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The First Array

By | August 25, 2003

Foundations | The First Array Courtesy of Mark Schema Ron Davis and I were studying plant transcription factors in 1990, but progress was slow and arduous because the gene expression tools were so primitive. We conceived of the DNA microarray in 1993 to speed up gene expression analysis by combining biology and high technology. We adapted Affymetrix VLSIPS technology to synthesize yeast microarrays, and measured gene expression in yeast cells by hybridizing fluorescent probes derived from

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Foundations | The Transforming Principle Click for larger version (74K) On May 13th, 1943, Oswald T. Avery (1877-1945) wrote a 14-page meandering letter to his brother Roy about his research, his despondence, his fears, and his dreams. His emotions range from excited explanation of what was happening in his lab to trepidations that the scientific community wouldn't accept his results. At one point, Avery questions whether he should leave the Rockefeller Institute, give up science, and retu

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Foundations | The Holy Grail of Immunology Click for larger version (27K) In 1983, Tak Mak's lab cloned the beta chain of the T-cell receptor, helping to accomplish what the immunology community had been anticipating for 20-plus years. But the T-cell receptor's structure was believed to be heterodimeric, and no one had deciphered what the other piece looked like. In 1984, Mak sketched his thoughts on its shape for a student, Pamela Ohashi, who then made antibodies to peptides, using the a

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Evil Science

June 30, 2003

Foundations | Evil Science Click for larger version (39K) Few events signify science gone awry more than the Tuskegee experiments. Started in 1932 to study the effects of untreated syphilis in 399 black men, the scientific rationale for the work became inconsequential by the late 1930s, when it was proven that the symptoms could be treated with heavy-metal therapy. Yet bureaucratic inertia compelled its continuation. In 1943, the morally questionable descended to the intentionally harmful

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The Death of a Cell

June 16, 2003

Foundations | The Death of a Cell  Click for larger version (21K) In the autumn of 1974, more out of curiosity than of any particular plan, I sat down to watch newly hatched nematodes. The idea was to see where certain, late-developing neurons came from. At first the details were hard to follow, because the larvae jittered around. But I learned to keep them well fed, contented, and growing normally. The first time that I saw a cell division from beginning to end was a wonderful revelat

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The Genesis of Prozac

June 2, 2003

Foundations | The Genesis of Prozac  Click for larger version (71K) Fifty-plus years ago, Julius Axelrod and his colleagues discovered the phenomenona of neurotransmitter inactivation by reuptake into the nerve terminal, a finding that led to the development of antidepressant drugs. By increasing the neurotransmitter amount in the synaptic cleft, this allowed greater amounts of the neurotransmitter to act on postsynaptic receptors more intensely. "This is an example of basic important

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Foundations | 'Unlimited in its Implications...'  Click for larger version (30K) One cold night in 1945, a Columbia University medical school student named Joshua Lederberg read Oswald Avery's 1944 landmark paper that identified deoxyribonucleic acid as the chemical that carries genetic information. Lederberg wrote his immediate reactions in a diary entry the next day: "I had the evening all to myself, and particularly the excruciating pleasure of reading Avery ... Terrific and unlimi

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Foundation | The Might of Mitochondria Courtesy of Art Horwich Sometimes, science happens in a eureka moment. For Art Horwich, a molecular biologist at Yale University, the idea that the cell has foldases that assist folding of polypeptides to the native state came at 11:00 p.m. on a September night in 1987 when Horwich and his student Ming Cheng were chatting about a yeast mutant library. Horwich asked: "'What if there is a machinery inside mitochondria that actually helps imported protein

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Foundations | Barbara McClintock, On Her Own  Click for larger version (49K) Geneticist Barbara McClintock, since her death in 1992, has become a feminist hero. She held steady in the male-dominated world of science, earning her first award in 1947 and culminating her career in 1982 with the Nobel Prize. Her observations and discoveries laid the groundwork for modern genetics research. Her theory that the genome constantly changes and regulates itself, derided in her time as being outl

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Foundations | DNA Base Pairs, and Erwin Chargaff  Click for larger version (32K) Erwin Chargaff's groundbreaking research, which showed that DNA base pairs had a complementary relationship, laid the foundation for James Watson's and Francis Crick's DNA model. When word spread that Watson and Crick had solved the structure, Chargaff wrote to Maurice Wilkins, who worked with Rosalind Franklin at Kings' College, London--and who later received the Nobel Prize, along with Watson and Crick.

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