Biology for AP Courses · DNA Structure and Function
Historical Basis of Modern Understanding
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In 30 seconds
It is easy to take for granted that DNA is the molecule of heredity, but that fact was not established until the middle of the twentieth century. Before the 1940s, most geneticists suspected protein was the genetic material: proteins are large, complex, and enormously diverse, while DNA seemed monotonous — just four building blocks repeated over and over. This topic follows the experiments that overturned that assumption, from Griffith's transformation studies in 1928 through the Hershey–Chase phage experiments of 1952, and then the structural breakthrough of Watson, Crick, Wilkins, and Franklin in 1953. The story is a masterclass in experimental design: each experiment isolates one variable, includes controls, and answers one narrow question, and each result builds on the last.
The timeline worth remembering: 1928 Griffith discovers a "Transforming principle The unknown substance that permanently changes one bacterial strain into another Full entry →"; 1944 Avery, MacLeod, and McCarty identify it as DNA; 1952 Hershey and Chase confirm that DNA (not protein) enters cells during phage infection; in parallel, Chargaff's rules A = T and G = C in every DNA sample; ratios vary by species Full entry → (late 1940s) and Franklin's X-ray diffraction Technique revealing repeating structure by scattering X-rays off a fiber Full entry → images (1952) supply the chemical and physical clues; and in 1953 Watson and Crick propose the Double helix Two antiparallel DNA strands wound together, paired A–T and G–C Full entry →. In 1962, Watson, Crick, and Wilkins shared the Nobel Prize in Physiology or Medicine; Franklin's pivotal contribution was recognized more widely only later, after her death.
Why this matters
- How science actually works: These experiments are the textbook's clearest examples of the evidence-and-reasoning loop — hypothesis, controlled experiment, interpretation, revision — and AP Biology questions routinely ask you to evaluate them.
- The logic of controls: Griffith's and Hershey–Chase's designs introduced "label and follow" and "kill and observe" reasoning still used in research today.
- Foundation for everything after: Every topic in this chapter (structure, replication, transcription, biotechnology) assumes the conclusion these experiments proved: DNA is the hereditary material, and its structure explains how it is copied.
- Real-world payoff: Radioisotope labeling, fractionation, and X-ray crystallography are ancestors of today's DNA sequencing, forensics, and structural biology.
The college version
Core Concepts
The question before the experiments
By the early 1900s, Morgan and others had shown that genes are physically located on chromosomes, and chromosomes were known to contain both DNA and protein. So by 1928 the open question was not where heredity lives but which molecule — DNA or protein — actually carries the information. Because proteins have 20 different amino acids and DNA seemed to have only four repeating nucleotides, most biochemists bet on protein. The experiments below had to overcome that bias with hard evidence.
Griffith's transformation experiment (1928)
Frederick Griffith worked with Streptococcus pneumoniae, which has two strains: S (smooth) strains have a polysaccharide capsule and cause pneumonia; R (rough) strains lack the capsule and are harmless. His mouse-injection series:
- Live S bacteria → mice die (S is virulent).
- Live R bacteria → mice live (R is harmless).
- Heat-killed S bacteria → mice live (heat destroys virulence).
- Live R + heat-killed S → mice die, and the blood contains live, encapsulated S bacteria.
The only explanation for result 4: something in the dead S cells transformed harmless R cells into virulent S cells — permanently, since the recovered S bacteria passed the trait to offspring. Griffith called it the "transforming principle" but did not identify it.
Avery, MacLeod, and McCarty (1944): the transforming principle is DNA
Two decades later, Oswald Avery, Colin MacLeod, and Maclyn McCarty repeated the transformation in vitro (in a test tube, no mice) and set out to identify the transforming substance. They extracted the S-cell mixture and treated separate samples with enzymes that destroy specific molecule classes: proteases (destroy protein) and RNase (destroy RNA) left transforming activity intact, but DNase (destroy DNA) eliminated it. The logic is airtight: if destroying DNA is the only treatment that kills transforming activity, DNA is the transforming principle. This was the first experimental demonstration that DNA carries hereditary information — yet some scientists still doubted, arguing that a trace of protein might remain in the preparation.
Hershey and Chase (1952): DNA enters the cell, protein does not
Alfred Hershey and Martha Chase settled the argument using Bacteriophage A virus that infects bacteria Full entry → T2, a virus that infects E. coli and consists of a DNA core inside a protein coat. Their strategy was to radioactively label each component separately and follow where it went. One phage batch was grown so its DNA contained phosphorus-32 (³²P) — phosphorus is found in DNA but not in phage protein. Another batch was grown so its protein contained sulfur-35 (³⁵S) — sulfur is found in protein but not in DNA. After infection, blending and centrifugation separated the empty phage coats from the bacteria. Most of the ³²P (DNA) ended up inside the bacteria, while most of the ³⁵S (protein) stayed in the empty coats. Since the injected DNA alone directs production of new phages, DNA — not protein — is the genetic material.
Chargaff's rules and Franklin's X-ray data
Erwin Chargaff analyzed the base composition of DNA from many species and reported two patterns: the proportions of the four bases differ between species (so DNA is not a boring repeating polymer), and in every species the amount of adenine equals thymine and guanine equals cytosine (A = T, G = C). Rosalind Franklin's X-ray diffraction images of DNA fibers — including the famous "Photo 51" — revealed a cross-shaped pattern indicating a helix and a repeat spacing of about 0.34 nm (3.4 Å), the distance between stacked base pairs. These data became critical clues for the structure.
Watson and Crick (1953): the double helix
Using Franklin's diffraction data, Chargaff's rules, and molecular models, James Watson and Francis Crick proposed that DNA is a double helix of two antiparallel strands held together by specific hydrogen-bonded base pairs (A with T, G with C). The pairing rules immediately suggested a copying mechanism: each strand can serve as a template for the other. Watson, Crick, and Maurice Wilkins shared the 1962 Nobel Prize; Franklin, who died in 1958, was not included under the rules of the time, though her data were essential to the discovery.
Common Confusions
| Do Not Confuse | With | Difference |
|---|---|---|
| Griffith discovering the genetic material | Griffith discovering its nature | Griffith proved a transforming principle exists (1928); Avery, MacLeod, and McCarty proved it is DNA (1944). |
| ³²P labeling protein | ³²P labeling DNA | Phosphorus is in DNA, not phage protein; sulfur (³⁵S) labels protein. |
| Franklin's photo being the whole model | Franklin's data being one key piece | The final model also needed Chargaff's rules and model building; Franklin supplied the helix geometry and spacing. |
| Base ratios being identical across species | Base ratios varying by species | Composition differs between species, but A = T and G = C within every species. |
| The 1962 Nobel reflecting full credit | The prize reflecting all contributors | Only Watson, Crick, and Wilkins received it; Franklin's contribution was recognized later. |
Eli explains
The same idea, in plain words
Explain it like I’m 10
Scientists once thought proteins carried your heredity, because proteins do many jobs and DNA looked boring. One experiment showed that a dead, harmless-looking mixture could change living bacteria into dangerous ones, and only destroying the DNA stopped that change. A later experiment put glowing tags on virus DNA and virus protein: only the DNA-tagged material got inside the bacteria. So the "recipe book" of life is DNA — and knowing its shape later explained how it gets copied.
Worked example
Imagine you are a scientist in 1952 with two questions: "Does phage protein or phage DNA enter the host cell?" and "How can I tell them apart if they look identical under a microscope?" The answer is to make each component uniquely detectable:
- Make two labeled phage stocks. Grow phages in bacteria supplied with ³²P (radioactive phosphorus) so the phage DNA becomes radioactive; grow another batch in bacteria supplied with ³⁵S (radioactive sulfur) so the phage protein becomes radioactive. Because phosphorus appears only in DNA and sulfur only in protein, each batch is tagged in exactly one component.
- Infect. Add each labeled stock to fresh, unlabeled bacteria and allow infection to begin.
- Separate. Blending shears the empty phage coats off the bacterial surface; centrifugation pellets the heavy bacteria and leaves lightweight coats in the supernatant.
- Measure. The bacterial pellet is radioactive with ³²P-labeled phages (DNA entered the cell); the supernatant is radioactive with ³⁵S-labeled phages (protein stayed outside).
- Conclude. Only DNA gets inside the bacteria, and the infected bacteria produce new phages. Therefore the genetic material is DNA, not protein.
This "tag one part, follow the tag" design is the same logic used in modern molecular biology, from tracking proteins in cells to locating genes.
Key takeaways
- Timeline: Griffith 1928 → Avery–MacLeod–McCarty 1944 → Hershey–Chase 1952 → Chargaff + Franklin → Watson & Crick 1953.
- Griffith: live R + heat-killed S → mouse dies; transformation is permanent and heritable.
- Avery: only DNase (not protease or RNase) destroys transforming activity → DNA is the transforming principle.
- Hershey–Chase: ³²P (DNA) in bacteria; ³⁵S (protein) in phage ghosts → DNA is the genetic material.
- Chargaff's rules: A = T and G = C; base ratios differ between species.
- Franklin's X-ray diffraction showed a helix with ~0.34 nm spacing between stacked bases.
- The double helix's base pairing (A–T, G–C) immediately suggested a copying mechanism (next topics).
Check yourself
5 review questions from the chapter. Try each one, then open the answer.
What was the "transforming principle," and what did Griffith's mouse-injection results demonstrate about it?
Show answer
The transforming principle is the substance that permanently converts harmless R bacteria into virulent S bacteria. Griffith showed that live R + heat-killed S killed mice and produced live S bacteria — a heritable change — but he did not identify the substance.
How did Avery, MacLeod, and McCarty identify the transforming substance as DNA?
Show answer
They treated the S-cell extract with enzymes that destroy specific molecules. Proteases and RNase left transforming activity intact, but DNase destroyed it, proving DNA was required — and therefore was the transforming principle.
In the Hershey–Chase experiment, which isotope ended up inside the bacteria, and which stayed in the phage coats? What did that show?
Show answer
³²P (DNA) was found inside the bacteria; ³⁵S (protein) remained in the empty phage coats. This showed that DNA — not protein — enters the cell and directs phage production.
State Chargaff's rules and explain why they mattered for the double-helix model.
Show answer
In every species, A = T and G = C, while overall base composition varies between species. The A = T / G = C pattern suggested specific base pairing between the two strands.
What evidence did Franklin's X-ray diffraction provide, and what did Watson and Crick add to it?
Show answer
Franklin's X-ray images showed DNA is a helix with regularly spaced stacked bases (about 0.34 nm apart). Watson and Crick combined that geometry with Chargaff's pairing rules to build the antiparallel, base-paired double-helix model.
Study tools & related lessonsKey vocabulary · Related
Key vocabulary
- Transforming principle
- The unknown substance that permanently changes one bacterial strain into another
- S and R strains
- Smooth (capsule, virulent) and rough (no capsule, harmless) S. pneumoniae
- Bacteriophage
- A virus that infects bacteria
- Radioactive labeling
- Using isotopes (³²P, ³⁵S) to mark a molecule so it can be tracked
- X-ray diffraction
- Technique revealing repeating structure by scattering X-rays off a fiber
- Chargaff's rules
- A = T and G = C in every DNA sample; ratios vary by species
- Double helix
- Two antiparallel DNA strands wound together, paired A–T and G–C
Sources & references
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