- Person
- Marshall Nirenberg
- Lived
- 1927–2010
- Field
- Biochemistry, genetics
- From
- American
The story
Why do people who take morphine need ever-larger doses, and why does stopping bring on withdrawal? By the early 1970s Marshall Nirenberg, already a Nobel laureate for deciphering the genetic code, had moved into neurobiology and had a new tool to tackle questions like these.
Starting in the late 1960s, he and the NIH neurophysiologist Phillip Nelson had grown neuroblastoma cells, tumour cells derived from developing neurons, in tissue culture. Fully mature neurons no longer divide, so they are hard to study in a dish, but neuroblastoma cells keep many neural properties while multiplying freely. Nirenberg's team cloned the cells and selected lines with chosen traits, including how sensitive they were to morphine.
Werner Klee, a biochemist at the National Institute of Mental Health, was interested in how morphine acts chemically on the brain. Working together, he and Nirenberg developed a neuroblastoma cell line with an unusually high number of morphine receptors. That gave them a clean, uniform population of nerve-like cells in which to watch the drug's effects.
They found that morphine inhibits adenylate cyclase, an enzyme that makes a key signalling molecule used in nerve cells. With continued exposure, the cells compensate by boosting the enzyme's activity, so normal signalling returns despite the drug. When the morphine is removed, that excess activity is suddenly unopposed and the cells are flooded with the signalling chemical, producing withdrawal until the system slowly returns to its normal level.
The work offered one of the first clear molecular explanations of opiate tolerance and dependence, worked out in a laboratory model of nerve cells.
It also demonstrated the value of the cell lines Nirenberg had built. For decades his laboratory supplied them to researchers worldwide, and children's hospitals and other laboratories used them to study neuromuscular connections, hormone regulation and nerve growth. The picture that emerged, of nerve cells adapting to a drug and then over-reacting when it is withdrawn, gave researchers a concrete mechanism to test in the search for better ways to understand and treat dependence.
Why it matters
Understanding the cellular mechanism of opiate dependence helped lay groundwork for research on addiction and its treatment.
About Marshall Nirenberg
NIH biochemist who in 1961 read the first word of the genetic code, UUU for phenylalanine, then led the race to decipher all of it, sharing the 1968 Nobel Prize in Medicine.
More about Marshall Nirenberg
- Nirenberg's lab found genes that shape the nervous systemIn the late 1980s Marshall Nirenberg's laboratory discovered four new homeobox genes in fruit flies, NK-1 to NK-4, which help control nervous system development.
- Nirenberg and Leder found how to read codon orderIn 1964 and 1965 Marshall Nirenberg's lab, with postdoc Philip Leder, devised a filter-binding method that revealed the exact letter order of genetic code words.
- Nirenberg's nerve-cell lines served labs worldwideFrom the late 1960s Marshall Nirenberg built a bank of neuroblastoma cell lines with chosen nerve traits and supplied them to scientists worldwide for decades.
- NIH colleagues rallied to help Nirenberg crack the codeIn the 1961–62 'coding race' against Severo Ochoa's large lab, many NIH scientists set aside their own work to help Marshall Nirenberg decipher the genetic code.
- Marshall Nirenberg read the first word of the genetic codeAt 3 a.m. on 27 May 1961, Marshall Nirenberg's NIH experiment showed that the RNA 'word' UUU codes for phenylalanine, the first codon ever deciphered.
- Nirenberg warned society to prepare for genetic engineeringIn a 1967 Science editorial, Marshall Nirenberg predicted humans would one day program cells and urged society to prepare to use that power wisely.
- Nirenberg spoke up for persecuted scientists and peaceMarshall Nirenberg protested Brazil's 1969 purge of scientists, backed appeals against hunger and nuclear escalation, and urged ratification of the Chemical Weapons Convention.
Sources
- Neuroblastoma Research, 1967–1976 NLM Profiles in Science
- From Neuroblastoma to Homeobox Genes, 1976-1992 U.S. National Library of Medicine
Another act of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.