In the long history of biology, there have been so many amazing discoveries! Advancements in the origins of life, the mechanisms of life, cures for new (and some rediscovered) maladies, and so many other interesting things in between are what consistently make biology one of my favorite subjects.
And while nearly all scientific discoveries help us understand a little more about this amazing world in which we live, some discoveries help us to Discover More. Below are 15 scientific breakthroughs that have helped scientists see even more deeply into life, the universe and everything.
The Structure of DNA (1952-1953)
Fluorescent protein markers (1992)
Inheritance/Evolution (1800s)
By now, the stories of Charles Darwin’s finches, Gregor Mendel’s peas, and Alfred Wallace’s wide traveling naturalist studies have become common lore both in and outside the world of biological sciences. But their long reaching conclusions helped to spur the explosion of growth in the area of biology for the last 170 years. And while it would take the discovery of DNA in the 1950s to sow the seeds of genetic evolutionary studies, we all owe a debt to these naturalist founders who laid the groundwork for many of the things we now take for granted while conducting our research.
Antibiotics (1928)
Alexander Fleming wasn’t setting out in 1928 to revolutionize biological science when he discovered that something in Penicillium mold spores was able to kill staphylococcus bacteria in a petri dish. As is often the case in science, discoveries make remarkable impacts on research that are totally unrelated to the field they were created to help. Fleming was just trying to find a way to prevent infections from being so deadly, not looking to find the world’s first antibiotic. But along the way, the discovery of antibiotics have been utilized in innumerable research, as selection tools in transformation and cell culture, as well as a host of other fields and studies.
Gel Electrophoresis (1930s)
It’s difficult to imagine any of my labs without the ever-present bench of gel rigs, either humming with the sound of electrical current, dutifully separating proteins, DNA or RNA; or sitting vacant and patiently waiting for another agarose or acrylamide gel. It is just as remarkable to realize that electrophoresis, as we know it, was discovered in the 1930s by Arne Tiselius and even earlier work was done in the early 1800s that provided the groundwork for the Tiselius apparatus to differentiate between proteins. But it wasn’t until the 1940s that scientists started using gel matrices to separate compounds into discrete bands. And it wasn’t until the 1960s that gel electrophoresis would really be used to start identifying DNA and other biological molecules that would give birth to the field of molecular biology.
HeLa Cell Discovery (1951)
The cervical cancer cells that were taken from Henrietta Lacks before she died in 1951 have become a benchmark in the history of cancer research and knowledge. The immortal HeLa cells made medical research easier, more robust and repeatable. The cell line is what allowed for the creation of Salk’s first polio vaccine in 1952. Since its discovery, there have been over 11,000 patents created involving the HeLa cells. It is safe to say that without Henrietta’s cells, a great body of research would have been slower and biomedical advancements a great deal more ponderous.
The Structure of DNA (1952-1953)
As with the discovery of inheritance and evolution, the story of the discovery of the structure DNA is well known; starting with the Rosalind Franklin’s first image of the double helix in 1952 and then subsequently James Watson’s and Francis Crick’s model of the double helix structure in 1953. However, Oswald Avery had already identified DNA in 1944 as the primary point for hereditary information. But the structure of DNA cannot be overlooked for its relevance in our understanding of so much of what is now considered common knowledge in biological sciences.
DNA Polymerase (1956)
In 1956, Arthur Kornberg and his lab forever changed the world of molecular biology with the discovery of DNA polymerase from E. coli cells. In one instant, scientists were now finally capable of synthesizing new DNA sequences onto an existing DNA strand. The use of the original DNA Polymerase and subsequent polymerases discovered by Arthur’s son, Thomas Kornberg, and others have created the bedrock of molecular biology in regards to PCR, cloning, transformation and sequencing. Without these workhorses of the lab, much of what we currently understand about our DNA and life would be nonexistent.
Reverse transcriptase (1970)
Reverse transcriptase was independently discovered by both Howard Temin and David Baltimore in 1970. As a revolutionary tool, RT finally allowed scientists to synthesize cDNA (and double stranded DNA) from RNA, bridging the large gaps in knowledge of the character and sequence of RNA by use in PCR. Discovering the roots of RNA and its translation into proteins is a fundamental necessity of biology and the realization that RNA could be transcribed into DNA was paramount in the understanding of retroviruses and, later, antiviral drugs.
Restriction enzymes (1970)
The first restriction enzymes were discovered in the early 1950s by Salvadore Luria, Jean Weigle and Giuseppe Bertani. But the enzymes they found were all type I enzymes that cleaved DNA randomly from a recognition site. In 1970, Hamilton Smith and associates discovered the more popular type II restriction enzymes that cleave at their site of recognition, and Daniel Nathans showed that by cleaving in those places, they could separate the fragments via gel electrophoresis in order to map the DNA. The use of restriction enzymes to produce a predictable cleaving pattern to work from has become a benchmark in cloning and mapping.
E. coli transformation (1970)
Bacterial transformations have been around since the 1920s. Escherichia coli was being utilized as a model organism in microbiology and other biological fields for most of the 20th century, but was considered intractable to transforming until Morton Mandel and Akiko Higa were able to induce it to take up DNA with the use of calcium chloride. The discovery of artificially induced competent E. coli cells created one of the easiest and most efficient transforming bacteria which allows for even simpler cloning methods in all of biological science. The use of E. coli has only grown in popularity as one of the most common model organisms in science, and was one of the first organisms to be completely sequenced in 1997.
PCR (1983)
Few discoveries have revolutionized their fields as much as polymerase chain reactions (PCR). Likewise, PCR owes its own revolution to the previously discovered thermally stable DNA polymerase. Prior to Kary Mullis’s work in reinventing an enzymatic assay to utilize a DNA template, primers and heat cycles (first described in the Journal of Molecular Biology in 1971 by Kjell Kleppe), cloning was slow and tedious. And even in the early days of PCR, the heat cycles would denature the polymerase, requiring it to be added anew every cycle. PCR may be the single most indispensable technique used in modern biology.
Bioluminescent markers (1986)
Bioluminescence has been observed for millennia, but the understanding of its nature and the reaction that produces it remained a mystery. In 1955, Osamu Shimomura was the first to crystallize luciferin from ostracods, and was later instrumental in the discovery of GFP in jellyfish. Firefly luciferase was finally cloned in 1985, but the use of bioluminescence as a marker really began in 1986 when it was first utilized as a gene marker in both tobacco and Arabidopsis plants. And by 1988, it was being used in mammalian cell lysates as a prominent tool for in vivo studies of gene regulation. Bioluminescent imaging is still one of the most widely used applications in both in vivo and in vitro research in nearly every biological system.
Gene Therapy (1990)
Gene therapy had been seen as science fiction for most of the 20th century; a nearly magical way to cure genetic diseases. In 1972, Theodore Friedmann and Richard Roblin first introduced the possibility that it might become reality someday, even if they believed that humanity needed to be extremely cautious about taking that giant leap into the unknown of genetic manipulation. But by 1990, William French Anderson was given permission by the US National Institute of Health to conduct a clinical trial for a patient with a severe immune system deficiency. Cancer gene therapy trials were approved by 1992 and many other genetic disease therapies have been conducted in the decades since. While gene therapy remains a miraculous opportunity for many of our worst genetic diseases, there is also much to be concerned with over its possible misuse and the ethics surrounding it.
Fluorescent protein markers (1992)
Along with bioluminescence, fluorescent markers have made an unequivocal impact on research. Perhaps it is appropriate then that Osamu Shimomura would have been instrumental in discovering both. Green fluorescent protein (GFP) was first discovered by Osamu in jellyfish in the 1960s along with the blue aequorin protein. Later, Douglas Prasher utilized GFP and reported its genetic sequence in 1992, which allowed it to be expressed in E. coli in 1994 and later in C. elegans. The use of bioluminescent and fluorescent markers have let us visualize the mysteries of the cell, protein-protein interactions inside, outside and even in between cells. We can see how cancers react with cell lines or even inside the bodies of experimental animals. Due to the enormous range of colors that species have developed through evolution, we now have the capability to personally witness the magnitude of microscopic interactions that were only imagined before.
RNAi (1998)
Scientists had been aware of a system of co-suppression or quelling for quite a while. Plant biologists had been aware that sometimes, overexpression of genes in plants to create more vibrant colors would unexpectedly produce plants with variegated color patterns or even no pigment at all.In 1998, Craig Mellows and Andrew Fire published their work documenting the intentional silencing of genes in C. elegans via a new process called RNA interference, in which they combined both a sense and anti-sense sequence of a gene. The process would evolutionarily be used to defend against viruses that try to insert themselves into the DNA. The use of RNAi has become critical in the development of gene expression and suppression, in identifying components of cellular processes, and as a practical tool in many other biological fields.
CRISPR-Cas9 (2012)
CRISPR was first described, unknowingly, in 1987 by Yoshizumi Ishino. However, it wasn’t fully characterized as “Clustered Regularly Interspaced Short Palindromic Repeats” until 2002 by Francisco Mojica and Ruud Jansen. The magnificence of CRISPR as a gene editing tool finally came about when Jennifer Doudna and Emmanuelle Charpentier reengineered the Cas9 endonuclease and showed that the new system could be programmed to target any DNA sequence for cleavage. But the future, and real value, of CRISPR-Cas9 might lie far beyond its targeted gene therapy in a variety of CRISPR adaptations that we’ve written about previously.
All of these discoveries have affected nearly every facet of biological science and have driven research into new and ever expanding directions. It is always amazing to look back and wonder at the greatness of all of these discoveries. At the time of these discoveries, these scientists saw their work as simply solving a problem on their bench in order to discover the answer to their particular project. Sometimes that is both the beauty and the pain of research, that the relevance of any particular result aren’t fully realized until years (or even decades) later. But we can be comforted that our research, even our research failures, can be used to further the overall understanding of the world in which we live. And every discovery we make might be used by someone else down the research pathway to Discover More. Isn’t that what we are all really trying to do anyway?
References
Anderson, W. F. (1984). Prospects for human gene therapy. Science, 226(4673), 401-409.
Brownlee, C. (2005). Danna and Nathans: Restriction enzymes and the boon to modern molecular biology. Proceedings of the National Academy of Sciences, 102(17), 5909-5909.
Burke, B., & Epperson, B. (2003). W. French Anderson: Father of gene therapy. Oklahoma Heritage Association.
Campbell, M. Francis Mojica: The Modest Microbiologist Who Discovered and Named CRISPR Article Published: October 14, 2019.
Chalfie, M., Tu, Y., Euskirchen, G., Ward, W. W., & Prasher, D. C. (1994). Green fluorescent protein as a marker for gene expression. Science, 263(5148), 802-805.
Chial, H. (n.d.). Restriction Enzymes. Nature news. Retrieved January 20, 2020, from https://www.nature.com/scitable/spotlight/restrict...
Cobb, M. (2016). A speculative history of DNA: What if Oswald Avery had died in 1934?. PLoS biology, 14(12), e2001197.
De Wet, J. R., Wood, K. V., Helinski, D. R., & DeLuca, M. (1985). Cloning of firefly luciferase cDNA and the expression of active luciferase in Escherichia coli. Proceedings of the National Academy of Sciences, 82(23), 7870-7873.
Editors of Encyclopedia Britannica. (2008, October 10). Osamu Shimomura. Encyclopædia Britannica. Retrieved January 20, 2020, from https://www.britannica.com/biography/Osamu-Shimomu...
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., & Mello, C. C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. nature, 391(6669), 806-811.
Friedmann, T., & Roblin, R. (1972). Gene Therapy for Human Genetic Disease? Proposals for genetic manipulation in humans raise difficult scientific and ethical problems. Science, 175(4025), 949-955.
Gingold, E. B. (1984). Bacterial transformation. Nucleic Acids, 237-240.
Ishino, Y., Shinagawa, H., Makino, K., Amemura, M., & Nakata, A. (1987). Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. Journal of bacteriology, 169(12), 5429-5433.
Jansen, R., Embden, J. D. V., Gaastra, W., & Schouls, L. M. (2002). Identification of genes that are associated with DNA repeats in prokaryotes. Molecular microbiology, 43(6), 1565-1575.
Kadri, K. (2019). Polymerase chain reaction (PCR): Principle and applications. Synthetic Biology-New Interdisciplinary Science.
Khan, F. A. (2011). The immortal life of Henrietta Lacks. The Journal of IMA, 43(2), 93.
Lehman, I. R. (2003). Discovery of DNA polymerase. Journal of Biological Chemistry, 278(37), 34733-34738.
Mojica, F. J., Díez‐Villaseñor, C., Soria, E., & Juez, G. (2000). Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. Molecular microbiology, 36(1), 244-246.
Nair, P. (2011). QnAs with David Baltimore. Proceedings of the National Academy of Sciences, 108(51), 20299-20299.
Prasher, D. C., Eckenrode, V. K., Ward, W. W., Prendergast, F. G., & Cormier, M. J. (1992). Primary structure of the Aequorea victoria green-fluorescent protein. Gene, 111(2), 229-233.
Ow, D. W., Wood, K. V., DeLuca, M., De Wet, J. R., Helinski, D. R., & Howell, S. H. (1986). Transient and stable expression of the firefly luciferase gene in plant cells and transgenic plants. Science, 234(4778), 856-859.
Roberts, R. J. (2005). How restriction enzymes became the workhorses of molecular biology. Proceedings of the National Academy of Sciences, 102(17), 5905-5908.
Rosenberg, S. A. (1992). Gene therapy for cancer. Jama, 268(17), 2416-2419.
Willis, M. S. (2009). Arne Tiselius: clinical chemistry. Laboratory Medicine, 40(10), 627-628.
