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How We Learned to Stop Worrying and Love the Bomb

The Manhattan Project is infamous for its creation of the world’s first nuclear bomb and ushering in the *atomic age*. Few people, however, recognize the project’s invaluable contribution to the dawn of the *biological age*.

This [relatively] unsung tale begins as early as 1944 when the government started making post war arrangements regarding the transfer of atomic energy from military to civilian control. This transition was facilitated by the projected utility of the large quantities of radioactive isotopes being produced by the nuclear reactors at labs across the country. By June 1946, science magazine had published a catalog of readily available radioisotopes for sale. As a result, in less than two decades, the *central dogma* for modern biology was put in place: very generally, DNA is transcribed to make RNA, which is translated to make proteins.

The nuclear-reactor-induced chain of discoveries culminating in this central dogma really began in 1952 with the finding that DNA is the genetic material. Alfred Hershey and Martha Chase infected bacteria with bacteriophages, or bacterial viruses, to determine what material was transferred upon infection. Bacteriophages are essentially made up of DNA enclosed in a protein coat. To trace the phage molecules, sulfur-35 was used to radioactively label the phage protein coat and phosphorous-32 was used to radioactively label the phage DNA. Hershey and Chase found that the 32P-labeled DNA entered bacterial cells, while the 35S-labeled protein coat remained outside. Bacteriophage were passing their DNA, not their proteins, to their host cells! These results strongly suggested that proteins were not the hereditary material.

That such a relatively simple molecule could contain all the information necessary to make us was completely revolutionary // revelationary. Despite the Hershey + Chase experiment, it was not until Watson and Crick elucidated the structure of the double helix in 1953 that DNA finally entered the zeitgeist as the genetic material.* Focusing on the parallels between DNA’s linear structure of A’s, C’s, T’s, and G’s and the linear structure of the amino acid sequences making up proteins, scientists began thinking of dna as a *template* for life.

over time, rna’s radioactivity (in counts per minute) decreases as 14C-leucine is transferred to the growingly radioactive protein chain**

Between 1956-57, the zamecnik group led by Mahlon Hoagland at Massachusetts General Hospital identified RNA as an intermediate between DNA and protein synthesis by tracking the incorporation of the amino acid leucine labelled with carbon-14 into growing protein chains. Scientists already knew that ribosomes, made up of ribosomal RNA and proteins, were the sites of protein synthesis; however, no other forms of rna had yet been observed. Hoagland and Zamecnik demonstrated that to build proteins, a soluble RNA intermediate—later identified as transfer RNA—first becomes radioactively labeled by binding a 14C-leucine before this amino acid is transferred and added to the nascent chain (see Hoagland + Zamecnik’s original figure on right).

1961 saw the discovery of the link between all the pieces of the puzzle: messenger RNA.  mRNA literally carries the genetic message from dna in the nucleus to the ribosome where is acts as a scaffold for ordered protein assembly. Sydney Brenner, Matthew Meselson, and Francois Jacob are formally credited with proving mrna’s existence by using uracil, an RNA nucleotide, radiolabeled with carbon-14 to trace the formation of a transient RNA species that associates with ribosomes to make protein.

The Manhattan Project allowed scientists to follow their Geiger counters to fill in long-standing gaps in our knowledge since we first became aware of this concept of the gene, coined by Gregor Mendel in 1866. Over fifty years later, the central dogma is taught in [almost] every high school biology classroom across the world. Granted over the years, as with most everything in science, our understanding has been complicated and enriched by subsequent discoveries, such as rna’s ability to reverse transcribe to DNA and RNA’s ability to self replicate. Nonetheless—and in the spirit of some belated Thanksgiving gratitude—it is no exaggeration to say that biology owes its rapid and continuing advancement to the Manhattan Project’s [totally rad] leftovers.

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