Published by the Students of Johns Hopkins since 1896
August 14, 2022

Professor awarded for finds in genetics

By MICHAEL YAMAKAWA | September 20, 2012

Hopkins added another decoration to its faculty’s ranks with Dr. Donald Brown’s receipt of the prestigious Lasker-Koshland Special Achievement Award in Medical Science. Brown, an adjunct professor in the department of biology since 1969, won the award for his work in genetics. He was also acknowledged for his role mentoring young scientists. Tom Maniatis of the Biochemistry and Molecular Biophysics department at Columbia University was also recognized.

The Lasker-Koshland Special Achievement Award is presented to individuals who have demonstrated exceptional leadership and unparalleled achievements in biomedical science. It takes everyone by no surprise that Brown was one of two recipients this year, as his contributions to science have revolutionized molecular genetics and have nurtured a wave of top-notch biologists for the next generation.

He is the founder of the Life Sciences Research Foundation, which provides qualified young scientists with the means for an independent postdoctoral fellowship.

He has also directed the Department of Embryology at the Carnegie Institution from 1976 to 1994, where five of eight laboratory heads in the department were members of the U.S. National Academy of Sciences during his tenure.

Furthermore, two of the remaining three would later become members and one of them would win the Nobel Prize.

Brown’s first step into research was in the midst of his medical school career at the University of Chicago, where he gained a deep interest in developmental biology. As a biochemically-oriented student, he pursued a master’s degree in biochemistry after he concluded his medical education.

It was 1960 when he joined the Carnegie Institution, which, to put into reference, was shortly after the discovery of DNA in 1953. Molecular biology was still a very young field at that time.

At the Carnegie Institution, he worked with frog embryos, a model that was commonly used at that time due to the abundance of material provided by their eggs. With these eggs, he was able to grind, extract, and purify materials through biochemical procedures, instead of using Drosophila, a species of flies very frequently used in modern genetics labs.

In the early 1960s, RNA was discovered to be the direct product of genes rather than proteins. The central dogma of genetics says that proteins come from RNA, which is initially produced from DNA. In other words, protein is not directly manufactured from DNA. Instead of examining protein activity to study differential gene expression, gene activity could be investigated via measurements of RNA production. With the ability to study RNA of different sizes through a technique that used sucrose gradients to separate RNA particles by mass, Brown found that various RNA are synthesized differently and are activated at different times.

While working with the frog embryos at the Carnegie Institution, an almost accidental procedure change led Brown to new discoveries. He decided to nurture eggs in distilled water, instead of tap water. As a biochemist who commonly used distilled water for experiments, he found that distilled water instead killed the eggs. It became clear that the eggs required certain metallic ions found in tap water to make it to the next stages of development. Specifically, magnesium ions were necessary to stabilize the structure of ribosomes. He deduced that the deaths were caused by the inability of the eggs to produce functional ribosomes.

In 1962, he read about a frog mutation in a species known as Xenopus laevis that led to a lack of nucleoli—back then, it was only suspect that the nucleolus was responsible for ribosomal production.

Through a series of experiments, he found that the eggs with magnesium deficiency and eggs with the nucleolar mutation died at approximately the same time, and thus the magnesium deficiency was a phenocopy, or an identical physical trait, of the anucleolar mutation. The nucleolus was verified as the source of ribosomal manufacturing.

The egg of a frog embryo carries around 200,000 times the number of ribosomes in most somatic cells. In fact, in frog embryos, the first transcriptional processes that occur are done with pre-existing ribosomes and mRNA.

Therefore, anucleolar zygotes can actually survive a few days until the feeding tadpole stage when more ribosomes are necessary for development. Brown showed that one of the mechanisms for producing this spectacular amount of ribosomes is through the repetition and amplification of rRNA, or ribosomal RNA, genes.

This discovery allowed Brown to take advantage of the abundance of amplified rRNA genes to isolate and study them. The first set of genes that were purified were the 18S and 28S rRNA genes, which subsequently paved way for the advent of recombinant DNA technology in the late 1970s. Soon with recombinant DNA technology, DNA — which Brown used to describe as “sticky goo” before this new era — became easily manageable macromolecules.

Thus, most of Brown’s work attributed for winning the Lasker was concentrated in his early 1960s research — when his study on the anucleolar mutant was published. In 1970, he purified 5S RNA; this would later be implicated in important functions of regulating RNA production. As scientists entered a new era of recombinant DNA technology, the repetition and amplification of genes was no longer a requisite for their studying. Today, we are able to easily investigate globin genes, skin genes, and a myriad of others that constitute an extremely small portion of our genome, which back in the 60s would have been impossible to isolate.

Currently, Brown continues to work with the metamorphosis of amphibians at the Carnegie Institution. He offered some advice for the young, undergraduate scientists at Hopkins: “It may sound highly theoretical in this day in age when there are economic problems and worries about jobs, but you have got to like what you do — it’s just so important to enjoy it. Science is a young person sport. When you’re young and energetic, that’s when it’s really exciting. It doesn’t matter how trivial your project is — it’s yours, and it’s fun.”

Comments powered by Disqus

Please note All comments are eligible for publication in The News-Letter.

News-Letter Special Editions