Mullard, A. (2020). 2019 FDA drug approvals. Nat. Rev. Drug Discovery 19: 79–84.4 4 Stevens, A.J., Jensen, J.J., Wyller, K. et al. (2011). The role of public‐sector research in the discovery of drugs and vaccines. N. Engl. J. Med. 364: 535–541.
5 5 Nayak, R.K., Avorn, J., and Kesselheim, A.S. (2019). Public sector financial support for late stage discovery of new drugs in the United States: cohort study. BMJ 367: l5766.
6 6 Edwards, J.C.W., Cambridge, G., and Abrahams, V.M. (1999). Do self‐perpetuating B lymphocytes drive human autoimmune disease? Immunology 97: 188–196.
7 7 Protheroe, A., Edwards, J.C.W., Simmons, A. et al. (1999). Remission of inflammatory arthropathy in association with anti‐CD20 therapy for non‐Hodgkin's lymphoma. Rheumatology 38: 1150–1152.
8 8 Edwards, J.C.W., Szczepanski, L., Szechinski, J. et al. (2004). Efficacy of B‐cell‐targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med. 350: 2572–2581.
9 9 (a) Sheskin, J. (1965). Thalidomide in the treatment of lepra reactions. Clin. Pharmacol. Ther. 6: 303–306.(b) Sheskin, J. (1980). The treatment of lepra reaction in lepromatous leprosy – 15 years experience with thalidomide. Int. J. Dermatol. 19: 318–322.
10 10 D'Amato, R.J., Loughnan, M.S., Flynn, E., and Folkman, J. (1994). Thalidomide is an inhibitor of angiogenesis. Proc. Natl. Acad. Sci. U. S. A. 91: 4082–4085.
11 11 Singhal, S., Mehta, J., Desikan, R. et al. (1999). Antitumor activity of thalidomide in refractory multiple myeloma. N. Engl. J. Med. 341: 1565–1571.
12 12 Olson, K.B., Hall, T.C., Horton, J. et al. (1965). Thalidomide (N‐phthaloylglutamimide) in treatment of advanced cancer. Clin. Pharmacol. Ther. 6: 292.
13 13 Krumbhaar, E.B. and Krumbhaar, H.D. (1919). The blood and bone marrow in yelloe cross gas (mustard gas) poisoning: changes produced in the bone marrow of fatal cases. J. Med. Res. 40: 497–508. 493.
14 14 Gilman, A. and Philips, F.S. (1946). The biological actions and therapeutic applications of the B‐chloroethyl amines and sulfides. Science 103: 409–415.
15 15 Fenn, J.E. and Udelsman, R. (2011). First use of intravenous chemotherapy cancer treatment: rectifying the record. J. Am. Coll. Surgeons 212: 413–417.
16 16 Goodman, L.S., Wintrobe, M.M. et al. (1946). Nitrogen mustard therapy; use of methyl‐bis (beta‐chloroethyl) amine hydrochloride and tris (beta‐chloroethyl) amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. J. Am. Med. Assoc. 132: 126–132.
17 17 (a) DeVita, V.T. Jr. and Chu, E. (2008). A history of cancer chemotherapy. Cancer Res. 68: 8643–8653.(b) Verrill, M. (2009). Chemotherapy for early‐stage breast cancer: a brief history. Br. J. Cancer 101 (Suppl 1): S2–S5.(c) Galmarini, D., Galmarini, C.M., and Galmarini, F.C. (2012). Cancer chemotherapy: a critical analysis of its 60 years of history. Crit. Rev. Oncol. Hematol. 84: 181–199.
18 18 (a) Silverman, R.B. (2016). Basic science to blockbuster drug: invention of Pregabalin (Lyrica (R)). Technol. Innov. 17: 153–158.(b) Silverman, R.B. (2008). From basic science to blockbuster drug: the discovery of Lyrica. Angew. Chem. Int. Ed. 47: 3500–3504.
19 19 Krnjevic, K. (1970). Glutamate and gamma‐aminobutyric acid in brain. Nature 228: 119.
20 20 Baxter, C.F. and Roberts, E. (1961). Elevation of gamma‐aminobutyric acid in brain – selective inhibition of gamma‐aminobutyric‐alpha‐ketoglutaric acid transaminase. J. Biolumin. Chemilumin. 236: 3287.
21 21 Kuriyama, K., Roberts, E., and Rubinstein, M.K. (1966). Elevation of gamma‐aminobutyric acid in brain with amino‐oxyacetic acid and susceptibility to convulsive seizures in mice: a quantitative re‐evaluation. Biochem. Pharmacol. 15: 221–236.
22 22 Loscher, W. (1980). A comparative study of the pharmacology of inhibitors of GABA‐metabolism. Naunyn‐Schmiedeberg's Arch. Pharmacol. 315: 119–128.
23 23 Silverman, R.B. and Levy, M.A. (1980). Irreversible inactivation of pig brain gamma‐aminobutyric acid‐alpha‐ketoglutarate transaminase by 4‐amino‐5‐halopentanoic acids. Biochem. Bioph. Res. Co. 95: 250–255.
24 24 (a) Taylor, C.P., Vartanian, M.G., Andruszkiewicz, R., and Silverman, R.B. (1992). 3‐Alkyl GABA and 3‐alkylglutamic acid analogs – 2 new classes of anticonvulsant agents. Epilepsy Res. 11: 103–110.(b) Silverman, R.B., Andruszkiewicz, R., Nanavati, S.M. et al. (1991). 3‐Alkyl‐4‐aminobutyric acids – the 1st class of anticonvulsant agents that activates l‐glutamic acid decarboxylase. J. Med. Chem. 34: 2295–2298.
25 25 Verrey, F. (2003). System L: heteromeric exchangers of large, neutral amino acids involved in directional transport. Pflug. Arch. Eur. J. Phy. 445: 529–533.
26 26 Patridge, E., Gareiss, P., Kinch, M.S., and Hoyer, D. (2016). An analysis of FDA‐approved drugs: natural products and their derivatives. Drug Discovery Today 21: 204–207.
27 27 Fleming, A. (1929). On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzæ. Br. J. Exp. Pathol. 10: 226–236.
28 28 Gaynes, R. (2017). The discovery of penicillin – new insights after more than 75 years of clinical use. Emerg. Infect. Dis. 23: 849–853.
29 29 Tan, S. and Tatsumura, Y. (2015). Alexander Fleming (1881–1955): discoverer of penicillin. Singapore Med. J. 56: 366–367.
30 30 Schatz, A., Bugie, E., and Waksman, S.A. (1944). Streptomycin, a substance exhibiting antibiotic activity against gram‐positive and gram‐negative bacteria. Clin. Orthop. Relat. Res. 2005: 3–6.
31 31 (a) Pringle, P. and Moss, D.W. (2012). Experiment eleven: deceit and betrayal in the discovery of the cure for tuberculosis. London; New York: Bloomsbury.(b) Wainwright, M. (1991). Streptomycin – discovery and resultant controversy. Hist. Phil. Life Sci. 13: 97–124.
32 32 Gall, Y.M. and Konashev, M.B. (2001). The discovery of Gramicidin S: the intellectual transformation of G.F. Gause from biologist to researcher of antibiotics and on its meaning for the fate of Russian genetics. Hist. Phil. Life Sci. 23: 137–150.
33 33 Zubrod, C.G., Schepartz, S.A., and Carter, S.K. (1977). Historical background of the National Cancer Institute's drug development thrust. Natl. Cancer Inst. Monogr.: 7–11.
34 34 Wall, M.E., Wani, M.C., Cook, C.E. et al. (1966). Plant antitumor agents. I. Isolation and structure of camptothecin a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata. J. Am. Chem. Soc. 88: 3888–3890.
35 35 Stork, G. and Schultz, A.G. (1971). The total synthesis of dl‐camptothecin. J. Am. Chem. Soc. 93: 4074–4075.
36 36 (a) Danishefsky, S., Etheredge, S.J., Volkmann, R. et al. (1971). Nucleophilic additions to allenes – New synthesis of alpha‐pyridones. J. Am. Chem. Soc. 93: 5575.(b) Volkmann, R., Danishefsky, S., Eggler, J., and Solomon, D.M. (1971). Total synthesis of dl‐camptothecin. J. Am. Chem. Soc. 93: 5576.
37 37 Boch, M., Winterfeldt, E., Nelke, J.M. et al. (1972). Reactions with indole‐derivatives. 17. Biogenetically orientated total‐synthesis of dl‐camptothecin and 7‐chlorocamptothecin. Chem. Ber‐Recl. 105: 2126.
38 38 (a) Hertzberg, R.P., Caranfa, M.J., and Hecht, S.M. (1989). On the mechanism of topoisomerase‐I inhibition by camptothecin – evidence for binding to an enzyme
