User:Oceanflynn/sandbox/Bibliography LIfeSciences

Selected Bibliography Life sciences industry, selected bibliography, selected timeline...

This selected bibliography traces the history of the new biotechnology industry that began to grow rapidly beginning in the mid-1970s. Each new scientific advance became a media event designed to capture investment confidence and public support. Although market expectations and social benefits of new products were frequently overstated, many people were prepared to see genetic engineering as the next great advance in technological progress. By the 1980s, biotechnology characterized a nascent real industry, providing titles for emerging trade organizations such as the Biotechnology Industry Organization (BIO).

History


Genetic engineering in biotechnology stimulated hopes for both therapeutic proteins, drugs and biological organisms themselves, such as seeds, pesticides, engineered yeasts, and modified human cells for treating genetic diseases. From the perspective of its commercial promoters, scientific breakthroughs, industrial commitment, and official support were finally coming together, and biotechnology became a normal part of business. No longer were the proponents for the economic and technological significance of biotechnology the iconoclasts. Their message had finally become accepted and incorporated into the policies of governments and industry.

There has been little innovation in the traditional pharmaceutical industry over the past decade and biopharmaceuticals are now achieving the fastest rates of growth against this background, particularly in breast cancer treatment. Biopharmaceuticals typically treat sub-sets of the total population with a disease whereas traditional drugs are developed to treat the population as a whole. However, one of the great difficulties with traditional drugs are the toxic side effects the incidence of which can be unpredictable in individual patients.

"The biotechnology industry is unusual in that it is defined, not by a set of products, but by a set of enabling technologies, which are used by a broad array of companies. The thrust of this collection of technologies is to apply DNA sequencing data to engineer the metabolism of microorganisms or green plants to create new products or processes."

Harvard chemistry professor George M. Whitesides (born 1939-) pointed out that building this biotechnology industry is different from two other models of industry building—micro electronics and chemistry (personal communication). In microelectronics, government, industry, and universities all collaborate. Whitesides believes the effort in the chemical industry is far less fluid, far less collaborative, and probably less effective. As the chemical industry takes on biotechnology, modes of collaboration will need to change to transform basic science into meaningful products and services. Biotechnology comprises a web of collaborative efforts—basic research is conducted in universities, venture capitalists test prototypes in the form of small startup companies, medical schools are “test beds”, and larger companies acquire the startups or collaborate directly with government, universities, or medical schools (Figure 2)."


 * The pharmaceutical branch of the life sciences industry began with the commercial manufacturing of Salicylic acid, a traditional medicine. found naturally in the bark of trees of the Salix genus— commonly known as willows. Salicylic acid (from Latin salix) is a monohydroxybenzoic acid, a type of phenolic acid and a beta hydroxy acid. It has the formula C7H6O3.  This colorless crystalline organic acid is widely used in organic synthesis and functions as a plant hormone. It is derived from the metabolism of salicin and is an important active metabolite of aspirin (acetylsalicylic acid). "Bark containing salicin was used by the Romans and American Indians to treat cold, flu, aches, pains and infections."
 * 1763 In 1763 Edward Stone of Wadham College, University of Oxford wrote a short letter to the Royal Society in which he observed the success of the use of willow bark as a therapy for Agues. Felix Hoffmann, a chemist with the German company Bayer, is credited with the synthesis of aspirin in 1897, though whether this was of his own initiative or under the direction of Arthur Eichengrün is controversial. Many historians believe Arthur Eichengrün to be the true inventor. Aspirin is one of the most widely used medications in the world, with an estimated 40,000 tonnes of it being consumed each year. In countries where "Aspirin" is a registered trademark owned by Bayer, the generic term is acetylsalicylic acid (ASA). It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.

The pharmaceutical industry began in the last decade of the 19th century when the manufacturing of acetylsalicylic acid (more commonly referred to as aspirin) in Germany was started by Bayer. The first time a drug was systematically improved was with arsphenamine (trade name Salvarsan). Though numerous derivatives of the dangerous toxic atoxyl were examined by Paul Ehrlich and his group, the compound with best effectiveness and toxicity characteristics was selected for production.


 * In 1946 William Zisman and co-workers first reported spontaneous formation of highly ordered amphiphilic monolayers on solid surfaces by adsorption from organic solutions at the liquid–solid interface. They studied the preparation of mono molecular layers by adsorption (self-assembly) of a surfactant onto a clean metal surface. Attention was focused on the remarkable wetting properties of such monolayers, which were not only hydrophobic, but also oleophobic. By 1983 the term self-assembling monolayer was coined with reference to the planned layer-by-layer assembly of organized films thicker than a single monolayer. The planned layer-by-layer assembly of organized films thicker than a single monolayer which gained momentum in the 1980s and continue strongly today, are forging new avenues of development. With the advent of relatively recent technologies for small-scale patterning, interest in self-assembled films has seen a surge of activity throughout a wide range of areas ranging from biointerfaces to data storage and devices.
 * 1959 The Research Triangle Park (RTP) was established in North Carolina’s Research Triangle to reverse the "brain drain" of "graduates from the area’s top research universities seeking science and engineering jobs in the Northeast and elsewhere." RTI International was the original research institute that launched the park. The Raleigh-Durham-Chapel Hill Triangle is anchored by three major research universities, North Carolina State University, Duke University, and University of North Carolina.
 * 1959 Michael Rubinstein was the first person to use plasmapheresis to treat an immune-related disorder when he "saved the life of an adolescent boy with thrombotic thrombocytopenic purpura (TTP) at the old Cedars of Lebanon Hospital in Los Angeles in 1959".
 * 1965 IBM expanded into North Carolina’s Research Triangle Park (RTP) setting the stage "for an influx of highly-trained workers attracted to the state’s moderate climate and inexpensive housing on large, green lots."
 * 1963-1982 Whitesides was a a member of the faculty of the Massachusetts Institute of Technology from 1963 to 1982.
 * 1970s Peter Lobban, a graduate student of Prof. Dale Kaiser in the Biochemistry Department at Stanford University Medical School first proposed the idea of recombinant DNA.
 * 1970s Cancer was a central target in the 1970s because increasingly the disease was linked to viruses.
 * 1971 The Cetus Corporation, which was founded in 1971, may be the first biotechnology firm.
 * 1972 The first publications describing the successful production and intracellular replication of recombinant DNA appeared in 1972 and 1973.
 * 1973 Stanley Cohen, Paul Berg and Herbert Boyer made what would be one of the first genetic engineering experiments, in 1973. They demonstrated that the gene for frog ribosomal RNA could be transferred into bacterial cells and expressed by them. First they developed a chemical cell transformation method for Escherichia coli, then they constructed a plasmid, which would be the vector, called pSC101.
 * 1974 Stanford University applied for a US patent on recombinant DNA in 1974, known as the Cohen-Boyer patents, listing the inventors as Stanley N. Cohen and Herbert W. Boyer. The patent was awarded in 1980. The first licensed drug generated using recombinant DNA technology was human insulin, developed by Genentech and Licensed by Eli Lilly and Company. The Cohen-Boyer patents eventually had more "than 200 licensees - biotechnology and pharmaceutical companies - and earned Stanford and UCSF more than $100 million in royalties."
 * 1975 Building on the work of many others, in 1975, Georges Köhler and César Milstein succeeded in making fusions of myeloma cell lines with B cells to produce hybridomas that made antibodies to known antigens. They shared the Nobel Prize in Physiology or Medicine in 1984 for the discovery, contributing to a healthcare revolution.
 * 1975 The Asilomar Conference on Recombinant DNA, an influential conference organized by Paul Berg to discuss the potential biohazards and regulation of biotechnology, held in February 1975 at a conference center at Asilomar State Beach. A group of about 140 professionals (primarily biologists, but also including lawyers and physicians) participated in the conference to draw up voluntary guidelines to ensure the safety of recombinant DNA technology.
 * 1976 As a result of the Asilomar Conference, the National Institutes of Health (NIH) set guidelines regarding the safety of manipulating DNA from different species. he meeting resulted in a set of NIH published "Guidelines for Research Involving Recombinant DNA Molecules" which has been revised several times since 1976.
 * 1976 Newell-McGloughlin and Re in their book entitled The Evolution of Biotechnology: From Natufians to Nanotechnology that "venture capital created biotechnology as an industry and without patent." Tom Perkins, the partner in Klein Perkins, and the venture capitalist financing Genentech, helped invent the business model to succeed in fully integrating Genentech pharmaceutical operations from discover to marketing. Perkins, an American businessman, capitalist and was one of the founders of venture capital firm Kleiner Perkins Caufield & Byers, "created a petri dish upon which the technology of recombinant DNA became an independent firm which sprouted the biotechnology industry.  Perkins was chairman of Genentech from 1976 until 1990 when it merged with Roche Holding Ltd.


 * 1976 Genentech was founded in 1976 by venture capitalist Robert A. Swanson and biochemist Herbert Boyer. Boyer is considered to be a pioneer in the field of recombinant DNA technology. In 1973, Boyer and his colleague Stanley Norman Cohen demonstrated that restriction enzymes could be used as "scissors" to cut DNA fragments of interest from one source, to be ligated into a similarly cut plasmid vector. While Cohen returned to the laboratory in academia, Swanson contacted Boyer to found the company. Swanson
 * 1976 In January 1976, 28-year-old venture capitalist Robert Swanson, and biochemist Herbert Boyer started Genentech to seek practical uses for Boyer and Cohen's engineered proteins.
 * 1976 Tom Perkins, the partner in Klein Perkins, and the venture capitalist financing Genentech, helped invent the business model to succeed in fully integrating Genentech pharmaceutical operations from discover to marketing. Perkins "created a petri dish upon which the technology of recombinant DNA became an independent firm which sprouted the biotechnology industry. Genentech nurtured "novel alliances" and invented new financial instruments.
 * 1977 Herbert Boyer, biochemist and founder of Genentech, working with Arthur Riggs and Keiichi Itakura successfully expressed a human gene in bacteria when they produced the hormone somatostatin in 1977. David Goeddel and Dennis Kleid were then added to the group, and contributed to its success with synthetic human insulin in 1978.
 * 1975-2000 "In the quarter century since the development of recombinant DNA technologies, thousands of new biotechnology firms have emerged in the United States. Dozens of new products have reached the medical market, and several hundred are in human clinical trials. The market for such products is expected to grow from $7.6 billion in 1996 to more than $24 billion by 2006. Similarly, the market for agriculture biotech products is expected to increase from $300 million to $1.8 billion in the same period. All of this growth is driven by R&D spending of more than $10 billion per year (3)."

1980s
 * 1980The main focus of attention after insulin were the potential profit makers in the pharmaceutical industry: human growth hormone and what promised to be a miraculous cure for viral diseases, interferon. Cancer was a central target in the 1970s because increasingly the disease was linked to viruses.  By 1980, a new company, Biogen, had produced interferon through recombinant DNA. The emergence of interferon and the possibility of curing cancer raised money in the community for research and increased the enthusiasm of an otherwise uncertain and tentative society. Moreover, to the 1970s plight of cancer was added AIDS in the 1980s, offering an enormous potential market for a successful therapy, and more immediately, a market for diagnostic tests based on monoclonal antibodies.   By 1988, only five proteins from genetically engineered cells had been approved as drugs by the United States Food and Drug Administration (FDA): synthetic insulin, human growth hormone, hepatitis B vaccine, alpha-interferon, and tissue plasminogen activator (TPa), for lysis of blood clots. By the end of the 1990s, however, 125 more genetically engineered drugs would be approved.
 * 1980 Harvard Business School professor, Michael E. Porter, a leading authority on competitive strategy and the competitiveness published Porter is the author of 18 books and numerous articles including Competitive Strategy, Competitive Advantage, Competitive Advantage of Nations, and On Competition. A six-time winner of the McKinsey Award for the best Harvard Business Review article of the year, Professor Porter is the most cited author in business and economics. Porter taught courses to newly appointed CEOs of very large corporations. Porter described Termeer's strategy as a cluster, the new economics of competition with all members benefiting from "a strong base of supporting functions and institutions." Porter has devoted considerable attention to understanding and addressing the pressing problems in health care delivery in the United States and other countries. He co-authored Redefining Health Care in which they developed a new strategic framework for transforming the value delivered by the health care system, with implications for providers, health plans, employers, and government, among other actors. The book received the James A. Hamilton award of the American College of Healthcare Executives in 2007 for book of the year. His New England Journal of Medicine research article, "A Strategy for Health Care Reform—Toward a Value-Based System" (July 2009), lays out a health reform strategy for the U.S. His work on health care is being extended to address the problems of health care delivery in developing countries, in collaboration with Dr. Jim Yong Kim and the Harvard Medical School and Harvard School of Public Health.
 * 1981 Physicists Gerd Binnig and Heinrich Rohrer (at IBM Zürich), the Nobel Prize in Physics in 1986. invented the first scanning tunneling microscope which allowed them to image surfaces at the atomic level, only one nanometer in size. "[S]canning tunneling microscopes work more like a person reading Braille, moving across the surface of structures by using a tiny stylus. The physicists, who won a Nobel Prize a mere five years later, built a stylus with a tip that was just one atom across (less than one nanometer). As it moves, the stylus detects the material’s structure by recording electrical feedback, and then the microscope translates the recordings into images." They warned the the Nobel Prize in Physics in 1986.
 * 1981 "Whitesides and other chemists got very interested in nanoscale materials. And what they learned amazed them. Materials this small, it turns out, have unexpected properties—we were just clueless until we could see them up close. Molecules with different surfaces—surfaces that don’t usually combine well, if at all—can suddenly bind. Glass, normally an insulator of electric currents, can conduct electricity. Materials that could not carry electric charges suddenly become semiconductors. The metal gold, in small enough particles, can appear red or blue."
 * 1981 George M. Whitesides co-founded Genzyme with venture capitalist Sheridan Snyder and Henry Blair. Whitesides is a capitalist and encourages scientists to start their own companies.
 * 1982 The the U.S. Patent and Trademark Office (USPTO) began to accept patents on isolated DNA sequences as a composition of matter and continued to do so until the Supreme Court made it illegal in Association for Molecular Pathology v. Myriad Genetics.
 * 1983 The first identification of self-assembled monolayers (SAMs) -"highly ordered molecular assemblies with controllable properties" was made by Allara and Ralph Nuzzo. They produced SAMs at Bell laboratories. This meant chemists could engineer or control macroscopic properties by designing molecules, a molecular-scale synthesis and produce functional materials. Different kinds of molecules caused water to bead or to spread on a surface.  self-assembled monolayers that have led to entirely new areas of surface chemistry with important extensions into physics, biology and materials, and with numerous applications ranging from bio-sensors to advanced electronics. His work has made important contributions to soft lithography - a low cost alternative to conventional photo-lithography for patterning circuits on microchips. This work in material science paved the way for working on processes that occur at surfaces and interfaces. Allaro and Nuzzo's work led to new techniques for fabricating and manipulating materials at the nano scale level, including functional device structures for microelectronics, optics and chemical sensing. SAMs would be used in materials science and life science investigations.
 * 1983Orphan Drug Act of 1983 Food and Drug Administration
 * early 1980s George Whitesides began to research materials science when he came to Harvard. Previously at MIT he studied inorganic chemistry and catalysis. Early work by Ralph G. Nuzzo and David L. Allara on spontaneously organized molecular assemblies informed Whitesides' work on soft lithography. Whitesides and his research group have made significant contributions by developing techniques for soft lithography and microcontact printing.  Both microscale and nanoscale techniques are based on printing, molding and embossing, and can be used for the fabrication of patterns and features on many different materials. Soft lithography uses a patterned elastomer as a stamp, mold, or mask to create micropatterns and microstructures.  Soft lithography has some unique advantages over other forms of lithography (such as photolithography and electron beam lithography) including applications in biotechnology.
 * 1983 The polymerase chain reaction(PCR), a technology in molecular biology used to amplify a single copy or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence was developed in 1983 by Kary Mullis, PCR is now a common and often indispensable technique used in medical and biological research labs for a variety of applications.  These include DNA cloning for sequencing, DNA-based phylogeny, or functional analysis of genes; the diagnosis of hereditary diseases; the identification of genetic fingerprints (used in forensic sciences and DNA paternity testing); and the detection and diagnosis of infectious diseases. In 1993, Mullis was awarded the Nobel Prize in Chemistry along with Michael Smith for his work on PCR.

1990s
 * mid-1980s Monsanto (later a part of Pharmacia) "steered the $9 billion company toward engineered products for agriculture, animal and human health, and nutrition."
 * I985 Monsanto ivestment in Pearle Vision Centers is completed and Monsanto Company acquires Searle for $2.7 billion, making Searle a wholly owned subsidiary of Monsanto.
 * 1989 The paper by Bain et al. on the "use of principles of physical organic chemistry to create functional surfaces based on self-assembled monolayers (SAMs)" is one of the "most highly cited papers in the Journal of the American Chemical Society history.
 * 1989 Whitesides formed a company called DI. Whitesides views his own history through the lens of The Innovator's Dilemma by Christensen, a business school history that examined the impact of big technological changes and how companies reacted very badly to those changes. Companies managed their technology programs poorly. Christensen argued that the mantra in the United States is unfortunately to "listen to the voice of the customer" and let the customer "tell you what you do." This does not work in a field that is is technologically changing because the customer never wants change. Conservative customers have capital invested and they do not want change. Whitesides argued that we should look at the history of science as the business school thinks about it. Analyse the history of science in terms of future impact.
 * 1990s specialized pharmacies were mainly mom-and-pop organizations and the specialty pharmacy industry was highly fragmented.
 * 1989 Preimplantation genetic diagnosis (PGD or PIGD) refers to genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. In 1967, Robert Edwards and Richard Gardner reported the successful identification of the sex of rabbit blastocysts. It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful tests happened in October 1989, with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination of patients carrying X-linked diseases.


 * 1990s PGD became increasingly popular during the 1990s when it was used to determine a handful of severe genetic disorders, such as sickle-cell anemia, Tay Sachs disease, Duchenne’s muscular dystrophy, and Beta-thalassemia.
 * 1990s more expensive lifesaving therapies became available. Pharmacies like Stadtlanders began to do more than fill prescriptions. They would fill out the cumbersome insurance paperwork for patients to secure reimbursement — often from Medicare — coordinate "benefits to eliminate the potentially enormous out-of-pocket costs." They were able to keep these specialty drugs in stock when most retail pharmacies could not. In this way they could intervene for patients who "needed immediate access to therapies to prevent organ rejection" but who "did not have the money for such payments, nor did they have the expertise they needed to complete the forms." These "pharmacies also coordinated referrals from hospital discharge planners and delivered the medication to the patients’ homes to allow therapy to begin immediately upon hospital discharge."
 * 1991 FDA approved Genzyme's orphan drug Alglucerase Cerezyme® only treatment Gaucher's disease.  Genzyme CEO Henry Termeer


 * 1991 GelTex Pharmaceuticals, Inc. was formed on 1991-12-13 in Massachusetts by Prentice-Hall Corporation Systems Inc located at 153 SECOND AVE., WALTHAM, MA 02451, USA. Mark B. Skaletsky was President and Chief Executive Officer of GelTex Pharmaceuticals, Inc. since May 1993.  New Enterprise Associates (NEA) Non-absorbed, polymer-based pharmaceuticals for the selective gastro-intestinal elimination of substances. Whitesides co-founded over 12 companies with a combined market capitalization of over $20 billion.  These companies include Genzyme, GelTex (1991), Theravance, Surface Logix, Nano-Terra, and WMR Biomedical.
 * 1991 Dupont and Merck formed a joint venture in 1991.
 * 1994 Genetic engineering also reached the agricultural front as well. There was tremendous progress since the market introduction of the genetically engineered Flavr Savr tomato in 1994.
 * 1993 Carl B. Feldbaum (born 1944) is considered to be a pioneer in the biotechnology industry. He helped found the Biotechnology Industry Organization (BIO) and was CEO from 1993-2005. He worked in Washington, DC for thirty years. The Biotechnology Industry Organization became the largest trade organization to serve and represent the biotechnology industry in the United States and around the world.   Its members include companies that make Pharmaceutical drugs, biofuels, industrial enzymes, and genetically modified crops. It was founded 1993 in Washington, D.C. and Carl B. Feldbaum was the president from BIO's founding until he retired in 2004, and was succeeded by James C. Greenwood. As of 2013, it represents 1,000 biotech companies in all 50 U.S. states, which employ 1.61 million Americans and support an additional 3.4 million jobs. He served as CEO of He is CEO of Life Sciences Foundation,  Actelion, Ltd., Exelixis, BioVentures for Global Health. He served as Inspector General for Defense Intelligence in the Pentagon (1976-1979), Assistant to the Secretary of Energy (1979-1981), as President of Palomar Corporation (1981-1988), Chief of Staff to Senator Arlen Specter (1988-1993).
 * 1994 new version of Cerezyme, Imiglucerase® (Genzyme) 1994 genetically modified cells  marketing imiglucerase, Termeer introduced successful business strategy specialty pharmacy


 * 1995 Salt Lake City-based Myriad Genetics acquired the patent on the gene associated with increased risk for breast cancer, the (BRCA1) gene.

2000s
 * 1999 Hoechst AG, a German company began to break apart transforming from a chemicals company into a life-sciences company, merged with France's Rhône-Poulenc S.A. In 2004 in a merger with Sanofi-Synthélabo, it became a subsidiary of the resulting Sanofi-Aventis pharmaceuticals group.
 * 1996 George Whitesides co-founded Theravance in 1996 and has served as a member of our Board of Directors since inception.
 * 1997 Dow Chemical spent approximately $1 billion to buy out Eli Lilly’s 40% share of DowElanco to form Dow AgroSciences.
 * 1998 DuPont acquired Merck's portion of their pharmaceutical joint venture, DuPont Merck Pharmaceutical Company, for $2.6 billion. DuPont "sold off Conoco (its oil and energy subsidiary) and purchased Protein Technologies International (PTI, a global supplier of soy proteins to the food and paper processing industries), and most recently acquired Pioneer Hi-Bred International with its research on the genetic modification of corn, soybeans, and other oil seeds."
 * 1998 In 1998, about 30% of the US cotton and corn crops were also expected to be products of genetic engineering. Ernst and Young reported that in 1998, 30% of the U.S. soybean crop was expected to be from genetically engineered seeds.
 * 1998 Salt Lake City-based Myriad Genetics acquired the patent on the gene associated with increased risk for breast cancer, the BRCA2 gene.
 * 2000 Stadtlanders "generated annual revenues of $500 million by selling drugs by mail-order to patients with chronic conditions."
 * 2000 "The industrial chemicals business had annual sales of $340 billion a year in the United States and $1.4 trillion worldwide."
 * 2000 A number of chemical firms reinvented "their businesses, moving away from chemicals and basing new businesses on the life sciences."
 * 2000 "As of December 14, 2000, GelTex Pharmaceuticals, Inc. was acquired by Genzyme Corp. GelTex Pharmaceuticals, Inc. [for $1 billion. GelTex was] engaged in developing and marketing non-absorbed polymer drugs that bind and eliminate targeted substances within the gastrointestinal tract, as of September 30, 2000. In addition, GelTex is developing small-molecule pharmaceuticals consisting of novel polyamine analogues and metal chelators. Therapeutic areas of interest included hyperphosphatemia, hypercholesterolemia, cancer, iron overload, and infectious diseases. The company is based in Waltham Massachusetts."
 * 1991 The Science, Technology, and Economic Policy (STEP) board, which was established "to improve policymakers' understanding of the interconnections among science, technology, and economic policies and their importance to the U.S. economy."
 * 2001 The Government-Industry Partnerships in Biotechnology and Computing conference was held.
 * 2002 George Whitesides co-founded Brighton-based Surface Logix. Since 2002 Surface Logix raised more than $92 million from investors. "Both companies sprung out of intellectual property developed in the Harvard laboratory of George Whitesides, a chemistry and nanotechnology luminary who has helped to found a slew of companies, including biotechnology company Genzyme Inc." "Surface Logix makes coatings for small-molecule pharmaceuticals that make the compounds more effective. The company helps to make drugs for obesity, hypertension and metabolic disease."
 * 2003 Researchers announced that the Human Genome Project had finished a high-quality sequence of the human genome in 2003. Venture capital investors began to back a number of companies in the field of "genomics providing services ranging from DNA laser printing to personal genetic testing."
 * 2003The Medicare Prescription Drug, Improvement, and Modernization Act was signed by President George W. Bush on December 8, 2003, after passing in Congress by a close margin. the largest overhaul of Medicare in the public health program's 38-year history. The MMA's most touted feature is the introduction of an entitlement benefit for prescription drugs, through tax breaks and subsidies. In the years since Medicare's creation in 1965, the role of prescription drugs in patient care has significantly increased. As new and expensive drugs have come into use, patients, particularly senior citizens at whom Medicare was targeted, have found prescriptions harder to afford. The MMA was designed to address this problem. The benefit is funded in a complex way, reflecting diverse priorities of lobbyists and constituencies. It provides a subsidy for large employers to discourage them from eliminating private prescription coverage to retired workers (a key AARP goal);  It prohibits the federal government from negotiating discounts with drug companies;
 * It prevents the government from establishing a formulary, but does not prevent private providers such as HMOs from doing so. W.J."Billy" Tauzin, the Louisiana Republican who chaired the Energy and Commerce Committee from 2001 until February 4, 2004 was one of the chief architects of the new Medicare law. In 2004 Tauzin was appointed as chief lobbyist for the Pharmaceutical Research and Manufacturers of America (PhRMA).
 * 2004 WGBH-TV, a PBS member television station in Boston, Massachusetts, owned by the WGBH Educational Foundation, produced the 4-part television series entitled They Made America based on the book by Harold Evans. WGBH profiled twelve of these individual "who made America," including Herbert Boyer. WGBH-TV produces more than two-thirds of the nationally distributed programs broadcast by PBS.
 * 2005 According to Burrill and Company, an industry investment bank, over $350 billion has been invested in biotech since the emergence of the industry, and global revenues rose from $23 billion in 2000 to more than $50 billion in 2005. The greatest growth has been in Latin America but all regions of the world have shown strong growth trends.
 * 2005 Termeer created feature service of specialty pharmacy (hired 34 people to help patients acquire insurance plans that would cover the cost of their drugs.
 * 2005 Cerezyme cost adult patient $520,000 a year
 * 2005 Tania Simoncelli as American Civil Liberties Union's science advisor, and ACLU lawyer Chris Hansen worked on filing a case against Salt Lake City-based Myriad Genetics, a company that held a complete monopoly on BRCA testing in the United States as Myriad held the patents on the gene associated with increased risk for breast cancer, the (BRCA1) gene, since 1995 and BRCA2 gene since 1998. They charged $3000 a test and "refused to update its test to include additional mutations that had been identified by a team of researchers in France." It became a "significant barrier to biomedical discovery and innovation."
 * 2006 "Nano Terra was founded in 2006 and licensed a large technology portfolio from the George Whitesides lab at Harvard University." "Scientists and engineers perform their work at the company’s own labs in Cambridge, MA." "Nano Terra makes nanotech-based coatings for a range of other industries, including solar power and water purification. The company makes the coatings on demand for a variety of customers, but it doesn't disclose many details about the projects it has completed."
 * 2008 North Carolina’s Research Triangle Park (RTP)
 * 2007 - 2008 In the United Kingdom there was a decline in investments in the life sciences (biotechnology) as because of the "failure of biotech pipelines to deliver.
 * 2009 The Biologics Price Competition and Innovation Act of 2009 (BPCI Act), was passed as part of Obamacare. The FDA gained the authority to approve biosimilars (including interchangeables that are substitutable with their reference product) as part of the Patient Protection and Affordable Care Act signed by President Obama on March 23, 2010; on March 6, 2015, Zarxio obtained the first approval of FDA. The FDA has previously approved biologic products using comparability, for example, Omnitrope in May 2006, but this like Enoxaparin was also to a reference product, Genotropin, originally approved as a biologic drug under the FD&C Act. Sandoz’s Zarxio is biosimilar to Amgen’s Neupogen (filgrastim), which was originally licensed in 1991. This is the first product to be passed under the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), which was passed as part of Obamacare. But Zarxio was approved as a biosimilar, not as an interchangeable product, the FDA notes. And under the BPCI Act, only a biologic that has been approved as an “interchangeable” may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product. The FDA said its approval of Zarxio is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen.
 * 2009 Eculizumab (brand name Soliris) is designated as an orphan drug under the United States Orphan Drug Act (ODA). The ODA is meant to encourage pharmaceutical companies to develop drugs for rare disorders such as aHUS and PNH that have a small market because their patient population is too small to attract pharmaceutical research. Under the law, companies that develop such a drug (a drug for a disorder affecting fewer than 200,000 people in the United States) may sell it without competition for seven years, and may get clinical trial tax incentives.


 * 2010 In March 2010 the Southern District Court of New York Judge Robert Sweet ruled in favor of the Association for Molecular Pathology (AMP) that all the challenged claims were not patent eligible.  The lead plaintiff of 20 plaintiffs defenced by Chris Hansen in the ACLU-sponsored lawsuit, was the Association for Molecular Pathology (AMP).
 * 2010 According to the Generic Pharmaceutical Association (GPhA) CEO Ralph G. Neas referred to the often-cited GPhA/IMS September 2011 annual savings analysis, "Savings: an economic analysis of generic drug usage in the U.S." in the GPhA 2011 Annual Report, generic drug usage "generated $158 billion in health care savings in 2010 alone, a remarkable rate of $3 billion every week."
 * 2011 In a Nature article Whitesides and Deutch argued that "Chemistry must also change its coursework, to include…’non-science’ subjects — especially economics and corporate finance and manufacturing — useful in generating practical technologies."
 * 2011 The National Science Foundation provided a six-year, $13.6 million grant to the Raleigh-Durham-Chapel Hill Research Triangle to establish a Materials Research Science and Engineering Center (MRSEC) in recognition that some of the top scientists and engineers in this "promising field" are located there. Soft matter like foams, gels, polymers or emulsions are produced by combining smaller particles - such as DNA, proteins, nanoparticles - to "form larger structures with novel properties."
 * 2012 "Obinutuzumab is unique because it is the first drug approved with the FDA’s breakthrough therapy designation, since the administrative agency began using that designation in 2012 as per the requirements in the 2012 Food and Drug Administration Safety and Innovation Act (FDA SIA)."
 * 2013 On June 13, 2013, in a unanimous decision, the Supreme Court invalidated Myriad's claims to patent isolated genes in Association for Molecular Pathology v. Myriad Genetics, ruling that merely isolating genes that are found in nature does not make them patentable.


 * 2013 In 2012 venture capital financed about $473M across 46 deals in geonomics.
 * 2013 In 2013 biotech firms in the Cambridge, Massachusetts super cluster received over $500 in venture capital (VC) funding. In 2013 other Massachusetts-based biotechs received about $400 million VC funding.
 * 2013 The average cost of a specialty drug in the US was $65,000 annually in June 2013 (about $5,416 a month). The price of Xyrem in the US has inflated by an average of 40% annually since it became available as a prescription.
 * 2013 In the Canadian Institute for Health Information (CIHI) report, "Prescribed Drug Spending in Canada, 2013" it was confirmed that "cost-saving generic prescription medicines have been the key to controlling drug costs in Canada." However, "those savings were offset by increased spending on newer classes of biologic drugs" with "biologic drugs as the biggest cost-driver." The Canadian Generic Pharmaceutical Association (CGPA) emphasizes "the need for clear rules for the approval and reimbursement of cost-saving biosimilar products in Canada to ensure the ongoing sustainability of drug benefit plans, and improve patient access to treatments."
 * 2013Jazz Pharmaceuticals raised the price of Xyrem 841% earning a total of $569 million in 2013 and representing more than 50% of Jazz Pharmaceutical's revenues. In 2007 it cost $2.04; by 2014 it cost $19.40 per 1-millimeter dose. Jazz offers copay assistance to help patients access the expensive drug. According to DRX, a drug-data published by Bloomberg, Jazz Pharmaceuticals price increase on Xyrem topped the list of price hikes in 2014.
 * 2013 According to the Huffington Post, in 2013 critics of the Trans-Pacific Partnership many nations involved in these trade negotiations were very concerned about the "new standards concerning access to key medicines" and that proposed intellectual property rights "would grant pharmaceutical companies long-term monopolies on new medications. As a result, companies can charge high prices without regard to competition from generic providers. The result, public health experts have warned, would be higher prices around the world, and lack of access to life-saving drugs in poor countries. Nearly every intellectual property issue in the November chart is opposed by a broad majority of the 12 nations."


 * 2012 Breakthrough therapy 2012 Food and Drug Administration Safety and Innovation Act, to grant priority review to drug candidates if preliminary clinical trials indicate that the therapy may offer substantial treatment advantages over existing options for patients with serious or life-threatening diseases.  According to the FDA, in 2013 breakthrough therapy designations were assigned to Obinutuzumab, Ibrutinib and Sofosbuvir. In 2014 Ivacaftor, Ofatumumab, Ceritinib, Idelalisib, Ibrutinib (2nd approval), Eltrombopag, Pembrolizumab, Ledipasvir/Sofosbuvir, Nintedanib, Pirfenidone, Blinatumomab, Viekira Pak ombitasvir, paritaprevir, ritonavir and Nivolumab received the breakthrough therapy designation in 2014. In 2015 Ibrutinib (3rd approval) and Palbociclib received FDA breakthrough therapy designation. See also List of drugs granted breakthrough therapy designation
 * 2014 Tax inversion is a largely American term for the relocation of a corporation's legal domicile to a lower-tax nation, or corporate haven, usually while retaining its material operations in its higher-tax country of origin.  Since 2014 because of changes in US law, a second wave of corporate inversions took place by way of merger with companies in lower-tax foreign countries such as Ireland.  The issue drew public attention in 2014 when Pfizer proposed to invert to the U.K. through a takeover of AstraZeneca.
 * 2014 By 2014 North Carolina’s Research Triangle Park (RTP) was home to 170 companies that include Biogen Idec, Syngenta, United Therapeutics, Cisco, Bayer CropScience, Eisai, BASF, the U.S. EPA, NIH’s National Institute of Environmental Health Sciences (NIEHS; the only NIH institute/center outside of the DC metro area), and RTI International
 * 2014 According to a Massachusetts Biotechnology Council (MassBio) report compiled with EvaluatePharma, venture capital investment in Massachusetts biotech companies "rose to a record $1,802 billion in 2014."
 * 2015 According to San Francisco Chronicle journalist Kathleen Pender, there is a boom in the life sciences industry (biotechnology and pharmaceuticals) which she calls a "biotech frenzy" in the United States because of four main factors. There is an increase in Research and Development productivity. "[M]more drugs are progressing through every phase of the approval process. There "is a more favorable regulatory environment. The life sciences industry have "pricing power." During a sluggish economy there is more interest by investors in industries- like the life sciences- which are not cyclical and are not as sensitive to the economy. Life sciences industry stocks are a long-term investment with potential for strong revenue growth. In a strong economic environment in a period of growth, investors prefer cyclical industries like technology, financial, materials and industrial stocks. The top managers at four biotechnology companies some of the highest-paid executives in the U.S. Chief Executive Officers of startup or smaller biotechnology companies take their compensation in options and for many years the companies make no profit. When a larger pharmaceutical company acquires the company and fires the CEO, the compensation can be substantial. According to Mark Oelschlager, a manager of the Live Oak Health Sciences mutual fund, the interest in life sciences industry “increasing R&D productivity,” which means more drugs are progressing through every phase of the approval process; a favorable regulatory environment; and pricing power.
 * 2015 By 2014 the annual cost of prescription drugs in Canada reached nearly $29 billion dollars. Ten-year old Katharina McGregor, from Blackfalds, Alberta, who was diagnosed with Niemann-Pick disease, a rare genetic disease, requires the orphan drug called Zavesca, as a therapy and it costs $120,000 annually. It is not a cure and she will need this for the rest of her life. When their insurer refused to cover the cost of the drug, the Swiss manufacturer Actelion Pharmaceuticals Ltd. agreed to provide them with the drug for free until they could find another insurer. The prohibitive cost of orphan drugs and new speciality drugs is pressuring "governments and businesses with health insurance plans." Canada "already has some of the highest prescription drug prices in the world."
 * 2015 In their final recommendation of Obinutuzumab (Gazyva), in the January 2015 Pan-Canadian Oncology Drug Review (pERC) for treatment of chronic lymphocytic leukemia, published by the Canadian Agency for Drugs and Technologies in Health, the list price of obinutuzumab provided by the manufacturer Hoffmann-La Roche was $CDN 5,275.54 per 1,000 mg vial. At the recommended dose obinutuzumab costs $15,826.50" for the first 28 day cycle cycle and "$5275.50 per 28 day cycle for subsequent cycles."
 * 2015 Cheryl Larson, of the Midwest Business Group on Health (MBGH), a nonprofit business coalition of human resources and health benefits professionals is "a faculty speaker for and has received honoraria from Merck. She is also on "the Advisory Board for Amgen, Genentech, Eisai, and Novo." F. Randy Vogenberg is founder and director of Integrated Healthcare (IIH), an education and benefits strategy consulting firm working with coalitions or member employers. MBGH is a Chicago-based 501(c)(3) business coalition comprised primarily of human resource and health benefit professionals along with other health care stakeholders.
 * March 6, 2015 Zarxio obtained the first approval of FDA. The FDA has previously approved biologic products using comparability, for example, Omnitrope in May 2006, but this like Enoxaparin was also to a reference product, Genotropin, originally approved as a biologic drug under the FD&C Act. Sandoz’s Zarxio is biosimilar to Amgen’s Neupogen (filgrastim), which was originally licensed in 1991. This is the first product to be passed under the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), which was passed as part of Obamacare. But Zarxio was approved as a biosimilar, not as an interchangeable product, the FDA notes. And under the BPCI Act, only a biologic that has been approved as an “interchangeable” may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product. The FDA said its approval of Zarxio is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen.


 * 2015 According to Sachdev Sidhu, a University of Toronto scientist who spent years researching monoclonal antibodies, "the underlying elements in Soliris, for a U.S. biotech company," claimed that 80 or 90 per cent of Soliris research and development was done by publicly funded university researchers working in academic laboratories.

Specialty pharmacy refers to distribution channels designed to handle specialty drugs — pharmaceutical therapies that are either high cost, high complexity and/or high touch. cancer, rheumatoid arthritis, hemophilia, H.I.V. psoriasis, inflammatory bowel disease (IBD) and Hepatitis C.  Specialty pharmacies may handle therapies that are biologics, and are injectable or infused (although some are oral medications).

use Online pharmacy, Orphan drugs,

The list of designated orphan drugs includes such blockbuster drugs as Abilify, Provigil, Vioxx, Botox, and Cialis
 * List of orphan drugs (usually handled by special pharmacy)
 * Major Pharmacy benefit management
 * Specialty drugs are designated as specialty if they are high cost (as in therapies for Rare disease, orphan disease


 * Interferon beta 1a (tradename Avonex®) by Biogen, a treatment for MS that requires a refrigerated chain of distribution and costs $17,000-a-year is a specialty drug only available through a specialty pharmacy.


 * Alglucerase is Genzyme's treatment for for Gaucher's disease, an orphan disease.
 * Lenalidomide (trade name Revlimid), a specialty drug received FDA approval in 2006. Celgene Corporation certified McKesson Specialty in 2006, a specialty pharmacy, as one of a select group of RevAssist(SM) Lenalidomide is a derivative of thalidomide introduced in 2004.


 * Philidor Rx Services
 * Valeant Pharmaceuticals J. Michael Pearson


 * Lodosyn®, a treatment for Parkinson's disease costs $1,860.28 for a thirty day supply or $5,339.04 for ninety days.
 * Nitropress Valeant raised the price of Nitropress 212 percent based in Laval, Quebec, Canada.


 * Isuprel Valeant raised the price 525 percent
 * CVS Pharmacy
 * Actelion
 * Alexion Pharmaceuticals
 * Amgen
 * Amicus Therapeutics
 * Bayer
 * BioMarin Pharmaceutical
 * Bristol-Myers Squibb
 * Catalyst Pharmaceuticals


 * Eli Lilly and Company
 * Genentech
 * GlaxoSmithKline
 * Hoffmann-La Roche
 * Johnson & Johnson
 * Merck & Co.
 * Novartis
 * Novo Nordisk
 * Onyx Pharmaceuticals
 * Pfizer
 * Pharmacyclics
 * ProMetic Life Sciences Inc.
 * Sanofi
 * Sarepta Therapeutics
 * Scioderm
 * Shire (pharmaceutical company)
 * Spectrum Pharmaceuticals
 * Vertex Pharmaceuticals
 * ViroPharma


 * History
 * Baxter International


 * Major specialty pharmacy
 * CVS Health
 * Walgreens
 * Express Scripts
 * Henri Termeer


 * CEOs of Biopharmaceuticals among top-paid CEOs in 2015

According to an "annual collaborative report" from Equilar and The New York Times, biopharmaceutical executives and healthcare-related companies make up 31 of the "200 highest-paid CEOs of large publicly traded companies.
 * Leonard Schleifer CEO of Regeneron oversaw the "approval and growth of high-priced drugs," received a total compensation of $41,965,424 in 2014. According to the "annual collaborative report" from Equilar and The New York Times, Schleifer ranked 15th in the May 2015 list of "200 highest-paid CEOs of large publicly traded companies." He ranked first in the list of biopharmaceutical executives with the highest total compensation. Regeneron’s Eylea for "age-related macular degeneration grossed $1.735 billion" in 2014.


 * Jeffrey Leiden CEO of Vertex Pharmaceuticals, who oversaw the "approval and growth of high-priced drugs," received a total compensation of $36,635,468 in 2014. According to the "annual collaborative report" from Equilar and The New York Times, Leiden ranked 18th in the list of "200 highest-paid CEOs of large publicly traded companies." He ranked second in the list of biopharmaceutical executives with the highest total compensation. Vertex "established a unique foothold in the specialty marketplace with Kalydeco, which costs more than $300,000 per year.


 * Herve Hoppenot CEO of Incyte received a total compensation of $32,691.026 in 2014. According to the "annual collaborative report" from Equilar and The New York Times, Hoppenot ranked 19th in the list of "200 highest-paid CEOs of large publicly traded companies." He ranked third in the list of biopharmaceutical executives with the highest total compensation.


 * Martine Rothblatt CEO of United Therapeutics received a total compensation of $31,581,896 in 2014. According to the "annual collaborative report" from Equilar and The New York Times, Hoppenot ranked 24th in the list of "200 highest-paid CEOs of large publicly traded companies." He ranked fourth in the list of biopharmaceutical executives with the highest total compensation.


 * 5. Lamberto Andreotti, Bristol-Myers Squibb Total compensation: $26,116,771 Rank in survey: 37


 * 6. Robert J. Hugin, Celgene Total compensation: $24,236,113 Rank in survey: 45


 * 7. Kenneth C. Frazier, Merck & Co. Total compensation: $21,387,205 Rank in survey: 66


 * 8. Leonard Bell, Alexion Pharmaceuticals Total compensation: $20,570,703 Rank in survey: 68


 * 9. Alex Gorsky, Johnson & Johnson Total compensation: $30,383,164 Rank in survey: 70


 * 10. John C. Martin, Gilead Sciences Total compensation: $18,957,994 Rank in survey: 84


 * 11. George A. Scangos, Biogen Total compensation: $18,544,735 Rank in survey: 88


 * 12. Ian C. Reid, Pfizer Total compensation: $18,016,498 Rank in survey: 92


 * 13. Alan H. Auerbach, Puma Biotechnology Total compensation: $17,797,606 Rank in survey: 98


 * 14. Richard A. Gonzalez, AbbVie Total compensation: $16,961,462 Rank in survey: 108


 * 15. Miles D. White, Abbott Laboratories Total compensation: $16,179,509 Rank in survey: 84


 * 16. Paul L. Berns, Anacor Pharmaceuticals Total compensation: $14,132,317 Rank in survey: 164


 * 17. Robert A. Bradway, Amgen Total compensation: $13,961,667 Rank in survey: 168


 * 18. G. Frederick Wilkinson, Impax Laboratories, Inc. Total compensation: $12,978,870 Rank in survey: 185

T
 * 19. Robert L. Parkinson, Jr., Baxter International $12, 835, 618 #192