seminal work of giuseppe brotzu and edward abraham), streptomycin (discovered during a merck-funded research program in selman waksman's laboratory), the tetracyclines (discovered at lederle laboratories, now a part of pfizer), erythromycin (discovered at eli lilly and co.) and their extension to an increasingly wide range of bacterial pathogens. streptomycin, discovered during a merck-funded research program in selman waksman's laboratory at rutgers in 1943, became the first effective treatment for tuberculosis. at the time of its discovery, sanitoriums for the isolation of tuberculosis-infected people were an ubiquitous feature of cities in developed countries, with 50% dying within 5 years of admission. a federal trade commission report issued in 1958 attempted to quantify the effect of antibiotic development on american public health. the report found that over the period 1946–1955, there was a 42% drop in the incidence of diseases for which antibiotics were effective and only a 20% drop in those for which antibiotics were not effective. the report concluded that "it appears that the use of antibiotics, early diagnosis, and other factors have limited the epidemic spread and thus the number of these diseases which have occurred". the study further examined mortality rates for eight common diseases for which antibiotics offered effective therapy (syphilis, tuberculosis, dysentery, scarlet fever, whooping cough, meningococcal infections, and pneumonia), and found a 56% decline over the same period. notable among these was a 75% decline in deaths due to tuberculosis. measles cases reported in the united states before and after introduction of the vaccine percent surviving by age in 1900, 1950, and 1997 during the years 1940–1955, the rate of decline in the u.s. death rate accelerated from 2% per year to 8% per year, then returned to the historical rate of 2% per year. the dramatic decline in the immediate post-war years has been attributed to the rapid development of new treatments and vaccines for infectious disease that occurred during these years. vaccine development continued to accelerate, with the most notable achievement of the period being jonas salk's 1954 development of the polio vaccine under the funding of the non-profit national foundation for infantile paralysis. the vaccine process was never patented but was instead given to pharmaceutical companies to manufacture as a low-cost generic. in 1960 maurice hilleman of merck sharp & dohme identified the sv40 virus, which was later shown to cause tumors in many mammalian species. it was later determined that sv40 was present as a contaminant in polio vaccine lots that had been administered to 90% of the children in the united states. the contamination appears to have originated both in the original cell stock and in monkey tissue used for production. in 2004 the united states cancer institute announced that it had concluded that sv40 is not associated with cancer in people. other notable new vaccines of the period include those for measles (1962, john franklin enders of children's medical center boston, later refined by maurice hilleman at merck), rubella (1969, hilleman, merck) and mumps (1967, hilleman, merck) the united states incidences of rubella, congenital rubella syndrome, measles, and mumps all fell by >95% in the immediate aftermath of widespread vaccination. the first 20 years of licensed measles vaccination in the u.s. prevented an estimated 52 million cases of the disease, 17,400 cases of mental retardation, and 5,200 deaths. development and marketing of antihypertensive drugs hypertension is a risk factor for atherosclerosis, heart failure, coronary artery disease, stroke, renal disease, and peripheral arterial disease, and is the most important risk factor for cardiovascular morbidity and mortality, in industrialized countries. prior to 1940 approximately 23% of all deaths among persons over age 50 were attributed to hypertension. severe cases of hypertension were treated by surgery. early developments in the field of treating hypertension included quaternary ammonium ion sympathetic nervous system blocking agents, but these compounds were never widely used due to their severe side effects, because the long-term health consequences of high blood pressure had not yet been established, and because they had to be administered by injection. in 1952 researchers at ciba discovered the first orally available vasodilator, hydralazine. a major shortcoming of hydralazine monotherapy was that it lost its effectiveness over time (tachyphylaxis). in the mid-1950s karl h. beyer, james m. sprague, john e. baer, and frederick c. novello of merck and co. discovered and developed chlorothiazide, which remains the most widely used antihypertensive drug today. this development was associated with a substantial decline in the mortality rate among people with hypertension. the inventors were recognized by a public health lasker award in 1975 for "the saving of untold thousands of lives and the alleviation of the suffering of millions of victims of hypertension". a 2009 cochrane review concluded that thiazide antihypertensive drugs reduce the risk of death (rr 0.89), stroke (rr 0.63), coronary heart disease (rr 0.84), and cardiovascular events (rr 0.70) in people with high blood pressure. in the ensuring years other classes of antihypertensive drug were developed and found wide acceptance in combination therapy, including loop diuretics (lasix/furosemide, hoechst pharmaceuticals, 1963), beta blockers (ici pharmaceuticals, 1964) ace inhibitors, and angiotensin receptor blockers. ace inhibitors reduce the risk of new onset kidney disease and death in diabetic patients, irrespective of whether they have hypertension. oral contraceptives prior to the second world war, birth control was prohibited in many countries, and in the united states even the discussion of contraceptive methods sometimes led to prosecution under comstock laws. the history of the development of oral contraceptives is thus closely tied to the birth control movement and the efforts of activists margaret sanger, mary dennett, and emma goldman. based on fundamental research performed by gregory pincus and synthetic methods for progesterone developed by carl djerassi at syntex and by frank colton at g.d. searle & co., the first oral contraceptive, enovid, was developed by e.d. searle and co. and approved by the fda in 1960. the original formulation incorporated vastly excessive doses of hormones, and caused severe side effects. nonetheless, by 1962, 1.2 million american women were on the pill, and by 1965 the number had increased to 6.5 million. the availability of a convenient form of temporary contraceptive led to dramatic changes in social mores including expanding the range of lifestyle options available to women, reducing the reliance of women on men for contraceptive practice, encouraging the delay of marriage, and increasing pre-marital co-habitation. thalidomide and the kefauver-harris amendments malformation of a baby born to a mother who had taken thalidomide while pregnant in the u.s., a push for revisions of the fd&c act emerged from congressional hearings led by senator estes kefauver of tennessee in 1959. the hearings covered a wide range of policy issues, including advertising abuses, questionable efficacy of drugs, and the need for greater regulation of the industry. while momentum for new legislation temporarily flagged under extended debate, a new tragedy emerged that underscored the need for more comprehensive regulation and provided the driving force for the passage of new laws. on 12 september 1960, an american licensee, the william s. merrell company of cincinnati, submitted a new drug application for kevadon (thalidomide), a sedative that had been marketed in europe since 1956. the fda medical officer in charge of reviewing the compound, frances kelsey, believed that the data supporting the safety of thalidomide was incomplete. the firm continued to pressure kelsey and the fda to approve the application until november 1961, when the drug was pulled off the german market because of its association with grave congenital abnormalities. several thousand newborns in europe and elsewhere suffered the teratogenic effects of thalidomide. without approval from the fda, the firm distributed kevadon to over 1,000 physicians there under the guise of investigational use. over 20,000 americans received thalidomide in this "study," including 624 pregnant patients, and about 17 known newborns suffered the effects of the drug. the thalidomide tragedy resurrected kefauver's bill to enhance drug regulation that had stalled in congress, and the kefauver-harris amendment became law on 10 october 1962. manufacturers henceforth had to prove to fda that their drugs were effective as well as safe before they could go on the us market. the fda received authority to regulate advertising of prescription drugs and to establish good manufacturing practices. the law required that all drugs introduced between 1938 and 1962 had to be effective. an fda - national academy of sciences collaborative study showed that nearly 40 percent of these products were not effective. a similarly comprehensive study of over-the-counter products began ten years later. statins main article: discovery and development of statins in 1971, akira endo, a japanese biochemist working for the pharmaceutical company sankyo, identified mevastatin (ml-236b), a molecule produced by the fungus penicillium citrinum, as an inhibitor of hmg-coa reductase, a critical enzyme used by the body to produce cholesterol. animal trials showed very good inhibitory effect as in clinical trials, however a long-term study in dogs found toxic effects at higher doses and as a result mevastatin was believed to be too toxic for human use. mevastatin was never marketed, because of its adverse effects of tumors, muscle deterioration, and sometimes death in laboratory dogs. statins above daily dose of 80 mg can cause serious muscle injury and rhabdomyolysis. p. roy vagelos, chief scientist and later ceo of merck & co, was interested, and made several trips to japan starting in 1975. by 1978, merck had isolated lovastatin (mevinolin, mk803) from the fungus aspergillus terreus, first marketed in 1987 as mevacor. in april 1994, the results of a merck-sponsored study, the scandinavian simvastatin survival study, were announced. researchers tested simvastatin, later sold by merck as zocor, on 4,444 patients with high cholesterol and heart disease. after five years, the study concluded the patients saw a 35% reduction in their cholesterol, and their chances of dying of a heart attack were reduced by 42%. in 1995, zocor and mevacor both made merck over us$1 billion. endo was awarded the 2006 japan prize, and the lasker-debakey clinical medical research award in 2008. for his "pioneering research into a new class of molecules" for "lowering cholesterol," 21st century since several decades, biologics have been rising in importance in comparison with small molecules treatments. the biotech subsector, animal health and the chinese pharmaceutical sector have also grown substantially. on the organizational side, big international pharma corporations have experienced a substantial decline of their value share. also, the core generic sector (substitutions for off-patent brands) has been downvalued due to competition. torreya estimated the pharmaceutical industry to have a market valuation of usd 7.03 trillion by february 2021 from which usd 6.1 trillion is the value of the publicly-traded companies. small molecules modality had 58.2% of the valuation share down from 84.6% in 2003. biologics was up at 30.5% from 14.5%. the valuation share of chinese pharma grew from 2003 to 2021 from 1% to 12% overtaking switzerland who is now ranked number 3 with 7.7%. the united states had still by far the most valued pharmaceutical industry with 40% of global valuation. impact of mergers and acquisitions a 2022 article articulated this notion succinctly by saying "in the business of drug development, deals can be just as important as scientific breakthroughs", typically referred to as pharmaceutical m&a (for mergers and acquisitions). it highlighted that some of the most impactful of the remedies of the early 21st century were only made possible through m&a activities, specifically noting keytruda and humira. research and development main articles: drug discovery and drug development drug discovery is the process by which potential drugs are discovered or designed. in the past, most drugs have been discovered either by isolating the active ingredient from traditional remedies or by serendipitous discovery. modern biotechnology often focuses on understanding the metabolic pathways related to a disease state or pathogen, and manipulating these pathways using molecular biology or biochemistry. a great deal of early-stage drug discovery has traditionally been carried out by universities and research institutions. drug development refers to activities undertaken after a compound is identified as a potential drug in order to establish its suitability as a medication. objectives of drug development are to determine appropriate formulation and dosing, as well as to establish safety. research in these areas generally includes a combination of in vitro studies, in vivo studies, and clinical trials. the cost of late stage development has