071, I at least hope it's living in your intestine.  We'll get to why I hope that in a moment, but first, a little bit about your intestine.  Readers of this blog know that the human gastrointestinal (GI) tract is populated, top to bottom, with many 100s of different species of bacteria - the collective bacterial population is known as the human microbiota.  Our bacterial cohabitants cover our inner surfaces and they fill the spaces in the middle.  The vast majority do not cause disease and are actually supposed to be there.  They help us digest and absorb food and nutrients, they share resources with each other, they stimulate our immune system, and sometimes they even protect us from disease causing microbes.  It is now commonly accepted in the research community that the composition of our microbiota (what bugs are there?, where are they?, how many of them are there?) is dependent upon diet.  For a healthy adult, studies have shown that A. muciniphila comprises no less than 3-5% of the bacteria residing in the human gut.  This bug certainly makes its presence known.  It lives in the layer of mucus that lines the surface of the gut.  In every day parlance, "mucus" usually elicits a "yuck!" response, but the mucus lining of the GI tract is exceptionally important.  It plays a large protective role for the delicate tissue underneath and it is important for nutrient absorption into the rest of the body.  The researchers in this impressive study were able to show that A. muciniphila is far more abundant in lean, healthy mice compared to obese and/or diabetic mice.  More interestingly, feeding obese/diabetic mice live cultures of A. muciniphila helped reverse the effects of obesity, diabetes, and the low-level systemic inflammation associated with these disorders.  Lastly, they were able to show that a high percentage of A. muciniphila was correlated with a healthier, thicker mucus layer.  Given these results, the popular scientific press as well as high visibility research journals couldn't help but slyly suggest that A. muciniphila could be the next big weight loss therapy or treatment for adult onset diabetes.  Like good microbiota researchers, the authors asserted similar sentiments (see quote at top), but delivered their message along side a solid dose of, "... but there's still a lot that we don't know, so let's not get carried away."  Let's look at some details, shall we?

Mice are the model organisms for microbiota research.

The most headline worthy result was that administering live Akkermansia muciniphila cells to obese and diabetic mice counteracted many of the deleterious issues associated with these disorders.  Reductions in fat tissue, body weight, toxic metabolic byproducts, glucose tolerance (diabetes symptoms), and improved mucus layer health were all observed by providing living A. muciniphila cultures orally (i.e. the mice "ate" the bacteria).  None of this was observed by administering nonviable ("dead") A. muciniphila in the same fashion.  Thus, the positive effects are only observed if a diseased individual is populated with some threshold level of living, metabolizing, A. muciniphila cells, and not simply from chemical factors that would have been present from the dead cells passing through the GI tract.  To get the benefits, you need a viable population of this microbial symbiont!

Giving diseased mice a healthy dose of live bacteria seems like a very obvious thing to test, right?  After all, probiotics - cultures of living "good" bacteria that you take like medicine - are kind-of all the rage right now (think Activia*, for example).  But the beauty of this paper is that it demonstrates more subtlety than meets the eye, at least from our discussion thus far.  Recall one very important thing: A. muciniphila comprises 3-5% of a healthy microbiota.  The obese and diabetic mice aren't missing the bug, they just have less of it.  Given that the composition of the microbiota, and many of the negative effects associated with obesity and diabetes, are impacted directly by diet, the researchers explored the possibility of rehabbing the microbiota directly.  What would happen if you fed mice something that would favor the regrowth of A. muciniphila to the levels associated with a healthy mouse gut?  To answer this question, the group fed obese mice a diet rich in oligofructose, a mixture of short-chain sugar polymers that avoid digestion in the upper GI tract and that A. muciniphila can tap as a preferential food source.  The team found that feeding the mice oligofructose resulted in the restoration of healthy levels of A. muciniphila, and they observed a concomitant reversal of the adverse effects of obesity and diabetes - just like feeding the mice live cultures of the bug.  This suggests that diet alone can help reverse the most common problems associated with these health disorders.  You might read this and think, "Well, duh!  You're telling me all I have to do to lose weight is change my diet!"  And you might say this because you aren't thinking like a drug manufacturer or purveyor of dietary supplements.  Here's the vision you ought to be having:  1 pill, consisting of 50% A. muciniphila and 50% oligofructose, a bright shiny label reading, "The #1 All Natural Weight Loss Probiotic-Prebiotic on the Market!", and full page adds and billboards declaring, "Buy 1 bottle for $24.99, get the second one Absolutely Free!".  Yeah, that's what I'm talking about.  Snake oil peddling aside, the link the researchers made here is important and interesting.  It ties a specific probiotic bacterium, A. muciniphila, to a very specific prebiotic - the stuff you can eat that favors the growth of your "good" bugs.  Oligofructose anyone? (Hint: this shows that the high-fiber "hype" may not be all hype.)

Anti-inflammatory endocannabinoids

The chemically minded reader my now be asking, "So, what are the mechanisms here?  It sounds like this bug is altering metabolism, so what are the chemical details of this system?"  It's a good question, and to be honest, many of the chemical issues still need to be worked out.  However, this study did look at the effect A. muciniphila had on a suite of anti-inflamatory compounds called endocannabinoids.  Specifically, the inflammation fighting compounds 2-arachidonoylglycerol (2-AG), 2-oleoylglycerol (2-OG), and 2-palmitoylglycerol (2-PG) were found to be produced at higher levels by intestinal cells when the A. muciniphila population was maintained at healthy levels.  The factors stimulating the production of these natural anti-inflamatory compounds needs to be investigated further, but this paper now gives chemists a viable system and target to study.  This should come as welcome news to patients suffering from inflammatory bowel disorders, who currently must undergo surgery to affect long-term fixes to any of a number of given disease states.

If anything, this study once again demonstrates the centrality of human bacterial symbionts - our microbiota - in maintaining good health.  A. muciniphila now has its claim to fame as a jack-of-all-trades bug that can potentially be used to combat a lengthy list of metabolic issues that negatively impact huge portions of the western population.  Whether or not this bug can or will be sold as a panacea remains to be seen.  Well informed scientists would caution that we still have much to learn about our microbial symbionts.  That the ecosystem we call our gut is very complex and that we've barely scratched the surface.  Indeed, the overblown promises of the human genome project ("Sequence the genome, and cancer and diabetes will be a thing of the past!") are fresh in the minds of all stripes of biological scientist.  Nevertheless, this study is important in its detailed looked at a microbe that is clearly consequential to human health.  This ought to illustrate that, even though the media usually hypes the bad bugs, we have a lot of friends in the microbial world.

- @EJDimise

(* Not an endorsement of Activia and/or the health/nutritional benefits claimed by the manufacturer.)

Bugs on Your Meat - A Trending Topic This Week

"First line antibiotics were no longer curing basic infections,

and doctors were concerned.  I thought, 'Wow this is obvioiusly

crazy, I have to do something about this.'"

- Dr. Lance Price (George Washington Univ., Washington, DC)

- Sabrina Tavernise (New York Times, 29 July 2013)

In yesterday's post, I discussed how the use of antibiotics in livestock feed is becoming a mainstream topic; that it is no longer relegated to the peer reviewed scientific journals.  We then took a look at a recent article from C&EN that nicely summed up some of the most current scientific research and legislative action addressing the issue.  My take away: consumers are increasingly leaning towards antibiotic-free meat when they shop (relatively speaking), but would the fledgling market pressure really cause agribusiness to braodly change the way it raises livestock before the antibiotic resistant bugs they are breeding take over the world?  [Zombie apocalypse, remember?]

Well, every once in a while, life finds a way of totally validating your world view (uh huh...).  This happened to me today when I was perusing the latest Science Times section of the New York Times, where the topic of antibiotic use in animal husbandry got some front page (below the fold... a-hem) attention.  In an article titled "Tracing Germs Through the Aisles", NY Times journalist Sabrina Tavernise reports on work being done in the laboratory of Dr. Lance Price (quoted above).  His team has been purchasing all brands and types of meat at the major supermarkets in Flagstaff, AZ, where his lab is based, and testing for a specific strain of antibiotic resistant E. coli that is a major causative agent of urinary tract infections in women.  The question: are women contracting the bug from the meat they are buying at the grocery store?  The article tells us to look for the results of the study this fall.  If Dr. Price's team concludes that contaminated meat is causing drug-resistant disease in the consumer population, it will go one step further than the studies we discussed in my post yesterday, where bugs were observed to be transmitted between live animals and livestock workers.  Watch this space.  

The article also referenced the legislative actions Rep. Lousie Slaughter (D-NY) has taken to address the public health challenges posed by antibiotic use in the rearing of livestock.  I found it notable that "nine out of ten" lobbying disclosure reports - out of a total of 225 - that were filed in response to her legislative efforts from the last Congress, were from agribusiness sources opposed to the legislation.

For those interested in reading up more on this hot topic, the article referenced previous coverage in the The New York Times (16 April 2013; "Report on U.S. Meat Sounds Alarm on Resistant Bacteria") regarding a report published by the National Antimicrobial Resistance Monitoring System (joint between FDA, Dept. of Agriculture and the CDC) that found drug resistant bugs in astoundingly high percentages of supermarket meat products.  The article doesn't go into great detail about the modes of resistance, whether or not the bugs were multi-drug resistant, etc., so it may be less satisfying of a read for my microbiologically inclined readers.  For those of you who prefer a peer-reviewed look at the subject, I would recommend checking out a review article by Dr. Price and colleagues:  Curr. Op. Microbiol., 2011, 14, 244-250, "An ecological perspective on U.S. industrial poultry production..."

I have no doubt that there are many more articles and reports on this subject that have come out recently.  If you know of something that is particularly interesting, please leave a link in the comments.  

- @EJDimise

Animal-Human Transimission of Dangerous Bugs Catches the Attention of Congress

"It remains unclear whether Congress will pass any of

the current legislation related to antibiotics in farm animals

this year.  But because of the increasing awareness of the 

issue, consumer demand for antibiotic-free meat is growing."

 

- Britt E. Erickson, Chemical and Engineering News (22 July 2013)

Antibiotics have been utilized in the rearing of livestock ever since industry discovered that they helped grow bigger, healthier animals during the antibiotic heydays post WWII.  The growth enhancing affect of the bactericidal compounds yielded larger quantities of meat and healthier animals, so who could blame mid twentieth century farmers for packing their feed supplies full of the new "miracle drugs"?  But, as the history of antibiotics has proven time and again, drug resistant bugs have been showing up in livestock ever since the practice started.  Agribusiness, government regulators, Congress, and lobbying groups have, not surprisingly, been arguing about this for decades, and have been getting nowhere... for decades.  In more recent history, as the threat of antibiotic resistance in the clinical and public heath setting has become ever more acute, consumer consciousness and government attention to the problem has been increasing.  Remember going to the grocery store during the 90's and picking out steaks and chicken breasts that were guaranteed "antibiotic free"?  Yeah, I don't either.  

Now, antibiotics are no longer the sole property of the scientific journals.  One is hard pressed to avoid coverage of the subject in all the major media outlets.  With the proviso that the coverage seems to be overwhelmingly geared towards scaring the hell out of everybody, it's refreshing to see the topic of antibiotic resistance and human microbiological ecology covered so widely.  One could argue that this broad, frequent coverage has helped spur meat suppliers to offer antibiotic-free choices at the meat counter.  Of course, the growing popularity of the organic food movement, localterianism, veganism, flexitarianism, foodieism, and the extraordinary success of "food TV", and ________ (insert other -ism I may have forgotten) has played a huge role too.  Whatever the motivation, the mounting concern over antibiotic use in livestock is reaching levels in which elected officials are actively proposing legislation to curb use and abuse of the 20th century miracle cures.  

As I was perusing the 22 July 2013 edition of Chemical & Engineering News, the American Chemical Society's weekly science news magazine, I came across a nice piece of reporting by Britt E. Erickson titled "Animal Antibiotics Under Scrutiny" (linked above).  Here, two recently published journal articles were highlighted that unambiguously documented animal-to-human transmission of drug resistant bacteria.  In an article in the journal PLoS One, J. L. Rinsky et. al. published the isolation of livestock-associated drug-resistant Staph from the noses of farm workers.  In a related article in EMBO Mol. Med., E. M. Harrison et. al. used genomic techniques to pin down a separate case of animal-to-human transmission of the infamous multidrug resistant S. aureus (MRSA), a scourge in hospitals and a benchmark bug for determining if a new antibiotic is worth developing.  These finding are important because they show that filling food animals full of antibiotics can generate antibiotic resistant strains (which we knew already) and that these strains can jump from the animals to their human handlers (an area where evidence was lacking).  Have you seen a zombie movie start this way?  Some kind of exotic bug jumps from an animal into a human, and boom, apocalypse city.  Sound familiar?  Should you really be concerned about the end of times?  No.  But will this give some fodder to those scientists, activists, and elected officials who feel that we need to be preserving our precious supply of antibiotics for treating human diseases?  It most certainly ought to, at the very least.

Indeed, there currently exists four bills to address this issue directly:

1. Preservation of Antibiotics for Medical Treatment Act (H.R. 1150); Rep. Louise Slaughter (D-NY) sponsor
2. Delivering Antimicrobial Transparency in Animals Act (H.R. 820); Rep. Henry Waxman (D-CA) sponsor
3. Preventing Antibiotic Resistance (PAR) Act (S. 1256); Sen. Diane Feinstein (D-CA) sponsor
4. Antimicrobial Data Collection Act (S. 895); Sen. Kirsten Gilllibrand (D-NY) sponsor

All of these bills would introduce new rules or regulations on the use of antibiotics in animal husbandry.  Some would serve to directly restrict the quantity, manner, and type of antibiotics that could be used in livestock (H.R. 1150, S. 1256).  Others would make the use of antibiotics much more transparent to the government and the public (H.R. 820, S. 895), as it is currently difficult to obtain detailed information from the FDA and livestock producers.  In all cases, the legislation would produce a stricter regulatory framework than  exists today.  Currently, the FDA works with farmers to spur the voluntary reduction of antibiotic use in feed stocks.  The thinking is not necessarily without merit, but many feel that the escalating drug resistance problem needs to be addressed quickly with regulatory measures that have "teeth".  Instead of telling livestock farmers that "we sure would like you to address this issue", it would be more, "you have to address this issue". 

It is easy to be pessimistic about anything getting done in Congress given the current political climate.  We can look to examples of legislation like the GAIN Act, which passed both houses in a bipartisan manner and was signed into law just over a year ago, as an example of both parties working together to solve an obvious problem.  But it's easy to argue that the agribusiness lobby will use its strength to bury the legislation highlighted here.  Wouldn't that feel more like "business as usual"?  Thus we come to the quote at the top of this post.  Wouldn't it be great if industry really did voluntarily reduce/eliminate the use of antibiotics because we (the consumer) would please like them to do that thank you very much?  If there's one thing that everyone in Washington loves, it's when the market solves a problem all by itself.  I'll remain hopeful, but you won't catch me holding my breath... unless I'm hanging out with MRSA infected farm animals.

- @EJDimise

Microbial Media Snippets

Hello Spent Media readers!

Wow, it's July.  My apologies, I've been away for a while.  This blogger has been busy looking for a new job, an activity that turns out to be a bit of a time suck.  I'm currently bouncing back from a very nice vacation last week, visiting family and friends on the west coast and in the south.  (Yes, the avocados and biscuits were all delicious!)

I have some interesting articles from the primary literature picked out and will prepare posts for them in the near future.  For today, I've pulled together a few quick reads from the popular press regarding some topics of interest.  Not surprisingly, mainstream media sources give a lot of attention to microbes that cause disease.  For my next post, we'll return to our focus on the gut microbiota by highlighting recent research on a bug that may help fight obesity (cool, right?), so please check back soon!  

Here are the links to the articles and a quick digest of what you can find therein:

Developing New Antibiotics

(New York Times, 6/7/2013 letter to the editor, Jeffrey Stein)

In a response to the NY Times article that I highlighted in my previous post, Jeffrey Stein, the president and chief executive of Trius Therapeutics, a San Diego based biopharmaceutical company, argues that there is a lack of market incentive for new antibiotic production.

Spurious Tuberculosis Drugs Pose a Threat

(New York Times, 7/1/2013, Donald G. McNeil Jr.)

We have focused on the challenges posed by drug resistant tuberculosis in a previous post.  In this brief highlight from the NY Times, a recent PLoS Medicine report is described.  The researchers show that in poorer nations, TB drugs are often "substandard", contributing to the rise of drug resistant tuberculosis strains.  The remedy may be simple; enforce existing World Health Organization standards.

Myths And Stigma Stoke TB Epidemic in Tajikistan

(NPR, 7/2/2013, Jason Beaubien)

Not to belabor the TB theme, but here is another interesting - and unfortunately sad - story out of Tajikistan, an example of a "poorer nation" discussed in the snippet directly above.  It turns out that in addition to having only limited access to quality drugs to treat tuberculosis, there are broad societal misconceptions about how the pathogen is spread.  To add insult to injury, contracting TB is considered shameful, causing patients to lie about or hide their illness.

Obesity, cancer and bacteria in the gut: Scientists explore link

(LA Times, 6/26/2013, Eryn Brown)

This LA Times Science Now highlight reports on a study by S. Yoshimoto et. al. in the recent issue of Nature, where it is shown that obesity triggers changes in the gut microbiota that leads to the release of deoxycholic acid, a bacterial metabolite that causes DNA damage.  The researchers believe that this points to a link between obesity and an increased risk of developing liver cancer (via a small molecule signaling mechanism).

Antibiotics in infancy linked to eczema

(Chicago Tribune, 7/3/2013 , Kathryn Doyle; Reuters)

 

A new study shows that exposure to antibiotics during the first year of life increases the risk of the allergic skin disease eczema.  The researchers suggest that this reveals a link between the resident microbes in babies, the developing immune system, and autoimmune diseases.  Alternately, there was no link found between prenatal antibiotic exposure and increased eczema risk.

Scientists Discover Thriving Colonies of Microbes in Ocean 'Plastisphere'

(ScienceDaily, 6/27/2013)

This is a fascinating one!  So, it should surprise no one that plastics, completely man-made chemicals, are pollutants in our waterways and marine ecosystems.  Tiny particles of plastic are now creating a unique environment in the Earth's oceans, referred to as the "plastisphere".  Yes, this is a bit sad and troubling, for sure.  But, this ScienceDaily post reports on a recent article in the journal Environmental Science & Toxicology by E. Zettler et. al., where the authors have found completely unique populations of microbes living in and adapting to the "plastisphere" environment.  Electron microscopy analysis of some of the plastic particles revealed pits and imperfections on the plastic surface, indicating microbial processing of the polymer.  The authors certainly did not fail to point out that it would be cool to tap the plastisphere to discover hydrocarbon and plastic degrading microbes that could be used to clean up polluted environments!  (Lemons into lemonade I suppose?)

Happy reading and Happy 4th of July!

- @EJDimise

New and Not-So-New Media Highlights

I'd like to recommend two interesting articles for your consideration and reading enjoyment.

Policies to Find New Drugs for Bad Bugs

The first is an article from the June 2nd New York Times titled, "Pressure Grows to Create Drugs for 'Superbugs'" by Barry Meier.  It highlights the growing urgency for the discovery and development of new antibiotics to treat drug resistant bacteria, a topic we've discussed here before.  Potential legislation, FDA rule changes, and new government subsidies for big pharma companies (GlaxoSmithKline is mentioned as an example where this is already in the works) are all floated as ways to streamline and incentivize the discovery, production, and marketing process for new drugs.  Here are a few snippets:

"The need for new antibiotics is so urgent, supporters of an overhaul say, that lengthy studies involving hundreds or thousands of patients should be waived in favor of directly testing such drugs in very sick patients"

"The overuse of antibiotics in people and animals, often for conditions for which the drugs are ineffective or not needed, is seen as a driving force in the development of resistant bacteria.  As these organisms have evolved and developed resistance, the development of new drugs has not kept pace."

Our Bugs, Ourselves - Current and Future State of the Human Microbiota

The second article is from the March 2013 issue of Nature Reviews Microbiology, which I somehow managed to miss until just a few days ago (my bad).  In a Perspectives piece titled, "The microbiome explored: recent insights and future challenges" - FYI this is not open access, so my apologies to those without full-text journal access - the journal interviews 5 prominent figures in the field regarding the current state and future directions of human microbiome/microbiota research.  We've touched on this subject several times here at Spent Media!  To give you a taste for the content of the discussion, here are some words from each of the featured scientists:

"The most important findings [regarding the human microbiota] to date are: the notion that we as humans are a superorganism, with our biology determined by the genes encoded in our DNA together with the genes of our microbial partners"

"... the current regulatory environment conspires against large-scale trials of prebiotics and probiotics for therapeutic purposes, and a more enlightened regulatory approach is necessary..."

- Dr. Claire Fraser, University of Maryland School of Medicince

"A very surprising finding has been that disruption of the homeostasis between the microbiota and the host, known as dysbiosis, has a more important role than host genetics in the development of a range of diseases, such as inflammatory bowel disease, obesity and type 2 diabetes."

- Dr. Jun Wang, Beijing Genomics Institute

"The human metagenome is orders of magnitude more manipulable than the human genome.  This difference provides the opportunities to intercede to prevent and treat illness, if only we knew what was important!  The use of faecal transplantation to treat colitis caused by Clostridium difficile seems to have at least some definite efficacy."

- Dr. Martin Blaser, New York University School of Medicine

"For formula-based nutrition supplements, we need to know more than simply the species composition of microbial communities; we need to understand how the communities function as ecosystems."

- Dr. Peer Bork, European Molecular Biology Laboratory, Heidelberg, Germany

"... characterizing the microbiota of divergent populations, including geographically and culturally isolated populations before they adopt elements of the Western lifestyle, may be crucial for understanding the suite of so-called Western diseases..."

"... we really lack the ecological and mechanistic understanding of the parameters that control composition and change in the microbiota to make it do our bidding."

- Dr. Rob Knight, University of Colorado at Boulder

[Notice the emphasis - again and again - on needing to gain a more complete understanding of our microbiota as an interconnected, complicated community functioning within a self-contained ecosystem - you.]

Happy reading!

- @EJDimise   

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