Tag Archives: science

The Day Italy United for Science – 8 June 2013

It seemed like a crazy plan when we first heard about it from our friends in Pro-Test Italia at the end of April, to organize a day of events in cities across Italy to campaign for correct scientific information, and to do so in less than 6 weeks…and with a starting budget of precisely nothing.

On Saturday 8 June 2013 the seemingly impossible didn’t just happen, it was a triumph!

In 16 cities across Italy some 1,500 people joined in “Italia Unita Per La Corretta Informazione Scientifica” to hear and spread the message that the culture of dishonesty that has afflicted the public discourse on scientific issues in Italian society must end.

An appropriate setting for the talks and discussion in Padua.

An appropriate setting for the talks and discussion in Padua.

Events ranged from talks and debates with audiences in the hundreds in conference rooms and lecture theatres in Milan and Padua, to a smaller “Cafe Scientifique” style discussion in Naples and Trieste.

Hundreds attended the lectures and discussions in Milan

Hundreds attended the lectures and discussions in Milan

Time to talk science in Milan

Time to talk science in Milan

The topics discussed by over 50 scientific experts who spoke at these events reflected the wide variety of issues of concern to those who value science in Italy, including vaccination, GM crops, stem cell therapies, seismology, chemtrails, alternative medicine,  and of course animal research. Discussions were often lively, with many audience members joining the speakers to challenge anti-scientific claims.

Talking science in the library in Naples

Talking science in the library in Naples

In addition to these public talks and discussions scientific activists held flash mobs in several cities to highlight the way that science is often sidelined in Italy, and how this has to change if a better future for the country is to be secured. As La Republica and Science Insider report these included 30 scientists who gathered to silently display placards and banners on the famous Spanish Steps in Rome.

The days leading up to and following June 8 saw discussion of the events in Italian newspapers, science magazines and blogs, many of which are listed on the Italia Unita Per La Scienza website, and the TV stations LA7 and D1 Television also ran reports on them. These discussions highlighted the fact that this is the first time that scientists across Italy have joined together in such a public way to call for better scientific information, but it was also clear that among the many subjects tackled it was animal research that caught the media’s attention. It is perhaps not surprising, Pro-Test Italia  and its members played a lead role in organizing the day of action, and animal research was discussed at most of the talks.

It won’t come as a much of a surprise then to learn that animal rights activists sought to disrupt, and even to stop, several of the planned events from taking place.  Needless to say they failed in almost every case, but their behaviour is an interesting aspect of last Saturday’s events that we will have come back to in another post.

June 8 was the brainchild of Pro-Test Italia members Giulia Corsini and Federico Baglioni, but making the event a success was a task that involved more than 200 researchers and scientific activists across Italy, most of them young, all of them volunteers, working together to put the day’s events together at only a few week’s notice. Among the scientific groups joining Pro-Test Italia in to help organise and support the day were Fondazione IDIS – Città della Scienza, Associazione Luca Coscioni, Istituto Nazionale di Geofisica e Vulcanologia, Coordinamento Nazionale Studenti di Biotecnologie, Osservatorio Malattie Rare and more than 20 others. This may be the most important legacy of June 8; it brought together for the first time passionate and committed individuals and organizations from around Italy, and from a wide range of scientific backgrounds, to unite against misinformation, unite for science, and above all unite for the future of their country.

Federico, a biotechnology graduate with a passion for education who writes for the biotechnology magazine Prometheus and also discuss a wide range of life sciences topics on his personal blog, noted how the day of action marked the birth of a new movement in Italian society.

For the first time students and scientists from all parts of Italy have united to fight together against scientific disinformation. Much more needs to be done, but we are here, and this is just the beginning.

Well done Pro-Test Italia on holding another highly successful event so soon after your rally for animal research in Milan, you’ve certainly got people’s attention now, so keep up the excellent work!

Speaking of Research

Challenging Scientific Dishonesty Across Italy

With the Pro-Test Italia rally only 2 weeks away, there is a growing movement against the widespread misrepresentation of science in Italy. To counter this, two members of Pro-Test Italia – Giulia and Federico – have set up “Italy United against Scientific Disinformation“. They will hold a set of public talks around Italy on June 8th 2013, one week after Pro-Test Italia hold a rally in defence of medical research using animals. Click on the image below to share it on Facebook.

Italia Unita Per La Corretta Informazione ScientificaThe new organisation intends to debunk scientific misinformation wherever it exists. This includes issues surrounding vaccinations (and the myth that it causes Autism), stem cell research and of course the use of animals in biomedical research.

The group provided Speaking of Research with the following message:

“Italy United against Scientific Disinformation” is a mega-project. A very ambitious grass-roots initiative, it is the brain child of two young members of Pro-Test Italia , who worked together to reach out to the community, and found that there are many good people who share their ideals and were willing to join them.

Starting with a budget of zero, and in record time, the project already involves events in several Italian cities and volunteers from all over Italy, with more joining every day.

At the heart of this movement are young science enthusiasts, who are fed up with the way that the Italian public are being manipulated.

Are you fed up with how science is condemned by ordinary people, who prefer to be carried away by phantasmagorical conspiracy theories, despite all the contrary evidence?

If the problem was limited to merely erroneous beliefs it would be tolerable, but in Italy legislative measures are often taken based on mistaken beliefs, so research also suffers many limitations (funding cuts, incorrect regulations and so on). As a result of this we witness daily the phenomenon of brain drain, which afflicts our country severely.

Science is our future. Everything starts with the correct scientific information, but in Italy this is sadly absent from public discourse.

Young people have thus decided to involve their universities and their teachers, to involve associations, to call on the experts, who together will expose the most common misconceptions in this country!

On June 8 we will all unite against misinformation, unite for science, and above all unite for the future of our country.

Giulia and Federico

Contacts: italiaxlascienza@live.com

Events are planned all over Italy

Events are planned all over Italy

So stand up and be counted in support of science. Such events will no doubt play an important part in the developing public dialogue about how Italian politics and media interact with important scientific issues.

Speaking of Research

Are scientists sadists?

Scientists working with animals are often accused by animal rights activists of being ‘monsters’, ‘murderers’, ‘sadists’ and worse.  On the other side, animal rights leaders see themselves standing on a moral pedestal above the rest of the population, while simultaneously inciting to violence against fellow human beings they have never met.  The contradiction is lost on them.

Their appalling allegations don’t deserve a reply.  And yet I was asked recently by a colleague to answer the recurring claim that, somehow, scientists must enjoy harming animals in their research.

The brief answer is… of course not.

Scientists don’t enjoy harming animals. To enjoy means, literally, to take pleasure in, to get a thrill out of, to be entertained by, to relish, to savor or to delight in. I never felt any of these emotions during an experiment nor I have ever met anyone who has. In fact, the opposite is the norm. Typical emotions reported cover the range from sadness, anxiousness, nervousness, uncertainty, to uneasiness. All involved,  the scientists, the students, the veterinarians and animal technicians, acknowledge that there is a personal, emotional toll that results from this work. Those that are directly involved in the daily care of animals explain that their primary motivation is their love of animals and their wish to see them treated as well as possible.

One reason for these mixed feelings comes from the recognition that harm is done to the animals, despite doing everything possible to minimize their pain and suffering. A second reason is due to the inherent uncertainty in scientific work. Put simply, there is no guarantee that the harm caused in any one individual experiment will lead to palpable advancements. In science, one cannot determine ahead of time which lines of research are necessarily going to lead to medical breakthroughs. Decisions to approve and fund an experiment are based on expert opinion based on what studies show most promise, based on well-defined hypotheses and preliminary data, but there are no guarantees.

At the same time there is no denying that animal research has produced tremendous benefits. There is universal consensus among scientists that failure to do this type of work will bring many areas of medical research to a complete halt.  Importantly, and relevant to the ethical debate, there is a shared conviction that halting such research, as requested by animal rights activists and organizations like PeTA and HSUS, would result in much harm to human and non-human animals alike.

It is a failure of animal rights activists to persistently ignore this part of the ethical equation that that works against any meaningful conversation. Instead, they prefer to stick to the tenet that “do no harm” is an absolute moral principle that admits no exceptions. They find comfort living in an utopian black/white moral universe devoid of moral dilemmas, where “a rat is a pig is a dog is a boy”.

The refusal of animal rights activists to acknowledge the benefits of past work, and their failure to recognize the tremendous harm one would inflict by stopping the use of animals in medical research, leads one to ask — Who exactly is being cruel?

Dario Ringach

Speaking of 2012: A year in Summary

It has been a fantastic year for Speaking of Research, reflected in the fact that the website traffic has more than doubled (130% growth and still rising). Thus trying to summarise will be the 127th post of the year thanks to the commitment of our committee. An extra special thanks has to go to four of our most regular authors – Allyson Bennett, Dario Ringach, Paul Browne and Tom Holder.

This year has provided many posts on the ethics and welfare discussions surrounding animal research – starting with the very first post of 2012 on the meaning of “being humane”. We also discussed the ethics of negative results, why not doing research is morally wrong, why animal rights groups are wrong to use marginal case arguments (e.g. cognitively impaired people), the idea of graded moral status, and the relevance of moral intelligence. Another common theme was that of Free Speech and how it can be used to stifle the free speech of others. Parallels were made with how anti-abortion extremists create a climate of fear among their opposition.

Science has always been at the centre of the Speaking of Research website. Among many topics we have written about early successes with using stem cells to repair damaged heart tissue, how cooling the body could improve life chances of stroke victims, huge leaps forward in facial transplant surgery, using Preimplantation Genetic Diagnosis to prevent genetic diseases in IVF embryos, several  different advances in paralysis treatment (in dogs as well), new treatments for TB, a new Meningitis B vaccine, and how human embryonic stem cells have helped gerbils’ hearing. Breath. Oh, and both the Nobel Prize in Physiology or Medicine and the Nobel Prize in Chemistry went to work requiring animal models.

GM mice have made crucial contributions to our understanding of Fragile X syndrome. Image courtesy of Understanding Animal Research.

We discussed how GM mice are helping research Fragile X Syndrome

Other than scientific advances, we also spend a fair amount of time debunking common animal rights crank myths such as surrounding Adverse Drug Reactions, that research is just about money and . SR has helped defend a number of organisations from animal rights misinformation, including Cardiff University’s research on kittens, UW Madison’s research on cats, and the University of British Columbia’s research on monkeys. We have called on people to build their own networks for science to counter the animal rights nonsense (#ARnonsense) they propagate online.

Speaking of Research has always taken a strong stance against animal rights extremism, posting about Camille Marino’s threats, arrest and prosecution as well as Stephen Best’s war against fellow activists, baseless legal threats against us, and why he may have breached ethical standards on academic conduct.

A number of outreach initiatives started this year including Speaking Honestly – Animal Research Education (SHARE), Brainfacts.org, and Keep Research Afloat. Many organisations could still do more as was shown by the statements about research from pharmaceuticals and charities. However, we must congratulate those institutions, like Leicester University, that did outreach right. Of course one of the biggest outreach stories of the year was one we covered only last week, the launch of Pro-Test Italia!

Our own outreach efforts have included a series of guest postings, starting with David Abbott’s post on polycystic ovary syndrome. This precipitated the “Many Voices Speaking of Research” series of guest posts [See post 2, 3, 4, 5, 6, 7].

So to finish our roundup with a bit of fun, go and play our hugely popular Animal Rights Bingo game.

Merry Christmas Mouse

So Happy Holidays, and have a great New Year!

Speaking of Research

Cancer Stem Cells: Mouse studies lead to paradigm shift in cancer research

For the past 15 years one of the most intriguing ideas in cancer research has been that the growth and spread of most – if not all – cancers is driven by cancer stem cells. The hypothesis is that only a tiny proportion of cancer cells, cancer stem cells, have the stem cell-like ability to proliferate indefinitely to produce cells that can differentiate into other cancer cell types. It suggests that the reason why cancer often returns after apparently being eradicated is that while the therapy (surgery/radiation/chemotherapy) may remove the differentiated cancer cells it fails to remove all the cancer stem cells, whose subsequent proliferation results in the cancer’s return.

Multicolored intestine tissue in genetically modified mice allows scientists to track which cells give rise to tumors.
Credit: A. G. Schepers et al., Science (2012) DOI: 10.1126/science.1224676

Today 3 teams of scientists have announced important results that provide the strongest evidence to date that cancer stem cells are indeed at the heart of cancer proliferation.

The first evidence that only a small minority of cancer cells may have the ability to proliferate indefinitely came from a study of leukemia cells in 1997, when Dr Dominique Bonnet and Dr John Dick, then both working at the University of Toronto, observed that when they injected a variety of acute myeloid leukemia (AML) cell populations obtained from human biopsy into immunodeficient mice and analyzed which cells gave rise to leukemia cells in the mice, and found that regardless of the characteristics of injected AML cells the cells that initiated the leukemic cell populations in the mice always expressed the cell surface marker CD34 and lacked the cell surface marker CD38, a key characteristic of stem cells.

Since then similar observations have been made for a wide variety of cancer types, and scientists have discovered important new facts about cancer stem cells, for example in 2009 we discussed how scientists at Stanford University had used genetic modification of bone marrow stem cells to show that leukemia stem cells were very similar to embryonic stem cells.  However, these studies all involved the transplantation of cancer cells into mice, and there has always been some concern that the manipulation of these cells during their isolation from humans and sorting into specific populations before injection into mice may have affected their behavior.

Today, three independent studies of mouse models of brain, skin and intestinal tumours, led respectively by Dr Luis Parada at the University of Texas Southwestern Medical Center, Dr Benjamin Simmons of the Gurdon Institute and Dr Cédric Blanpain of the Free University of Brussels, and Dr Hans Clevers of the Hubrecht Institute, and published in the prestigious scientific journals Nature and Science,  provide the first evidence that cancer stem cells do arise during tumour formation in intact organs, and drive tumour formation.

What these studies all share is that they were able to do this because rather than injecting cancer cells into the mice they used genetically modified mice in which cancer develops spontaneously. Using additional genetic modification to label certain types of cells they were able to track the different cell types involved in the growth and spread of cancer, and even assess the differing effects of standard cancer therapies and therapies that included drugs that specifically target cancer stem cells.

There is an excellent discussion of the three projects and their implications for cancer research in Nature News, and Science Now also offers a informative prespective on the work.  From its very first paragraphthe Nature News article highlights how these studies provide crucial information that could not be obtained through other methods:

Cancer researchers can sequence tumour cells’ genomes, scan them for strange gene activity, profile their contents for telltale proteins and study their growth in laboratory dishes. What they have not been able to do is track errant cells doing what is more relevant to patients: forming tumours. Now three groups studying tumours in mice have done exactly that. Their results support the ideas that a small subset of cells drives tumour growth and that curing cancer may require those cells to be eliminated.”

Commenting in an article in the LA Times, Dr. Owen Witte of the UCLA Broad Stem Cell Center was clear about what these results mean for cancer research.

People can stop arguing…Now they can say, ‘OK, the cells are here. We now need to know how to treat them.’ ”

And “how to treat them” will not be an easy problem to solve, perhaps drugs that target the cancer stem cells or prevent their development may be the answer, but as the Nature News, Science Now and LA Times articles stress we don’t yet know enough about the origins of cancer stem cells to be sure which approach will work.

What is true is that thanks to advanced animal research methods a huge gap in our knowledge of how cancer develops and spreads – a gap that we only recently realised existed – has been filled. As research accelerates to turn this new knowledge into effective cancer therapies we can be certain of one thing; animal research will continue to provide key insights that turn hypothesis into cures.

Paul Browne

The Animal Rights Crank

We live in a world where science is increasingly being denied, an age where some appear to value ignorance more then knowledge, where everyone is an expert, where celebrities give medical advice, where every idea is equally valid and worthy of being called a theory, where evidence and fact attain the same stature as delusions and fabrications, where information is diluted in noise, and where bullying is activism.

We see this play out every day, when apparently thoughtful people reject scientific facts to conjure their own, making it nearly impossible to have a reasoned and civil debate on any number of important topics in our society, from climate change, to vaccines, stem-cells, evolution and the use of animals in research.

That’s why today an increasing number of people spend their time decrying the denial of science:

Some animal right activists are veterans in this game. They have a long history of twisting facts,  cherry-picking data, and quoting others out of context to suit their interests. The intelligent crank has become an essential ingredient of the animal rights movement.  The crank regards everyone else as ignorant and stupid, except for himself, of course.  He will accuse scientists of dishonesty, and of having other ulterior motives for their work and opinions. If his ideas are ignored, the crank will declare victory and his arguments to be unanswerable. He will display public tantrums when his work is rejected from scientific journals or when he is refused to lecture in academia. His “theories” are typically based on complexity rather simplicity, ambiguity rather than clarity, and fabrications rather than facts.  He will publicize these ideas in volumes that advertise his vast erudition.

When the crank and his followers face a simple fact that contradict their views, such as the discovery of a novel therapy from breast cancer based on the antibody from a mouse, they will have to offer an explanation. Rather than accepting the rejection of their beliefs, they will make up a story, such as suggesting the discovery was the outcome of chance. In this regard, there is absolutely no difference between their behavior and that of the Seekers who, upon realizing the Aliens did not show up to rescue them as their prophet had assured them, had to rationalize an explanation to prevent their entire belief system from collapsing.

We appear to live in an age where a prophet and his cult have the same standing as a scientist and his method. But science, facts and knowledge will prevail, and together, we will get through the STORM:

Empathy and Altruism in Rats?

A recent paper in Science discussed behavioral data in rats suggestive of empathically motivated behavior. This is a potentially very important report for two major reasons. First, a deep understanding of the mental and psychological abilities of rats, and other species, is a crucial goal for comparative psychologists, evolutionary biologists and other basic scientists. Second, the autism spectrum disorders are characterized by atypical reciprocal social interactions, and difficulty with experiencing and understanding the emotions of others appear to contribute; therefore, an animal model system in which we can learn how the brain responds to and processes the emotions of others is crucial to progress in this area. For these reasons, the experiments address a very significant question.

The experiment consisted of having a rat placed in an arena (the free rat) who is able to see and interact  with a companion that is trapped in a cylindrical restrainer with a door (the trapped rat).  It was found that the free rat learned over time to free the trapped rat by intentionally opening the door.  In control experiments, rats did not open empty tubes or ones containing an inanimate object.  When given a choice between getting access to chocolate and freeing the trapped rat, they would often free the rat even before eating the chocolate, suggesting that the motivation to liberate its companion trumped even its desire for the chocolate, a potential sign of altruism.

The authors concluded that “the free rat was not simply empathically sensitive to another rat’s distress but acted intentionally to liberate a trapped conspecific.”

The media reported on the finding by declaring science has shown altruistic behavior in rats.  Some media titles include “Rats: Holiday spirit in rodent form”, “If someone calls you a rat, take it as a compliment”, “Rats kind-hearted, generous creatures”, “Rats show Empathy and Altruistic Behavior”, “Rats are as compassionate as humans” and so on.

It appears that both the press, and perhaps even the authors, interpret the findings as implying the following:

  1. The free rat has a mental state that represents the well-being of a conspecific.
  2. This representation generates a distressful response in the free rat.
  3. The free rat learns it can act in a way to relieve the distress of the caged rat by opening the door of the cage.
  4. The rat intentionally acts to relieve the caged rat from distress even when there it has nothing to gain from the action.

Dr. Daniel Povinelli, in a Nature coverage of the paper, had a different view, saying that “This work is not evidence of empathy — defined as the ability to mentally put oneself into another being’s emotional shoes.”

Though the view that rats exhibit empathic behavior may be consistent with the data, we must ask if there could be alternative, simpler explanations that do not necessarily involve invoking assumptions 1-4, above.

One possibility is that the trapped animal is generating an alarm signal, either in the form of vocalizations or pheromones, that generates stress in the free rat.  The free rat may then learn it can stop the distressing signal by opening the door (so-called negative reinforcement).  In acting in such a way, the free rat would then be relieving its own distress rather than the perceived and shared stress of a conspecific.

Is this possible?

The authors did not measure chemical signals but did measure vocalizations during their experiments and found that “significantly more alarm calls were recorded during the trapped condition (13%) than during the empty and object conditions.”

So this alternative scenario is, in principle, a possibility.  The authors dismissed this alternative explanation because the rate of alarm calls was relatively low and yet they remained open to the possibility when they concluded:

Thus, the most parsimonious interpretation of the observed helping behavior is that rats free their cage-mate in order to end distress, either their own or that of the trapped rat [...] This emotional motivation, arguably the rodent homolog of empathy, appears to drive the pro-social behavior observed in the present study.

This is a bit confusing and requires clarification.

There are at least two different interpretations of the data.  Not one.

Either the rat is freeing the companion to end its own stress (caused by an alarm signal) or it is doing it to end the perceived stress of the caged rat.   The interpretation of a pro-social, empathically motivated, altruistic behavior is only applicable to the second interpretation and not the first one.

To differentiate among these possibilities one can conduct some additional control experiments.  One could, for example, just play alarm calls that are stopped once a rat presses a lever once placed in the arena.  Or we could use chemical signaling if we learn the behavior is mediated by pheromones and identify the pheromone in question. One could have offered the free rat the option to leave the arena to a dark, quiet place, potentially ending its own distress and leaving the companion trapped.  Or the free rat could be offered the possibility of a “personal sacrifice” (such as a mild shock) to free the other rat, thus paying a price to help his companion.  These are all doable experiments that would help tease apart the different interpretations of these data.

Another potential explanation of the data is raised by video records of these experiments provided as part of the Science article shown below.

In this example, taken after the rat has learned to free its counterpart, we see the free rat going right into the restraint immediately after opening the door.  Why would the rat enter the tube if it truly felt and understood the distress the other rat experienced by being confined?

If one has ever seen rats at the pet store, you know that you will often find them snuggled up together in tubes and tight spaces because they apparently enjoy the safety and security of these types of experiences. This view was raised in an online discussion of the data:

Rats enjoy access to tight enclosures.  We routinely put plastic tubes in home cages for “environmental enrichment” and the rats are often found “snuggled” together in them, especially when resting – presumably an inherent protective response.  In fact, if you try to grab a rat in a cage with a tube, the rat will immediately go for the tube and try to stay in it.  Thus the “trapped” rat could also be seen by the “free” rat as enjoying a protected situation, and the free rat could in fact be displaying “envy” by freeing his companion so that he can enjoy the same protection and/or being motivated for social reasons to have a companion to “snuggle” with.  Indeed, the first thing the free rat did in the video after opening the enclosure was to go right into the tube with the other rat! 

So the basic question is, does the free rat want to get in, believing that his cagemate enjoys the privilege of a protected space, or does he fear for his cagemate and want to release him?   

Again, only additional experiments can address this. Resolution of these alternative views is crucial in terms of both of the prevailing motivations for conducting the study. Either rats are acting to relieve their own distress, or that of another – the difference bears strongly on our understanding of their mental abilities. In addition, if the former, but not latter, phenomena is correct, the value of studying the biology of empathy using rats is significantly challenged.

Still, we are left with a provocative phenomena —  rats freeing one another, invoking similarities with human behavior. There are plenty of other examples in nature where individuals of a species cooperate and interact in ways that could be described in terms of our own (human) mental states as altruistic or empathic behavior.  The examples range from bonobos, to bats, to even single-cell organisms, such as social amoeba (see here and here.)  The behavior is essentially the same across all these species and yet one would be hard pressed to argue that single-cell organisms have a notion of altruism and empathy in the same sense humans do.

Our brains (including those of scientists) are wired in such a way that they readily interpret the behavior of others in terms of our own mental states.  Such ability is useful in many situations, form navigating daily social interactions and even in the description of scientific data.  Care must be exercise in descriptions based on our own mental states when the outcome can have clear moral and scientific consequences.

Scientists must always keep an open mind.  But before rushing to declare that humans must seek moral guidance from rats, we should pause and try to understand exactly what the data say.  As new experiments are done and more information is available, we will surely be able to discern which of the alternative explanations is the correct one. If additional work confirms the (premature) conclusions of the authors, it will lay the ground work for developing new animal models for human psychological disorders, which will be a welcome development. For now, however, we must await that conclusive work.

J. David Jentsch and Dario Ringach

How to build a lung

Tissue engineering, a field that combines cell biology, engineering, and materials science to manufacture tissues – and more recently even whole organs – to replace those lost to injury or illness, must be one of the most exciting areas in modern medicine.  Since the earliest reports about a mouse with a human ear growing on its back over a decade ago progress has been rapid, and last year we reported on how animal research enabled scientists to use a patient’s own stem cells to successfully replaced a trachea that suffered irreparable damage from tuberculosis.

Now science writer Ed Yong has written an excellent article on his Not Exactly Rocket Science blog about how a team of scientists at led by Laura Niklason Yale University are moving on from the trachea to a far more complex part of the respiratory system – the lung – and successfully transplanted it into rats.  As Ed points out, this technology needs to be improved significantly before it can be attempted in humans, and further research in rats is underway to do just that.  This work will take time, and as it progresses will almost certainly require studies in larger animals such as pigs whose lungs are closer to ours in size and structure than those of rats. Human trials are not expected for perhaps a decade or more.

Ed Yong was not the only one to note the importance of this research, the journal Science, in which the study was published (1), have included an interview with Laura Niklason in their latest podcast.

How to build a lung. Courtesy of Laura Niklason and Thomas Petersen.

Laura Niklason’s past record certainly gives cause for optimism. In 1999 they published a paper describing how they engineered arteries in vitro that supported blood flow when transplanted into pigs, an animal whose cardiovascular system is a valuable model for our own, and determined that a culture technique that mimics the pulsating arterial blood flow produced stronger and safer engineered arteries. Following a decade of refinement through in vitro tissue culture and animal research the artery is expected to enter human clinical trials next year.

And Laura Niklason’s group is not the only one that is working hard to develop tissue engineered lungs for transplant, at the Harvard University Medical School in Boston Professor Harald Ott and his colleagues have also had promising results with transplanted lab grown lungs in rats.

Engineered rat lungs in a bioreactor at Dr. Harald Ott's lab in Boston. Credit: National Geographic Explorer.

This wasn’t the only exciting lung-related research to be published in Science this week.  Scientists at Harvard University have used microfluidics to re-create the interface between the alveoli and capillaries (2) in the lung where exchange of oxygen and other gasses takes place. The response of this “Lab-on-a-chip” model to bacterial infection and inflammatory signals was similar to that seen in previous animal studies.

This technology represents huge advance over existing in vitro models of the lung; which, in addition to being a very promising research tool in its own right, has the potential to reduce the number of animals used in testing the effect of new drugs or toxins on lung function.  Eventually an improved version, perhaps combined with chips that simulate other tissue types, might replace animal use in the evaluation of toxicity in the lung entirely, though that goal is still years of dedicated research away.  Lab-on-a–chip technologies such as this that can integrate several cell types into a system that mimics real tissues in vivo are a great example of the 3Rs in action.

How to build a lung on a chip. Image courtesy of Huh D. et al. Science Volume 328 (5986), pages 1662 - 166 (2010)

One area the Harvard scientists were particularly interested in is using this lab-on–a-chip to evaluate the potential toxicity of nanoparticles, since existing in-vitro cell and tissue culture technologies are not adequate for this task, and using rodents is slow and expensive. Since nanoparticles are becoming increasingly common in daily life there is an urgent need to develop ways to rapidly assess their safety before humans and animals are exposed to them. So they examined how their lab-on–a-chip responded to a variety of nanoparticles, and then compared the results to those of parallel studies performed on the lungs of mice.

A key question was whether inhaled nanoparticles can cross into the bloodstream, several animal studies indicate that they can while in vitro studies suggest otherwise, though as mentioned the relevance of these in vitro methods has been questioned. With the new technology the results were in close agreement, the nanoparticles can cross into the bloodstream. This demonstration indicates that the lab-on-a-chip may provide a suitable platform for future evaluation of aspects of nanoparticle toxicity, as part of new pathways for the evaluation of chemical safety that use as few animals as possible.

So, all in all it is a very great week for building lungs in Science, one to which animal research made a huge contribution.

Paul Browne

1)      Patersen T.H. et al. “Tissue-Engineered Lungs for in Vivo Implantation”   Science Published Online June 24, 2010 DOI: 10.1126/science.1189345

2)      Huh D. et al. “Reconstituting Organ-Level Lung Functions on a Chip”  Science Volume 328 (5986), pages 1662 – 1668 (2010) DOI: 10.1126/science.1188302

Addendum

In my rush to finish the above post I forgot to mention another advance in the use of decellularized scaffold and in vitro cell repopulation approach to tissue engineering, scientists at Harvard Medical School produced artificial livers that appeared to function almost as well as normal tissue when transplanted into rats and connected to their blood supply . In the research paper published online in Nature Medicine the authors stress that the artificial liver needs further development before human transplants can be contemplated, but this is further evidence of just how quickly progress is being made in the field of complex tissue engineering.