Legacy of CRISPR: Remembering Co-Discoverer Hamilton Smith

Hamilton Smith, co-discoverer of type two restriction enzymes, revolutionized molecular biology by providing precise tools for cutting DNA at specific sequences. His groundbreaking work in 1978, alongside Werner Arber and Daniel Nathans, earned them the Nobel Prize in Physiology or Medicine.

Smith's career continued to flourish when he collaborated on sequencing the genome of Haemophilus influenzae in 1993, which was published in 1995 as the first complete genome of any organism. This collaboration laid the groundwork for significant advancements, leading to the first draft of the human genome in 2001 and the creation of the first cell with a synthetic genome in 2010.

Born in New York City and raised in Champaign-Urbana, Illinois, Smith's interest in biology ignited while studying mathematics at the University of California, Berkeley, which culminated in a medical degree from Johns Hopkins University.

After serving in the Navy and completing his medical residency, Smith joined the University of Michigan, where he worked with Myron Levine on bacteriophage P22. This experience allowed him to master DNA isolation techniques that became crucial to his later contributions.

In 1967, he joined Johns Hopkins' microbiology department, where he discovered a restriction enzyme by analyzing DNA viscosity changes. His innovative techniques proved the enzyme's ability to recognize unique DNA sequences, leading to critical publications in the Journal of Molecular Biology in 1970.

The day he received the Nobel Prize in 1978 was memorable for his family, as they initially doubted the news until confirmed. Smith's impactful work continued in 1993 when he met at a conference in Bilbao, Spain, and agreed to collaborate with the Institute for Genomic Research, leading to the sequencing of H. influenzae using whole-genome shotgun sequencing.

This method relied on achieving a precise statistical distribution of DNA fragments, a technique that Smith developed further. The sequencing effort involved 25,000 fragments, which were mathematically assembled into a complete circular genome.

Smith's tenure at the Institute for Genomic Research spanned 25 years, during which he collaborated on numerous genomes, including Neisseria meningitidis, paving the way for the first meningococcal B vaccine that has saved countless lives.

Smith's legacy is a testament to the vital role of foundational research in genetics and biotechnology, influencing the development of CRISPR technology and future genetic innovations.