Tag Archives: Speaking of Your Research

SYR: How sheep can help us understand why girls are reaching puberty at younger ages

michelle-bedenbaughThis guest post is the second written by Michelle Bedenbaugh, a Ph.D. student in the Physiology and Pharmacology Department at West Virginia University. Check out her first post on the benefits of using large animal models to study reproduction. It is also part of our Speaking of Your Research series of posts where scientists discuss their own research. In this post, Michelle discusses some of the cells and signaling pathways that are important for controlling the timing of puberty and how the use of sheep as a model is beneficial for this type of research. If you would be willing to write a guest article for Speaking of Research, please contact us here.

For those of you who have been watching the news in the United States over the past 5-10 years, you have probably heard a few discussions about the fact that girls are reaching puberty at younger ages.  In the 1980s, girls normally reached puberty around the age of 13.  In 2010, the average age of girls reaching puberty had dropped to 11 and has since continued to decline.  Reaching puberty at earlier ages is associated with several adverse health outcomes, including polycystic ovary syndrome (PCOS), metabolic syndrome, obesity, osteoporosis, several reproductive cancers and psychosocial distress.  The public and researchers have pointed fingers at several potential culprits, including an unhealthy diet, chemicals that disrupt the body’s normal hormonal environment, and an individual’s genetic predisposition to disease.  In reality, a combination of factors have probably led to the decrease in the age at which girls reach puberty, but I don’t want get into a discussion about these factors today.  Instead, I want to talk about some of the signaling molecules in the body that these factors may be influencing to affect the initiation of puberty.

As with many processes in the human body, the brain plays a critical role in the control of reproduction and the timing of puberty.  Within a specific area of the brain called the hypothalamus, several populations of neurons (specialized cells in the brain) exist that control reproduction.  The activity of these neurons is influenced by various factors that are communicated from other parts of the body and outside environment to the brain, including nutritional status, concentrations of sex steroids (like estrogen and testosterone), genetics, and many other external factors.  All of these factors tell the brain when an individual has obtained the qualities necessary to successfully reproduce and therefore undergo pubertal maturation.  Gonadotropin-releasing hormone (GnRH) neurons found in the hypothalamus are the final step in this chain of communication and are essential for the initiation of puberty.

A GnRH neuron present in the hypothalamus.

A GnRH neuron present in the hypothalamus.

Most of these nutritional, hormonal, genetic and environmental signals are not directly communicated to GnRH neurons.  Instead, they are conveyed through other types of neurons that then relay this information to GnRH neurons which either stimulates or inhibits the release of GnRH.  Because GnRH is a signaling molecule that ultimately stimulates the maturation of male (sperm) and female (egg) gametes, stimulating GnRH in turn stimulates reproductive processes while inhibiting GnRH inhibits reproductive processes.  The perfect balance of stimulatory and inhibitory inputs is needed for GnRH to be released and for puberty to be initiated.  Consequently, if stimulatory inputs signal to increase GnRH prematurely, puberty will occur earlier, which may result in several of the health concerns that were mentioned above later in life, including reproductive cancers and psychosocial distress.  In contrast, if inhibitory inputs block the release of GnRH, puberty will never occur and result in infertility.

My research looks at some of these stimulatory and inhibitory inputs and how they communicate with each other, as well as with GnRH neurons.  Two of the stimulatory signaling molecules that we research are kisspeptin and neurokinin B (funny names, I know).  We also study dynorphin (another funny name), a molecule that inhibits GnRH release.  These three molecules can all individually affect GnRH release and therefore reproduction.  However, the really cool thing about these three molecules are that they are actually present together in a special type of neuron that is only found in one small and highly specific area of the hypothalamus.  Because these neurons contain kisspeptin, neurokinin B, and dynorphin, they are often called KNDy (pronounced “candy”) neurons.  The fact that kisspeptin, neurokinin B, and dynorphin are all present in these KNDy neurons together allows for them to communicate directly and affect each other’s release.  This communication then ultimately affects the release of GnRH.  Before puberty, inhibitory inputs, like dynorphin, dominate and don’t allow for adequate amounts of GnRH to be released to stimulate reproduction.  As an individual matures, stimulatory inputs, like kisspeptin and neurokinin B, begin to outweigh inhibitory inputs, and GnRH can be released in adequate amounts to support reproductive processes.  Below is a figure that summarizes how we think all of this works within the body.  However, there is still a lot that we don’t know about how kisspeptin, neurokinin B and dynorphin interact with each other that is waiting to be discovered!

Hypothesized model for the initiation of puberty. (1) Internal and external factors are communicated to the body. (2) Next, these factors are relayed through various signaling pathways to stimulatory and inhibitory molecules present in neurons located in the hypothalamus. (3) Stimulatory and inhibitory molecules travel to GnRH neurons and affect the release of GnRH. (4) GnRH stimulates reproductive processes that are critical for the initiation of puberty. (5) Once all of the proper conditions are met, reproductive maturity is attained.

Hypothesized model for the initiation of puberty. (1) Internal and external factors are communicated to the body. (2) Next, these factors are relayed through various signaling pathways to stimulatory and inhibitory molecules present in neurons located in the hypothalamus. (3) Stimulatory and inhibitory molecules travel to GnRH neurons and affect the release of GnRH. (4) GnRH stimulates reproductive processes that are critical for the initiation of puberty. (5) Once all of the proper conditions are met, reproductive maturity is attained.

To complete all of these studies, we use sheep as our model.  I know what some of you are thinking.  “How in the world would sheep serve as a good model for how puberty is initiated in humans?  I don’t think I am similar to a sheep at all!”  In fact, sheep are actually an excellent model in which to do this research.  The signaling pathways that affect the release of GnRH in sheep are very similar to the signaling pathways in humans, and in some cases, are even more similar to the human pathways than the pathways present in mice or rats.  In humans and sheep, neurokinin B has only been found to stimulate GnRH release.  However, in rodents, there have been reports of neurokinin B both stimulating and inhibiting GnRH release.  Since neurokinin B is one of the main signaling molecules that we study, using sheep instead of mice or rats is more beneficial for modeling what is occurring in humans.

sheep-in-reproduction-research

Because we have to collect several blood samples from the sheep in order to measure hormone concentrations, having an animal with a larger blood volume is also advantageous.  Several hormones in the body (including GnRH) are released in a pulsatile manner, meaning one minute GnRH concentrations are high and a few minutes later they are low.  Therefore, in order to appropriately measure GnRH, blood samples need to be taken every 10-12 minutes for several hours.  This is not feasible in rodents.  If you took blood samples as frequently in rodents as is possible in sheep, you would risk killing the animal.  Some scientists who use rodents as their research model attempt to get around this issue by taking blood samples less frequently.  However, this means their hormone measurements are less accurate.

These are just a few of the many reasons why we conduct our research in sheep (to learn more about the advantages of using sheep and other large animal models to conduct research involving reproduction, see my previous post).

While most people (including myself) do not look back fondly on our awkward pubertal years, I absolutely love studying the signaling pathways the body uses to determine when it is ready to successfully reproduce.  We have discovered quite a bit over the past few decades concerning how different internal and external factors affect pubertal maturation, but there are still so many unknowns left to be determined.  I look forward to hopefully discovering some of these unknowns and improving our understanding of how puberty is initiated in both humans and livestock species.

Michelle Bedenbaugh

SYR: The case for using large animal models to study reproduction

michelle-bedenbaughThis guest post is written by Michelle Bedenbaugh, a Ph.D. student in the Physiology and Pharmacology Department at West Virginia University. It is part of our Speaking of Your Research series of posts where scientists discuss their own research. Michelle’s research involves examining the brain’s role in the initiation of puberty.  In this post, Michelle discusses the benefits of using large animal models to study reproduction.  If you would be willing to write a guest article for Speaking of Research, please contact us here.

With the increasing pressure to publish papers and the decreasing amount of funds made available to conduct experiments, it has become more difficult for researchers to survive and thrive in an academic setting (see here, here, and here). Scientists have had to adapt, and in many situations, this has led to a significant amount of research that relies heavily on small animal models, including rodents and invertebrates.  In addition to being less expensive than large animal models (sheep, pigs, cows, horses, etc.) there are also more genetic tools and techniques available to use in small animal models.  For example, transgenic mice, where certain genes can be either deleted or overexpressed, are used commonly by researchers worldwide.  Other cutting edge techniques, like optogenetics, where light can be used to control the activity of cells in the brain, are also being used on a more routine basis in rodent models and currently don’t exist in large animal models.

Optogenetics involved using light to control genetically modified cells inside the body

Optogenetics involved using light to turn off or on cells in the brain

While it is most likely easier, cheaper, and faster to conduct experiments using small animal models, in certain situations they are not always the most comparable to humans.  When modeling certain diseases or understanding certain physiological processes, larger animals, like sheep, pigs, and cows, provide a better model for scientists.  This post aims to look at some areas where larger mammals can provide important knowledge or understanding.

A few of the more obvious benefits to using large animal models when compared to small animal models are that large animals are more analogous to humans in regards to body size, organ size, and lifespan.  In addition to these similarities, animals like sheep, cows, and pigs are much less inbred when compared to rodents.  Some would argue that it is advantageous to use animals that are highly inbred because this decreases the amount of variability in an experiment.  However, each human has a unique genetic makeup, and sometimes solutions for problems in inbred rodents cannot be translated for use in humans.  Therefore, in these instances, it is probably more beneficial to use a less inbred large animal model.  Most large animal models also have the added benefit of being an economically important species.  The majority of researchers who use large animal models are attempting to find solutions to health issues that are present in humans.  However, successful experiments in large animal models have the ability to affect both human and animal health.  For example, if a researcher made an important discovery about the way food intake is controlled in cows, it would have the possibility of improving human health, as well as increasing profitability for cattle producers.  Because cows are very similar to sheep, it may also benefit sheep production as well.  Rodents are not an economically important species that provides food, fiber, or other essential products used by the human population.  Consequently, discoveries made in rodents and other small animal models may only benefit humans if the results are translatable.

My particular research focuses on furthering our understanding of how puberty is initiated in girls, and we use sheep as our animal model.  I won’t get into the specific benefits of using sheep to conduct puberty research today because I will discuss this more in my next post.  However, I did want to touch briefly on some of the advantages of using large animals to perform research used to study reproduction in a broader sense.

The brain plays an essential role in controlling reproductive processes.  The brain structure of large animals is more closely related to humans than small animals because large species have a sulcated cortex (meaning the surface of the brain is wrinkly) as opposed to small animal species which have a smooth cortex.

Comparison between mouse (smooth cortex) and human (sulcated cortex) brain. [Credit: Elizabeth Atkinson, Washington University in St. Louis]

Comparison between mouse (smooth cortex) and human (sulcated cortex) brain. [Credit: Elizabeth Atkinson, Washington University in St. Louis]

Sheep also have the advantage of their brain and the cellular pathways present within it being similarly organized to what is observed in non-human primates.  Hormones serve a major role in relaying information from the brain to reproductive organs and vice versa.  The actions of several hormones that aid in controlling reproduction in female sheep (like estrogen and progesterone) parallel the actions of these hormones in humans.  Older sheep also have a similar response to estrogen replacement therapy when compared to post-menopausal women.  The development and function of several structures on the ovary of sheep is also similar to that which is observed in women.  These structures have a major influence on the reproductive cycle and are critical for the maturation of female gametes (sometimes referred to as eggs).  Assisted reproductive technologies, many of which are used for in vitro fertilization (IVF) protocols in women who are having trouble conceiving, have been adapted from procedures used in livestock species.  For example, artificial insemination, where semen is collected from a male and usually frozen so that it can be used to inseminate a female at a later time, is commonly used in cows, sheep, horses and pigs and is similar to procedures conducted in humans.

Credit: Livestock Breeding Services - http://www.livestockbreedingservices.com.au/images/servicesai.jpg

A laparoscopic procedure is used to artificially inseminate sheep

 

Embryo transfer, where embryos from one female are placed into the uterus of another female, are also used in livestock species and humans.  In addition, sheep are also an excellent animal model for studying pregnancy.  Sheep are used often to examine how stress, maternal nutrition, and exposure to excess hormones or toxins affect the development of a fetus.

These are just a few examples that display reproductive processes occurring in many large animal species are easily relatable to those same processes which also occur in humans.  I only touched on a few species today, but there are many more animal models that are underused in research and would serve as great models for humans.  In addition, I only discussed some of the ways these animals can be used to study reproduction when in fact they can be used to mimic many other biological processes that occur in humans.  Depending on the subject matter being researched, the use of some animal models is more appropriate than others.  Regardless of cost or time, researchers should always consider which animal model may be the most appropriate for their experiments.  I believe conducting research in a variety of species as opposed to just one or two species will always be more advantageous and will aid us in solving health issues in humans more quickly.

Michelle Bedenbaugh

Reigniting My Fire for Animal Research

lisa-headshotThis guest post is written by Lisa Stanislawczyk, a Veterinary Scientist at a pharmaceutical company. She plays a key role in ensuring the standards of animal care are always improving at her institution. Having been introduced to Speaking of Research through a committee member, Lisa kindly agreed to share her experiences. In this post, Lisa explains her passion for innovation in the field of animal welfare and her experiences, positive and negative, in delivering animal care at numerous institutions in the US. If you would like to write for Speaking of Research please contact us here.

When I started out after college working as an animal care technician at a contract research organization (CRO), I never thought I would want to perform the procedures I saw being done to the animals. I didn’t want to make them uncomfortable or scared. I loved animals and had always wanted to be a vet (like so many others in the field of animal research). While working at the CRO I began to see the care and attention that the technicians took in performing these procedures and how careful they were to make the animals comfortable and at ease. I realized they too cared for the animals as much as I did and we all wanted nothing more than to take the best possible care of these animals.

lisa-veterinary-scientist

Later, after 15 years in the animal research field, I found myself looking for a new role. I was always proud of what I did and left work each day with a sense of accomplishment. However, I was finding it difficult to find work, a common problem for so many in the world we live in today.

I realized that in order to stay in the field and get a good job I was going to have to move outside of my comfort zone, away from everything and everyone familiar. It was scary, but I moved to another part of the country, away from my family and all my friends, to pursue a new job. I was anxious and felt isolated. I came to the harsh realization that not everyone holds themselves or others to the same standards I had been taught, or was accustomed to. This realization almost made me stop doing the work that I had grown to enjoy and get a huge sense of accomplishment from.

I didn’t quite know how to deal with what I perceived as poor animal welfare in my new job. This feeling was not from the technicians doing the work, they were doing the best they knew how with what they were taught. There just seemed to be a lack of knowledge of the regulations which one should have working in a vivarium. It was the management that needed to be held accountable. I spoke with the Chair of the Institutional Animal Care and Use Committee (IACUC) in order get a better understanding of what I felt was just not good research. After our conversation, I still felt there was a lack of accountability from the IACUC Committee. I was at a loss and felt drained and hopeless because there continued to be mistakes and mis-steps which could have been avoided.

I spoke with the veterinarian and was told, “I didn’t understand the field that I was in and I was too soft”. I didn’t believe that. I believed I was there to be an advocate for the animals in my charge. I was told there was not a “magic ball” to know outcomes of certain studies, I knew there were humane endpoints that should be followed. I did my best to make things better. We began a better training program so the people performing the procedures had a better understanding of the Animal Welfare Act and the Guide. We updated procedures and SOPs (standard operating procedures.)

It took its toll. I found myself working long hours to make sure the studies I was to oversee were executed correctly and at the same time educating the personnel working with me. I was exhausted and overworked. So were my technicians. I began to become so emotional about some of the things I was seeing that I would spend what free time I had at home, crying myself to sleep. Just thinking about it now, makes my eyes water. We all began seeing things that we could not bear any longer and more people began to have concerns and fill out whistleblower forms. It was heartbreaking and I just didn’t feel like I could do it any longer. Then the day came, I was laid off. It was a blessing!

Thankfully my negative experience is not common and the facility I worked at was taken over by another company. I have heard that they are still overworked (many of us can sympathize) but that things regarding the animals have definitely improved.

Image of macaques for illustrative purposes.  Image courtesy of: Understanding Animal Research

Image of macaques for illustrative purposes.
Image courtesy of: Understanding Animal Research

I moved back to my family and friends. I needed the moral support from them. Still, I didn’t want to go back to it. I was burnt out. I worked at a home improvement contracting office fielding phone calls and organizing the office. It just wasn’t what I could see myself doing long term. I needed a challenge. I missed the animals. I held guilt for not doing more for them even though I still don’t know what more I could have done at the time.

A previous boss of mine who happened to be a veterinarian reached out to me about a job. Again it was a big pharmaceutical company. I was skeptical but I needed to give it one last chance and it was only a temporary position. It was great to experience the investigators working with the animal care technicians to communicate how the animals did while on study and this empowered everyone to know exactly what was going on with each and every animal on a daily basis. The communication between all the investigators, technicians and veterinary staff truly improved the welfare of the animals. The veterinary staff really cared for the animals and the animal care technicians knew every animal’s quirks, likes, and dislikes. Everyone would make sure the animals that were on study got some extra favorites whether it be food enrichment, human contact, or toys. The people there renewed my faith. I could see the ethical behaviors and integrity of each and every person there. It gave me the desire to stay in the industry. This was what I was accustomed to. I felt like I had a “place” again.

Once the temporary position was over, I moved to another company also working with the veterinary technical staff. There I was allowed to attend ILAM (Institute for Laboratory Animal Management). It is a 2 year program and the information, relationships, and contacts you come away with are immeasurable. I shared my story with others I met there (from all over the world) and I realized we all shared in the desire to deeply care for the animals. We go to work every day to make sure everyone does their best to take care of every need of all the animals in their charge. For some time, I have passively been in the industry, not really wanting to be a part of all the external committees and public outreach opportunities available. After attending ILAM, all that changed. Experiencing the love and desire to improve and do better within our industry and making connections and friendships with people with this common thread has re-ignited my passion for the industry. My company encourages people to innovate and strive for better animal welfare. I am so proud to be a part of a program that has refined techniques performed on multiple species to make it easier for both the animals and the technicians. This is how it should be. This is the industry we are in.  Change is key. Once again I am so proud of what I do and the program I am a part of everyday. I flourish when someone asks me what I do, instead of talking vaguely so they won’t understand or want to hear more about it. I am happy to explain why what we do is so important and necessary.

We make miracles happen and improve the lives of humans and animals every day! This is what we do for a living! This is why people and their pets are living longer, happier lives. This is the reason I am proud to be in animal research. I urge my fellow technicians to speak out, be proud, and get involved explaining what you do and why you do it!

Lisa Stanislawczyk

Guest Post: How do birds see the world?

Professor Aaron Blaisdell

Professor Aaron Blaisdell

Today’s guest post is from Professor Aaron Blaisdell and graduate student Julia Schroeder in the Department of Psychology at the University of California Los Angeles. Prof. Blaisdell’s area of research is animal learning and comparative cognition. He received his Ph.D. in Experimental Psychology and Behavioral Neuroscience at Binghamton University in 1999. Julia Schroeder is a graduate student in the Psychology Department at UCLA. This project is the basis of her dissertation research which she hopes to complete by May, 2016. She received a BS in Psychology at Whitman College where she compared rational decision processes in pigeons and humans. You can support their research through their crowdfunding campaign.

How do birds see the world?

How do birds fly around objects without crashing into them? Their object perception must be similar to ours, despite having a dramatically different brain and separate evolutionary history. Birds and mammals share a last common ancestor roughly 275 million years ago! Nevertheless, most birds and mammals, especially primates, rely on sight to navigate their world, find mates, avoid foes and predators, seek food and water, and care for their young.

Vision, both sensation and perception, has been one of the top areas of research in experimental psychology and neuroscience, going back to the visual psychophysics scientists of 19th century Germany. Visual perception and cognition is currently a dominant area of study in cognitive neuroscience. Much of what we’ve learned about human vision actually comes from research in nonhuman primates, especially the macaque monkey. This makes sense, since the human visual system is like that of just monkeys and apes.

One picture that has emerged is that, when we open our eyes, we see a world populated with objects. Our object-centered view of the world is also shared with the rest of the primates.

Pigeon in a test of comparative cognition.

Pigeon in a test of comparative cognition.

What about birds? They also navigate their world using vision. Flying puts high demands on the ability to rapidly detect and process visual information. The last thing a birds wants to do is to fly into an object because it couldn’t see it in time! This suggests that bird brains also engage in visual computational processes similar to that of the primate. But we currently don’t know much about how they do so. We want to know if birds solve the incredibly complex computational process of object perception the same way that primates do.

In our next research project, we plan to test whether bird brains handle object perception the same way that the human brain does. Pigeons will play a video game where they have to rapidly peck objects as they appear on a computer touchscreen located in a Skinner box. As soon as the object is pecked, a small food reward will be delivered to the pigeon from a hopper located below the screen. The faster the pigeons peck at the object, the sooner they get fed. The speed of their responses will tell us how the birds see the objects.

Specifically, we will show the pigeons four different objects, A, B, C, and D, one at a time (actual objects are different colored geometric shapes). The objects will appear in one of four locations on the screen (see a demo here). The objects will appear in a specific order that repeats. The locations in which the objects appear will also repeat. This will allow us to test how pigeons bind features into objects. If pigeons integrate features as humans and other primates have been shown to do, then they should learn that specific objects always appear in a specific location. This is called object-place learning. The object’s identity and location become bound as shared properties of a unique, coherent object. After the pigeons learn to play the game, we can then test for object-place learning by presenting special non-reinforced probe test trials. On these test trials, we will change the order of some of the objects, locations, or both.

Stimuli in learning sequence.

Stimuli in learning sequence.

Changing only the object or location should break the object-place association. Changing both together, however, preserves the object-place association, even though the sequence order has changed. If, like humans, pigeons bind object and location information together into perceptual memory, then changing only the object or the location order should be more disruptive than changing both!

What is life like for a laboratory pigeon?

Like all other vertebrates in research, housing and laboratory conditions for pigeons are well regulated. All research protocols go through the same stringent processes of review by the University’s IACUC, and the health and welfare of each pigeon is overseen by the Division of Laboratory Animal veterinarian staff. They receive the best possible care. In a typical pigeon laboratory, the pigeons are maintained as part of a flock in a vivarium. Birds are typically individually housed in large, comfortable cages, with constant access to water and grit. Feeding times are typically restricted to the afternoon after all subjects have completed their behavioral training. This keeps them motivated to work for food reinforcement in the operant chamber, and maintains subjects at a healthy weight similar to that of pigeons in the wild. Despite being housed in individual cages, the birds can see, hear, and smell the birds in the surrounding cages, thereby simulating a flock as it would be found in the wild. Unlike most mammals, or even parrots, pigeons do not engage in much touching or grooming of each other. Rather, pigeons in a flock hang out in close proximity to one another.

While some labs acquire wild-caught pigeons from their local area, we purchase ours from a vendor that breeds pigeons and other fowl for research purposes. Pigeons are a domesticated species, having lived in human environments since the dawn of agriculture in the Mediterranean region of Europe, Asia, and North Africa. Darwin was a known pigeon fancier, and bred pigeons as part of his own experimental investigations into the process of evolution by natural selection! To this day, there are pigeon fanciers and clubs around the world that breed pigeons for show, racing, and aerial acrobatics.

Why is this research significant?

The bird brain has a very different organization than the brains of humans and other mammals. Birds don’t have a visual cortex, for example. Thus, our research can lend insight into how a brain of such different structure solves the same computational process as does the mammalian brain.

Also, the brain of a pigeon is the size of your thumb! So how can birds, like pigeons, see objects the way that we do with far fewer neurons than in the human or monkey brain? Knowing how birds see the world can tell us a lot about what is unique about human vision, and what we share with other species.

Finally, we can also use our knowledge of how small bird brains efficiently create visual objects out of messy input to find new and powerful ways to build artificial visual systems for small mobile devices, such as drones and robots.

Many neuroscientists believe object perception is one of the most important and central processes of human vision. Nevertheless, object vision has been incredibly difficult to build into robot vision using AI approaches. Perhaps we can reveal the secrets to complex object perception in the small pigeon brain that will allow for breakthroughs in computer vision. This would be a huge win for human society!

Aaron Blaisdell and Julia Schroeder

SYR: Animal Tales

Today’s post in the Speaking of Your Research series of posts is by Ardon Shorr, a PhD student at Carnegie Mellon University. The post originally appeared on the Science Non Fiction blog and was reposted here with permission from the original author.

I want to share a personal perspective. I’ve lived my whole life caring for pets: cats, turtles, frogs, a praying mantis I found in the backyard. I wrote a rock opera about my sister’s hamster. In my professional life, I work with zebrafish for research. In short, I’m a vegetarian who believes strongly in the ethics of animal research. In this column I want to share stories of working with animals, its joys and frustrations, and pay some small tribute to the animal lives that make it possible for me to live so long, and in such extraordinary health. Working with animals can be emotionally hard. Sometimes it’s hard even to watch, the way surgery is hard to watch – a part of me knows the higher purpose, another part has a hard time ignoring a knife that cuts into a person’s chest. In the same way, in research, I see the kindred spark of life in every mouse I’ve ever held, and when they pass through that thin boundary between living and dead, I feel it. Here’s why I keep doing it:LotR Animal Models

We need animals because they’re simpler than humans

Animals are much simpler than we are in certain ways, and that’s an incredible advantage for research. The human body is convoluted – it’s a problem that’s too hard to untangle without solving an easier one first. If you wanted to learn English, you wouldn’t start with the triple puns of Shakespeare. If you wanted to understand how a car engine works, you wouldn’t start with a hybrid electric Prius. But you can learn a lot from an old Toyota engine, and from there, understand how the hybrid engine builds on that idea with new layers of complexity. Animals are that gateway into understanding the human body.

Here’s my favorite summary of criticism against animal research. I found it on a bumper sticker:

If animals are like us, animal research is cruel;
If animals are unlike us, animal research is useless.

It’s incredibly pithy, but it falls into that logical fallacy of the “false dilemma:” it’s either one thing or the other. Our world is more complicated. Because animals are simpler, things that cure cancer in a mouse aren’t guaranteed to work on us. But it’s precisely this simplicity that allows us to get a foothold. I was surprised to find out that we can even learn about mental health from animals. One classic experiment for mental health involves letting a mouse swim around in a pool and see how long it takes to give up. It’s hard for me to say what goes on in the brain of a mouse when that happens, but the drugs that make the mouse try longer are antidepressants in humans.

Animal research is more carefully controlled than any other use of animals

Working with animals does not mean we can do whatever we want. Every experiment must be approved by a committee consisting of scientists, vets, and a member of the community. The ethical review process considers the potential benefits of the research and questions whether they’re justified. At every decision, research decisions are driven by “The Three R’s:”

  • Replace animals with non-animal alternatives. Don’t use “higher” more aware animals like mice when we can use fish, don’t use fish when we can use fruit flies, don’t use flies when we can use yeast.
  • Reduce the number of animals used in experiments – use just the minimum we need to convince us that we’re looking at a real effect.
  • Refine scientific procedures to minimize suffering. For example, animals are euthanized with anesthetics so they don’t feel pain.

These measures are far beyond the standards of humanity’s much larger intersection with the animal world: the meat industry. To give a sense of the current state of affairs, a California law scheduled to take effect in 2015 proposed increasing the size of chicken cages to 200 square inches. This would allow chickens to turn around, and increase egg prices by about half a cent. This move is considered contentious, and representative Steve King amended Iowa’s farm bill to prevent that increase. Research mice are housed with enough room to play, form social groups, and are given enrichment to build nests. Mice must be euthanized with minimal pain using anesthetics. Chickens are not covered by the humane slaughter act.

Animal research is more ethical than the alternative

I would argue that animal research is more ethical than not doing animal research. But I want to be clear about some assumptions that this argument is making: human life is worth more than animal life. It is worth sacrificing the lives of animals to obtain information that would save and improve the lives of future humans, as well as animals, provided that we can minimize animal discomfort, and there is no better way to obtain that information.

Zebrafish postIt may not always be this way. Scientists are working towards the goal of replacing animals with computer simulations, or even lab-grown clusters of cells, called organs-on-chips. I’m personally looking forward to that day when we can grow artificial meat and I won’t be a vegetarian any more. But right now those systems don’t work well enough, and animals are our best hope. I can wait for my hamburger, but not for a chance at treating Alzheimer’s.

It’s no exaggeration that I am alive today thanks to animal research – I would have likely died at age five from an athsma attack that put me in the hospital, where I was treated with medicine that was developed with animals. Animal research helped double human life expectancy over the last century, and continues to bring us life-saving breakthroughs like the insulin that kept my grandfather alive for decades. For that, all I can be is grateful to research, and to the animals who made that research possible.

SYR: Why I Became a Biologist

The Speaking of Your Research (SYR) series gives scientists a voice to discuss their own research. We welcome posts by animal researchers explaining the science and motives behind what they do. Contact us for more details.

I am a biologist. At heart, I have been a biologist ever since I can remember. Life, in its many forms, fascinates me and, even though my interests aren’t confined to biology (or sciences, for that matter), it was always very clear to me that I would pursue the task of trying to understand life a little bit better.

As a kid, my most vivid memories go back to those Saturday mornings when I use to wake up at 7 a.m. to turn on the TV. First, there were cartoons to watch, but – at around 10 a.m. – the “Wildlife” shows would start: documentaries from the BBC Wildlife or from the National Geographic Channel. David Attenborough’s or Jacques Cousteau’s voices were my companions, as I flew above mountains or dived into the depths of the oceans, watching the most bizarre animals or the most fascinating flowers. There was a whole diversity of life around me that I was relentlessly drawn to. In my mind, I had this naïve idea that I wanted to be the next David Attenborough. I felt like it must be great just to grab a camera and follow animals around just to catch that perfect moment! But life got in the way… Not because I didn’t have opportunities to follow my dreams, but because the dream itself changed.

When I was eleven, one of my cousins checked into the hospital, quite suddenly, with what would later be diagnosed with measles encephalitis. During the early stages, I wasn’t completely aware of what was happening. Indeed, not even the doctors knew what was happening. When he was finally diagnosed, it was already too late for the interferon treatment. After years struggling with the disease, he fell into a coma and eventually could no longer struggle. Looking back, my change of field of interest started there. Suddenly, I started thinking about diseases, about what causes them and how incredibly little we know about it all. I started looking at microorganisms in a whole different way: I started realising I wanted to know more about what makes them tick and how to stop that ticking. So, by the 7th grade, I already had my mind settled on Biology.

The path since there has been one of seizing opportunities: I finished college (Biology with a minor in Evolution and Development) and I went on to take my MSc in Applied Microbiology. By the beginning of the second semester, I saw an ad for a trainee position studying the neurological sequelae of cerebral malaria. For me, it couldn’t get more interesting than that!

When I joined the lab, the first thing I had to do was read. Among all those articles, the first thing that struck me (having little knowledge of this before) was the numbers: according to the World Health Organization’s World Malaria Report 2013, there are around 200 million new cases of malaria and around 700 000 deaths per year, the majority of which (around 500 000) are children under the age of 5 years. I was shocked by these figures and, most importantly, by the ones related to the funding of anti-malarial research and preventive measures. And even though these numbers are finally starting to rise, they are still very much below what would be desirable.

Mosquitos Malaria animal research

Anopheles stephensi is the most commonly used mosquito vector for Plasmodium (the malaria parasite) in research labs

And so it was that, at 21 years of age, I did my first in vivo experiment, using rodent models of malaria. The moral challenge wasn’t easy and the decision wasn’t taken lightly. But, while I regard all living things as worthy of respect, I cannot disregard the good that comes from the use of animal models. I had to look at the ugly effects of what malaria does to people and especially to children. And I had to look at them in mice; in the mice I was handling, observing and taking care of every day. I had to look at all that and still make a decision. It is emotionally hard, but I truly think that using animal models is the only way we have of really studying this disease (and so many others!). The ethical decision that I make every day has become less difficult to make when I see it as the best chance we have of saving the lives at stake here: the millions infected every year, by a disease Jeffrey Sachs described as a disease of “poverty”.

The lesson I was taught on my very first day was: “the first thing to keep in mind is the animal’s distress. If it is distressed, not only will it be bad for the animal but it will also be bad for you, because your experiment will be jeopardized”. Four years have gone by, and I have passed it on to the students I’ve trained as well, because I truly believe this should be the golden-rule for everyone doing this work!

From cerebral malaria I moved on to other fields of research, screening compound libraries for new anti-malarials, and integrating the search for an anti-malarial vaccine. Now, the goal is there all the time, in front of my eyes! But I can only do what I do, because others before me have studied the biological processes I want to tackle. And they have done so using animal models.

Inês S. Albuquerque, MSc

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Your Turn to Speak of Your Research…

Speaking of Research have regularly had guest posts. Scientists have different fields of expertise, and who better to get to write about a scientific field than an expert in it. The most powerful voice on this issue continues to be that of the scientist.

We need more scientists to explain their research. Why do they use animals? How do they look after them? Why can’t you use cell cultures or people? What do you hope to find out?

We call out to our followers and supporters. We need you not only to help us by writing an article about your research, but by passing this post to your friends and colleagues, your students and your teachers. Help us find people who will write about their research for the Speaking of Your Research campaign.

There has never been a better time to get involved in Science Communication. More scientists than ever before are talking about the research they do across the internet, and it’s time that those involved in animal research join the trend.

Internet Writing Science Blog

The internet wants to know about your research.

The guidelines for Speaking of Your Research are simple:

– Articles should preferably be between 400 and 1500 words (much shorter than a grant proposal!)
– Articles should include a picture if possible (No copyrighted images please)
– Articles should be signed.
– Articles should be written in a manner accessible by non-scientists (we can help with this)
– Articles should cover some of the following questions:

  • What does your research involve?
  • What are you researching? What applications might your research have in the future?
  • Why do you need to use animal models, why not alternatives?
  • How do you specifically consider the welfare needs of the animals?

The Speaking of Research committee is more than willing to offer help and advice to support you writing your article. Please email us on contact@speakingofresearch.com