Avery's Study and How It Changed Biology as We Know It - Essay Example

Averys Study and How It Changed Biology as We Know It In the 1940s, Avery et al. did something that was astounding and changed the complexion of theworld as we know it – they showed that DNA transmit genetic information. Ironically, this was not entirely clear to the researchers themselves, as they concluded that their work has some use for genetics and viruses. However, their work is truly groundbreaking and is the basis for any number of processes that are extant in modern biology today. They also showed that mutations can be induced, and that these mutations are passed from one progeny to another in a predictable fashion. Averys work is the springboard for everything from recombinant DNA work to human cloning to cancer research. It has been used as a basis for other experiments that do not merely change the host genetic makeup, but actually replace one gene with another gene, and this process has even further widened the implication of Averys work. Drug resistant bacterial infections have been stemmed in part because of the processes used by Avery, in which injurious agents are introduced into the drug resistant strains, and these injurious changes are passed down through the progeny. The implications of this work for every aspect of life, from the environment to medicine to crop engineering is explored within the confines of this paper. Averys Study, Its Implications, and How It Has Been Adapted for Modern Times The basis for the studies were previous studies that induced changes in higher organisms that were permanently embedded and passed on to next generations as hereditary characteristics. The first description of this phenomenon is by Griffith, who transformed variant that was non-encapsulated and attenuated into a fully encapsulated and virulent cells of another type (Avery, et al., 1943, p. 137). The present study deals with an attempt to determine the chemical nature of a substance that produces transformation of the pneumococcal types. This experiment, in which a DNA fraction, which is isolated from Type III pneumococci, transforms unencapsulated R variants, which are derivated from Pneumococcus Type II, into a fully encapsulated Type III cells, builds upon earlier studies that showed that changes induced into various pneumococcal types is determined by the encapsulated cells that are used to evoke the reaction (Avery, et al., 1943, p. 152). The researchers found it striking that variants from a Pneumococcus Type II are changed into Pneumococcus Type III cells by the addition of highly purified and protein-free material that consisted mainly of DNA. Also striking is that the capsular substance and the substance evoking the reaction were chemically distinct (Avery et al., 1943, p. 152). In this case, the inducing substance, which is the DNA fraction, is polymerized and viscous, while the capsular substance, which is what was formed by the induction of the DNA fraction, is a polysaccharide. Since each of these substances are chemically and biologically distinct, they are both a requisite in the determination of the cell specificity in which they play a part. This experiment is important to the study of biology, because it showed that inducing a chemically and biologically distinct agent into a substance can transform that substance in a predictable way, and that this change embeds in the transformed substance so that the transformation is carried on through successive generations. Moreover, in the transformed substance, the amount of the substance that induced the change is greater in the transformed substance then in the original inducing substance. The transformed substance therefore has different properties from the parent, and these properties have new antigenic and invasive properties, and the changes are heritable, type-specific, and predictable (Avery, 1944, p. 154). This experiment is therefore one of the pioneers in changing molecular structure to where the changes are passed on the successive generations in a predictable fashion. This experiment also was a pioneer because it established that DNA has the ability to transfer genetic information, which can transform other cells. This is the most significant finding from the experiment, even if this was not realized by the researchers at the time. This experiment has significance to modern molecular biology because it has implications for everything from recombinant DNA to human cloning, and has contributed to the evolution of mutation by induction. It also has profound implications in the area of the study of DNA mutations, for it established DNA as the “molecular substrate of inheritance” (Stratton, 2009, p. 1). This has implications in the study of cancer, in which DNA is damaged by agents and genetic mutations (Stratton, 2009, p. 1). It also has been used as a bases for replacing one bacterial species with another, which has implications for medicine and the environment (Lartigue et al., 2007, p. 632). Of course, the most significant implication of Averys experiments is that Avery discovered that DNA transmits genetic material. This was a springboard for understanding the structure and function of DNA, and it was discovered that DNA defines the genetic code and regulates genetic expression (Jain, et al., 2008, p. 1). This, in turn, has an array of applications, far too many to list all of them in the context of this paper. However, the following are just a few – molecular targeted therapies, in which specific genes are targeted for their structure to be modified, is a basis of many biotechnological, biological and medicinal uses; critical genes are regulated and manipulated by using Triplex technology; using triples as targeted DNA damaging agents (Jain et al., 2008, p. 3). Other implications are that the genome can be mapped to see where the “fragile sites” or “hotspots” are located, which has implications for cures for lymphoma and leukemia, among other diseases (Jain et al., 2008, p. 8). Averys experiment also was a pioneer in that it showed how mutations are induced, which also has led to widespread implications. To review one area upon which this experiment has impacted the practice of inducing mutations, it has long been known that bacterial strains can mutate to become drug resistant by obtaining a new property that is passed along to its progeny (Demerec, 1955, p. 818). However, as far back as the 1950s, drug resistant strains of bacteria were decreased in virulence and resistance to penicillin by introducing injurious agents to the cells, and these characteristics remained unchanged through 50 passages (Voureka, 1952, p. 352). This has obvious implications for todays medicine, as drug resistant bacteria becomes increasingly common. While Avery did not realize that he was discovering how DNA transmits genetic information, he did realize that his experiments had implications for genetics. Avery compared the phenomenon being studied to genes, stating that the inducing substance is like a gene, and the capsular antigen that is produced by the induction is like a gene product, then citing Dobzhansky in stating that, with this study, “we are dealing with authentic cases of induction of specific mutations by specific treatments” (Avery et al., 1943, p. 155). Springboarding off Averys experiments, in 1957, researchers introduced 5-Broumouracil into the DNA structure, which produced a specific mutation that is induced at specific places in the genetic structure (Benzer & Freeze, 1958, p. 117). Nawa et al. (1975) also used Averys processes by translocating DNA from the stock of a red pepper plant to that plants scion, after having already used the hereditary changes on insects (Nawa et al., 1975, p. 241). This has clear implications for genetically engineered crops that can be engineered to be heartier, larger, more tasty, or adapt any kind of trait that a farmer can engineer to make his or her crop better. Malik et al. (2010) used mutation suppression that is induced by an aminoglycoside as a therapy for Duchenne muscular dystrophy, which is clearly based upon Averys findings, as Malik et al. used induction to change the characteristics of a targeted cell. Duchenne muscular dystrophy is one of the more lethal and common forms of muscular dystrophy, and attacks 1 in 3,500 male births (Malik et al., 2010, p. 379). There is no cure for the disease, only ameliorative and palliative measures, such as using glucocorticoids and prednisone. They used aminoglycosides, which are antibacterials that are used to primarily treat Gramm-negative bacterial infections, and have been shown, since the 1960s, to “reduce the fidelity of translation by inhibition of ribosomal proof reading” (Malik et al., 2010, p. 380). These antibiotics bind to ribosomal RNA of both the eukaryotes and prokaryotes, thus bringing about a change in the codon-anticodon pairing during translation (Malik et al., 2010, p. 380). The nonsense mutation inherent in the Duchenne muscular dystrophy is suppressed by the aminoglycoside “with special emphasis on gentamicin-induced readthrough of disease-causing premature termination codons” (Malik et al., 2010, p. 379). Stratton et al. (2009) used Averys findings as one of the bases for their assertion that cancer is caused by damaged DNA. As Avery showed that the DNA from one process can recombine to change another substance, so cancer is caused by DNA invading healthy cells. This process involves either substituting the bases, much like with Lartigue, where one genome is replaced by another genome; rearrangement, which is where DNA is broken and rejoined by another DNA segment that came from someplace else in the genome; copy number increases and copy number reductions (Stratton et al., 2009, p. 2). Additionally, the cancer cell may have acquired completely different DNA from a variety of sources, mainly viruses such as Epstein-Barr and the human papilloma virus (Stratton et al., 2009, p. 2). Averys findings also showed that mutations, once induced, are heritable and passed onto progeny. So are cancer cells, in which the mutation on one cell replicates itself (Stratton, 2009, p. 3). Therefore, the study of cancer is, in many ways, based upon Averys findings. Furthermore, studies on DNA as a potential gene targeting strategy has been discovered to be among “the most effective agents in cancer therapeutics” (Jain et al., 2008, p. 10). Viruses and the study of viruses is another area that is based upon Averys findings. There are several strains of viruses, including the Mimivirus, which have genes that were acquired from a host by HGT (Moreira & Lopez-Garcia, 2009, p. 309). This implies that the viruses cannot synthesize their own proteins, but that they need help from an injection of DNA from another host. Viruses also modify pre-existing genes, and create completely new genes, which helps in the evolution of new protein functions (Moreira & Lopez-Garcia, 2009, p. 309). Averys technique has been adapted for modern biology, by Lartigue et al., among others. In 2007, Lartigue et al. used Averys findings as a basis for their own experiment, noting that Avery proved that some bacteria “can take up naked DNA” (Lartigue et al., 2007, p. 632). Lartigue et al. took Averys processes one step further, taking a whole bacterial genome from one species and transformed it into another bacterial species, and the new cell has the same genotype and phenotype of the input genome (Lartigue et al., 2007, p. 632). Whereas with Averys experiment, there is a recombination, Lartigue took Averys findings an additional step by showing that the recipient genome can be entirely replaced by the donor genome (Lartigue et al., 2007, p. 632). This genome replacement is a basis for synthetic genomics, which can be used to solve problems in such fields as energy production, medicine and environmental stewardship (Lartigue et al., 2007, p. 632). Lin et al. (1990) have also used processes that are related to Averys research. They used somatic gene therapy in an effort to “introduce recombinant genes efficiently into the appropriate cells and tissues and to program the high-level and, in many cases, stable expression of these recombinant genes in vivo” (Lin et al., 1990, p. 2217). They used this technique to program recombinant gene expression into cardiac myocytes by directly injecting DNA into the left ventricular wall of the heart. Also relying upon Averys findings, Lin et al. found that skeletal muscle cells are able to take up and express DNA that has been recombined. Their experiment found that successful transfection of cells with DNA is not reliant upon mitosis, and that, while the mechanism for DNA uptake is yet unclear, it must be reliant upon structural or functional properties that skeletal and cardiac muscles share (Lin et al., 1990, p. 2220). They also found that using direct DNA injection into myocardium as somatic gene therapy has advantages, in that viral vectors are not required, which eliminates the possibility of the host being persistently infected; because recombinant DNA is an episome, it is not susceptible to host cell mutagenesis; and the method does not require that recipient cells grow in vitro (Lin et al., 1990, p. 2220). Conclusion The research put forward by Avery et al. experiment was truly groundbreaking, even if the researchers themselves did not fully appreciate this fact as it was occurring. Building upon previous studies that demonstrated that changes can be induced in higher organisms, and that these changes are replicated to the subsequent progeny, Avery et al. showed that one type of pneumococcus can be transformed into another type of pnemococcus by adding DNA, and that these changes are also replicated to all subsequent progeny of the targeted cell. Moreover, they were able to do this when both the capsular substance and the targeted substance were chemically distinct. In the process, they showed that DNA can transmit genetic information, and this has had a profound impact upon mankind. This finding has led to a way to decrease the virulence of drug resistant bacteria, and to a way to engineer crops to make them better. It has led to processes that have helped patients with a virulent form of muscular dystrophy, and to groundbreaking findings regarding cancer and heart disease. Viruses are better understood because of Averys work, as viruses sometimes work by receiving DNA from another host. And Lartigue et al. has used Averys work as a springboard for their own, taking it one step farther and actually replacing one gene with another gene, and this will have implications for energy production, the environment and medicine as we know it. In short, the world changed because of Averys findings. The finding that DNA transmits genetic information, and that injecting DNA into a cell changes that cell permanently, and that these changes are heritable, is one whose impact cannot be underestimated. Along with the examples shown in this paper, this procedure could have implications for human cloning, as the process of cloning relies upon some of the same principles as Averys work. It can lead to the findings of cures for diseases that afflict man now, but might not in the future. It has inspired imagination, as researchers might be able to create any number of ways to make our world better, as shown by the fact that Averys work has already had implications for crops, environment, energy and medicine. Averys work has helped us better understand heredity, and how DNA affects the expression of our genes and how these genes are passed down. In short, Averys work was groundbreaking and, without it, our world would be much less rich. Sources Used Avery, O., MacLeod, C., McCarty, M. 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Malik, V., Rodino-Klapac, L., Violiet, L & Mendell, J. (2010) “Aminoglycoside- induced Mutation Suppression as a Therapeutic Stategy for Duchenne Muscular Dystrophy,” Therapeutic Advances in Neurological Disorders, vol. 3, no. 6, pp. 379-389. Moreira, D. & Lopez-Garcia, P. (2009) “Ten Reasons to Exclude Viruses from the Tree of Life,” Nature, vol. 7, pp. 306-311. Nawa, S., Yamada, M. & Orta, Y. (1975) “Hereditary Changes in Capsicum Annum,” Japanese Journal of Genetics, vol. 50, no. 4, pp. 341-344. Stratton, M., Campbell, P. & Futreal, P. (2009) “The Cancer Genome,” Nature, vol. 458, pp. 1-15. Voureka, A. (1959) “Induced Variation in a Penicillin-Resistant Staphylococcus,” Journal of Genetic Microbiol, vol. 6, pp. 352-360. Read More