Nobel Prize 1995

Nobel Prize 1995

Introduction

The Nobel Prize in the Physiology or Medicine category in 1995 involved threescientists, who identified, localized and classified a group of genes that were responsible for early development of the embryo of Drosophila melanogaster, the fruitfly. They determined that the group of genes influenced the body plan as well as segmentation of the body in the embryonic D. melanogaster. They preferred to use the fruitfly in their study due to its quick embryologic development.

Nüsslein-Volhard and Eric F. Wieschaus were working at the European Molecular Biology Laboratory in Heidelberg, Germany at the time they began their research in the late 1970s. They discovered that they had a common interest in researching on the embryonic development in D. melanogaster and the genes involved. On the other hand, Edward B. Lewis was doing independent research on the causes of mutations in the fruit fly. His focus was on the genes that cause the growth of an extra pair of wings which was the most common mutation. He began his research in the late 1970s and was working at the California Institute of Technology in Pasadena, California. He discovered that there is a group of genes that not only influenced the mutation that caused the duplication of wings but also created duplication of the body segments that supported the wings.

At the time Nüsslein-Volhard and Eric F. Wieschaus, very little was known concerning molecular and genetic mechanisms that influenced the development of multicellular organisms from a single cell into complex forms during the process of embryogenesis. There was no research on the influence of genetics on embryogenesis at the time. Most of what was known at the time on embryology and molecular biology was limited to the structure of the DNA after the helical structure was discovered in 1950. The alternative point of view came from the germ layer theory of development as proposed by Heinz Christian Pander and Karl Ernst von Baer.

Citations

http://resolver.caltech.edu/CaltechETD:etd-10172002-112502

http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.521.9929&rep=rep1&type=pdf

Methodology

Nüsslein-Volhard and Wieschaus began their research with the intention to find out how a segmented embryo developed from a newly fertilized egg. They chose the fruit fly due to its rapid development of nine days. Additionally, the fruit fly was easier to work with since it possesses only one set of genes that are involved in development;in comparison to human beings who have four sets. They first needed to identify and isolate the genes required for development. After this, they damaged the male flies’ DNA by “knocking out” one gene. The male fly was then used to breed generations of fruit flies without the specific gene that was knocked out. Through the method, they were able to isolate certain genes and their effects on the progeny. They performed their research on about 20,000 genes from the fruit fly. On the other hand, Lewis wanted to find out the reasons that cause duplication in wing development. He researched by mutating the embryos so that the resultant flies would have an extra pair of wings.

Their findings of Nüsslein-Volhard and Wieschaus included the fact that about 150 genes played an essential role in embryologic development. Moreover, out of the 150 genes, mutations in 15 of them would cause defects in the body segmentation. Through their findings, they were able to classify the genes. The first class of genes, the gap genes, influenced the body plan along the longitudinal axis from the head to the tail. Loss of these genes resulted in a reduced number of segments. The second class, pair-rule genes, had an influence on every second segment. Loss of this class of genes resulted in an embryo possessing only the odd-numbered body segments. The third class of genes, segment polarity genes, influenced the longitudinal polarity of each body segment.

Lewis found out that in flies that had an extra set of wings, the body segments bearing the wings were also duplicated. Additionally, he discovered that the duplication was caused by a family of genes referred to as bithorax-complex. These genes control the body segmentation along the head-tail axis. Moreover, the genes at the beginning of the complex influenced the development of an anterior segment while genes found towards the end influenced the development of posterior regions. These were the foundations of the colinearity principle. Furthermore, the genes in the complex overlapped, and if one was to knock out one gene, the genes next to it might influence the development of the region the affected gene was responsible for.

Figure 1. This image illustrates the defects from gene mutations. Adapted from http://gn434.shoutwiki.com/wiki/Nusslein_Volhard_and_Eric_Weischaus_-_Anterior_posterior_patterning_in_Drosophila_melanogaster

Figure 2. This image illustrates the colinearity principle. Adapted from http://thenode.biologists.com/molecular-control-of-embryonic-development/research/

 

Impact

The impact of the discovery in medicine is that the genes that control the development of the embryo in D. melanogaster have their counterparts in more complex multicellular organisms like human beings. Therefore, the findings are relevant in applications that deal with the human genome as the counterpart genes also perform the same functions in embryonic development. The results are relevant in the study of the influence of genes on human birth defects. Moreover, the findings are relevant in the study of in vitro fertilization, the discovery of congenital birth defects and the effects of teratogenic substances during organogenesis. Furthermore, the research can help in the development of ways to treat individuals with a high propensity to have offspring with birth defects. The findings have been applied in the development of genetically-modified organisms that are more resistant to diseases and have higher yields such as chicken.

Leave a Reply