Showing posts with label Research. Show all posts

Showing posts with label Research. Show all posts

Branswell On Lifting The H5N1 Research Moratorium

BSL-4 Lab Worker - Photo Credit –USAMRIID

# 6456

Six months ago, in response to the rising chorus of concern over the biosecurity aspects of conducting H5N1 research, a 60 day moratorium was announced by a group of 39 leading scientists (see Scientists Announce 60 Day Moratorium On Some H5N1 Research).

While the research papers that originally sparked this controversy have now been published, the self-imposed moratorium remains in place.

Next week a meeting will be held in New York City of members of the Centers of Excellence for Influenza Research and Surveillance (CEIRS), and the subject of what to do about these research restrictions is expected to be part of their talks.

The inimitable Helen Branswell of the Canadian Press brings us the inside details on the difficult and controversial path ahead to undoing the H5N1 research moratorium:

As key flu scientists meet, question looms: When will bird flu studies resume?

By Helen Branswell, The Canadian Press | The Canadian Press – 42 minutes ago

Six months after leading influenza scientists announced they would voluntarily halt research into what it takes to make bird flu viruses transmit among mammals, it's still not clear when and how the cease-work order will be lifted.

(Continue . . .)

Highly recommended.

The Return Of The Hygiene Hypothesis

Photo Credit-CDC

# 6394

While I often use this blog to promote better hand and respiratory hygiene, I must confess to a fascination with the hygiene hypothesis.

For those unfamiliar with it, this is multi-faceted and controversial theory that proposes that some diseases common to modern man may come about due to a lack of exposure to various biological agents (bacteria, viruses, and even parasites) . . . particularly in early childhood.

Research over the past decade has increasingly linked the use of household cleaners (bleach, disinfectants, carpet cleaners, etc) and other chemicals (turpentine, insecticides, etc) to childhood onset asthma and allergies (see MedNews Today Asthma in kids linked to household cleaning products and chemicals).

Essentially, the hygienic hypothesis says we may be trying to be `too clean’ for our own good.

Back in 2010, I wrote about a University of Michigan study that addressed growing concerns over two commonly used chemicals – Triclosan and Bisphenol A (BPA) - and their possible impacts on our immune systems.

Study: Bisphenol A, Triclosan and The Hygienic Hypothesis

While my article focused mostly on BPA, Maryn McKenna took a deeper look at the use of Triclosan, and at the `hygienic hypothesis’ in her Superbug Blog entry called: Triclosan, allergies and the “hygiene hypothesis”.

Very much worth reading.

All of which serves as prelude to a new study today, from the Johns Hopkins Children’s Center, that links antibacterial chemical exposure to a higher incidence of allergies in children.

First some excerpts from the press release, followed by a link to the study, and finally a few closing comments.

Antibacterials in Personal-Care Products Linked to Allergy Risk in Children
MEDIA CONTACT: Ekaterina Pesheva
EMAIL: epeshev1@jhmi.edu
PHONE: (410) 502-9433
June 18, 2012

Exposure to common antibacterial chemicals and preservatives found in soap, toothpaste, mouthwash and other personal-care products may make children more prone to a wide range of food and environmental allergies, according to new research from Johns Hopkins Children’s Center.

Results of the NIH-funded study are published online ahead of print June 18 in the Journal of Allergy and Clinical Immunology.

Using existing data from a national health survey of 860 children ages 6 to 18, Johns Hopkins researchers examined the relationship between a child’s urinary levels of antibacterials and preservatives found in many personal-hygiene products and the presence of IgE antibodies in the child’s blood. IgE antibodies are immune chemicals that rise in response to an allergen and are markedly elevated in people with allergies.

“We saw a link between level of exposure, measured by the amount of antimicrobial agents in the urine, and allergy risk, indicated by circulating antibodies to specific allergens,” said lead investigator Jessica Savage, M.D., M.H.S., an allergy and immunology fellow at Hopkins.

The researchers caution that the findings do not demonstrate that antibacterials and preservatives themselves cause the allergies, but instead suggest that these agents play a role in immune system development.

<SNIP>

Children with the highest urine levels of triclosan had nearly twice the risk of environmental allergies as children with the lowest urinary concentrations. Those with highest levels of propyl paraben in the urine had twice the risk of an environmental allergy. Food allergy risk was more than twice as pronounced in children with the highest levels of urinary triclosan as in children with the lowest triclosan levels. High paraben levels in the urine were not linked to food allergy risk.

(Continue . . . )

The study, which appears in the Journal of Allergy and Clinical Immunology, is called:

Urinary levels of triclosan and parabens are associated with aeroallergen and food sensitization

Jessica H. Savage, MD, MHS, Elizabeth C. Matsui, MD, MHS, Robert A. Wood, MD, Corinne A. Keet, MD, MS

For more on the Hygiene Hypothesis, a couple more resources to consider.

First, from a Scientific American podcast from April of 2011, an interview with Johns Hopkins School of Medicine researcher Kathleen Barnes, who studies this theory.

Can It Be Bad to Be Too Clean?: The Hygiene Hypothesis

Johns Hopkins School of Medicine researcher Kathleen Barnes talks about the hygiene hypothesis, which raises the possibility that our modern sterile environment may contribute to conditions such as asthma and eczema

Another, highly controversial aspect of this theory, is that intestinal parasites (ie. worms) – which have been largely eliminated in the western world - are actually beneficial, and can help prevent (or even cure) certain types of inflammatory bowel disease.

NPR (along with many other media outlets) covered this story at length back in 2010 (see Eat Your Worms: The Upside Of Parasites).

This past week, with the release of an avalanche of News From The Human Microbiome Project, we are learning just how much of our body consists of non-human microbes – which exist in or on just about every part of the human body.

Over hundreds of thousands of years man has evolved to co-exist with – and yes, even depend upon - many of these micro organism to protect our skin, digest our food, and even produce vitamins and anti-inflammatory compounds in our intestines.

Chemicals (and drugs - see The Other Reason Not To Abuse Antibiotics) that can upset the balance of these naturally occurring – often beneficial – organisms have the potential to affect our health in unexpected ways.

While intriguing, the Hygiene Hypothesis remains both controversial and unproven.

Good hand hygiene, avoidance of infection, and general cleanliness remain essential parts of staying healthy, and no one is seriously suggesting we indulge in geophagy (eating dirt), intentionally ingest worms, or move down into the sewers to enhance our immune system.

But there is increasing evidence to suggest that our modern mania for cleanliness - particularly with the use of chemicals like triclosan and parabens – may exact an unexpected cost on our overall health.

How much of a penalty is involved, and whether the tradeoff is worth it, are questions that are yet to be answered.

NIH: News From The Human Microbiome Project

Photo Credit HMP

# 6385

Last year in The Other Reason Not To Abuse Antibiotics I touched briefly on beneficial intestinal bacteria (gut flora or microbiota), and how the use of antibiotics can adversely disrupt their balance.

The study of these ubiquitous micro-organisms that reside not only in our intestines, but on our skin, in our nasal passages, oral cavities, gastrointestinal tract, and urogenital tract has gained momentum over the past several years.

One of the big reasons is the NIH sponsored Human Microbiome Project, which defines their goal as:

The Common Fund's Human Microbiome Project (HMP) aims to characterize the microbial communities found at several different sites on the human body, including nasal passages, oral cavities, skin, gastrointestinal tract, and urogenital tract, and to analyze the role of these microbes in human health and disease. HMP includes the following initiatives.

Today, in advance of the publication today and tomorrow of a number of research articles in PLoS and in the journal Nature, we’ve a couple of lengthy press releases describing this international project’s recent accomplishments, along with an announcement on the PLoS Blog of the availability of this collection.

First, from the NIH – news that researchers have defined the normal bacterial makeup of the human body.

NIH Human Microbiome Project defines normal bacterial makeup of the body

Genome sequencing creates first reference data for microbes living with healthy adults

Microbes inhabit just about every part of the human body, living on the skin, in the gut, and up the nose. Sometimes they cause sickness, but most of the time, microorganisms live in harmony with their human hosts, providing vital functions essential for human survival. For the first time, a consortium of researchers organized by the National Institutes of Health has mapped the normal microbial makeup of healthy humans, producing numerous insights and even a few surprises.

Researchers found, for example, that nearly everyone routinely carries pathogens, microorganisms known to cause illnesses. In healthy individuals, however, pathogens cause no disease; they simply coexist with their host and the rest of the human microbiome, the collection of all microorganisms living in the human body. Researchers must now figure out why some pathogens turn deadly and under what conditions, likely revising current concepts of how microorganisms cause disease.

In a series of coordinated scientific reports published on June 14, 2012, in Nature and several journals in the Public Library of Science (PLoS), some 200 members of the Human Microbiome Project (HMP) Consortium from nearly 80 universities and scientific institutions report on five years of research. HMP has received $153 million since its launch in fiscal year 2007 from the NIH Common Fund, which invests in high-impact, innovative, trans-NIH research. Individual NIH institutes and centers have provided an additional $20 million in co-funding for HMP consortium research.

“Like 15th century explorers describing the outline of a new continent, HMP researchers employed a new technological strategy to define, for the first time, the normal microbial makeup of the human body,” said NIH Director Francis S. Collins, M.D., Ph.D. “HMP created a remarkable reference database by using genome sequencing techniques to detect microbes in healthy volunteers. This lays the foundation for accelerating infectious disease research previously impossible without this community resource.”

(Continue . . . )

In another press release from the University of North Carolina at Charlotte, we get details on how this research was conducted, and the surprising individuality and diversity among health human biomes.

Human Microbiome Project finds vast individuality in healthy human bacterial populations

(EXCERPT)

To define the normal human microbiome, HMP researchers sampled 242 healthy U.S. volunteers (129 male, 113 female), collecting tissues from 15 body sites in men and 18 body sites in women (including three vaginal sites). Researchers collected up to three samples from each volunteer at sites such as the mouth, nose, skin (two behind each ear and each inner elbow),and lower intestine (stool).

Where doctors had previously isolated only a few hundred bacterial species from the body, HMP researchers now calculate that more than 10,000 species occupy the human ecosystem. Moreover, researchers calculate that they have found between 81 and 99 percent of all the genuses of microorganisms in healthy adults.

Defining "a" human biome, however, can be difficult, as HMP researchers found immense variation in bacterial communities, both in bacterial diversity and in bacterial group abundances -- variation that includes population differences both between areas in each body and between similar areas in different bodies.

Each body site can be inhabited by organisms as different as those in the Amazon Rainforest and the Sahara Desert. Further, these sites on different individuals are populated with different assemblages of bacteria, or with some of the same bacteria, but in markedly different proportions.

(Continue . . . )

From the Public Library of Science Blog we get details on this expanding collection of research.

Announcing the Human Microbiome Project Collection

Posted on June 13th, 2012 by Jen Laloup

For the first time, a consortium of researchers has mapped the full community of microbes that inhabit various parts of the healthy human body. Many of these findings will be published today in a new PLoS collection. The PLoS Human Microbiome Project Collection consists of articles from the project’s consortium members, who generate, leverage, and explore microbiome analytical techniques. The articles have been culled from PLoS ONE, PLoS Genetics, and PLoS Computational Biology with more being added to the collection as they are published.

(Continue . . .)

The PLoS Microbiome collection features 13 new research papers published today. To access these papers, please visit:

PLoS Collections: The Human Microbiome Project Collection (2012) www.ploscollections.org/hmp

More Reaction To The Kawaoka Paper

# 6314

As promised, some additional reports on the publication in Nature today of Yoshiro Kawaoka’s H5N1 study (see Nature Publishes The Kawaoka H5N1 Study).

First from Carl Zimmer, an in-depth (and extremely well done) explainer of the issues surrounding the publication of this study.

Behold The Forbidden Flu: A Loom Explainer

Ed Yong for Discover Magazine writes:

Mutant flu paper is finally published, reveals pandemic potential of wild viruses

And the journal Nature runs an editorial:

Nature | Editorial

Publishing risky research

Nature 485,5 (03 May 2012)
doi:10.1038/485005a

Imperfect global biosafety standards and a threat to researchers' motivations from biosecurity concerns are among the significant risks in current flu research.

Via The Scientist we get the following.

Bird Flu Transmission in Mammals

After much ado, Nature publishes the first report of a bird flu virus adapted for transmission in ferrets. By Ruth Williams | May 2, 2012

And lastly, from Science Magazine:

One of Two Hotly Debated H5N1 Papers Finally Published

by Martin Enserink and Jon Cohen on 2 May 2012, 1:18 PM

Nature Publishes The Kawaoka H5N1 Study

BSL-4 Lab Worker - Photo Credit –USAMRIID

# 6312

Although it was Ron Fouchier’s announcement last September (see New Scientist: Five Easy Mutations) of his successful manipulation of the H5N1 virus to make it transmissible among ferrets that set off biosecurity alarm bells (see NPR: Bio-Terrorism Concerns Over Bird Flu Research) and instigated an international debate, in a laboratory halfway around the world Dr. Yoshiro Kawaoka was quietly duplicating the feat.

Today (the embargo having lifted at 1pm) the journal Nature publishes Kawaoka’s study, which details how he created a modified H5N1 – H1N1 hybrid that transmits via respiratory droplets among ferrets.

While its virulence in ferrets was reduced over that of its parental H5N1 virus (exactly why is unknown), the big news is that it only took the introduction of 4 mutations into the H5N1’s hemagglutinin (HA) to allow it to bind efficiently to the alpha (2-6) sialic acid receptors found in ferret (and human) upper respiratory tracts.

Three of these mutations were directly involved in the binding to the a2,6 receptor cell, while the 4th stabilized the virus to fuse with receptor cells at pH levels typically found in the upper respiratory tract.

An affinity for a2,6 receptor cells has long been thought vital for the virus to adapt to humans, but this 4th mutation - that facilitates virus-cell fusion - may prove equally important.

Given its highly public and bumpy road to publication, Kawaoka’s study (see below) is certain to receive an inordinate amount of scrutiny and review over the next couple of days.

Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to areassortant H5 HA/H1N1 virus in ferrets

doi:10.1038/nature10831

Masaki Imai, Tokiko Watanabe, Masato Hatta, Subash C. Das, Makoto Ozawa, Kyoko Shinya, Gongxun Zhong, Anthony Hanson, Hiroaki Katsura, Shinji Watanabe, Chengjun Li , Eiryo Kawakami , Shinya Yamada, Maki Kiso5,Yasuo Suzuki , Eileen A. Maher, Gabriele Neumann & Yoshihiro Kawaoka

Kawaoka’s 11-page study is, as you might imagine, highly technical and may prove tough sledding for those without a solid background in virology.

Nature published a 2-page synopsis by Hui-Ling Yen & Malik Peiris that helps to explain some of the details, but this is a pay-to-view article.

Bird flu in mammals

An engineered influenza virus based on a haemagglutinin protein from H5N1 avian influenza, with just four mutations, can be transmitted between ferrets, emphasizing the potential for a human pandemic to emerge from birds.

According to Malik Peiris, this study reaffirms the pandemic potential of the H5N1 virus, and reinforces the need for better surveillance of the virus in the wild.

While Kawaoka identified several mutations in the H5 HA that allowed the virus to bind to a2,6 receptors there are likely other combinations that could lead to greater transmissibility.

For the best all-around coverage of this story, we can always rely on Helen Branswell of The Canadian Press. Helen has just posted the following article on this research’s publication.

Bird flu study: Three mutations might give virus ability to transmit to humans

By: Helen Branswell, The Canadian Press

There will, undoubtedly, be a large number of stories and opinion pieces regarding the publication today of Kawaoka’s research.

Already I note that Vincent Racaniello has blogged on this publication:

Kawaoka paper published on aerosol transmission of H5 influenza virus in ferrets

2 May 2012

Meanwhile Laurie Garrett takes a more cautionary route in:

Manmade H5N1 Paper Finally Published, And Worrying

I’ll update this blog with more links to articles and opinion pieces on this research later today or tomorrow.

Reminder: National Academies Webcast Today On H5N1 Research

# 6308

Today the National Academies will stream a day-long webinar on the issues surrounding Dual Use Research of Concern (DURC). The webcast begins at 8:30 EDT.

You can view the agenda watch via the web at:

http://events.tvworldwide.com/Events/IOM/IOM120501.aspx

Issues Raised, Lessons Learned, and Paths Forward for Dual-Use Research in the Life Sciences: The H5N1 Research Controversy

National Academies Webcast On H5N1 Research: May 1st

# 6304

On Tuesday, May 1st, the National Academies will host a day long workshop on the far reaching implications of life sciences research and associated technologies. These issues have recently come to the forefront during the public debate over H5N1 research.

The workshop, put together by the National Research Council and the Institute of Medicine, will be webcast starting at 8:30 a.m. EDT and running to 5:15 p.m. EDT on May 1st, and may be accessed from the National Academies' homepage (www.nationalacademies.org).

Below you’ll find the press release, and a link to further details on the National Academies webpage.

National Academy of Sciences

Lessons learned from the H5N1 research controversy -- May 1 workshop

Recent debate about whether to publish research findings on more easily transmitted strains of the H5N1 avian influenza virus has sparked an international discussion about the appropriateness of this type of research and the ways that research risks are assessed. At this National Research Council-Institute of Medicine workshop, scientists, policymakers, and the public will examine the implications of advances in the life sciences and associated technologies on assessments of risk and benefits; research-related decisions and social responsibility; current measures for minimizing research risks to individuals and the larger public; and whether additional measures may be necessary to deal with new risks raised by new scientific capabilities.

The workshop will take place from 8:30 a.m. to 5:15 p.m. EDT at the 20 F Conference Center, 20 F St., N.W., Washington D.C. Seating is limited; reporters who wish to attend should contact the Office of News and Public Information; 202-334-2138 or e-mail news@nas.edu. Registration for the meeting and an agenda are available at http://www.nationalacademies.org/stl. Those who cannot attend may watch a live video webcast at http://www.nationalacademies.org.

For more information, or to register to attend in person, visit:

Issues Raised, Lessons Learned, and Paths Forward for Dual-Use Research in the Life Sciences: The H5N1 Research Controversy - A Workshop

Dutch Govt. Grants Fouchier Export License For H5N1 Research

# 6300

Four days after holding hearings in the Netherlands, the Dutch government today announced the granting of an export license to Ron Fouchier which clears the way for the publication of his research on transmissible strains of the H5N1 virus.

The decision was announced today in a letter of authorization posted on the Dutch Ministry for Agriculture and Foreign Trade website.

Letter authorization for export manuscripts on bird flu research

Letter authorization for export manuscripts on bird flu research

Page | 1 page | 31 KB

Unknown type | 27/04/2012 | EL & I

Letter from Secretary Bleacher (EL & I) about the status of the license for the export of manuscripts with detailed information about the modified avian flu virus (H5N1). The Secretary of State has decided to grant the license.

Fouchier Research To be Debated In The Netherlands This Week

BSL-4 Lab Worker - Photo Credit –USAMRIID

# 6296

Although the United States has officially withdrawn its objections to the publication of Ron Fouchier’s H5N1 ferret research study (see The Biosecurity Debate On H5N1 Research for background on this issue), there remains another bureaucratic obstacle to publication in the form of an export license from the Dutch government.

According to a Radio Netherlands report, the debate will be taken up tomorrow, and there remains considerable opposition to the publication.

A hat tip to Pathfinder on FluTrackers for this link.

Publication ban on virus research: security or censorship?

Published on : 21 April 2012 - 6:41pm | By Willemien Groot

On Monday, Dutch experts will debate whether or not Dr Ron Fouchier should be allowed to publish the results of his research, which has created a potentially dangerous strain of the H5N1 bird flu virus. The United States biosecurity watchdog has withdrawn its objections to publication. Dutch Deputy Minister for Innovation Henk Bleker, on the other hand, still fears the research could be used by terrorists. Fouchier rejects any ban on publication of his work. A row is in the making.

(Continue . . . )

Fouchier has reportedly not applied for an export license, and has stated that he intends to publish his research with – or without – the sanctioning of his government.

According to a report by CIDRAP NEWS last week (see Fouchier plans to flout Dutch export law, publish H5N1 study), Fouchier could conceivably find himself facing criminal charges if he attempts to publish his data without government permission.

While the U.S. has withdrawn its objections to the publication of Fouchier’s research (and Professor Yoshihiro Kawaoka’s in Wisconsin), and has recently issued new regulations regarding oversight of Dual Use Research of Concern (see U.S. Issues New DURC Oversight Rules), there remain many unresolved bio-security issues surrounding the life sciences and bioengineering fields.

Among them:

How are we to handle this brave new world of life sciences, where new viruses and other life forms can be created in the laboratory?
Who is to decide on what is appropriate, or safe research?
Who decides what should be published, and who should have access to redacted information?
What laboratory protocols and protections are necessary for working the the H5N1 virus, and other virulent pathogens?

Regardless of what the Dutch government decides in the near term on the publication of Fouchier’s research, the problem of what to do about future DURC research projects are not going away.

These are serious biosecurity concerns that must be faced, debated, and agreed upon internationally, not just by individual countries.

And better sooner, rather than later.

Royal Society H5N1 Symposium: Day 2

# 6260

At 4 am EDT, 9 am BST (UTC+1), day two of the Royal Society’s H5N1 research: biosafety, biosecurity and bioethics symposium will get underway.

This two-day event is being live-streamed on the internet, and the full video will soon be made available on the Royal Society’s website.

Lisa Schnirring of CIDRAP news provides us with an excellent overview of the first day’s presentations.

H5N1 mutations, other details unveiled at H5N1 meeting

Lisa Schnirring Staff Writer

Apr 3, 2012 (CIDRAP News) – New details about H5N1 transmission studies emerged today during a Royal Society conference on the topic in London, but with Dutch export restrictions blocking what one research group could share.

Scientists who led the two studies in question both took the stage during the first day of a 2-day meeting to discuss a host of issues on the topic, from basic research to ethics. The Royal Society is offering a live webcast of the meeting.

(Continue . . .)

Today’s offerings should be quite lively, with perspectives from the scientific publishing sector, the media, Professor Peter Doherty, Professor Arthur Caplan, and an extended Q&A session.

Webcast: Royal Society Meeting on H5N1 Research

Note: Due to this Symposium my blogging over the next couple of days will probably be light.

# 6258

Tomorrow (Apr 3rd) and the following day (Apr 4th), The Royal Society, London will host a 2 day international symposium on the `practice and policy of H5N1 research’.

Attending will be some of the biggest names in influenza research - including Ron Fouchier and Yoshihiro Kawaoka – whose H5N1 research papers got the green light by the NSABB for publication last Friday.

Other recognizable names include (but are not limited to) Robert Webster, Malik Pieris, Dr. Paul Keim, Michael Osterholm, Thomas Inglesby, Dr Philip Campbell, Dr. Bruce Alberts, Laurie Garrett, David Brown, Professor Peter Doherty, and Arthur Caplan.

The good news is that this two day session will be live streamed on the web.

Note: Broadcast times listed are for local London Time. So adjust for your time zone accordingly.

For details, including a list of sessions and participants, follow the link below.

H5N1 research: biosafety, biosecurity and bioethics

9:00 am on Tuesday 03 April 2012 – 6:00 pm on Wednesday 04 April 2012

For details on how to watch live, visit the following link:

H5N1 research: biosafety, biosecurity and bioethics

An international symposium

Tuesday 03 April 2012 - Wednesday 04 April 2012
at The Royal Society, London

Organised by the Royal Society in partnership with the Academy of Medical Sciences and the Foundation for Vaccine Research with support from the American Society for Microbiology, the Bill & Melinda Gates Foundation, Fondation Mérieux, the German National Academy of Sciences Leopoldina, Institut Pasteur, and the Society for General Microbiology.

Webcast requires Windows Media Player and a 500k or better broadband connection. Test your connection speed here. For best results use Internet Explorer and 1024X768 or higher resolution. Latest Windows Media Player download here. MAC users: if the video does not play, please ensure you have the appropriate media player or flip4mac. If you are still having problems with a MAC try this test and this live link.

Since I will be away from my computer for part of the day tomorrow and will miss some of these broadcasts, I am hoping that these videos will appear on the Royal Society TV website within a few days.

The Scientist: Deliberating H5N1 Research

# 6256

The decision on Friday by the NSABB to clear the way for the publication of the Fouchier and Kawaoka research papers has not lessened the debate over the risks and benefits of DURC (Duel Use Research of Concern).

Today The Scientist published an extended debate over the appropriateness of this type of research, soliciting opinions on three different questions from a variety of experts.

The questions being:

QUESTION 1: To Research or Not to Research?

QUESTION 2: To Publish or Not to Publish?

QUESTION 3: How to Regulate?

Responding to these issues are Rob Carlson, Peter Doherty, Richard H. Ebright ,David L. Heymann, Michael J. Imperiale, Yoshihiro Kawaoka, Lynn Klotz,Randall Murch, Daniel Perez,John Steinbruner, and Ed Sylvester.

Follow the link below to read:

Deliberating Over Danger

The creation of H5N1 bird flu strains that are transmissible between mammals has thrown the scientific community into a heated debate about whether such research should be allowed and how it should be regulated.

April 1, 2012

NSABB Clears H5N1 Studies For Publication

# 6254

From Helen Branswell this evening, a report that the NSABB – after reviewing new data submitted by flu researcher Ron Fouchier – has cleared the way for the publication of both his, and Yoshihiro Kawaoka’s work on ferret transmissible H5N1.

The vote to publish Karaoka’s paper was unanimous, while the vote for Fourchier’s was 12 to 6.

The NSABB serves in an advisory capacity only, and it will be up to the United States government to either accept or reject their recommendations.

Follow the link below for the story by Helen Branswell.

US biosecurity panel clears publication path for controversial bird flu studies

By Helen Branswell, The Canadian Press |

For more on what the future of U.S. government sponsored life sciences research will look like, you may wish to revisit yesterday’s blog on U.S. Issues New DURC Oversight Rules.

U.S. Issues New DURC Oversight Rules

BSL-4 Lab Worker - Photo Credit –USAMRIID

# 6252

While the current H5N1 research row has centered around the publication of two specific research projects (see NSABB To Re-examine H5N1 Research Risks), the bigger issues at play involve how we oversee (and fund) future life sciences research in order to avoid future controversies.

To that end, today the Office of Science Policy at the NIH released a 4 page set of guidelines for DURC (Duel Use Research of Concern) projects, and ordered a review of all current life sciences projects.

For those unfamiliar with the lexicon of biomedical research, DURC in this new policy is defined as:

. . . life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security

The scope of this new policy is to cover research on the most dangerous of biological organisms, listing;

a) Avian influenza virus (highly pathogenic)
b) Bacillus anthracis
c) Botulinum neurotoxin
d) Burkholderia mallei
e) Burkholderia pseudomallei
f) Ebola virus
g) Foot-and-mouth disease virus
h) Francisella tularensis
i) Marburg virus

j) Reconstructed 1918 Influenza virus

k) Rinderpest virus
l) Toxin-producing strains of Clostridium botulinum
m) Variola major virus
n) Variola minor virus
o) Yersinia pestis

Specifically any research that seeks to:

a) Enhances the harmful consequences of the agent or toxin;

b) Disrupts immunity or the effectiveness of an immunization against the agent or toxin without
clinical or agricultural justification;

c) Confers to the agent or toxin resistance to clinically or agriculturally useful prophylactic or
therapeutic interventions against that agent or toxin or facilitates their ability to evade detection methodologies;

d) Increases the stability, transmissibility, or the ability to disseminate the agent or toxin;

e) Alters the host range or tropism of the agent or toxin;

f) Enhances the susceptibility of a host population to the agent or toxin; or

g) Generates or reconstitutes an eradicated or extinct agent or toxin listed in Section (III.1) above.

While this new policy does not automatically halt or defund research found to meet the DURC definition, it does require greater agency oversight and an assessment of the risks and benefits of any research, along with the development of appropriate risk and safety measures.

As far as `teeth’ in this new policy, if perceived risks cannot be satisfactorily mitigated Federal Agencies may request voluntary redaction of scientific papers, may move to `classify’ the research, or may withhold or terminate financial support.

Agencies that conduct or fund life sciences research are instructed to perform a review to identify any projects that meet the DURC definition, and if found, to:

c) Assess the risks and benefits of such projects, including how research methodologies may
generate risks and/or whether open access to the knowledge, information, products, or technologies generates risk.

d) Based on the risk assessment, in collaboration with the institution or researcher, develop a risk
mitigation plan to apply any necessary and appropriate risk mitigation measures. In addition:

i) For DURC that is proposed and not yet funded, departments and agencies will assess
whether to incorporate risk mitigation measures in the grant, contract, or agreement.

ii) For currently funded DURC, funding departments and agencies will consider modifying the grant, contract, or agreement to incorporate risk mitigation measures. If such modifications are not possible or desirable, departments and agencies will seek voluntary implementation of mitigation measures by the institution.

You can access the full policy on the Office of Biotechnology Activity’s News Page:

US Government Issues Policy on Oversight of Life Science Dual Use Resarch of Concern:

The purpose of this Policy is to establish regular review of United States Government funded or conducted research with certain high-consequence pathogens and toxins for its potential to be dual use research of concern (DURC) in order to: (a) mitigate risks where appropriate; and (b) collect information needed to inform the development of an updated policy, as needed, for the oversight of DURC. The fundamental aim of this oversight is to preserve the benefits of life sciences research while minimizing the risk of misuse of the knowledge, information, products, or technologies provided by such research.

(March 29, 2012)

And just as I was finishing this post up, I saw that Lisa Schnirring at CIDRAP NEWS has an excellent overview of this new policy. Read it at:

US debuts life sciences dual-use research policy

Lisa Schnirring Staff Writer

It will be interesting to see how this new policy is received by scientists working in the life sciences field.

NSABB To Re-examine H5N1 Research Risks

# 6249

Today and tomorrow the NSABB (National Science Advisory Board for Biosecurity) will reconvene to re-examine the issues surrounding the publication of controversial H5N1 research that produced a ferret-transmissible strain of bird flu.

Last September, Ron Fouchier from the Netherlands (and almost simultaneously Professor Yoshihiro Kawaoka from Wisconsin) announced success in creating enhanced strains of the avian flu virus in the laboratory, which subsequently unleashed a firestorm of controversy.

For some background, see Katherine Harmon’s Sci-Am article , New Scientist: Five Easy Mutations, & NPR: Bio-Terrorism Concerns Over Bird Flu Research.

Over the ensuing six months we’ve seen a steady stream of opinion pieces from both sides of this debate (see H5N1 Research: A Plethora Of Positions), including side forays into the lethality of the H5N1 virus (see The Great CFR Divide).

This week we’ve seen the release of additional dueling commentaries, three of which Lisa Schnirring of CIDRAP NEWS highlighted last night in her article:

Scientists volley ahead of more dual-use H5N1 debate

Lisa Schnirring Staff Writer

Mar 28, 2012 (CIDRAP News) – As researchers from both sides of the debate over two controversial H5N1 studies weighed in yesterday on full publication versus a more cautionary approach, two US journals said they are developing policies to address any future such instances.

(Continue . . .)

The NSABB serves strictly in an advisory role, and any policy decisions must come from the United States government. Nonetheless, all eyes will be on the NSABB as they consider this issue.

And I can think of no one better than Helen Branswell of the Canadian Press to preview this meeting for us:

Biosecurity panel reconvenes to reexamine controversial bird flu studies

3-28-12 6:31 PM EDT By Helen Branswell

A bid from some quarters in the U.S. to resolve the ongoing controversy over two unpublished bird flu studies will begin to play out over the next two days as government biosecurity advisers reconvene to reconsider the issue.

The National Science Advisory Board for Biosecurity will meet Thursday and Friday in Washington, D.C., to go over revised versions of the two studies and hear about the work from their principal authors, noted flu virologists Ron Fouchier of Erasmus Medical Centre in Rotterdam, the Netherlands, and Yoshihiro Kawaoka of the University of Wisconsin-Madison.

(Continue . . . )

Dysfunctional Science

# 6246

Six weeks ago in Science at the Crossroads, I wrote about the decline the public’s trust in science.

While I cited a number of reasons for this disturbing trend, prime among them has been the abrupt rise in the number of scientific papers that have been retracted – sometimes for outright fraud - over the past decade.

Today the editors-in-chief of two prominent journals made a presentation before a committee of the National Academy of Sciences, where they warn of a growing dysfunction in scientific research, and call this rise in retracted studies a symptom of a much larger problem.

You’ll find detailed and thought provoking editorials authored by Ferric C. Fang, Editor in Chief, Infection and Immunity and Arturo Casadevall, Editor in Chief, mBio on the challenges facing researchers in the current issue of Infection and Immunity (IAI).

The press release from the American Society for Microbiology follows, with the links to a pair of Infection and Immunity editorials on the subject at the end.

Highly recommended.

Has modern science become dysfunctional?

The recent explosion in the number of retractions in scientific journals is just the tip of the iceberg and a symptom of a greater dysfunction that has been evolving the world of biomedical research say the editors-in-chief of two prominent journals in a presentation before a committee of the National Academy of Sciences (NAS) today.

"Incentives have evolved over the decades to encourage some behaviors that are detrimental to good science," says Ferric Fang, editor-in-chief of the journal Infection and Immunity, a publication of the American Society for Microbiology (ASM), who is speaking today at the meeting of the Committee of Science, Technology, and Law of the NAS along with Arturo Casadevall, editor-in -chief of mBio®, the ASM's online, open-access journal.

In the past decade the number of retraction notices for scientific journals has increased more than 10-fold while the number of journals articles published has only increased by 44%. While retractions still represent a very small percentage of the total, the increase is still disturbing because it undermines society's confidence in scientific results and on public policy decisions that are based on those results, says Casadevall. Some of the retractions are due to simple error but many are a result of misconduct including falsification of data and plagiarism.

More concerning, say the editors, is that this trend may be a symptom of a growing dysfunction in the biomedical sciences, one that needs to be addressed soon. At the heart of the problem is an economic incentive system fueling a hypercompetitive environment that is fostering poor scientific practices, including frank misconduct.

The root of the problem is a lack of sufficient resources to sustain the current enterprise. Too many researchers are competing for too little funding, creating a survival-of-the-fittest, winner-take-all environment where researchers increasingly feel pressure to publish, especially in high-prestige journals.

"The surest ticket to getting a grant or job is getting published in a high profile journal," says Fang. "This is an unhealthy belief that can lead a scientist to engage in sensationalism and sometimes even dishonest behavior to salvage their career."

Funding is just one aspect of a very complex problem Casadevall and Fang see growing in the biomedical sciences. In a series of editorials in the journal Infection and Immunity they describe their views in detail, arguing that science is not as healthy as it could be or as it needs to be to effectively address the challenges facing humanity in the 21st century.

"Incentives in the current system place scientists under tremendous stress, discourage cooperation, encourage poor scientific practices and deter new talent from entering the field," they write. "It is time for a discussion of how the scientific enterprise can be reformed to become more effective and robust."

The answers, they write, must come not only from within the scientific community but from society as a whole that has helped create the current incentive structure that is fostering the dysfunction. In the editorials they outline a series of recommended reforms including methodological, cultural and structural changes.

"In the end, it is not the number of high-impact-factor papers, prizes or grant dollars that matters most, but the joys of discovery and the innumerable contributions both large and small that one makes through contact with other scientists," they write. "Only science can provide solutions to many of the most urgent needs of contemporary society. A conversation on how to reform science should begin now."

###

Copies of the Infection and Immunity editorials can be found online at

http://iai.asm.org/content/80/3/891.full

and

http://iai.asm.org/content/80/3/897.full

Luck Of The Draw

Photo Credit – CDC PHIL

# 6242

While it may seem curious to some, your humble flu blogger here at AFD has never – to his knowledge – ever suffered from a `classic’ bout of flu.

Oh, sure. I’ve had plenty of respiratory infections, albeit mostly upper respiratory. And a couple of times I’ve had what I’ve thought was probably influenza.

But I’ve never had the running fever, crushing body-aches, want-to-die kind of flu that many others seem to report.

I could just be lucky, I guess.

But I’ve always figured I really wasn’t very susceptible to influenza. That when I’d had the flu, they had been relatively mild cases.

Of course, I have no way of proving that . . .

But new research published in Nature by Wellcome Trust Sanger Institute lends credence to the idea that some people are genetically more likely to experience severe flu symptoms than others.

First some excerpts from the press release (worth reading in its entirety), then a link to the research article, then I’ll return with some other data suggestive of a genetic susceptibility to influenza.

Genetics of flu susceptibility

Researchers find gene that can transform mild influenza to a life-threatening disease

A genetic finding could help explain why influenza becomes a life-threating disease to some people while it has only mild effects in others. New research led by the Wellcome Trust Sanger Institute has identified for the first time a human gene that influences how we respond to influenza infection.

People who carry a particular variant of a gene called IFITM3 are significantly more likely to be hospitalised when they fall ill with influenza than those who carry other variants, the team found. This gene plays a critical role in protecting the body against infection with influenza and a rare version of it appears to make people more susceptible to severe forms of the disease. The results are published in the journal Nature.

A central question about viruses is why some people suffer badly from an infection and others do not. IFITM3 is an important protein that protects cells against virus infection and is thought to play a critical role in the immune system's response against such viruses as H1N1 pandemic influenza, commonly known as 'swine flu'. When the protein is present in large quantities, the spread of the virus in lungs is hindered, but if the protein is defective or absent, the virus can spread more easily, causing severe disease.

(Continue . . . )

IFITM3 restricts the morbidity and mortality associated with influenza

Aaron R. Everitt,Simon Clare,Thomas Pertel,Sinu P. John,Rachael S. Wash,Sarah E. Smith,Christopher R. Chin,Eric M. Feeley,Jennifer S. Sims,David J. Adams,Helen M. Wise,Leanne Kane,David Goulding,Paul Digard,Verneri Anttila,J. Kenneth Baillie,Tim S. Walsh,David A. Hume,Aarno Palotie,Yali Xue,Vincenza Colonna,Chris Tyler-Smith,Jake Dunning,Stephen B. Gordon,The GenISIS Investigators.et al.

Nature (2012) doi:10.1038/nature10921

Although this research is the first to identify a specific gene that may make influenza a much more serious illness in some people than others, for some time there’s been evidence suggesting that heritable factors influence how people react to influenza.

In 2008, in the Journal of Infectious Diseases, we saw a study that suggested there might be a heritable susceptibility to death from the influenza virus.

Evidence for a heritable predisposition to death due to influenza.

Albright FS, Orlando P, Pavia AT, Jackson GG, Cannon Albright LA.

Abstract (extract)

Evidence for a heritable contribution to death due to influenza was examined using a resource consisting of a genealogy of the Utah population linked to death certificates in Utah over a period of 100 years. The relative risks of death due to influenza were estimated for the relatives of 4,855 individuals who died of influenza.

Both close and distant relatives of individuals who died of influenza were shown to have a significantly increased risk of dying of influenza, consistent with a combination of shared exposure and genetic effects. These data provide strong support for a heritable contribution to predisposition to death due to influenza.

While interesting, this study doesn’t provide us with a smoking gene.

However, the following year a PLoS ONE research article doi:10.1371/journal. pone.0004857) came a bit closer.

Entitled Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections by Srivastava B, Błażejewska P, Heßmann M, Bruder D, Geffers R, et al., it reports on the results of experiments utilizing seven inbred strains of lab mice that were exposed to influenza A viruses.

From the abstract:

The genetic make-up of the host has a major influence on its response to combat pathogens. For influenza A virus, several single gene mutations have been described which contribute to survival, the immune response and clearance of the pathogen by the host organism.

Granted, mouse models are often useful, but what happens in mice doesn’t always correspond to what happens with human physiology.

And last year, in Host Genetic Susceptibility to Avian Influenza, we saw an analysis of clusters of H5N1 infection in Indonesia that found that young age (under 30) and being a blood relative to the index case in a cluster, were both found to significantly increase the odds of catching the virus.

So there is anecdotal reason to believe that there may be genetic factors involved in either mitigating, or exacerbating, the effects of flu.

Never having suffered a `classic’ bout of flu admittedly gives me some hope that I might have some degree of built-in immunity to a pandemic virus.

But with an emerging or novel flu strain, who knows?

Of course, my good flu fortune may have more to do with my diligence in getting a seasonal flu shot every year, than with any genetic advantage.

But I can hope.

Peter Sandman On Talking To The Public About H5N1 Risks

# 6241

While I’ve vented my frustration over the way that the H5N1 research controversy has been `managed’ for public consumption (see here and here), today we get a far more useful and cogent commentary from risk communications expert Peter M. Sandman.

The Peter M. Sandman Risk Communication Website combines the expertise of Dr. Sandman, along with his wife Jody Lanard M.D., and is is a veritable treasure trove of risk communications information.

Anyone who must deal with communicating with the public, particularly during times of uncertainty or stress, would do well to regard this site as essential reading.

You’ll find two incarnations of the same article (a longer original and one edited down for publication in Genetic Engineering & Biotechnology News) on the mistakes Dr. Sandman sees being made in how H5N1 research issues are being communicated to the public.

Highly recommended.

Talking to the Public about H5N1 Biotech Research (original longer version)

Submitted to Genetic Engineering & Biotechnology News, March 18, 2012

Talking to the Public about H5N1 Biotech Research (accepted shorter version)

Published in Genetic Engineering & Biotechnology News, April 15, 2012

Laurie Garrett Dissects The Rationale For H5N1 Research

BSL-4 Lab Worker - Photo Credit –USAMRIID

# 6237

Pulitzer-prize winning journalist and author Laurie Garrett has a new blog up today where she once again takes a hard look at the H5N1 research controversy (see The Furor Over H5N1 Research Continues), and this time dissects the rationale being offered by scientists for doing these types of experiments.

Follow the link below to read:

Rationales for Man-made H5N1 Experiments Evaporating?

You can read some of her earlier takes on this controversy at the following links:

Laurie Garrett Blogs On The H5N1 Research Controversy

Laurie Garrett: Keeping Superbugs Away From Terrorists

Referral: Laurie Garrett On The Bird Flu Research Controversy

Branswell: WHO Hopes H5N1 Studies Can Be Published By Summer

# 6227

Helen Branswell has details this afternoon on the hopes, expressed by Dr. Keiji Fukuda – the World Health Organization’s lead official on influenza – that the two controversial H5N1 studies by Ron Fouchier and Yoshihiro Kawaoka can be published by summer.

Since I’m still nursing an injured wrist, I’ll just get out of the way and invite you to read:

The Canadian Press - ONLINE EDITION

WHO hopes controversial bird flu studies will be published by summer

By: Helen Branswell, The Canadian Press

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