In 1959, postdoctoral associate Dr. Thomas Caskey, participated in the Nobel Prize winning work of Dr. Marshall Nirenberg that helped unravel the genetic code of life. It was not just a “one-trick pony,” Caskey reflected.

Nirenberg won the Nobel Prize for this work which unveiled the set of rules by which information encoded without genetic material  (DNA or mRNA sequences) is translated into proteins by living cells.

For Caskey, senior National Institutes of Health investigator of the team, and his young colleagues Dr. Arthur Beaudet, research fellow at the NIH, and Dr. Joseph Goldstein, it was the start of three successful genetic research careers – careers that resulted in the advancement of genomics and the establishment of world leading genomics programs in Texas.

Evolution of field

In an anniversary commentary appearing in the current issue of the Proceedings of the National Academy of Sciences, genomics pioneer Caskey, currently a professor of molecular and human genetics at Baylor College of Medicine, reflected on this major milestone in the genetics field – on the 50th anniversary of the elucidation of the genetic code of life – and the evolution of the field ever since.

Caskey, Beaudet and Goldstein were a part of the team that discovered the “punctuation code words” of the genetic code, Caskey said.

“These ‘stop signals’ used protein recognition molecules – a major departure from the other 61 codons,” said Caskey. “Our identification of the three stop codons completed the 64 codon assignment. The ‘Rosetta Stone’ of how to translate from DNA to protein was finished.”

Codons are the sequence of three DNA or RNA nucleotides that corresponds with a specific amino acid or stop signal during protein synthesis.

“Today, this code is essential to identify genes and disease mutations from heritable disorders of children and adults and acquired mutations in cancer,” said Caskey.

“It was an extraordinary privilege to work in that very exciting NIH environment, first as a summer student in medical school and later as a research associate, learning about the roots of genetics and being exposed to such stellar colleagues,” said Beaudet.

Building a genetics program

In 1971, Beaudet and Caskey joined efforts to build a genetics program at Baylor. The program is now the number one in the country by National Institutes of Health funding status.

Caskey served as the director of the Center for Genetics at Baylor, the center that preceded the establishment of the Department of Molecular and Human Genetics at Baylor.

Beaudet became chair of the department in 1994.

Baylor is currently performing over 300 whole genome studies per month for childhood and adult disease. Computers search the 3.2 billion base pairs of sequence to find the genes (less than one percent of the total) by codon searching, Caskey said.

Dr. Richard Gibbs’ team in the Human Genome Sequencing Center at Baylor is involved with a major initiative to advance research in the field of cancer genomics using the code.

Goldstein is current chair of genetics at The University of Texas Southwestern Medical Center in Dallas, and a Nobel Prize winner for his work on the genetics of vascular disease.

Major contributions

Caskey, Beaudet and Goldstein have all made major contributions to the field of human genetics including: 

  • Caskey has identified the genetic basis of 10 major inheritable diseases and opened up the understanding of triplet repeat diseases (Fragile X, myotonic dystrophy and others.) The development of the method is used worldwide for forensics.
  • Beaudet is an internationally recognized scientist for his research on the role of epigenetics in human disease with a particular emphasis on genomic imprinting and diseases associated with an intellectual disability and autism.
  • Goldstein discovered the first gene responsible for heritable cardiovascular disease.

Caskey, Beaudet and Goldstein are members of the National Academy of Science, the Institute of Medicine and The Academy of Medicine, Engineering and Science of Texas.

Dr. Philip Leder, professor emeritus of genetics at Harvard Medical School, served as a co-author on this commentary. Leder was also a collaborator on the genetic code work.

The commentary appears in an anniversary special of the journal celebrating the 150th anniversary of the National Academy of Science that commemorated exceptional research published in the journal over the last century.

The journal selected Nirenberg’s code paper as the first “famous paper,” for their anniversary edition.