Time for a Nobel Prize for the human microbiome? I think so ... what do you think?

Well, previously I have written about how I thought that there should have been a Nobel Prize awarded  to Carl Woese and Norm Pace for pioneering work on microbial diversity.  See for example "Some arguments for why Carl Woese (and probably Norm Pace) deserves a Nobel Prize".  Alas Carl Woese passed away recently and is no longer eligible.  However, in a way this opens up things to a perhaps more medical driven Nobel prize in Medicine for the microbiome.  I believe that the human microbiome has been shown to be important enough in medicine to be deserving of a Nobel Prize in medicine.

And if that is true, then we can ask "Are there any people who would deserve a prize in this area?"  And the answer is pretty clearly yes.  I would suggest that there are two people who deserve such a recognition: Norm Pace and Jeff Gordon.  Norm Pace for his pioneering work on characterizing microbes indirectly via sequencing their RNA and DNA, especially their ribosomal RNA genes.  And Jeffrey Gordon for his pioneering work on animal and the human micro biome and in showing that the microbiome plays fundamental roles in animals and human health and phenotypes.

I will write more about this later but just wanted to get this thought out there ... and see what people think.

UPDATE September 2015 I note. I have been and continue to be concerned with the spread of "microbiomania" which is the term I use to refer to "Overselling the Microbiome". Even though this still is a problem, I also believe the microbiome has now been clearly shown to be critically important to human health in diverse ways and I do think it is appropriate to award a Nobel Prize in this area.

Also note Reuters is reporting that Jeffrey Gordon is on their candidate list this year (based on ISI predictions).

Fecal transplants as treatment for anxiety? Not so fast (but worth pondering)

 Just read this: Gut Bacteria Transplant: A New Treatment For Anxiety? | Psychology Today: calm vs. anxious.  On the one hand, I agree that the microbiome very well may have interesting effects on human behavior.  Well, actually, we know the microbiome does impact human emotion and behavior.  For example, I get pretty anxious when I have gut problems, and we certainly know that the microbiome has a major impact on gut health.  And of course, we know lots of examples of microbes affecting behavior of animals.  The latest on this that I am aware of comes from studies by Wendy Ingram in my brother's lab at UC Berkeley - who has been looking at Toxoplasma and it's effect on mouse behavior (e.g., see Toxoplasma infection permanently shifts balance in cat-and-mouse ... and Cats, Mice and Toxoplasma Gondii Parasite Weird Love Triangle and Mice Aren't Scaredy-Cats When Infected By Toxoplasma).

On the other hand, despite the apparent connections between microbes and emotion and behavior in some cases, this does not mean either that (1) microbes have a role in causing anxiety in people or (2) even if microbes CAUSE anxiety that microbiome transplants could treat the anxiety.  Anyway - I certainly think this is an interesting area of research but I urge caution before we go overboard in marketing fecal transplants for everyone with any issues connected to behavior or emotions ...

Best evidence yet that we should do away with the "Candidatus" terminology used for uncultured microbes

Just got this email:

Dear Jonathan , I am relatively new to phylogenetics and have developed a keen interest in bacterial phylogenies. I read one the papers which you have published in Nature on the same topic. I needed some help. Thing is, I have constructed a bacterial phylogeny based on 16s rRNA and have found that Candidatus species differ by a really great extent from one another, and appear to be in completely different clades. I need some way to verify this and was wondering if you could send me the phylogeny you have created in order for me to verify. Thank you

I have been arguing for years that the use of the term "Candidatus" to describe microbes is a bad idea.  This email is exactly the kind of thing I worry about.  Candidatus is a term used "for well characterized but as yet uncultured organisms." (A nice description of the history of the term is here).  The problem with Candidatus are many - including the confusion such as evidenced by this email - in that people who are not used to dealing with the term have no clue what it means.  But in addition, the constraint that one is not "allowed" to name things unless they have been cultured is silly, outdated, and damaging to the field.  But I can write about that some other time.  For now, this email will suffice ...

Some examples of Candidatus names from http://www.bacterio.net/candidatus.html

Lovely - Entangled Bank conference not only only includes men, but has obnoxious FAQ about doing that

Just got pointed to this: These men would like you to kindly shut up about gendered conferences | Feminist Philosophers.  It discusses a painful example of Gender Bias associated with Science conferences.  In this example a charity "or, a supposed charity" is organizing a meeting featuring only male speakers.  And they included a FAQ on the meeting website to explain why there were only men:

Wow.  That is just horrendous.

More about this is available now on Jezebel.

Note - the same group organized another meeting also with only male speakers. http://www.entangled-bank.co.uk/dawkins-in-bristol.html

Guest post by Josh Weitz: IP vs. PI-s: On Intellectual Property and Intellectual Exchange in the Sciences and Engineering as Practiced in Academia

Today I am pleased to publish this guest post from my friend and colleague Joshua Weitz. He does some fantastically interesting research but that is not what he is writing about here. Instead he is focusing on intellectual property and sabbaticals ...

Joshua S. Weitz

School of Biology and School of Physics

Georgia Institute of Technology

Email: jsweitz@gatech.edu

Web: http://ecotheory.biology.gatech.edu

Preface:

This blog entry is inspired by a recent personal experience. However, I believe it serves to illustrate a larger issue that requires open discussion amongst and between faculty, administrators, and the tech transfer offices of research universities.

Context:

I am temporarily based at the U of Arizona (hereafter UA) working in Matthew Sullivan’s group where I am on a 9 month leave from my home institution, Georgia Tech (hereafter GT), spanning the term: August 15, 2013 to May 15, 2014. I arrived on campus and began the process of signing various electronic forms to allow me to use the campus network, get keys, etc.

The gateway to this process was a request to sign a “Designated Campus Colleague (DCC)” agreement: http://www.hr.arizona.edu/dcc. The DCC agreement is the official way the UA establishes an “association” with long-term visitors who do not receive any form of payment from UA (as applies in my case). I would be an Associate of the Department of Ecology and Evolutionary Biology, where the Sullivan group is based. The privileges of the DCC include receiving a UA email, keys to an office, a “CatCard” (Cat = short for Wildcats, the UA mascot) which enables me to access the building after hours, as well as other discounts. The DCC makes it quite clear that I am not an employee and that I will receive no form of payment whatsoever from UA. Indeed, all of this is rather immaterial to my real reason for spending 9 months here – to work in closer collaboration with the Sullivan group on problems of mutual interest. The obligations I must affirm are largely boilerplate (i.e., do no harm) but do include the following identified in Clause 11 of the DCC:

“11. INTELLECTUAL PROPERTY – Associate hereby assigns to the ABOR all his or her right, title and interest to intellectual property created or invented by Associate in which the ABOR claims an ownership interest under its Intellectual Property Policy (the "ABOR IP Policy"). Associate agrees to promptly disclose such intellectual property as required by the ABOR IP Policy, and to sign all documents and do all things necessary and proper to effect this assignment of rights. Associate has not agreed (and will not agree) in consulting or other agreements to grant intellectual property rights to any other person or entity that would conflict with this assignment or with the ABORs' ownership interests under the ABOR IP Policy”

This clause is worth reading twice. I did. I then refused to sign the agreement. This clause, my refusal to sign the agreement, and what happened next are the basis for this blog entry.

Note that the template upon which my particular agreement is based can be found on the UA website. For those unfamiliar with intellectual property (IP) clauses that universities routinely request visitors to sign, here is a small (random) sample:

1. U of Texas
2. U of Maryland Baltimore
3. Emory University
4. Washington University @ St. Louis
5. Northwestern University

It would be possible to collect many more such agreements that apply to both employees and to visitors of research universities.

The issues
The central issue at stake is one of ownership of future intellectual property. Presumably a visitor has decided to visit U of X because U of X is the best in the world and that new, monetizable discoveries will emerge as a direct result of the “resources” at U of X. This may be true. Or, it may not be. However, rather than try and chase IP after it has been created (a tenuous legal position), universities would rather have all visitors assign future IP immediately upon arrival and sort it out later (if and when IP is generated).

This language of “hereby assigns” (as quoted above) is not chance legal-ese. To the contrary, it is clear that the legal staff and upper administration at universities are concerned with respect to the repercussions of Stanford vs. Roche. If you haven’t read up on this case, I encourage you to do so. The key take-away message is that the Supreme Court has ruled that inventions remain the property of the inventor to assign as they see fit unless the inventor assigns inventions to a specific entity (e.g., an employer). As the U of California memo to faculty makes clear, the way that many universities want to deal with this problem moving forward is to reword their employment contracts so that employees immediately assign their IP to their university, rather than “agree to assign” their IP. “Agree to assign” (a clause meant to describe a potential future action) was the language found in Stanford’s prior IP agreement and represented one key component of Stanford losing their Supreme Court case to Roche, to the disappointment of Stanford, other major research universities and the federal government.

Figure 1 - Supreme Court decision on Stanford vs. Roche, remainder available here: http://www.supremecourt.gov/opinions/10pdf/09-1159.pdf

However, scientific visits to other institutions create a complex contradiction whereby institutions ask their visitors to sign agreements that they would never want their own employees to sign while visiting other institutions!

Jerusalem Post on Allergy and Fecal transplants

Some interesting tidbits in this Jerusalem Post article: Health Scan: Ungluing the complexity of allergy | JPost | Israel News (a bit overenthusiastic too but just thought I would point some of these lines /quotes out):

• "Studies in adults show that more than 90 percent of patients are cured following such therapy and, experts say, they have every reason to believe the numbers would be equally impressive in children." - not sure this is true (i.e., the 90% cured level).
• In less than a decade, we’ll have lab-cooked poop that we can administer to restore balance in the guts of people with a wide array of conditions caused by the imbalance between good and bad germs.” OK - a bit overenthusiastic 
• But this is my favorite: "The concept is hardly new. The method originated with ancient Chinese healers who gave their diarrhea-ravaged patients “yellow soup,” a concoction of fecal matter and water. Thousands of years later, the delivery approach has evolved" - So - I have been writing and talking about fecal transplants for a while now (e.g., see this) and have linked them to coprophagy and poo tea and such but never heard of the yellow soup thing.

The Saga of Howard Zochlinski, ex-#UCDavis PhD Student

I met with Howard Zochlinski last week at UC Davis.  His story is like none I have ever heard.  Howard does not have ready web access.  He has little money.  He needs to go to the library to check his email.  And he met with me to ask me to share his story.  And I readily agreed to.  I do not know ANY of the history personally.  I do not even know whether all of what he says is true or not.  But the story is worth putting out there in my opinion for people to make their own judgements.

To begin to get to know the details behind the saga of Howard Zochlinski you might want to start with the petition he just posted on Change.Org: Petitioning To The Honorable John G. Roberts, Chief Justice, and the Honorable Justices of the Supreme Court of the United States.

Other sources of information about Howard's story are linked below:

• DavisWiki page: Howard Zochlinski‎ (with lots of background and links)
• Sacramento News and Review Story from 2001: Howard's End
• UC Davis student paper "The Aggie" story from 2011: Two-decade-long fight for Ph.D. continues
• Facebook Page maintained by Howard (I think): Justice for Howard Zochlinski

The DavisWiki page summarizes some of the details on the saga and I have copied the current text from there below:

Howard Zochlinski has been the center of academic and judicial controversy within California and the UC System, including at UC Davis. 

When Howard was an undergraduate at UC Santa Barbara in the early 1970s he was arrested; none of the charges stuck. 20 years later he was a Genetics doctoral candidate at UC Davis and was arrested by the same policeman who had arrested him back in Santa Barbara. 

The arrests in Santa Barbara resulted in either dropped charges or were thrown out of court. All three of these arrests were made by the same two officers, John Jones and John MacPherson. Howard believes that these arrests were the result of his being a Vietnam War protestor. During his detainment he claims that he was sexually assaulted while in police custody and believes that officer Jones was instrumental in arranging it.
He transferred to UC Berkeley where four years later he graduated with a Bachelors degree. He then earned two Masters over the next six years from University of Hawaii and John Hopkins University. During this time officer Jones transferred from UC Santa Barbara to the UC Davis Police Department. 

In 1984 Howard was admitted to UC Davis as a PhD candidate. In 1992 officer Jones again arrested Howard, this time for stalking. Jones claims that there was nothing personal or targeted about the arrest; Howard claims that the arrest was the result of Jones holding a vendetta and being an anti-semite. This charge as well was dropped when the victim did not appear in court. Howard also maintains that Jones arrest report does not meet the legal definition for the charges that were filled against him. 

In 1993 he was arrested again, but acquitted in court. His defense attorney claimed that the police were not conscientious in the manner in which they handled the case. It does not appear that officer Jones was involved in this case. 

Shortly prior to the time of this last arrest after having been a PhD candidate for 9 years Howard was dismissed for not filling an acceptable thesis by the deadline his committee had assigned. 

Howard believes that the stalking arrest had prejudiced his department against him. Part of his feelings of persecution stem from having had a conduct hold placed on his academic record; one with an end date in the year 2099. Student Judicial Affairs says that this was a clerical error. Howard thinks that this contributed to his difficulty in landing a job.
Howard filed a lawsuit with the University in regards to his dismissal as a student. As of 2006, the details and status of this lawsuit are unknown. In 2005, the Academic Senate of UC Davis overwhelmingly ruled to re-admit Zochlinski as a student. Such a ruling by the Academic Senate is fairly unheard of, prompting University officials to question what would happen next. However Jeff Gibeling, Dean of Graduate Studies, ruled against readmitting Zochlinski on the basis that his predecessor had made the same ruling. As such, this case is still ongoing.

I am still trying to wrap my brain around the whole saga.  But if even a tiny fraction of it is true, which certainly seems to be these case, he has been pretty badly treated.  Again, I do not know all the details or what is the "truth" but I can say for certain that Howard continues to struggle and I cannot for the life of me see any reason not to allow him to be readmitted as a student.

Really? Nature put the #HeLa genome paper behind a paywall? Time for Nature Publishing Group to return ALL money obtained from genome papers

This is just fucking ridiculous.  As I have written about many many times - Nature Publishing Group many years ago promised to make papers reporting genome sequence data freely available.  They do not generally live up to this promise well.  See for example

• Hey Nature Publishing Group - When are you going to live up to your promises about "free" genome papers? #opengate #aaaaaarrgh
• Please help keep the pressure on Nature Publishing Group to restore free access to genome papers #opengate
• I am highly skeptical of the CHORUS system proposed by scientific publishers as an end run around PubMed Central
• Calling on Nature Publishing Group to return all money received for genome papers and article corrections
• A Solution to Nature Publishing Group's Inability to Keep Free Papers Free: Deposit them in Pubmed Central

Today I discovered that not only are some important genome papers not freely available but one for the ages - the paper on the HeLa genome - reported with much fanfare recently as a triumph of an agreement with the family of Henrietta Lacks - is only available if you pay.

Once again I call on Nature Publishing Group to publicly disclose all financial gains that have come from people paying for the these genome papers and for the money to be returned.

Can academics use the "copyright termination" system to recover academic works?

Heard an interesting story on copyright termination on NPR last night: Taking Back 'Funkytown': Songwriters Prepare For A Custody Battle  By Joel Rose.  This in turn led me to a New York Times article on the same general topic: A Copyright Victory, 35 Years Later - NYTimes.com.

The gist of these stories is that it turns out UC Copyright law has a "termination" provision which allows artists / writers / etc to terminate copyright agreements that they made for work they produced.  This is allowed 35 years after the copyright was assigned.  And many musicians are using this provision of copyright law to reacquire some works they made three and a half decades ago.

So - I am asking the world out there - could this same provision be applied to scientific or academic works?  Would this be a way to move a lot of material that is behind a wall back into the hands of authors and/or into the public domain?  I am looking into doing this with work published by my father as a test case (as part of my long struggle of  Freeing My Father's Publications (since termination rights apparently transfer to family members if the holder passes away as my dad did in 1987).

So - anyone out there know if this termination has been used for scientific or academic works?

UPDATE: Other reading

• U.S. Copyright Office - Copyright Law: Chapter 2
• Navigating US Copyright Termination Rights - WIPO
• United States Copyright Termination Rights: What Does the Future ...
• Copyright Termination Rights: Giving Artists Their Second Bite at the ...
• Superman Lawsuit Tests Copyright Termination Rights | Astronomy ...

Story behind the paper guest post by Corey Nislow (w/ Metka Lenassi) on "Genomics w/o Borders"

Below is another in the "Story behind the paper" series of guest posts here.  This one is from Corey Nislow w/ Metka Lenassi.  If anyone else has published an open access paper on anything relating to this blog and would like to write a guest post on the Story behind the paper, please let me know.

---

Genomics without Borders: Genome Sequence of the Extremely Halotolerant Yeast Hortaea werneckii 

by Corey Nislow (with Metka Lenassi)

In this guest post (thank you Jonathan!) I wanted to tell the story behind a paper that my colleagues and I published two weeks ago in PLoS ONE. The story also offers an opportunity to talk about what role, if any, a middle author can play in a scientific study.

The story is set in Slovenia a beautiful country which was part of the former Yugoslavia and which is home to about 2 million inhabitants, 2400+ fungal species (thanks Wikipedia) and some very interesting environments. One of these environments is the Secovlje Salterns where one can find the yeast Hortaea werneckii.

A worker harvests sea salt in the Secovlje salterns, July 17, 2010. Some 2600 tons of salt is expected to be produced during the two and a half month season at the salterns.(Xinhua/Reuters Photo)

I hadn't heard of Hortaea until I started googling around looking for a yeast extremophile that I can grow in the lab to dissect out its nucleosomes to ask questions regarding nucleosome occupancy and transcription in the face of extreme environments. Turns out it was not a crazy idea--

13 years ago a peculiar black yeast Hortaea werneckii was isolated from its natural habitat: waters containing so much salt, it would kill most living organisms instantly. Since then, two small (but enthusiastic) Slovenian groups have tried to understand its halotolerance. This demanded field trips to the beautiful Slovenian coast, but also a lot of hard work and inventiveness to optimizing protocols used for other organisms – and to do it on a low budget. The first important obstacle was actually cultural - to persuade the scientific community that such extreme yeast even exists in nature! You can see it below. We now have ample evidence as Hortaea has been isolated from many seawater-related environments, saline lakes, but also from surface layers of tropical microbial mats in salterns and even from spider webs in Atacama Desert caves. All these different Hortaea strains are now waiting in their freezer (the Ex culture collection) to be analyzed.

Hortaea werneckii growing happily on 2M salt.

Nice show on KQED on Inspiring Girls and Women to Code #Diversity #STEM

Listened to a nice show on KQED this AM on my bike ride in to work (note - I listen with one earplug in, and one ear free to hear the world around me, and I listed on relatively low volume ...).  We still need to do so much to make STEM fields and related fields more diverse ...


Inspiring Girls and Women to Code:

 

Families that share everything: Health2Fit video on brother helping sister by being a donor for a fecal transplant

I guess today is fecal transplant day. So why not a little news story from Health2Fit about families that share everything ...

 

Fecal transplants taken up by American Hospital Association in letter to HHS about Medicare/Medicaid

Interesting discussion of Fecal Transplants is this letter from the American Hospital Association to HHS about Medicaid / Medicare: Marilyn Tavenner September 6, 2013 Page 1 of 33 September 6 ...

Key text is below:

"FECAL MICROBIOTA TRANSPLANTATION
Fecal microbiota transplantation (FMT), also known as fecal bacteriotherapy, or human probiotic infusion, is a medical treatment for patients with Clostridium difficile (C. difficile) enteritis or ulcerative colitis. C. difficile infection occurs in patients who have been administered antibiotics for a long period of time. The antibiotics destroy important disease-fighting bacterial flora in the intestine. Fecal transplants are believed to restore the bacteria back to normal, and the patient can recover. The fecal transplant works by repopulating friendly flora in the infected intestines. The donated feces is screened for disease and then mixed with a saline solution to the consistency of a “milkshake.” FMT can be performed by various routes including nasogastric (NG) tube, nasojejunal tube, upper tract endoscopy (EGD), colonoscopically or by retention enema. However, based on an editorial published in the Journal of Clinical Gastroenterology (Volume 45, Number 8, September 2011), colonoscopic FMT is the preferred method for the vast majority of C. difficile infection patients, and if carried out early, may prevent development of severe infection.

Effective with the 2013 edition of the CPT manual, the American Medical Association developed the CPT code 44705 (Preparation of fecal microbiota for instillation, including assessment of donor specimen) that includes:

• development of the intestinal instillate for the recipient; and
• evaluation of the donor specimen, including the physician review of results of testing the donor’s specimen for infectious pathogens

The CPT manual instructions require that the actual instillation or fecal microbiota transplant be coded separately using CPT 44799 for either oro-nasogastric tube or enema. Additional instruction in the CPT manual identifies that all laboratory testing provided for the patient is to be reported separately. Based on this instruction and the intent of the CPT code 44705, this is an add-on or “list separately in addition to the primary procedure,” which would be the instillation procedure, e.g., the oro-nasogastric tube or enema.

Fecal transplant recruiting on Craigslist

See this Craigslist post for the Boston area: Are you a healthy adult, 18-50 years old? - copied below.  It seems that fecal transplants really are everywhere ...

 Are you a healthy adult, 18-50 years old? (Massachusetts General Hospital)

Fecal Microbiota Transplant
Healthy adult volunteers 18-50 years old
Involves donation of stool samples and medical screening
Blood draws, complete medical exam
No medical problems
5-7 out-patient visits at MGH
Compensation up to $700 for completion of study
617-724-8625

• Location: Massachusetts General Hospital
• it's NOT ok to contact this poster with services or other commercial interests

Posting ID: 4050676649

Posted: 2013-09-06, 4:04PM EDT

Updated: 2013-09-06, 5:09PM EDT