Category Archives: News

Germany publishes 2014 animal research statistics

Germany has published in statistics that show the number of animals used for research and testing in 2014. Germany carried out 2,798,463 procedures on animals in 2014, 6.6% fewer than in 2013.

Species of animals used in German Research in 2014. Click to Enlarge

Species of animals used in German Research in 2014. Click to Enlarge

The fall in the number of experiments is mainly due to a reduction in the numbers of mice used. There was a significant rise in the number of fish (+35%) and birds (+29%) used. As well as rises in dogs (up 82% to 4,636 procedures) and primates (+31% to 2,842 procedures).

Animal Experiments in Germany in 2014. Click to Enlarge

Animal Experiments in Germany in 2014. Click to Enlarge

Mice continue to be the most commonly used species at 68%. Mice, rats and fish account for 91% of all animal procedures, rising to 95% if you include rabbits. This last point is interesting when compared to most other European countries where birds are the fourth most common species. Of countries we have assessed in Europe, only Spain uses a similar proportion of rabbits. Dogs, cats and primates accounted for less than 0.4% of all animals used despite the rises in number of procedures for these species.

Click to Enlarge

Click to Enlarge

This year was also the first year where there was retrospective assessment and reporting of severity (i.e. reporting how much an animal actually suffered rather than how much it was predicted to suffer prior to the study). The report showed that 60% of procedures were classed as mild, 21% as moderate, 6% as severe, and 13% as non-recovery, where an animal is anaesthetised for surgery, and then not woken up afterwards.

From historical statistics we can see that, like several other EU countries, the number of animal experiments rose steadily between 2000-12, before slowing and reversing in 2013-4. It is likely that some of this reflects the drop in science funding during the recession and economic turmoil of the past seven years. Such cuts to funding can often take some years to take effect as research projects often have agreed funding for several years.

Trends in German animal experiments 2000-14. Note 2014 is in a different color to reflect the different reporting requirements. Click to Enlarge.

Trends in German animal experiments 2000-14. Note 2014 is in a different color to reflect the different reporting requirements. Click to Enlarge.

This final number should be treated with some caution as it is the first year under the new EU reporting guidelines which requires retrospective reporting on severity, and now asks for numbers of procedures of studies ending in the reporting year (rather than starting). The UK statistical release (which follows the same EU guidelines) came with the following notes and word of caution:

As a result of the change to counting procedures completed as opposed to procedures started, all procedures started before 2014 but completed in 2014 should be in both the pre-2014 and 2014 figures. Any procedures started in 2014 but completed after 2014 will not be included in the 2014 figures. It is expected that these opposing effects will partly cancel each other out. Any impact of the change from counting procedures started to counting procedures completed will be temporary and will disappear from future years’ data collections.

Finally noting:

As a result, the 2014 data and comparisons with previous years’ data should be interpreted with some caution.

We will continue to report on national statistics as they are published.

Canada Releases 2013 Animal Use Statistics

Our statistical releases continue. Last week the Canadian Council on Animal Care released its report on the number of animals used in Canada for scientific purposes. The CCAC is an independent oversight body that oversees the ethical use of animals in research. They also develop guidelines and promote training programs to ensure that all individuals involved in animal research or welfare are properly trained before being allowed to work with the animals. The CCAC reports that in 2013, 3,023,184 animals were used for research, teaching and testing in Canada. This is an increase of 4.6% (134,175 animals), from the 2,889,009 animals that were used in 2012. These numbers include all vertebrates and Cephalapods, but do not include other invertebrates such as fruit flies or nematode worms.

Animals Used in Research in Canada in 2013

Table of animals used in research in Canada in 2013. Click to Enlarge

Mice (40.8%), fish (32.1%) and rats (7.5%) once again were the three animal types most often studied. The majority of animals (61.6%) were used in studies of a fundamental nature/basic research, representing 1,897,831 animals. Category of invasiveness describes the level of pain and or distress that an animal could potentially be exposed to while under study. Category B, which could include breeding activities for domestic animal herds or genetically engineered rodents, accounted for 812,118 (26.4%) animals. In the highest category of invasiveness E, 78,294 (2.5%) animals were counted. This number is down from 93,242 (3.1%) counted in 2012. 48.1% of animals in E protocols were studied for testing purposes, which are required by the Canadian governments to ensure that new drugs, vaccines and products are safe and efficacious for use in humans and other animals. The three types of animals most frequently used in E protocols were fish, mice and guinea pigs.

Animals used in research in Canada 2013 by species

Animals used in research in Canada in 2013

More information about animal research in Canada can be found within the Speaking of Research Media Briefing Notes for Canada.

Speaking of Research

Why are zebrafish such good models for scientists?

Today’s guest post comes from Alex Buxton from the University of Cambridge, based on her interview with Professor Lalita Ramakrishnan about her research on zebrafish. Prof Ramakrishnan’s research into immunology and infectious diseases at the University of Cambridge is funded by the Wellcome Trust and the National Institutes of Health. This article was originally posted by the University of Cambridge and has been reproduced with their permission.

This is not the first time Speaking of Research have discussed this important animal model; earlier this year Jan Botthof discussed both the increasing popularity of zebrafish as an animal model and the regulations and animal welfare considerations involved in such studies.

Why are zebrafish such good models for scientists?

Around 40 years ago scientists began to realise that zebrafish, as vertebrates, could tell us a lot about human development and human diseases. This discovery represented a real breakthrough in terms of what could be achieved using zebrafish in laboratories.

There are two key reasons why zebrafish, in particular, are so valuable. Firstly, when the new fish hatches as a tiny larva, it is optically transparent for the first two weeks of its development. This transparency means that, using powerful imaging technology, we are able to observe in real time the development of the organism as it grows to maturity. In our laboratory, we exploit the optical transparency to directly look at how the tuberculosis bacteria cause disease.

The second reason why zebrafish are such a good model is that a single mating can produce hundreds of eggs — and female zebrafish are capable of producing a new batch of eggs each week. So we have access to large numbers of animals for the work. On top of all this, zebrafish are relatively straight-forward to keep and easy to breed.

We can also create zebrafish with different mutations and we can then assess the impact of host genes on the course of disease. This kind of fundamental work enables us to identify, by a process of deduction and elimination, what genes do — which is essential to developing new medical interventions.

A two day old transgenic zebrafish embryo (Wikimedia Commons / IchaJaroslav)

A two day old transgenic zebrafish embryo (Wikimedia Commons / IchaJaroslav)

But surely zebrafish and humans have little in common — we’re not fish!

Humans and fish are much more alike than people might suppose — even though we diverged from our last common ancestor at least 300 million years ago. Most of the genes found in fish are also found in humans — and most of the genes that cause disease in fish also cause disease in humans. The human immune system, which fights off disease, is a lot like the immune system of fish.

My research is focused on tuberculosis in humans — a disease that affects millions of people worldwide. Without treatment, TB can be life threatening. We tend to associate human TB with the lungs, and of course fish don’t have lungs. TB does affect the lungs but it can affect almost all our organs. In humans, some 40% of TB infection is not in the lungs but elsewhere in the body — brain, bone, kidney, intestine, reproductive organs.

Fish are affected by a close relative of the human TB bacterium. If we can work out how TB works in fish, and how to prevent it and treat it in fish, then we’re a step closer to solving a major health problem in humans.

What is the life of a laboratory zebrafish like?

Our fish live in tanks that are kept pristine by a unit that cleans and circulates the water. We grow the food they need in the lab — it’s a kind of brine shrimp. Putting this live food into the tanks allows the fish to hunt for their food, creating a more natural environment for them. Zebrafish are sociable creatures so we keep them in groups. All our fish are on a programme of 16 hours of daylight and eight hours of night. This routine mimics, as much as possible, the natural environment in the regions of the world where they live. We make sure that they are as healthy and stress-free as possible. Happy fish are healthy fish — and the other way round!

You can identify the males from the females by the roundness of the female’s belly. When we want a new batch of eggs, we put a male and a female in a tank overnight, with the two fish separated by a transparent divider. When daylight comes, the two fish become excited and we take out the divider and they mate. When the eggs are laid, they fall through a fine grill that enables us to take them out of the tank.

All these procedures are done as carefully as possible so as not to harm the fish or eggs.

How do you use the zebrafish eggs?

In my laboratory, we’re studying TB so we need to infect some of the fish eggs, one by one, with bacteria so that we can observe what happens. This procedure is carried out under a microscope using a very fine needle that is hollow, enabling tiny amounts of bacteria to be delivered into the egg. Because zebrafish eggs are so tiny, it takes a while to learn how to do this. It requires good hand-eye coordination and a steady hand — but everyone learns to do it with time and practice.

Once the eggs are infected we put them into small dishes where we can observe them. Because the eggs and the larvae are transparent, we can observe the process by which the bacteria enters the cells — and we can watch what happens as the bacteria and immune system face off. By using fluorescence, we can colour the host (the organism affected by the disease) and the bacteria so that it’s easier to track what’s happening on a cellular level. We can, for example, observe how exactly bacteria invade and spread.

Zebrafish embryos (Wikimedia Commons / Adam Amsterdam, Massachusetts Institute of Technology)

Zebrafish embryos (Wikimedia Commons / Adam Amsterdam, Massachusetts Institute of Technology)

How is your work with fish helping to develop better ways of tackling TB?

At the moment, TB in the human population is treated with a long course of strong antibiotics — it often takes as long as six months to get rid of it. Strains of drug-resistant TB have developed, partly because people do not finish the courses of drugs prescribed to them.

The work that my colleagues and I are doing suggests that there could be another, and perhaps more effective, approach to tackling TB. Rather than only targeting the bacteria, which are so clever in their invasive strategies, it might be better to additionally target the host and help the immune system to fight it off. We might do this by boosting or tweaking the immune system.

We now need to put to the test our ideas for helping the immune system by trying out a list of available drugs — and, in the initial stages of the research, we will be using zebrafish as models.

What’s the future for zebrafish as a model organism in research?

The world of research using zebrafish is wonderfully collaborative and fast-moving. Our main partner is the Sanger Institute which is just a few miles from the LMB. We collaborate closely with the scientists there on tools and techniques — including producing the mutants in order to identify genetic pathways.

Zebrafish are still relatively new in terms of their contribution to research — but it’s difficult to overstate how important they are. Every research organism has its limitations, of course. However, there’s much, much more we can learn from zebrafish that will benefit humans in the future.

Can Cell Lines Replace Animal Research?

TeresaTeresa Romeo Luperchio is a graduate student at The Johns Hopkins University School of Medicine and is currently working as a FASEB Office of Public Affairs Fellow. In this post Teresa tackles the difficult question of why cell lines could not replace all animal studies.  

A common theme in alternatives to animal testing is that tissue culture, or growing cells in a dish, is a viable way to replace animals in research. And for sure, growing cells in dishes for experiments is a great system; cells can be easily grown, the number of cells can be expanded to accommodate the size of your experiment, and they grow in small containers you can work with at the bench. Researchers can also buy cell lines (derived from animals or humans) from a company or can borrow cells from a colleague and grow them up in their own laboratory.  Advances in culture techniques have made using cell lines an easy way to study almost every topic that relates to health and disease. However, often overlooked or forgotten is the real identity of these cells.

Tissue culture in the lab

Cells, when still in the body, are limited in the number of times they can divide to make new, daughter cells. This phenomenon, known has Hayflick’s limit, is critical. Bypassing this limit can lead to uncontrolled growth and cancer. In culture, however, it is typical to develop cell lines that grow indefinitely, occurring through a process called immortalization.  When normal cells are prepared for culture, the process is the same regardless of tissue type:  1) cells and tissues are extracted from an animal, 2) the tissue is ground up (homogenized) as necessary to produce single cells, and 3) the cells are provided the nutrients and chemicals they need to grow and divide in culture dishes. To “immortalize” the cells, scientists use a number of different methods to trick them into growing past their natural Hayflick limit, which normal cells in culture rarely meet. The end result is an immortalized cell line that provides researchers with an almost endless amount of material.

Immortalized cell lines, once established, are a powerful tool for experimental studies, but they are a distinct cell type with distinct features. Not only do the populations of cells continue to expand, but their metabolism, the way the cells communicate with each other, and even their genomes can change. At our peril, the research community forgets, and groups promoting tissue culture research as an alternative for using animals ignore this caveat. Eliminating tissue culture, however, is an unfair assessment. In fact, much great science has been performed using immortalized cell lines, and in some cases, their use is preferred when variability and comparison to normal tissues are not a concern.

One way to avoid some of the pitfalls of using immortalized cell can be to use primary cell cultures, or cells immediately grown from a donor organism. These cells are self-limiting in growth number and are generally short term cultures. They do reduce the numbers of animals needed in research because scientists are able to freeze cells for future use like immortalized lines, but every new experiment that needs a new line would require another cell or tissue donor. Elimination of animals in research would hinder the ability to study relevant biology for normal and disease states even in tissue culture models.

Acknowledge the problems

As research tools become more powerful and more exact, small variations in our experiments are becoming more obvious when analyzing data. This increased sensitivity and scrutinizing power is fantastic for scientific exploration but also sobering in that we are becoming more aware and more cautious of our experimental materials. The media has picked up issues of ‘reproducibility’ in science, especially relating to cell lines. As many as 36% of cell lines are not what they are labeled to be or are contaminated with other cell types and this can lead to confounding results. Sharing cell lines can lead to confusion and mislabeling of cell types and sub-culturing cells can introduce variability. The National Institutes of Health have also picked up on this issue plaguing science research and is working on providing support and guidelines for scientists using cell lines to minimize error or misinterpretation. Science is self-correcting, and each experiment imparts new information that shapes global health and wellness. Keeping animals in research and employing the use of primary cultures eliminates some of the inconsistencies and variability between experiments using immortalized lines.

Examples of the need for primary cells

Genomic studies are the new boom of science and medicine. Improved, faster and cheaper imaging, computing, and sequencing technologies have accelerated genomic research. Genomic studies have led to many breakthroughs in disease and revolutionized biotechnology and academic research.

Packaging of DNA into the nucleus

Packaging of DNA into the nucleus. Credit: National Institute of General Medical Sciences

Generally, the genome is thought of as linear, with genes located next to each other in a long string connected end to end. When there are changes to DNA, we imagine mutations to the sequence or breaks in that long ribbon (This year, the Nobel Prize in Chemistry was awarded to three researchers who discovered repair mechanisms for the genome). DNA is packaged into chromosomes, and all that genetic material is bundled into the cell’s nucleus. It is becoming clear that how it is folded and packaged in the nucleus can influence disease.  The organization of your genetic material is complex, decided by a vast array of proteins and structures within the nucleus, and it is constantly changing to allow for genes to be expressed or not expressed. While DNA sequence generally remains unchanged, gene position, organization of chromosomes and as well as epigenetic signatures are affected by changes to the environment, and these impact gene expression and can trigger disease.

Tissue culture can impact the genome and create confusion in results. When cell lines are generated, the end product does not resemble an organism at all. The genome becomes unstable and prone to mistakes, and after a few cycles of growth, or passes, the cell lines may not even resemble what you started with. We often see in culture that cells become polyploid (have more chromosomes than they should), which is characteristic of cancer.

Culture induced Polyploidy

An example of culture induced polyploidy. The image on the left shows two normal diploid wildtype nuclei (outline of the nucleus in green), each containing 2 copies of chromosome 11 (chromosomes in red). The right image shows 4 copies of chromosome 11 in a single nucleus, likely from instability of the genome due to sub-culturing. Cells depicted are primary cultures of mouse embryonic fibroblasts, grown in the same culture dish.

For this reason, to understand how the genome and epigenome behave in normal conditions and to study diseases that afflict humans and animals, using established immortalized cell lines can lead to confounding or irreproducible results. When using primary cells and limiting the time we study them in culture, we can eliminate the issue of unstable cell lines. In this case, the cells more closely resemble the cells in the body, genetically and in behavior, and they provide more realistic and applicable data. Primary cells are not immune to increases of ploidy or culture induced instability and metabolic changes. After time in culture, often-times even after only weeks, they also show signs of diverging from their original characteristics, similar to immortalized cell lines. Limiting the time in culture reduces the effects of tissue culture on the identity of primary cells, but requires a researcher to return to the tissue source once the population shows characteristics of population drift and for each new line or experiment. While primary cells that replace immortalized lines are more tedious to rely on because you must continue to return to an animal, they still can provide the opportunity for massive expansion of cells, which reduces the number of animals in research and allows for researchers to do basic science studies quickly, efficiently and effectively without compromising validity.

Remember where cells come from

Regardless of immortalized or not, cells used in tissue culture come from a donor. In the case of humans, they are often procured during biopsies or are excess material during surgeries. The amount of material from humans is small and limited. The use of animals expands the capacity to test and fully understand treatments that impact human and animal health in a way that would be impossible using products from human biopsy. While many primary cultures can be grown for a few weeks and some can be immortalized, there are many cell types such as neural tissues that are terminally differentiated (i.e., cannot replicate themselves in a dish), and must be taken from a donor to do experiments outside the body. This is an important point to note as there are no models of cell culture, immortalized or not, that will be able to eliminate animals when studying these body systems.

Other cell systems, such as induced pluripotent stem cells (iPSCs), have been suggested as an alternative source to using animals in research because they can potentially produce all cell types.iPSCs can be created from cells non-invasively obtained from a human or animal model, and then coerced to grow into cell types that are typically harvested from animals for studies. While iPSCs can potentially reduce the numbers of animals in research, iPSC populations are also plagued with issues of identity.  It has been reported that they often retain some signatures and features of their originating tissue types. Cells and tissues directly from a donor is the only way to be sure of cellular identity and ensure the most robust and relevant results.


Tissue culture is a powerful system that has led to significant scientific advances that have positively impacted human health and reduces the number of animals in research. The goals of using basic models such as cells in research is to create and discover strong, relevant and reproducible data that can eventually be used to diagnose and treat diseases that impact both humans and animals. By ensuring the quality of our reagents in doing even the most basic research, we ensure quality data that benefits the scientific and general community at large. Removing animals in research limits the ability for researchers to discover new and effective therapies that impact human health.

Teresa Romeo Luperchio

Spain publishes animal research statistics for 2014

In the last two weeks we have provided animal research statistics for Switzerland and Finland. Now Spain joins our statistical analysis as it released its 2014 statistics for the number of animal research procedures (for research and testing). Overall, 808,827 animal procedures were conducted in 2014, a 12% fall from 2013, but also the first statistical release under the new EU guidelines. The number of animals is likely to be very similar (with only 14,552 procedures on animals which had previously been used in research).

Animal Research in Spain in 2014. Click to Enlarge

Animal Research in Spain in 2014. Click to Enlarge

Most species saw a large drop in numbers, with the main exceptions being fish and birds which rose sharply. Zebrafish have been increasingly used in research all over the world due to their fast reproduction cycle and transparent embryos. Cephalalopoda (e.g. jellyfish) were included in 2014 for the first time.

Most research was on mice, rats, birds and fish

Most research was on mice, rats, birds and fish

Mice, rats, fish and birds accounted for 93% of research animals in Spain, roughly the same proportion as other EU countries. Dogs, cats and primates account for less than 0.2% of all research procedures in Spain in 2014; again, similar to other EU countries.

The new EU guidelines also require retrospective reporting of animal suffering in experiments. Of the 808,827 procedures, 53% were subthreshold or mild, 27% were mild, 8% were severe, and 12% non-recovery (where the animal is fully anaesthetised before surgery and then never woken up). For more information see Table 3 of the Government statistical release (in Spanish).

Animal research numbers have fallen in Spain since 2009

Animal research numbers have fallen in Spain since 2009

The number of animals used in testing and research since 2009 has fallen from a little over 1.4 million animals to just over 800,000 in 2014. These older statistics are available on the website of the Ministry for Agriculture.

Dangerous and Irresponsible: PETA attempts to intimidate NIH Director Francis Collins

PETA campaigns are rarely benign, from misrepresenting science to glorifying violence against women and scientists. Their latest campaign, reported yesterday by Science Insider, is no different. PETA have sent hundreds of letters to the neighbors of both NIH Director, Francis Collins, and world renowned researcher, Dr. Stephen J. Suomi, as part of a long running campaign against Dr Suomi’s NIH-funded research into the behavioral and biological development of non-human primates.


These letters, condemning Dr Suomi’s research, are full of inaccuracies. His work has been defended by several large scientific organisations. When PETA first launched their campaign against Dr Suomi earlier this year the American Psychological Association wrote:

We believe that the facts do not support PETA’s public statements about this research. Over the past three decades, Dr. Suomi and his collaborators have made significant contributions to the understanding of human and nonhuman animal health and behavior. Dr. Suomi’s work has been critical in understanding how the interactions between genes and the physical and social environments affect individual development, which in turn has enhanced our understanding of and treatments for mental illnesses such as depression, addiction, and autism.

The American Society of Primatologists statement noted:

The American Society of Primatologists supports research on non-human primates that is carefully designed and employs rigorous research protocols. Dr. Suomi’s research and consistent funding by the NIH attests to his adherence to prescribed protocols and regulations.

While the NIH’s own very robust statement, which it issued this January following a review of Dr Suomi’s research programme sparked by PETA’s complaint, concluded that it:

has achieved world class, enduring contributions to our understanding of the developmental, genetic, and environmental origins of risk and vulnerability in early life,” and “could be a truly remarkable point of departure for a unified theory describing the biological embedding of early social conditions and their developmental consequences.

Yet the letters are more than just another incident of misrepresented research. They are irresponsible and dangerous. By posting Dr Collins’ and Dr Suomi’s addresses, alongside a misleading picture of the NIH research, they have potentially given animal rights extremists the necessary information to carry out extremist actions. We have seen similar address releases in past result in terrifying home demonstrations as well as acts of vandalism and worse.

PETA have been involved in animal rights activism for decades and should be well aware of the potential risks – this whole strategy comes down to the harassment of scientists and their families to scare them from conducting important biomedical research. Indeed, a statement by PETA’s Alka Chandna to Science Insider that “If I had a neighbor who was doing this, I would want to know about it…It’s similar to having a sexual predator in your neighborhood.” suggests that harassment and intimidation is exactly what PETA have in mind. It becomes all the more sinister when you remember PETA’s record in glorifying and encouraging violence, and supporting violent animal rights extremists.

As Speaking of Research member Prof. David Jentsch noted in his comments to Science Insider:

PETA’s arguments about the value of the science fails on its merits, so they resort to these deeply personal attacks. We’re seeing more of these types of tactics across the animal rights movement. They’re essentially saying to scientists, ‘We know where you live.’

Is this what PETA want?

Is this what PETA want?

So will PETA’s approach succeed? The fact is that very few of the scientists targeted by PETA or other animal rights extremists have ever given up their research, and for some – and David Jentsch himself is a good example – being targeted has prompted them to become vocal advocates for animal research, which one suspects is not the result the animal rights groups intended.

It’s also worth noting that on previous occasions where animal rights extremists have targeted the neighbors of scientists on this way, they have responded with displays of support for the scientist and their family. We expect that this time will be no different (especially as PETA are hardly the most trusted of organizations).

It seems unlikely that Collins will be cowed by PETA’s tactics, after all as a researcher who has spoken up in favour of human embryonic stem cell research when it was under threat, and who as NIH Director frequently has to deal the demands of wilfully ignorant and frequently obnoxious politicians, he has probably developed quite a thick skin.

Indeed, during a discussion of the NIH’s flagship BRAIN Initiative at the Society for Neuroscience meeting last month Collins was asked directly about non-human primate research, and responded by acknowledging the need for non-human primate research in the BRAIN Initiative and the need for continued outreach to the public on the importance of animals in advancing biomedical research.

Some commentators have suggested a connection between the PETA campaign and yesterday’s announcement by the NIH that it has decided to retire all its remaining research chimpanzees. While some may be tempted to think this, it seems unlikely to be the case. As several researchers noted in the Nature News article reporting the NIH decision, there are still some question marks over the NIH’s decision. In particular how the NIH will ensure that the conditions in which the chimps are retired to meet the high welfare standards of current NIH facilities, and how it will affect valuable non-invasive neurocognitive, genomic, and behavioural research that most sanctuaries do not have the facilities to support, is still far from clear.

However, it is also readily apparent that this decision was driven by the fast decreasing use of chimps in biomedical research over the past 5 years, and in particular the US Fish and Wildlife Service’s recent decision to give research chimps endangered species protection, which prevents any invasive biomedical research that doesn’t benefit wild chimpanzee populations, a ruling that arguably made supporting even a small research chimp colony unviable for the NIH. PETA’s most recent harassment campaign is unlikely to have had much – if any – affect on the NIH’s decision making.

Francis Collins

The situation is very different for other non-human primate species, which continue to play a crucial role in many areas of NIH-funded research. Francis Collins himself noted this  in the official statement on the decision to no longer support chimpanzee research, when he concluded by writing:

These decisions are specific to chimpanzees. Research with other non-human primates will continue to be valued, supported, and conducted by the NIH.

Speaking of Research applauds Francis Collins’ continued support for non-human primate research, and his refusal to concede to PETA’s attempts to bully him into a decision that would do serious damage to the NIH’s status a world leader in biomedical research, and indeed to progress against a wide range of devastating diseases.

Speaking of Research condemns the efforts of PETA to stand in the way of medical research that can change lives. Almost 20% of the US suffered from mental health illnesses in the past year. The research community is morally obligated to do what it can to help understand and treat these devastating conditions. We also condemn a PETA tactic that risks exposing researchers to acts of violent extremism that PETA claim not to support.

We hope Francis Collins and the NIH will not bow to pressure, but will continue to stand up in defense of the research community and the importance of biomedical research.

Speaking of Research

Preventing neuronal death: the future of stroke therapy

In neurological research the importance of neuronal death is well known, as are its implications for the normal functions of your brain. Many serious neurological conditions, such as stroke, epilepsy, traumatic brain injuries, and degenerative diseases like Parkinson’s and Huntington’s Chorea, are a direct consequence of this type of neuronal death, which determines the clinical manifestation of the illness and, as a consequence, the prognosis for the patient.

For example, in stroke an ischemic attack (loss of blood flow), even if it is localized, can initiate the neuronal death program, due to excessive stimulation of neurons (nerve cells) by molecules known as neutotransmitters, the so-called excitotoxic triggers. This in turn leads to a worse clinical development and physical symptoms like palsies, sensory alterations, cognitive impairments and more.

One of the principal triggers of this event is the activation of the N-methyl-D-aspartate receptors on neurons, which are sensitive to glutamic acid, one of the most important excitatory neurotransmitter of the brain.

When these receptors are over activated due to the release of an enormous amount of glutamic acid as a consequence of the lack of oxygen in the affected area of the brain, this triggers a flow of Ca++ ions into the neuron, which activates many enzymes inside the nerve cell that directly damage the internal structure and ultimately cause the cells to die in a process known as apoptosis. (1)

It’s clear at this point how important it is to stop this process in order to prevent progressive damage in areas that are not directly affected by the original ischemic event.

What’s still not so clear is the precise molecular pathway from the liberation of glutamic acid to the neuronal death, but experimental evidence suggests that a membrane protein called JNK (c-Jun-N-terminal-kinase) has an important role in this activation. (2)

Although it has been shown that by blocking JNK it’s possible to reduce infarct size (the size of the damaged area of brain tissue) and neuronal death in an in vivo animal model of cerebral ischemia, the same studies have also shown serious side effects, as JNK has several important physiological functions in the body. As a result researchers have sought to identify means of blocking the role of JNK in ischemia–induced neuronal cell death without blocking its other functions.

It has been demonstrated that JNK is activated by two upstream molecules, called respectively MKK4 and MKK7, that respond to specific stress situations and represent a key bottleneck, and that in particular MKK7 shows an important role as mediator in the activation of JNK as ain response to cerebral ischemia.

Due to this observation, a team of neuroscience Italian researchers developed a specific MKK7 inhibitor peptide, called GADD45ß-I, to study its possible effects in vitro and in vivo in rodent models.(3)

This molecule showed an interesting neuroprotective effect in vitro and no toxicity itself on neurons, suggesting its application for in vivo treatments; during the in vivo (animal research) phase, the molecule was tested on two different rodent models which demonstrated that this peptide could reduce the infarct area of 43% after 24h, if administrated before the induced stroke. Very importantly this neuroprotective effect was still maintained when GADD45ß-I was administered 6h after the initial ischemic damage, which is critical as analysis of earlier failed candidate stroke therapies have stressed that potential therapies must be able to prevent damage when administered several hours after stroke onset (when treating stroke prompt diagnosis and treatment is vital). These protective effects are maintained for at least a week and show that the molecule does not merely delay apoptosis but actively blocks the process.

To prevent ischemic damage in the immediate aftermath of stroke onset, we can use rt-PA (recombinant tissue plasminogen activator) to promote the breakdown of a possible obstruction inside a cerebral artery and prevent a progressive stroke; and this is an important approach that has saved many lives in the last 20 years.  However, this therapy has side effects such as bleeding, and it can be not use in some specific but common conditions, for example in patients who use anticoagulant as Warfarin for atrial fibrillation, and is only effective if administered within 3,5-4,5 hours of stroke onset (although it may be effective later in some cases where the damaged area is clearly demarcated in brain imaging by MRI or CT scan).

All other therapies that are available to neurologists are only supporting therapy for the blood pressure, active anticoagulation and respiratory support where it is necessary.

GADD45ß-I offers the possibility that we could protect a patient under ischemic insult even when we could not use the thrombolytic therapy with rt-PA, and we could also protect them from future insults by regular administration of this drug, which may be especially useful for multimorbidity patient, those who suffer from two or more chronic health conditions.

This could also lead to reduce post-stroke consequences, to improve the prognosis for these persons and to a reduced need for rehabilitative therapies as physiotherapy, speech therapy and exercise therapy

If these promising early results are confirmed in clinical trials, this therapy could be one of the most important discoveries in the field of neurology in the recent years and could radically change our approach on stroke, allowing us to switch from a supportive therapy to a preventative therapy.

If we think that in 2010 circa 17 million stroke occurred worldwide, and that every 6 seconds a person somewhere suffers a stroke, we can also imagine the potential impact of this therapy.

  1. Lipton SA. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov 2006; 5: 160–170.
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