From the start of things, science has always relied on the organisms that can be made to be a representation of more complex systems. They were a model for either humans themselves or to show in their own simplicity how life builds up to larger formations of cells and processes. That has long been the purpose of model organisms.
In order to test experiments and the effects of compounds and changes to behavior, genetics, or any other system that makes up organic life, scientists have to have a specimen to test those things on. The beginnings of the scientific method saw those premature scientists using whatever was available, meaning dogs, mice, and flies. While some of these may have stuck around as useful test subjects since for specific disciplines, they weren’t being used for any precise purpose such as that back at the start of things.
At first, the scientific community stuck with simpler organisms because they bred quickly and you could do multi-generational studies over a much shorter length of time than it would take for larger conglomerate creatures. But as genetics grew out of its infancy and especially as we began to unravel what true genetic inheritance meant in regards to traits and competence, the organisms we used began to become more important and selectively chosen.
The reveal of DNA and genome sequencing has proven a massive boon to model organism research and the past few years has even seen the saying of “every organism is a model organism” become more common, though particular species remain the go-to for research purposes due to the larger depth of understanding we’ve developed on them over the decades. And another factor that looms over most anything in life certainly is involved in science as well: money. If certain species and sample organisms can be obtained for a better cost to use value, those turn out to be the preferable option. As it goes in most other things as well.
The unknown factor in organismal research is how well any particular organism will take to experimentation. Many can’t be easily cultivated in a lab, making them unsuitable for research, while others turn out to grow even better than their close relatives for no immediately obvious reason. It is these special organisms that often become the chosen model organisms. For plants, tobacco and Arabidopsis turned out to have this trait and plant science hasn’t looked back since. The only downside to this capability is that there’s no way to know which organisms are suitable for it without just testing them first. The solution always just ends up being the simple refrain that more science needs to be done.
There is a connected history to all of this. While model organisms crop up in a variety of scientific fields and their use is often unrelated to each other, the initial discovery of the big name ones that span the scientific community is a story of joint effort and competition. As with many things in the topic of biology and genetics, it all starts with one Gregor Mendel and his groundbreaking work on trait selection and so much more. In his 1866 publication, he hinted at the importance of model organisms in future research, but it would be three and a half decades after that before his genius would be properly recognized by the world and the real work could begin.
Let us start there and with one of the most well known of these models.
Drosophila melanogaster: The First Model Organism
Whenever new genetics experiments are tested or completely new trait variants are found, they almost invariably are thanks to the work done by the common fruit fly, Drosophila melanogaster. They were first described scientifically fairly early on in 1830, having originated as most fly species did from sub-Saharan Africa. Their involvement with human agriculture and expansion has led to them being found worldwide in practically every environment imaginable. The fruit fly relies on the refuse made by humans to survive and has little impact on the natural environment around it, meaning it also receives little competitive pressure in that regard.
The rediscovery of Mendel in 1900 was the beginning of this biological revolution. His laws of inheritance promoted several scientists to look more into the roles of chromosomes in these trait distributions. One Thomas Hunt Morgan sought to once and for all solve the conundrum of why there appeared to be more traits segregated than there are chromosomes and what that meant for inheritance. To determine this, he went with D. melanogaster as his lab animal for the experiment. This led to the confirmation in 1915 of the already proposed, but heavily debated, chromosome theory of inheritance that became a fundamental unifying theory of all genetics. It showed that genes are tied to specific sites on chromosomes and are segregated based on how those chromosomes are distributed to offspring.
Research since that time took Morgan’s work and continued the use of the fruit fly for further experiments. Several specific characteristics of D. melanogaster and its relatives helped contribute to its ascendent usage. The genus of Drosophila has one of the most varied reproductive systems found in nature, with some species having females that mate repeatedly during their fertile periods and others that only ever mate once in their entire lifespan. Their growth and development has similar variance to this, with some reaching adulthood almost immediately after emerging from pupation after the larval stage and others that require weeks even in their fly form before reaching sexual maturity.
It is these sexual characteristics, along with their morphological differences, that has proved perfect for testing genetic changes from single genes within an individual and a population. Surprisingly, the common fruit fly has also shown to be a great model for the impact of human diseases, as around 65% of all human diseases have a counterpart disease that affects fruit flies. These homologue diseases allow for more in-depth study of convoluted human conditions in flies, including heart disease, neurological and brain diseases, and even modern prevalent conditions like obesity. As these disorders are a complicated mess of multiple genes, work in flies can let scientists change and alter their genetics to try and find singular or directed solutions to help fix the diseases, along with more radical treatments that wouldn’t be ethical to test in humans without prior safety experimentation.
Per them being a global phenomenon as previously mentioned, environmental stress tests and the effects that has on genetic expression is perfect for use in D. melanogaster due to their high adaptability. The intriguing part is that, on just a species or population level, Drosophila flies are extremely susceptible to changes in abiotic stresses and conditions. The range of any one species is constrained to a limited region and small changes could be harmful to their long term survival. Their ubiquity is more due to just how many thousands of species there are in the genus and how they have each adapted themselves for different, isolated niches. Therefore, different stresses will have disparate results on them, depending on where they come from, making the species great fodder for differential gene expression between populations.
One of the major historical events where these characteristics of the fruit fly came into play was during the explosion of genetics research in the 1970’s and 80’s. The first mutant flies and details on their mutations were released into the scientific consciousness and how they can be made to have radically misshapen body plans. This discovery was the reveal of the Hox genes that control construction and placement of body parts throughout embryonic development. The research delving into these has given new insights into human disorders of development and possible treatments for the conditions through genetic engineering.
These mutants flies and the mutagenic reagents used to generate them have also been key in the study of mitosis and chromosome differentiation. That led to the finding of two protein kinases responsible for the progression of mitosis through the chromosome segregation phase and into cytokinesis where the cell begins splitting into two daughter cells. This work in the early 1990’s was critical to our current understanding of how cell division progresses and how defects in genes can cause harmful alterations to that process.
All of this research led to further expansions in what Drosophila species could be used for in science. In 2007, twelve additional fully sequenced genomes from other important fruit fly species in the genus were published and have allowed for those same flies to be used in an ever expanding bubble of scientific endeavor and in practically every field of study out there. By 2015, the number of sequenced genomes of the flies has reached 30 and the amount of knowledge we gain from them and their relatives continues to increase in scope and importance.
Drosophila melanogaster and all of its closely related species are truly the fundamental basis for biological research as a whole and deserve the spot as the first and de facto model organism.
Escherichia coli: The Versatile Model Organism
There should have never been any doubt that E. coli was going to become a hit of a model organism, the runway super model example if you will. Its ability to be used in almost anything inherently made it a microbiology darling and even more so a tool for materials science production at the advent of genetic modification. The hardy nature it exhibits makes it far more welcome in the lab than many other bacteria and the fact that it is non-pathogenic in almost every circumstance is a beneficial benefit. At the same time, the nutrients it needs to grow can come from a variety of sources, it isn’t restricted to a single growth medium, meaning it could be co-cultured with other specialized microorganisms for specific fields of work.
As we go on, you may notice that the beginning of many of these model organisms have their start around the turn of the prior two centuries. That is when the true start of genetics research took off, just before the world was plunged into the turmoil of two world wars. For E. coli, this all starts in 1884 with the German scientist Theodor Escherich, who was working on what could be called one of the first investigations into the human microbiome. He wanted to understand what role the microbes in infants had on their development and the influx of disease that was oh so common for the young at the time. In the process, he found a new bacteria that was fast-growing and ubiquitous in these digestive tracts, leading to him naming them Bacterium coli commune. But we all know what they eventually came to be known as and whom they are named after.
This fast growth ability lended itself to being used as a general teaching tool in early university laboratories for showing what bacteria are like and how they grow. Thus, E. coli became one of the most common bacteria found in the scientific world before its real nature was uncovered. In the 1920’s, when microbiologists began seeking a bacteria to use as a model organism for other bacterial studies, the one that was at the top of the recommended list was of course our little endemic friend. This early work changed everything we thought we knew about bacteria and introduced us to so many other members of the microscopic world, including viruses that attack bacteria and came to be known as bacteriophages.
By the middle of the 20th century, there was no other bacteria that anyone would offer when it came to basic microbial experiments. Which put it in the perfect spot for the emergence of molecular biology in the 1950’s and the truth of DNA as the basis for all of life’s instructions. The information on how all the basic genetic coding into proteins occurs was first explained through the use of E. coli as a model for the process on a molecular level.
The steps to making this model system arguably began in the late 1940’s by Joshua Lederberg and his hope that the bacteria reproduced by sexual mechanisms rather than through asexual replication. He was indeed correct and found that E. coli enter into sexual phases before daughter cell production where they transfer genetic information to each other through a common process known as bacterial conjugation. Could this be then used to ensure the transmission of desired genes throughout a bacterial culture and population?
That was the hope and it started by using radioactive x-rays in order to force mutagenic changes to the E. coli that could then be mapped and followed to see if those changes were picked up by the rest of the species within the petri dish. This was the start of attempts to directly manipulate DNA and its exchange between organisms. It also led to plenty of individual revelations, like the existence of DNA polymerase and how RNA is obtained from transcribing DNA.
A unique feature of the E. coli bacterium and all those that exist within the gut microcosm of other organisms is how they are adapted specifically for two extremely distinct lifestyles, those inside a body and the times spent outside after excretion from the digestive system. This exposure to the external environment necessitates their ability to survive exposure to sunlight, temperature changes, humidity alterations, and all the other stresses that happen in the wild. The ability to grow or remain stable under varying conditions is one trait that makes E. coli perfect for being a lab model organism and makes them require very little tending to.
This plasticity in their actions was further represented after genome sequencing became available. In 2002, three very different strains of E. coli were sequenced: the common non-pathogenic lab strain K-12, the horribly dangerous and infective O157:H7 strain, and the urinary tract pathogenic strain CFT073. These three together, while all being E. coli, only shared around 40% of their genes with each other. Consequent sequencing of even more strains showed that only around 20% of all E. coli genes are shared on average between strains as a whole.
It is this very genetic variance that makes up the rapid gene transfer between bacteria that is exhibited by E. coli in their reproductive cycle. They routinely drop and pick up genes from each other and their environment in order to better adapt themselves for any particular scenario they are facing at that time. Not all positive fitness genes are useful in every situation and many can become drains on fitness if they are kept at times where they are not needed. This mix and match lifestyle means genomes of any single E. coli specimen may vary wildly in not just content, but also size, from another.
It is quite obvious that this pick up and play capability means that Escherichia coli fits the mold for any kind of genetic alteration scientists may want to engineer and all of the aforementioned traits combine to make the bacteria the choice for producing medicine, industrial materials, and any other producible organic compound that has a gene connected to its production.
Without a doubt, E. coli will continue to be the darling of the microbiology field and of many industrial companies for decades to come, along with being an easy to use gene testing system for any possible single gene or combination of genes one would want to try out before placing them into more complex creatures. Its versatility will see endless purpose for science for likely the entirety of future progress.
Caenorhabditis elegans: The Consistency Model Organism
A major problem when conducting genetic research is being able to properly regulate and control the outcomes of an experiment. It doesn’t matter if a test is successful if the results obtained are different each time the experiment is undertaken. If a system is too complex and has results like this, then it is nearly impossible to decipher its individual components to find out just what variables are contributing to the variant outcomes. Being able to create an experiment that consistently comes back with results and that will do so no matter what team of scientists or lab is conducting the experiment is indispensable to scientific research.
Thanks to that desire, C. elegans has become the composite model organism the world needs to put plain and simple the complexities of living systems. The research showcasing the basic structure of this nematode began in the first half of the 1900’s, but it wasn’t until the 1960’s that one scientist took hold of what this worm could do. Sydney Brenner was the one who presented it to the world stage and demanded its inclusion as a model organism.
There are many reasons why Brenner did this and many positive arguments on why this nematode is great for complex organismal research. But there is one specific feature that trumps all the rest and that ability is known as eutely. What this term refers to is organisms that have a set number of cells. Depending on the species and sexual characteristics, the adults of that species will always have the same exact number of cells unless some major mutation diverts this path. Each cell has a predetermined purpose and place in the body and this is hardwired into its genetic code.
If one wants to study the impact of genetics and mutation on a multifaceted biological level, an organism with eutely is a goldmine. The hermaphroditic versions of C. elegans form 959 cells in total, while the male versions make 1031. These numbers are permanent after the worms exit from their larval stages.
In addition to this, the nematodes have the usual case of reproducing quickly when food is available and being amenable to growing in laboratory conditions. Their reproductive time to have more young is shorter compared to other members of their family and they can survive lack of nourishment and even freezing for several months. The fact that their reproduction involves cloning through self-splitting is perfect for experiments, as that means you’ll always be working with a homozygous line with the same genes, so long as you control interactions with outside conditions. Finally, their egg shells are highly resistant to bleaching and antimicrobial activities done in a lab. Meaning that this can be used to wipe out an adult population and restart with only the hatching eggs.
The last aspect that makes them so useful and that is also a ubiquitous part of the N2 strain used in labs is that C. elegans have an active RNA interference (RNAi) pathway, likely to defend against viral attacks. Therefore, they are crucial for RNAi research and in finding ways to manipulate that system.
Unfortunately for Brenner, the technology to do what he wanted with the nematode didn’t exist at the time. It would require the development of physical genome mapping, the capability to tag transposons, gene transformation of a germ-line, and more before C. elegans would really come into its own as a model organism. This wouldn’t occur until the 80’s and 90’s and arguably we’re still developing some of it to this very day.
Research into mutant isolates of C. elegans is severely lacking and we continue to learn about how it functions in the wild. To better characterize its RNAi system, we need to know more about the viruses that it defends against, how they attack, and what mechanisms the worms can use to fight back. The genes controlling these programs and other phenotypic responses are still being unraveled.
Even so, C. elegans have been essential in experiments into body plan structure, genetic expression, and even embryology. Much of the findings within this single model organism have been copied and replicated in other models too and we are continually newly perceiving the interconnectedness of all biological science through our ever-expanding pool of knowledge.
Arabidopsis Thaliana: The Genetic Modification Model Organism
When it comes to plant research, everyone knows the name of Arabidopsis. It has become an elementary part of plant science, akin to the station that Drosophila holds for animal life. Though its history as a segment of understood knowledge goes back quite far, with its description first happening in 1577. The species name of Arabidopsis thaliana was not given until centuries later in 1842. This interest kept up in the decades after, with in-depth studies of its phenotypes continuing in the 1900’s and after genetics arrived.
But, funnily enough, Arabidopsis didn’t become a model organism until quite late in the game in the middle of the 1980’s. It was biotechnology that was required before science could properly use the plant at its full potential. To that end, it was the first flowering plant to have a fully sequenced genome, which was released in 2000.
The traits it exhibits match other model organisms, with a short germination time period and the capability to self-fertilize. These unique features however bely the convoluted evolutionary history of the plant, one where its closest relatives in the Arabidopsis genus have significant divergences that are still being resolved. The amount of self-polyploidy and cross polyploidy events have muddled that timeline completely, though we do know that A. thaliana first diverged around 5 million years ago.
That didn’t prevent another polyploidy event occurring later between it and a relative that resulted in yet another new species emerging within the past 300,000 years. Even so, all this competition and growth in the genus has only further cemented the special nature of this one species as compared to all the rest. The expansion of its range coincided well with the migration of human populations and the spread of agriculture, despite not being a crop plant itself. It remains the broadest ranged species in the Arabidopsis genus, being the only one that has managed to spread from their commonly colder climes to the warmer regions of the planet and occupying both continuously. Those that did manage to simply move to the warmer areas usually regressed into only being found in certain local endemic populations.
These travels coincided with A. thaliana developing the self-fertilization mechanisms that its relatives lack, with all of those having a self-incompatibility barrier that prevent them from selfing. Additionally, the shift to being an annual plant capable of going from germination to flowering within only 6 to 8 weeks quickly allowed it to outstrip its cousins that remained on a biannual or perennial schedule that lets them spread seeds more than once in a lifetime. The change to only having a single growth and seed spreading cycle before dying meant that A. thaliana could spread more quickly throughout a region, while not becoming too dense in any one area. This robustness let them adapt to multiple environments and caused their worldwide spread beyond their original home in Western Eurasia.
A higher seed count and longer seed viability as contrasted with its cousins also means the species is perfect for scientific research into mutagenesis and the spread of traits. The ability to propagate transgenic lines is made simpler and more direct in this one plant than for countless other plant species. Imaging of live specimens and their cellular types is made easier thanks to A. thaliana having a very limited complexity in its tissues, with only one single layer of cells in its roots for each specialized type. The purpose and impact on its growth this simplicity has is still being researched.
As another characteristic, the species has one of the smallest known plant genomes, with only five chromosomes in total, far fewer than the 8 found in the rest of its genus. Thus, as a source for full genome sequencing and fundamental understanding of plant genes, there is no better option to choose as a model organism.
A list of all the science and discoveries that Arabidopsis thaliana has been party to would be a long list indeed and covers a span including almost everything we know about plants today. A. thaliana was involved in practically every such study that let to a new plant insight without fail. Plus almost all genetic modification and engineering research in plants has had to go through the species, with only a handful of those studies having done with its counterpart model organism in plants, the tobacco plant.
Today, A. thaliana remains a segment of ongoing research into abiotic stresses and the hope of developing plants with resistance to drought, flooding, salinity, and plenty more. The next generation of genetically engineered plants with traits to deal with the impact of climate change will be, at least in part, thanks to the work of Arabidopsis.
An Infinity of Model Organisms
There remains an open question on whether science will even need model organisms in the future. They retain their practicality for now due to the high amount of study into them that has built up over the decades. But as whole genome sequencing becomes more commonplace and accurate computer annotation of genes improves, the model organisms of the past have the possibility of falling to the wayside.
It may turn out that any individual organisms we wish to study can be, in themself, a model organism. If the technological capacity is there, then there would be no requirement of using an alternative model, but just use the actual thing itself or the closest species available. There would still need to be substitutes for things like human disease research and the like, but the limitations on choice of species to study would be removed.
Whether this will truly be the case or whether we’ll have model organisms around forever as our fallback choice is difficult to say. The world of biological sciences is too chaotic in the present times to truly guess at what its future will look like. Any assumption may just turn out to be a fanciful science fiction-esque dream that was never the right path science was taking at all.
As always, the only true way to know the future of scientific invention is to live through it ourselves, on the road to greater heights for all of humankind.
References
1. Hedges, S. B. (2002) The origin and evolution of model organisms. Nature Reviews Genetics 3, 838–849. doi: 10.1038/nrg929
2. Müller, B. & Grossniklaus, U. (2010) Model organisms — A historical perspective. Journal of Proteomics 73, 2054–2063. doi: 10.1016/j.jprot.2010.08.002
3. Yanagida, M. (2014) The Role of Model Organisms in the History of Mitosis Research. Cold Spring Harbor Perspectives in Biology 6. doi: 10.1101/cshperspect.a015768
4. Blount, Z. D. The unexhausted potential of E. coli. eLife 4, (2015). doi: 10.7554/eLife.05826.001
5. Markow, T. A. (2015) The secret lives of Drosophila flies. eLife 4. doi: 10.7554/eLife.06793.001
6. Frézal, L. & Félix, M.-A. (2015) C. elegans outside the Petri dish. eLife 4. doi: 10.7554/eLife.05849.001
7. Riddle, D. L., Blumenthal, T. & Meyer, B. J. C. elegans II. (Cold Spring Harbor Laboratory Press, 1997).
8. Liti, G. (2015) The fascinating and secret wild life of the budding yeast S. cerevisiae. eLife 4. doi: 10.7554/eLife.05835.001
9. Greig, D. (2007) Population Biology: Wild Origins of a Model Yeast. Current Biology 17. doi: 10.1016/j.cub.2007.02.009
10. Krämer, U. (2015) Planting molecular functions in an ecological context with Arabidopsis thaliana. eLife 4. doi: 10.7554/eLife.06100.001
11. Phifer-Rixey, M. & Nachman, M. W. (2015) Insights into mammalian biology from the wild house mouse Mus musculus. eLife 4. doi: 10.7554/eLife.05959.001
12. Silver, L. M. (2001) Mice as Experimental Organisms. Encyclopedia of Life Sciences 1. doi: 10.1038/npg.els.0002029
13. Parichy, D. M. (2015) Advancing biology through a deeper understanding of zebrafish ecology and evolution. eLife 4. doi: 10.7554/eLife.05635.001
14. Hake, S. & Ross-Ibarra, J. (2015) Genetic, evolutionary and plant breeding insights from the domestication of maize. eLife 4. doi: 10.7554/eLife.05861.001
15. Kourakis, M. J. & Smith, W. C. (2015) An organismal perspective on C. intestinalis development, origins and diversification. eLife 4. doi: 10.7554/eLife.06024.001
16. Rine, J. (2014) A future of the model organism model. Molecular Biology of the Cell 25, 549–553. doi: 10.1091/mbc.E12-10-0768
Photo CCs: Drosophila-melanogaster-Nauener-Stadtwald-03-VII-2007-10 from Wikimedia Commons
