Model Organisms

        In modern society, we have things known as clinical trials. A clinical trial is a research program that is conducted with patients to see if a new drug, treatment, or device is safe for humans (1). The patients, however, are not the first test subjects to use these new drugs, treatments, or devices. The very first test subjects are known as model organisms, which are basically a smaller and more affordable representation (or model) of a human.

https://piergen564s18.weebly.com/model-organisms.html

These subjects must meet all of the requirements necessary to participate in a specific research study. What does that mean? Scientists would not use a killer whale to determine how our cells grow and divide. They would strategically choose a test subject that has a similar biology to ours or a similar genetic makeup (2). Rather than using a random animal, scientists would use Saccharomyces cerevisiae (otherwise known as yeast) to study how human cells divide (2). These organisms allow scientists to have a better understanding of how our bodies will react to certain drugs or determine how certain parts of our bodies work. Who could possibly be a better representation of a human, than a human? The issue with using humans as primary test subjects is that it is simply unethical to do so. In order to test a disease, one must become infected with the disease first in order for the scientist to even consider what direction to go in so that he or she can find the cure. In other words, the scientist needs to study the disease and its behavior in the body, then decide where the disease is targeting, and then determine what is the best mode of treatment to not do more harm than good. Also, model organisms are generally easier to control when it comes to their breeding patterns, allowing for a large number of test subjects when needed and inexpensive sources when supplies run low. But how is using these organisms any more ethical? In a perfect world, everyone's questions would be answered and every disease would have a cure already created but unfortunately, that is not the case. Scientists still have to figure out all the answers to the "why" and "how" within our biological systems, and they need something to try and solve those types of puzzles with. On the bright side, the organisms used for such research are protected under the “NIH’s Office of Laboratory Animal Welfare (OLAW),” which are “laws, regulations, and policies to ensure the smallest possible number of subjects and the greatest commitment to their welfare (3).” Furthermore, every scientist is required to provide a justification for what kind of animal(s) will be used, how many are needed, how each will be used, describe how they will be housed and cared for, and how veterinary care will be provided to them (3). Ultimately, the organisms used in these `studies are protected and monitored by the NIH to ensure their safety and wellbeing. So what kind of organisms are used for these kinds of studies? Here are some examples (2):

         Saccharomyces cerevisiae:

https://www.researchgate.net/figure/Scanning-electron-microscopy-image-of-Saccharomyces-cerevisiae-The-budding-yeast-cells_fig1_308144762

Saccharomyces cerevisiae (9), also known as Yeast, has been used to understand how genes become involved with certain diseases, based on whether or not they are activated or not (for more on gene expression go to my previous post!). It has also been used to understand the cell cycle. Yeast has allowed scientists to understand how a cell will divide and duplicate itself, which has led to beneficial discoveries, like what we know this far about cancer. Cancer is the abnormal growth of cells, therefore, understanding the cell cycle and how cells grow is crucial if we ever plan to find a cure for cancer. Humans and yeast only share the same domain of Eukarya (8 &9). According to the NCBI, "a typical laboratory yeast strains produce 20-30 daughter cells per mother and one lifespan experiment requires 2-3 weeks (11)." Based on this information, we can see how fast an average Yeast reproduces. This is convenient for researchers who need a lot more time, than a Yeast's typical lifespan, to conduct their research or study. Here is a database that has been curated from over 2,000 publications about the pathways and genomes for the Saccharomyces cerevisiae S288c, https://yeast.biocyc.org. 

Drosophila melanogaster:

https://www.researchgate.net/figure/Scanning-electron-microscopy-image-of-Saccharomyces-cerevisiae-The-budding-yeast-cells_fig1_308144762

Drosophila melanogaster, also known as a fruit fly, has led to a broadened understanding of how fertilized eggs develop into complex organisms…otherwise known as babies…or you (10)! Fruit flies have also been associated in discoveries with the circadian rhythms, which are the “physical, mental, and behavioral changes that follow a daily cycle (4).” This is the explanation for why organisms generally sleep when it is dark and are awake when the sun is up. This research was able to connect certain circumstances like “sleep deprivation, obesity, diabetes, depression, and other human health conditions (2).” Fruit flies and humans are both in the Domain Eukarya and Kingdom Animalia, but branch off at the Phylum. Fruit flies are in the Phylum Arthropod, while humans are in Chordata (8 &10). Although the lifespan of a fruit fly is determined by the temperature, the typical lifespan of a fruit fly is about 40-50 days and in that time they can lay "several batches of eggs (12)." These are just a few reasons as to why fruit flies are such a vital model organism for biomedical research. The database provided, https://nucleus.iaea.org/sites/naipc/twd/Pages/Databases.aspx, contains different research publications involiving fruit flies.

  

Mus musculus:

https://biox.stanford.edu/highlight/toenail-trim-saves-lab-mice-common-life-threatening-skin-condition

Mus musculus (otherwise known as a laboratory mouse) is  considered to be one of the most common biomedical model organisms to ever be used (6). They have been used in drug testings for decades. The research conducted on this rodent has led us to understand “what we know about cancer-causing molecules (2).” Mice have contributed to the creation of Lyrica (for Fibromyalgia or Epilepsy), Lantus (for types 1 and 2 diabetes), Zetia (for high cholesterol), and so many more (5). The cause for their use is because their bodies react to certain drugs and diseases just as ours would. Both mice and humans can be found in the Kingdom Animalia, Phylum Chordata, and  Class Mammalia. The difference in taxonomy between humans and mice begins at the Order; mice are in the Order Rodentia, while humans are in Primates (7&8). The lifespan of a lab mouse (in a protected environment) can be approximately 24 months (13). These organisms clearly have a longer lifespan than fruit flies and yeast, making them valuable for longer research assignments. This database, https://www.labome.com/method/Laboratory-Mice-and-Rats.html, gives an overview of how mice (and rats) are involved in biomedical research  from a variety of different sources. 

In order for a drug to be approved, it must undergo animal and eventual human testing. The U.S. Food and Drug Administration requires that a drug is tested on animals before it can be used in clinical trials with humans (5). More than likely you or a loved one has taken a drug or had a vaccine that was used in animal testing and you just did not know it. Model organisms are very important because they allow us the ability to fight against harmful diseases, stay healthy, and discover new things about our biology that we would never have known before!  

http://dev.biologists.org/content/141/21/4042

References:

1)   This site reveals what a clinical trial is and the process that the patients will encounter if/when they participate in one. Clinical Trials: A Guide for Patients. WebMD. https://www.webmd.com/a-to-z-guides/clincial-trial-guide-patients#1. Updated October 28, 2017. Accessed February 14, 2019. 

2)   This site provides many examples of model organisms, as well as describe what an organism is and what it takes to become one. Using Research Organisms to Study Health and Disease. National Institute of General Medical Sciences (NIGMS). https://www.nigms.nih.gov/Education/Pages/modelorg_factsheet.aspx. Updated October 2017. Accessed February 15, 2019. 

3)   This website describes the NIH’s (National Institutes of Health) mission to ensure the welfare of those animals being used in research and also describes what they do to ensure that their mission is fulfilled. How does the NIH ensure animal welfare?. National Institutes of Health. https://grants.nih.gov/grants/policy/air/NIH_ensure_welfare.htm. Updated April 9, 2018. Accessed February 15, 2019. 

4)   This gives a thorough understanding of what the circadian rhythms are and how it connects with day to day occurrences like sleeping or being jet lag. Circadian Rhythms. National Institute of General Medical Sciences. https://www.nigms.nih.gov/education/pages/Factsheet_CircadianRhythms.asp. Updated August 2017. Accessed February 16, 2019. 

5)   This site provides a brief summary of the importance of animal testing and a list of the top 25 drugs that had been tested on animals. Animals Behind Top Drugs. Foundation for Biomedical Research. https://fbresearch.org/medical-advances/animal-testing-research-achievements/animal-research-behind-top-drugs/. Copyright 2016-2019. Accessed February 16, 2019. 

6) A database that provides information about laboratory mice and their involvement in biomedical research. SMI. An Introduction to the Laboratory Mouse : Mus musculus.  Soceity of Mucosal Immunology.  http://www.socmucimm.org/1038/. Published June 3, 2014. Accessed February 19, 2019. 

This site provides cool facts, along with the scientific naming of different animals. I searched each individual organism from this site to find information on their taxonomy. 

7) Mouse. A-Z animals. https://a-z-animals.com/animals/mouse/. Updated September 10, 2018.  Accessed February 19, 2019. 

8) Humans. A-Z animals. https://a-z-animals.com/animals/human/. Updated September 10, 2018. Accessed February 19, 2019.  

9) This site provides that information into each of the classification levels of Yeast. Baker's and Brewer's Yeast. Bioweb. http://bioweb.uwlax.edu/bio203/s2012/vandenla_beth/classification.htm. Accessed February 20, 2019. 

10) This site gives plenty of detail about fruit flies, from other types of flies to the life and habits of fruit flies. Fruit Flies. Bugwoodwiki. https://wiki.bugwood.org/HPIPM:Fruit_Flies. Updated January 27, 2010. Accessed February 20, 2019. 

11) This online journal gives a detailed description of of the life span of a budding Yeast. Measuring Replicative Life Span in the Budding Yeast. NCBI. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797481/. Published June 25, 2009. Accessed February 21, 2019. 

12) This website gives a brief summary of the life span and cycle of a fruit fly. Life Span & Life Cycle of Fruit Fly. Orkin. https://www.orkin.com/flies/fruit-fly/life-span-of-fruit-fly. Accessed February 21, 2019. 
  
13) This blog post gives descriptive reasoning as to how to determine when a mouse is considered old (while comparing mouse years to humans) and also gives their maximum lifespan. Hagan, C. When are mice considered too old?. Jax. https://www.jax.org/news-and-insights/jax-blog/2017/november/when-are-mice-considered-old. Accessed February 22, 2019.