IB 104 - Lecture 12 - DNA - September 22, 2006
Deoxyribose Nucleic Acid (DNA)
We are going to approach the structure of DNA from a historical perspective because it provides one of the
best examples of ingenious experiments and bold model building in biology. It is one of the most famous
stories in biology, and introduced the modern era of molecular biology that dominates much of biology
DNA was originally isolated in 1870.
A German by the name of Johann
became interested in
the chemical composition of the nucleus of cells, and became the first person to isolate DNA and RNA. He
. But proteins seemed much more interesting, and until the middle of the last (20
century most biologists paid little attention to DNA.
Griffith's transformation experiment in 1928.
A Brit, Fred Griffith, worked with an infectious or virulent
type (producing smooth colonies on agar plates) and a non-virulent type (producing rough colonies) of
- an infectious bacteria causing human diseases. When he injected mice with the
smooth strain, it killed them, but injecting them with the rough didn't. He could kill the smooth strain by
heating it, and it would not cause disease or kill the mice. But if he mixed heat-killed smooth bacteria with
rough bacteria and then injected mice, he found that the mice died. Moreover, he could isolate bacteria that
formed smooth colonies from these dead mice. Since the heat-killed smooth strain bacteria were probably
not coming back to life (not a Lazarus effect!), something chemical must be transferred from them to the
rough strain bacteria, which were thereby
into smooth infectious bacteria.
These three Americans -- professor,
postdoctoral fellow, and PhD graduate student, respectively -- working at Rockefeller University in New
York during World War II, used this bacterial transformation as an assay, to demonstrate that the chemical
responsible for transformation was DNA. When purified protein, carbohydrate, or lipid from smooth
bacteria was mixed with rough bacteria, they had no effect, but when DNA isolated from smooth bacteria
was used the rough bacteria were transformed to smooth and virulence, that is, they could kill mice when
injected; they had been
. Hence the hereditary messenger was DNA.
In 1943, when these experiments were at their peak, Oswald wrote a letter to his brother
that included the
"Sounds like a virus - may be a gene. But with mechanisms I am not now concerned -
One step at a time - and the first is what is the chemical nature of the transforming
principle? Someone else can work out the rest. Of course the problem bristles with
implications. It touches the biochemistry of the thymus type of nucleic acids which are
known to constitute the major part of the chromosomes but have been thought to be alike
regardless of origin and species. It touches genetics, enzyme chemistry, cell metabolism