# Alexander Rich
Alexander Rich (November 15, 1924 – April 2015) was an American biochemist and biophysicist who spent nearly six decades at the [Massachusetts Institute of Technology](https://www.edgepedia.org/massachusetts-institute-of-technology) as the William Thompson Sedgwick Professor in the Department of Biology. He is best known for two structural findings: the three-dimensional structure of a transfer RNA molecule, and the discovery of Z-DNA, a left-handed form of the DNA double helix that exists in certain biological contexts.[1](https://science.mit.edu/alex-rich/) • [2](https://news.mit.edu/2015/obituary-alexander-rich-dies-90-0428)
| | |
|---|---|
| **Field** | Biochemistry and biophysics; structure of DNA, RNA, and collagen |
| **Born; died** | November 15, 1924, Hartford, Connecticut; April 27 or 28, 2015, Boston, aged 90[3](https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(15)61056-X.pdf) • [4](http://biographicalmemoirs.org/pdfs/rich-alexander.pdf) |
| **Career** | Caltech postdoctoral fellow with Linus Pauling, 1949–1954; NIMH physical chemistry section chief, 1954–1958; MIT from 1958[2](https://news.mit.edu/2015/obituary-alexander-rich-dies-90-0428) |
| **Signature work** | Z-DNA crystal structure (Nature, 1979); yeast tRNA structure (1973); first nucleic acid hybridization (1956), as documented by the *Journal of Biological Chemistry* |
| **Honors** | National Medal of Science (1995), Bower Award (2000), William Procter Prize (2001), Lomonosov Large Gold Medal (2002), Welch Award (2008)[2](https://news.mit.edu/2015/obituary-alexander-rich-dies-90-0428) |
| **Industry** | Co-founder of Repligen, Alkermes, and a third biotechnology company in his 80s[5](https://www.nature.com/articles/521291a) |
## Education and early career
Rich grew up in [Hartford, Connecticut](https://www.edgepedia.org/hartford-connecticut), and served in the U.S. Navy from 1943 to 1946. He then earned a bachelor's degree in biochemical sciences from Harvard in 1947 and an M.D. from Harvard Medical School in 1949.[2](https://news.mit.edu/2015/obituary-alexander-rich-dies-90-0428) • [6](https://www.cshl.edu/oral-history/alex-rich/) According to a retrospective in the [Journal of Biological Chemistry](https://www.edgepedia.org/journal-of-biological-chemistry), he decided to go directly into research rather than take an internship, joining the laboratory of [Linus Pauling](https://www.edgepedia.org/linus-pauling) at Caltech's Gates and Crellin Laboratories, where he switched to X-ray structural analysis.[2](https://news.mit.edu/2015/obituary-alexander-rich-dies-90-0428) • [7](https://www.sciencedirect.com/science/article/pii/S0021925820375645) At Caltech he began work on the structure of RNA; the paper "Some Relations Between DNA and RNA" appeared in *PNAS* in August 1954, according to the journal's own record.[6](https://www.cshl.edu/oral-history/alex-rich/) • [8](https://www.pnas.org/doi/abs/10.1073/pnas.40.8.759)
In 1952 Rich enlisted in the U.S. Public Health Service and was appointed Chief of the Section on Physical Chemistry at the newly formed [National Institute of Mental Health](https://www.edgepedia.org/national-institute-of-mental-health), staying at Caltech two more years before moving to Bethesda.[7](https://www.sciencedirect.com/science/article/pii/S0021925820375645) He served as chief of the physical chemistry section from 1954 to 1958 and spent 1955 to 1956 as a visiting scientist at the [Cavendish Laboratory](https://www.edgepedia.org/cavendish-laboratory) in Cambridge, England.[2](https://news.mit.edu/2015/obituary-alexander-rich-dies-90-0428) In 1958 he joined the MIT biology department.[7](https://www.sciencedirect.com/science/article/pii/S0021925820375645)
## Career at MIT
Rich held the William Thompson Sedgwick Professorship of Biophysics and [Biochemistry](https://www.edgepedia.org/biochemistry) and remained at MIT almost to his last day in April 2015, at age 90.[4](http://biographicalmemoirs.org/pdfs/rich-alexander.pdf) He published more than 600 scientific articles.[3](https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(15)61056-X.pdf) From 1969 to 1980 he was an investigator on NASA's Viking mission to Mars, working on experiments designed to look for life on that planet.[2](https://news.mit.edu/2015/obituary-alexander-rich-dies-90-0428)
## Representative work
**Z-DNA.** In 1979 Rich led the MIT team that solved the crystal structure of the self-complementary DNA hexamer d(CGCGCG). The crystals diffracted to about 0.7 Å resolution, and the structure revealed a left-handed double helix with two antiparallel chains held together by Watson-Crick base pairs, named Z-DNA for its zigzag backbone. Every other base was rotated around its glycosyl bond, alternating anti and syn conformations, unlike the smooth continuous coil of B-DNA.[4](http://biographicalmemoirs.org/pdfs/rich-alexander.pdf) • [7](https://www.sciencedirect.com/science/article/pii/S0021925820375645) The structure appeared on the cover of Nature in 1979.[3](https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(15)61056-X.pdf)
In 1985 he published the Cell paper "Chemical probes of DNA conformation: detection of Z-DNA at nucleotide resolution."[9](https://doi.org/10.1016/0092-8674(85)90268-5) Three segments of SV40 were shown to form Z-DNA in the transcriptional enhancer region, the first specific example suggesting a role for Z-DNA in regulating transcription.[10](https://doi.org/10.1080/07391102.1983.10507424)
**Early nucleic acid work.** In 1955 Rich deduced the three-dimensional triple-helical structure of collagen with a colleague; in 1956, at NIH, he and a colleague performed the first nucleic acid hybridization reaction, mixing poly-rA and poly-rU, and finding an RNA double helix by [X-ray diffraction](https://www.edgepedia.org/x-ray-diffraction).[2](https://news.mit.edu/2015/obituary-alexander-rich-dies-90-0428) • [4](http://biographicalmemoirs.org/pdfs/rich-alexander.pdf) He showed in 1960, at MIT, that an RNA strand and a DNA strand can form a double helix, a structural basis for copying DNA sequence into messenger RNA.[2](https://news.mit.edu/2015/obituary-alexander-rich-dies-90-0428) • [1](https://science.mit.edu/alex-rich/) In 1962 he published the polyribosome finding, and in 1973 he determined the structure of yeast tRNA(Phe); its backbone tracing appeared on the front page of *The New York Times* on January 13, 1973.[7](https://www.sciencedirect.com/science/article/pii/S0021925820375645)
## Z-DNA and its biological significance
Z-DNA requires higher energy to stabilize than the common B form. It can be generated by negative supercoiling (twisting strain that unwinds the DNA helix) produced during DNA unwinding, gene transcription, and recombination, so its formation is transient and dynamic.[4](http://biographicalmemoirs.org/pdfs/rich-alexander.pdf) The most important biological factors stabilizing it are negative supercoiling and Z-DNA binding proteins.[10](https://doi.org/10.1080/07391102.1983.10507424)
Rich's laboratory developed a Z-DNA-specific monoclonal antibody and used it to probe the genome; these studies showed the Z conformation often resides in transcriptionally active rather than silent genes.[4](http://biographicalmemoirs.org/pdfs/rich-alexander.pdf) Z-DNA is largely found in transcribing genes, and cessation of transcription rapidly converts it back to B-DNA through the action of topoisomerases.[7](https://www.sciencedirect.com/science/article/pii/S0021925820375645) In 1995, researchers led by Rich reported the first biological role for Z-DNA: the identification of a protein that binds tightly to Z-DNA and is an RNA-editing enzyme.[2](https://news.mit.edu/2015/obituary-alexander-rich-dies-90-0428)
On how the discovery fits earlier work: in 1972 the ultraviolet circular dichroism of poly(dG-dC) was shown to be nearly inverted in 4 M sodium chloride; Rich confirmed a B-DNA to Z-DNA conversion by examining Raman spectra of Z-DNA crystals.[7](https://www.sciencedirect.com/science/article/pii/S0021925820375645)
## Honors, industry roles, and legacy
According to a [Cold Spring Harbor Laboratory](https://www.edgepedia.org/cold-spring-harbor-laboratory) oral history, Rich was elected to the National Academy of Sciences in 1970, and also to the American Academy of Arts and Sciences, the [Institute of Medicine](https://www.edgepedia.org/institute-of-medicine), the French, Russian, and Pontifical Academies of Sciences, and the Pontifical Academy (nominated in biophysics and biology on April 17, 1978).[6](https://www.cshl.edu/oral-history/alex-rich/) • [11](https://www.pas.va/en/academicians/deceased/rich.html) He received the National Medal of Science in 1995, a Bower Award worth about $200,000 from the [Franklin Institute](https://www.edgepedia.org/franklin-institute) in 2000, Sigma Xi's William Procter Prize in 2001, the Lomonosov Large Gold Medal in 2002, and was an early recipient of the roughly $240,000 Welch Award in Chemistry in 2008. In 1976 he was appointed to a six-year term on the U.S. National Science Board.[2](https://news.mit.edu/2015/obituary-alexander-rich-dies-90-0428)
He co-founded three biotechnology companies: Repligen, Alkermes (founded 1987), and a third company in his 80s.[5](https://www.nature.com/articles/521291a) Diagnostics for HIV and tests for genes that cause breast cancer were built on his discoveries, with continuing applications in diagnostics, forensics, genealogy, and gene sequencing.[12](https://nationalmedals.org/laureate/alexander-rich/)
Rich died in April 2015 in Boston at age 90; according to the MIT School of Science, The Lancet reports death from pneumonia on April 27, while the National Academy of Sciences memoir gives April 28.[3](https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(15)61056-X.pdf) • [4](http://biographicalmemoirs.org/pdfs/rich-alexander.pdf)
## References
1. Alexander Rich, the importance of RNA and the development of nucleic acid hybridization. MIT School of Science. https://science.mit.edu/alex-rich/
2. Alexander Rich dies at 90. MIT News, April 28, 2015. https://news.mit.edu/2015/obituary-alexander-rich-dies-90-0428
3. https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(15)61056-X.pdf
4. Alexander Rich. National Academy of Sciences Biographical Memoir. http://biographicalmemoirs.org/pdfs/rich-alexander.pdf
5. Alexander Rich (1924–2015). Nature, 2015. https://www.nature.com/articles/521291a
6. Alex Rich. Cold Spring Harbor Laboratory Oral History. https://www.cshl.edu/oral-history/alex-rich/
7. Classics: The Discovery of Z-DNA, the Work of Alexander Rich. Journal of Biological Chemistry. https://www.sciencedirect.com/science/article/pii/S0021925820375645
8. Some Relations Between DNA and RNA. PNAS 40(8):759-764, August 1954. https://www.pnas.org/doi/abs/10.1073/pnas.40.8.759
9. https://doi.org/10.1016/0092-8674(85)90268-5
10. Stabilization and Detection of Natural Left-Handed Z-DNA. Journal of Biomolecular Structure and Dynamics, 1983. https://doi.org/10.1080/07391102.1983.10507424
11. Alexander Rich. Pontifical Academy of Sciences. https://www.pas.va/en/academicians/deceased/rich.html
12. Alexander Rich. National Science and Technology Medals Foundation. https://nationalmedals.org/laureate/alexander-rich/
---
*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in structural biology, biochemistry, and biophysics › Nucleic acids, RNA, and chromatin › Chromatin and gene expression*
*Initially written Sep 20, 2026 · Reviewed: Sep 25, 2026; Sep 30, 2026 · Edited: Sep 25, 2026; Sep 30, 2026; Oct 25, 2026 · Last review: Sep 30, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license