Monthly Archives: July 2012

Natural Antibiotic Casts a Net Against Bacteria

A “natural antibiotic” protects the body against bacteria by tangling them in a net, not poking holes in them, UC Davis researchers have found. Experiments with genetically-modified, or transgenic mice were crucial to the discovery, along with cell cultures, biochemistry and sophisticated studies of how small proteins assemble together.

It’s an entirely new mechanism of action for defensins, a group of molecules with natural antibiotic activity found in the gut, on the skin and in white blood cells. Most defensins studied so far work by punching holes in the membranes around bacterial cells. The discovery, published June 22 in the journal Science, also points to possible causes of Crohn’s disease and other inflammatory bowel diseases.

The researchers led by Hiutung Chu and Charles Bevins at the UC Davis School of Medicine were studying human defensin 6 (HD6), one of six related small proteins made by humans. HD6 is secreted by cells deep in the folds of the small intestine and seems to help keep the gut microbes in balance.

Other defensins kill bacteria in a lab dish, but early research studies repeatedly showed that HD6 just does not kill bacteria in culture.

However, when the researchers used transgenic mice that make HD6 in their intestines, they found that the HD6 mice could not be infected with bacterium Salmonella entericum through the gut. In control mice, the infection spread to other organs. This result indicated that a novel anti-microbial mechanism was at work.

The authors tested if HD6 blocked infection by interfering with proteins that form the mechanism through which S.entericum invades cells, but when they found that the transgenic mice expressing HD6 were also protected against invasion by the bacterium  Yersinia enterocolitica – which uses a different mechanism to invade cells – it became clear that HD6 must block infection by a different method.

Through a series of other experiments in vivo and using the transgenic HD6 mice, the team found that when HD6 encounters a bacteria like Salmonella, the small proteins rapidly link up to form a net or web that tangles the bacteria. This forms a barrier lining that stops hostile bacteria from crossing the gut lining and infecting the rest of the body.

In order to determint what part of the bacteria HD6 interacted with, the Bäumler laboratory created bacterial mutants lacking surface structures known as flagella and type I fimbriae. When those structures were removed HD6 was unable to form the fibrils on the bacterial surface, indicating that these structures act as anchoring points that trigger HD6 nanonet formation.

Put together, the molecular, cell culture, and transgenic mouse experiments build a case to show how HD6 works and protects the gut from infections.

Indeed in a commentary in this week’s issue of Science Professor Andre Ouelette  and Professor Michael Selsted of the University of Southern California note that this study highlights the need to undertake in vivo animal studies to complement and understand the relevance of in vitro observations.

“Aside from delineating the role of HD6 and its unusual mechanism of action, the report by Chu et al. should give us pause for reflection. HD6 has no evident activity in in vitro assays, yet it affects mucosal immunity profoundly. Thus, in vitro bactericidal assays, although useful for comparing peptides in structure-activity studies, may not predict or even hint at the potential impact of a peptide in vivo. Given the diversity of in vitro biological functions that have been associated with defensins and other hostdefense peptides, the challenge is to establish the physiological relevance of those activities.”

Inflammatory bowel disease

People with Crohn’s Disease have unusually large amounts of bacteria in the crypts of the small intestine, causing chronic inflammation. It may be that the gut defensins HD5 and HD6 are defective in these people, so the bacteria can invade and colonize the gut folds more easily. Understanding how these defenses work could lead to insights and new treatments for Crohn’s and similar conditions. No doubt animal models such as transgenic mice will play an important role in that research, too, along with other techniques.

Read more about this study at the UC Davis Health system Newsroom

Regards

Andy

Amblyopia, kittens and BUAV’s deception

Normal vision relies on healthy eyes, retinas, and their proper wiring of the brain structures that process visual information.  Light which enters the eye is sensed by photoreceptors on the retina.  The information is then transmitted via the optic nerve to the lateral geniculate nucleus and from there to the first stage of cortical visual processing, the primary visual cortex.

Amblyopia refers to the loss or reduction of vision from one eye because it is improperly wired to the brain structures that process visual information.  Even an eye with normal optics and retina may be weakly or incorrectly connected to the brain, resulting in substantial vision loss from that eye.

What causes amblyopia?  Frontal- eyed animals combine the images of the two eyes into a single image.  The process also yields the percept of depth — estimates of the distance of objects from the observer.  When then the two eyes receive very different scenes that cannot be fused into a single one, the brain opts to ignore information from one of the eyes.  This can happen when the eyes are misaligned and pointing in different directions (strabismus), or when the one eye is much more nearsighted, farsighted, or astigmatic compared to the other.

About 3% of children are affected by the condition and, unless it is treated during a period of high plasticity in the brain that may allow external factors to help the brain rewire, called the critical period, the loss of vision might be permanent as the adult visual system becomes hardwired. In other words, if we do not treat them amblyopic patients would be effectively blind from the input of the affected eye.

It is important to correct amblyopia for the simple reason that we are born with only two eyes.  Starting your life with only one good eye means your likelihood of going blind during your lifetime is much higher. Thanks to advances in medical research, we are living 25 years more than our grandparents; thus it makes sense to ensure our children start their lives with a pair of healthy eyes.

Animal rights activists argue that because blindness is not a life-threatening disease using animals in this type of research is not justified.  I concede blindness is not life threatening, but I ask you to participate in the following exercise — blindfold yourself for just one week and try to go about your daily activities — helping the kids to school, getting to and from work, shopping at the supermarket, doing the laundry, cooking, washing the dishes, assisting your children with homework, and so on.  Please return to the comments section of this blog and share with us what you have learned about blindness and the suffering it can cause. This is the suffering the research is intended to prevent and alleviate.

Some of these points were well expressed by a Cardiff University statement in response to the Mirror’s  negative coverage of these experiments which included an on-line poll asking readers to participate. The Mirror article elicited the response of scientific blogger PZ Myers who tried once more to explain the true reasons for such experiments and asked scientists to make their voices heard in the poll.  The Mirror, apparently disliking the trends in the results, responded with a re-poll. Aside from the obvious scientific invalidity of such internet polls, it is evident from the comments in the article that those who voted against such experiments fail to understand the impact of severe vision loss on quality of life and the methods of the research.  While they appear ready to rule out the use of animals in sight-saving research, the same population appears to think differently when it comes to ruling animals out of their dinner plates.

So let me explain again how animals are involved in these studies. To study the early wiring of the brain scientists have used frontal-eyed mammals that have an early visual cortex organized similarly to that of humans.  Kittens have historically been used in many of these developmental experiments because they have frontal eyes and binocular vision, and their visual cortex expresses ocular dominance columns as other higher mammals and humans do.  Such “columns” represent the amount of cortical territory that each eye takes during development which changes if one eye is weakened. Animal work has shown how different rearing conditions influence the balance the input of the eyes into the cortex, the timescales involved, and the effects of multiple reverse occlusion procedures on visual acuity.  Mice also have a small area of binocular vision where the cortex receives inputs from the two eyes and exhibit similar plastic changes. The study of the molecular pathways and events that lead to the opening and closing of the critical period are now being studied almost entirely in mice.

Finally, studying the normal wiring of the brain during development has potential benefits for many other areas of medicine.  Amblyopia serves as a general model of a developmental disorder of brain wiring. Understanding the factors that control the opening and closing of the critical is key not only for vision but other diseases. Specifically, if we understood the molecular events that open and close the critical period we could potentially learn how to open such a window of plasticity in the adult.  This would allow us not only to treat amblyopia in the adult, but also to enhance neural repair in many conditions that involve damage to neural tissue, such as in stroke.

We do not currently have non-invasive methods that would allow us to study normal and abnormal brain wiring during development in humans.  Animal models allow us to understand the molecular and cellular events that take place during development.  The experiments involve artificial closure of one eye and recording form brain structures while animals are fully anesthetized. The anesthetic plane is monitored continuously by measuring the heart rate, electrocardiogram, end-tidal CO2, and core temperature.  Such monitoring parallels and even exceeds what one may see in human surgeries. The animals are euthanized at the end of the procedure with an overdose of anesthetics — the same way your pet may be euthanized by your veterinarian.

It is outrageous, ignorant or simply deceptive for Nick Palmer of the BUAV to claim on the BBC during a debate with Tom Holder on the justification for this experiments that “you wake up the animal” during the electrophysiological recording procedures. This is flat wrong. Animals are anesthetized for both the surgical procedures, and continuously during the recordings.  They never regain consciousness as they are euthanized at the end of the experiment.

We all benefit from the medical advances of the past.  Animal research has undeniably contributed to such advances. Opting out of such research without a viable alternative would cause much human and animal suffering.  Inaction needs a moral justification, one that our opponents have yet to spell out on moral and scientific grounds.

Addendum: It’s worth remembering that the Mirror – a British tabloid that is characterised by all the usual vices associated with such publications – has a history of making false allegations against scientists. Back in the 1980’s its Sunday edition was obliged to print a Press Council ruling that an earlier report on amblyopia research performed by the neuroscientist Professor Colin Blakemore was “exaggerated, unbalanced and unfair”. It seems that the Mirror is still living up to its “gutter press” reputation.

The Speaker’s Corner Trust Debate

The Speakers’ Corner Trust  —  a charity organization that promotes free expression, public debate and active citizenship — recently organized a debate on the role of animals in research. Michelle Thew of the British Union for the Abolition of Vivisection (BUAV) debated Tom Holder of Speaking of Research.

In her opening remarks Ms. Thew compared the non-consensual experimentation on human beings, such as those performed by the Nazis, to the use of animals in medical research.  She stated:

The BUAV strenuously opposes such experiments. The fact that they may advance medical science (as they are much more likely to do than experiments on animals) is no justification. It is simply not fair on the victims.

In other words, the claim is that if experimenting on non-consensual humans is wrong, then it must be wrong to experiment on animals as well.  This is true only if one adheres to the view that there is no morally relevant difference between a mouse and a human.  This is a key difference between our respective ethical positions. We agree that most people believe that all living beings are worthy of moral consideration.  Animal rights activists insist, in addition, that we owe all living beings the same moral consideration as any human.

Tom Holder pointed out some obvious implications of the animal rights view, such as the obvious fact that given such moral equivalence, eating a salmon would be equally wrong as eating your neighbor’s child.  Given the vastly larger number of animals used as food versus those used in medical research one can only wonder why BUAV does not focus its efforts in abolishing animal food rather than trying to eliminate life-saving medical research.  As it turns out, there is no British Union for the Abolition of Animal Food, which only shows the moral confusion and upside-down priorities of animal activists.

Ms. Thew is of the deplorable opinion that scientists use animals in research merely “because we have to power to subjugate them.” To which Tom Holder responded:

We do not research using animals simply because we can. It is the human ability to empathise with others and to have the tools to confront disease by means of scientific research that calls for us to act in the face of so much suffering. It is a moral dilemma that must be confronted.

Animal rights activists like Ms. Thew believe that they have the moral upper hand and that it is those that experiment on animals that offer a moral justification.  Not so. Those that oppose the work must offer an ethical justification for not acting when we can.  As an example, if we can find a therapy for breast cancer using mice, why shouldn’t we?  Is it merely because they assert our moral concern for a mouse ought to be the same as that for a mother dying of cancer and her family?

The truth is that if opponents could make a convincing ethical argument against animal research then this is where the debate would stop.  Humankind would concede the work is unethical and it would stop — as it was the case for slavery.  But because their ethical argument fails, they decide to attack the science instead. Thus, in the second part of the debate Ms. Thew denies the past benefits of the research, deplores the use of animals to understand fundamental biological processes in basic research, declares the existence of alternatives to the work and the reluctance of scientists to use them (never mind that it is scientists that actually develop and promote them), and that many drugs fail in the course of development (as one would expect from the very  nature of scientific work).  In the words of Tom Holder

The BUAV seems to have constructed a grand conspiracy theory according to which pharmaceuticals, governments, scientists and the medical community are all conspiring to suppress the “truth” that animal research doesn’t work. Similarly, the findings of highly respected polling organisations like Gallup and Mori, both of which show the public firmly behind animal research, must be “selective” because they don’t meet BUAV’s expectations.

What’s the reality? Understanding disease is a complex challenge, but there is no denying that animal research has contributed immensely to alleviating the suffering of humans and animals alike.

BUAV’s mission states that their goal is to “create a world where nobody wants or believes we need to experiment on animals.”  We share their goal, but it is scientists who actually work to create a world where there will no longer be a scientific need for the use animals to advance medicine and human health. So please, start supporting our work instead of misleading the public, denying the science, and irresponsibly suggesting that we can suspend the work immediately without grave consequences which include much human and animal suffering.

Part 4: Many voices speaking of animal research

We recently wrote about the many existing venues, activities, and materials designed to encourage public dialogue and informed discussion about animal research.  Many individuals, institutions, and organizations contribute to public outreach and education efforts, and also take active roles in dialogue about continuing changes in practice and policy concerning animal welfare and the conduct of animal research.  This post is the fourth in a series (Part 1, Part 2, Part 3) hosted by Speaking of Research to highlight a wide range of individuals and groups devoted to consideration of animal research.

The National Primate Research Centers Outreach Network

The eight National Primate Research Centers (NPRCs) are riding a wave of unprecedented communication, thanks to a new National Institutes of Health/Office of Research Infrastructure Programs (NIH/ORIP) outreach consortium. This consortium helps our members work together more effectively to educate the public on our many and varied educational programs.

Reaching thousands at the USA Science and Engineering Festival

One exciting result of the new consortium occurred April 27 to April 29 this year in Washington, D.C. Representatives from the National Primate Research Centers (NPRCs) spoke to an estimated 4,000 people who visited the NPRCs’ booth at the 2nd annual USA Science and Engineering Festival at the Walter E. Washington Convention Center.

The 2012 USA Science and Engineering Festival, which included a learning station hosted by the National Primate Research Centers, drew 150,000 people to the Walter E. Washington Convention Center in Washington, D.C., this April.

Billed as “the largest celebration of science in the U.S.,” the festival featured more than 3,000 interactive exhibits, more than 100 stage shows and 33 author presentations. More than 150,000 people attended. President Barack Obama promoted the festival in keynotes and public service announcements. Special visitors to the festival included The Myth Busters and Bill Nye the Science Guy, plus Nobel Prize winners, best-selling authors, astronauts, and even a rock guitar performance by NIH Director Francis Collins.

The NPRCs’ booth featured a set of touchable and inflatable real pig lungs representing healthy and cigarette smoke-riddled lungs. Our activity not only demonstrated how smoking harms the smoker, but also helped us convey how the Primate Centers have discovered that second hand smoke can stunt infant lung development. Our interactive display also included a flip board with questions and answers about animal research and care.

Volunteers from the National Primate Research Centers educated the public about the effects of smoking on infant lung development at the 2012 USA Science and Engineering Festival.

— The California NPRC outreach team spearheaded the NPRCs’ participation at the USA Science and Engineering Festival. Some of the consortium’s other recent activities   have included the following:

—  The Yerkes NPRC continues to host a booth on behalf of all of the NPRCs at the Society for Neuroscience’s annual meeting.

— Jordana Lenon (Wisconsin NPRC) represented the consortium at a PR/Media Forum sponsored by the New Jersey Association for Biomedical Research last October in Newark, N.J.

— Consortium participants plan to meet for the first time as a group this fall.

To share updates, materials and communicate effectively with one another­ — whether we’re planning for large events such as the USA Science and Engineering Festival, or sharing news releases and other announcements — center outreach specialists, supported by the NPRC directors and consortium facilitators, use a variety of websites and other e-media tools. We heartily contribute our share to the 188 billion emails still sent every day… and we still talk on the phone. So, although we’re working in three different time zones, from one coast to the other, we feel closer than ever in our working relationships. We plan to meet for the first time as a group this fall, and we all look forward to building new partnerships when we meet.

Students, lifelong learners benefit from many engaging programs

What are some of the many other outreach activities we plan and share? For one, we are fortunate to have developed thriving visitors programs at our centers. We host year-round K-12+ programs such as afterschool programs, campus science fairs, family science nights, science Saturdays, science teachers days, and many more activities, both on site as well as at schools and community venues. A few examples follow:

The Oregon NPRC’s tour program welcomes more than 3,000 people each year. The center also provides opportunities for young scientists to experience authentic research by supporting high school students and undergraduates in labs for summer apprenticeships.

At the California NPRC, many classroom outreach activities and lectures introduce K-12 students to nonhuman primates, biomedical research programs and careers. The center offers a large curriculum and classroom resources for teachers.

The Wisconsin NPRC provides lab demos and hands on activities for middle school and high school students participating in the annual State Science Olympiad, as well in the National Science Olympiad hosted by the University of Wisconsin-Madison last summer.

The Yerkes NPRC promotes an  active speakers bureaus and tours of its large indoor/outdoor facility. Yerkes also sponsors an eight-week summer internship program for high school students. The center received more than 130 applications this year for 10 spots.

In addition to tours and community outreach programs, the Tulane NPRC hosts programs for college honor societies, summer scholars, biomedical students and career tech students. Every summer, the TNPRC mentors students who work with research technicians.

The Washington NPRC recently participated in a three-day science education event at the Pacific Science Center in Seattle. In July, WaNPRC will again host science teachers participating in the annual CURE (Collaborations to Understand Research and Ethics) tour and seminar, a program funded by an NIH Science Education Partnership Award.

Southwest NPRC is hosting “Science Teachers Day at Texas BioMed” this summer, with bus and walking tours, demonstrations, and an “Ethics of Animal Research” panel.

More than 4,000 people participated in activities at the National Primate Research Centers’ booth over the festival’s three days at the end of April.

Specific programs for life-long learners are also growing, such as Oregon’s Road Scholar Week, and Wisconsin’s Grandparents University and College Days participation, and Yerkes’ coordination of eight-week series for two university-based life-long learning programs. In addition to coordinating active speakers bureaus that reach business, patient advocacy and other civic groups, the NPRCs’ outreach specialists themselves are also sought after as invited educational speakers at national and international conferences.

As far as outreach and higher education, most of the NPRCs are located at major research and teaching universities. They have active veterinary care training programs, in addition to offering undergraduate, graduate and post-doctoral research training programs. The New England NPRC’s commitment to education is reflected in its summer programs for pre-baccalaureate and veterinary students. The Oregon, California, and Washington NPRCs host two to three dozen veterinary and vet tech students throughout the year in two-week externships.

Learn more about the National Primate Centers and other National Institutes of Health nonhuman primate resources for research starting here.

Jordana Lenon is the Public Information Officer and Outreach Specialist for the Wisconsin National Primate Research Center at the University of Wisconsin-Madison.

Marino is Over … Hopefully

Speaking of Research has spent spoken many times about the dangers of Camille Marino and her Negotiation is Over blog (here, here, here and here … oh and here) , but finally the end may be nigh. On Friday, July 12th 2012, a judge ordered that Marino must stand trial for stalking Wayne State University researcher, Donal O’Leary. Furthermore, Marino was sent to jail after breaking the conditions of her bond – namely by posting threatening materials regarding O’Leary.

Camille Marino

Marino has shown time and time again that she has no qualms with pushing the legitimate limits of free speech. Her threats against individual researchers, as well as harassment and intimidation of students, shows an individual whose moral compass is substantially out of sync with the rest of society .

For more information I recommend reading the blog post by David Jentsch, founder of Pro-Test for Science. Here is an excerpt:

The pattern of criminal harassment and threats she directed against Michigan researchers was nearly identical to behavior she directed against me and other UCLA researchers since 2009 and that she has since repeated in her efforts to intimated Florida scientists. As I have previously stated, this pattern of behavior must not be tolerated in a civil society; it is neither Constitutionally protected, nor decent.

Regards

Tom

Speaking of Research welcomes 2011 UK statistics for animal use in scientific research

The UK Home Office has released the animal research statistics for 2011, which show a 2% increase overall in procedures compared to 2010 figures. A summary of the report is available here, while the full report can be downloaded here.  Once again basic research and breeding of GM animals accounted for the lions share – 88% – of the total number of procedures, with mice being the most commonly used animal, bring used in 71 % of procedures.

Some other interesting trends, the number of procedures involving fish increased again, reflecting a trend over the past decade as the importance of the Zebrafish in scientific research increases. The number of procedures involving non-human primates – both new world and old world – fell substantially in 2011 compared to 2010, but the number of procedures using non-human primates tends to vary quite a lot from year to year because of the small number used overall, so it’s too early to say whether or not this is part of an overall trend.

Another interesting fact to note is that over 7o% of procedures did not require anaesthesia, and as Understanding Animal Research point out in their commentary a procedure under the Home Office regulations can be as mild as a blood draw, or indeed breeding in the case of GM animals.

There’s some useful commentary in the Guardian, and the Association of Medical Research Charities blog also provides some insightful analysis of what the figures mean.

Speaking of Research welcomes these figures as evidence that the biomedical research in the UK remains a vibrant despite the tough economic climate, and as evidence that scientists in the UK continue to adopt the most up-to-date animal research techniques as they further understanding of biological systems and develop new therapies for human and animal disease.

Speaking of Research

Part 3: Many voices speaking of animal research

We recently wrote about the many existing venues, activities, and materials designed to encourage public dialogue and informed discussion about animal research.  Many individuals, institutions, and organizations contribute to public outreach and education efforts, and also take active roles in dialogue about continuing changes in practice and policy concerning animal welfare and the conduct of animal research.  This post is the third in a series (Part 1, Part 2) hosted by Speaking of Research to highlight a wide range of individuals and groups devoted to consideration of animal research.

Foundation for Biomedical Research

Until I started my summer internship at the Foundation for Biomedical Research in May of 2012, I never knew just how much animal research really does benefit medicine. I knew that important discoveries were made, but I didn’t know how biologically similar animals were to humans. I now know that research with animals is critical to the advancement of medical science. Treatments and cures for the most debilitating diseases are being discovered and tested with animals for the benefit of both animal and humankind, and FBR acts as a liaison between scientists and general public to communicate these important discoveries.

Established in 1981, the Foundation for Biomedical Research (FBR) is the oldest organization dedicated to educating the public about the vast benefits of responsible and humane biomedical research with animals. FBR focuses on outreach and education – everything we do is to promote and make the public aware of critical research being done with animals that benefits millions of people world-wide.

There are many ways FBR reaches out to the public, from lesson plans to award ceremonies – all for the purpose of highlighting the importance of animals in the field of biomedical research.

Every day we send out a newsletter called Total E-Clips to over one hundred and fifty thousand readers around the world, a number that grows every day. The newsletter is a compilation of the most important animal research-related news of the day. Contents include animal research news, animal activism news, political news and anything else of relevance we find that day.

FBR releases a quarterly magazine called ResearchSaves, which is a part of the larger ResearchSaves campaign. The campaign includes a website, TV, radio and print ads, and even the occasional billboard. The magazine is a compilation of stories submitted by non-profits, universities, companies from all over the country. Anyone can subscribe to the magazine and complimentary issues are offered to teachers K-12th grade.

FBR provides a lesson plan for middle-school aged children in the subject of animal research. These lesson plans are intended to educate students about the facts and ethical issues surrounding biomedical research and promote healthy, stimulating discussion. They encourage students to discuss their thoughts and questions about animal research. The lessons also inform students about the many benefits that have come from biomedical research with animals and provide them with possible career goals in this field.

As part of the educational outreach, FBR also provides a Career Day Kit for teachers to empower students to pursue biomedical research as an interest as well as a potential career. It also counters a different view than what school children are normally told by the animal rights organization: that animal research is cruel and unnecessary. The Career Day Kit was launched in response to the widening distrust of animal research within the general public, and the strengthening reach that animal rights groups have into the K-12 sphere.

Over the last year and a half FBR has been producing its new television show, Bench To Bedside. Each episode highlights a person who has gone through the diagnosis and treatment of a debilitating disease or injury. The most recent episode to air was called Liviya’s Story; it is about a six-year-old girl who develops a terrifying disease called aplastic anemia. In the end, she recovers with the help of a drug therapy that had been developed in horses.

Along with educating the general public, FBR acts as a liaison between scientists and journalists, encouraging a healthy relationship between the media and the scientific community and promoting balanced and responsible reporting of biomedical research. FBR is considered a definitive resource for both the news media and scientists.

For the last 11 years, FBR holds the annual Michael E. DeBakey Journalism Awards, which is considered one of the most prestigious awards in science journalism. Award winners are judged by an independent panel based on relevance, clarity, and technical skills. There are six categories, each one featuring a different medium – print, both small and large press, digital, TV, radio, and magazine. These journalists represent the forefront of outreach that FBR strives for. These journalists are telling stories about the beneficial outcomes of biomedical research with animals.

I’ve learned that research with animals is absolutely necessary in the search for treatments and cures, but much of the general public is not convinced. Scientists need help reaching out to the public, and the Foundation for Biomedical Research is here to help in that endeavor.

JoAnna Wendel