Discovery Of Aspirin Research Articles

Seventy-five volumes of "Die Pharmazie" - a historical review.

The journal "Die Pharmazie" was founded shortly after World War II in the German Sovjet occupation zone, and made its way to the leading pharmaceutical journal in the German Democratic Republic. From the early 1960s, and under the editorial responsibility of Siegfried Pfeifer (1961-1993) and Rudolf Voigt (1961-1988), the journal continuously increased its reputation and reached its present status of a peer reviewed international journal. Pfeifer served the journal as an editor-in-chief for 32 years in total. Other long-time editors were Peter Pflegel (1989-2012) and Theodor Dingermann (since 1994). Between 1946 and 2019 more than 12.000 manuscripts from almost 120 countries were published. From the very beginning up to the present day, "Die Pharmazie" has been accepting papers from all the pharmaceutical disciplines. The journal made history by publishing the first description of the thin layer chromatography technique and personal accounts of Arthur Eichengrün, personally involved in the discovery of aspirin.

Sharing Clinical Research Data: Perspectives on an IOM Workshop

Few people would argue that individuals in need of diagnostics and therapies would benefit from the sharing of clinical research data. Government research agencies, pharmaceutical companies, and academic investigators continually amass large amounts of such data. Sharing information both within and across institutions has great potential to advance science and public health. Unfortunately, little is shared in a useful manner. The Institute of Medicine of the National Academy of Sciences held a public workshop October 4–5, 2012 (http:// www.iom.edu/Activities/Research/SharingClinicalResearch Data.aspx), focused on the benefits of sharing clinical research data. Stakeholders from government, industry, academia, and advocacy participated in presentations and discussions about barriers to sharing data and concrete ways to overcome those barriers. The workshop also welcomed the unique perspective of patients who often find themselves frustrated and left out of the very studies that are designed for their benefit. The workshop began by articulating that ‘‘data sharing’’ means different things to different people in different situations. A variety of continua were described in a search for precise language that would enable clarity of potential solutions. The workshop’s main focus was on participant-level data sharing. However, various levels of aggregate data were also considered, as participants realized that a productive dialogue must take into account several continua. Clinical trial data are usually publically reported on a summary level, but this summary does not always accurately reflect the underlying participant-level data. A variety of issues can arise as the trial progresses, resulting in inaccuracies, or at least misrepresentations. For example, structural changes to studies— such as going from four groups to two—result in major discrepancies. Some participants in the workshop suggested that transparency in the transition of data from participantlevel data to aggregate data could aid in decision-making in both policy and therapeutic development. Another apparent continuum defines with whom to share data. Clinical research data could be shared among the original researchers only, or with approved researchers, or any researchers, or anyone at all. Although there is potentially more risk to individual’s privacy the more broadly participant-level data are shared, there is also potentially greater benefit if more eyes are on the data. Finally, another important continuum includes levels of data sharing. Data can be discovered, used, and accessed, with a variety of mechanisms allowing those levels of sharing. If data are discoverable, then this finding could be as simple as ‘‘they exist.’’ If data are used, then they might be part of an aggregate data set, but the researcher still may not be accessing the individual record. Accessing the participant-level data might include actually transferring the data or, conversely, leaving the data in a central store but accessing them nonetheless. Many scientific success stories illustrate what can be accomplished through pooling data from clinical trials. For example, a workshop presenter described the pooled data from drug therapy studies that enabled the discovery of aspirin as an effective means to decrease the risk of heart attacks. This information may be taken for granted now, but at the time it was a breakthrough precipitated by data sharing. Liberating data across trials has the potential to help answer important clinical questions. In another example, large pharmaceutical companies shared clinical data in the Biomarkers Consortium. The Consortium then was able to identify the biomarker adiponectin as a robust predictor of patient response to a certain class of diabetes drugs. The project demonstrated that crosscompany collaboration is a powerful approach to biomarker qualification, suggesting that data sharing might define a precompetitive space that would accelerate drug development. Similarly, NEWMEDS (Novel Methods Leading to New Medications in Depression and Schizophrenia) is one of the largest ever academic–industry research collaborations, with data from 91 clinical studies on depression and schizophrenia. This consortium has identified ways to design significantly more cost-effective studies. Along with the many benefits that data sharing can provide, a variety of disincentives and misalignment of incentives affect all stakeholders. Patients are understandably concerned about confidentiality, security, and privacy. As long as academic institutions build some of their credit systems on authorship, academic researchers may not see a good reason to share data, particularly if doing so results in being one of many authors. Further, data sharing would allow others to opine about or even analyze data, and, in the words of one participant: ‘‘Scientists don’t want to be scooped by their own

Letter by Fürstenwerth Regarding Article, “Aspirin: A Historical and Contemporary Therapeutic Overview”

To the Editor: I read with interest the article by Valentin Fuster and Joseph Sweeny, “Aspirin: A Historical and Contemporary Therapeutic Overview,”1 in which the discovery of the drug aspirin is presented as a logical sequence of activities inspired by the knowledge of pharmacological effects of willow extracts. In taking into account the scientific context in which the discovery of aspirin took place, I propose to revise this description. Neither Kolbe's synthesis of salicylic acid nor Gerhardt's synthesis of acetylsalicylic acid were performed in the context of drug development. The discovery of the drug aspirin only started with the efforts of chemists at Farbenfabriken Bayer …

A short history of anti-rheumatic therapy. II. Aspirin

The discovery of aspirin, an antipyretic, anti-inflammatory and analgesic drug, undoubtedly represents a milestone in the history of medical therapy. Since ancient times the derivatives of willow (Salix alba) were used to treat a variety of fevers and pain syndromes, although the first report dates back to 1763 when the English Reverend Edward Stone described the effect of an extract of the bark willow in treating malaria. In the XIX century many apothecaries and chemists, including the Italian Raffaele Piria and Cesare Bertagnini, developed the biological processes of extraction and chemical synthesis of salicylates, and then analyzed their therapeutic properties and pharmacokinetic and pharmacodynamic characteristics. In 1899 the Bayer Company, where Felix Hoffmann, Heinrich Dreser and Arthur Eichengrün worked, recorded acetyl-salicylic acid under the name "Aspirin". In the XX century, besides the definition of the correct applications of aspirin in the anti-rheumatic therapy being defined, Lawrence L. Crawen identified the property of this drug as an anti-platelet agent, thus opening the way for more widespread uses in cardiovascular diseases.

Travelling through Time with Aspirin, a Healing Companion

Four thousand years ago the willow tree was known for its palliative effects. Ancient Greeks used the extract from the cortex and leaves to treat pain, fever, calluses and to enhance semen quality. Bayer Company and Felix Hoffmann claimed discovery of aspirin, and chemists all over Europe dealt with the synthesis of the drug. During 1988 the use of Aspirin was extended from an analgesic, antipyretic to a life-saving drug as it was suggested that it reduced the danger of cardiovascular accidents. Aspirin is still a drug that can offer much to medicine.

Book review: happy accidents

Serendipity, as most physicians know, is the term coined in a letter by Horace Walpole in 1754, wherein he referred to three princes of Serendip (the Persian name for Sri Lanka) who made unusual discoveries by chance. The phrase was popularized by Walter Cannon much later. Scientists have often benefited from serendipitous observations, with the best-known example in medicine being the discovery of penicillin by Alexander Fleming. There is a large body of literature, mainly in journals, on serendipity in medicine. Morton Meyers, a radiologist, with an interest in serendipity and history of medicine, has put together a book detailing numerous examples. I, too, have a special interest in the subject and have written on it – though I cannot claim to have made any discoveries, serendipitously or otherwise! – but was pleasantly surprised to learn of so many examples of which I was not aware. There are four separate sections, with articles on infectious disease and pharmacology, cancer, cardiology and psychiatry. The usual suspects are covered, including the discovery of penicillin as an antibiotic and the beginnings of cancer chemotherapy due to an observation of leucopoenia in survivors of a bombing attack during World War II, when mustard gas was released into the atmosphere. However, we also learn about the role that serendipity has played in the discovery of aspirin’s efficacy as an agent against colon cancer, cisplatin as an antineoplastic, the acid fast stain for tuberculosis and thalidomide as an anti-angiogenesis drug, among others. Many anecdotes, not all of which are related to serendipity, come to light. Wilhelm Einthoven, the discoverer of the ECG, was an honourable man in addition to being a great researcher. After receiving the Nobel Prize in 1924, he tried to track down his assistant to give him a share of the prize money. On learning that his assistant had passed away but that his sisters were living in poverty, Einthoven gave them half of the money. On the other hand, von Behring, the winner of the 1901 Nobel Prize, did not acknowledge the contributions of Paul Ehrlich, a fact that is not well known to many – including Wikipedia. My only concern is that a few of the anecdotes would at best be bordering on serendipity. The use of thalidomide for blocking angiogenesis was indeed a direct offshoot of another observation, the unfortunate one of seal limbs in babies – yet to my mind, this does not qualify as classic serendipity. Nor, for that matter, does the discovery of salvarsan for the treatment of syphilis by Paul Ehrlich. While there was indeed some luck involved, the fact is that Ehrich was working specifically on a chemotherapeutic agent against the bacterium that causes syphilis (the actual story is too long to be recounted here). Luck forms an important part of any research venture, but to ascribe everything to serendipity is overkill. What message does the book carry, beyond informing and entertaining the reader? It is obvious to anyone reading this book that structured, linear-thinking research is not always successful. Luck favours those who investigate every curious, apparently irrelevant observation. Meyers suggests that the referees who sit on committees and give grants to evidence-based medicine take a fresh look at their beliefs and accommodate creative, unbiased thinking. To this end, he has interviewed numerous historians and researchers, including Nobel laureates, who have admitted that luck played a major role in their discovery. Meyers states, quite correctly, that maverick, outside-the-box thinking is unlikely to be accepted by peers who think within the accepted paradigms. Pharmaceutical research, too, he believes, suffers from the same problem of not taking risks. Meyers explains what factors make ‘lucky’ scientists tick and believes that it is essential for educators to emphasize the importance of original thinking in science.

Comment on: Prostaglandin F2α produced by inducible cyclooxygenase may contribute to the resolution of inflammation

The prevalence of inflammation in disease has driven investigations into methods for its inhibition for millennia. The first major step towards its treatment in modern medicine came with the discovery of aspirin, and the next by the discovery of antiinflammatory steroids. This has driven research to finding safer anti-inflammatory drugs and also to investigate the pro-inflammatory mechanisms that are heightened during disease. The discoveries of prostaglandins, leukotrienes and cytokines, as well as importance of cyclooxygenase by the late Sir John Vane FRS, have been the driving force behind this approach. However, ignored during this time by inflammologists, was the second half of the basic pathology of inflammation, namely resolution. Derek Willoughby earned his stripes as a classical experimental pathologist, along the lines of the founder of Experimental Pathology, Rudolph Virchow, and as such defined some of the cellular processes of chronic inflammation we now take for granted (Spector and Willoughby, 1968). He recognised the importance of the resolution process, and that chronic inflammation was a failure in this process. He started his search for factors that balanced the pro-inflammatory mediators he was investigating, and the prostaglandins caught his attention. Having dissected the role of a variety of mediators in inflammation and finding that some, such as the endogenous catecholamines,

Complementary and Alternative Medicine and Psychiatry

Complementary and Alternative Medicine and Psychiatry

The clinical developments and future of the COX-2 inhibitor drugs

A new era of analgesia began with the discovery of aspirin in 1899. Since that time, many newer NSAIDs (non-steroid anti-inflammatory drugs) have been discovered and utilized in clinical practice. The mechanism of anti-inflammatory action of NSAIDs is believed to result from inhibition of the enzyme cyclooxygenase (COX), discovered in the 1970s. This enzyme represents the key ratelimiting step in the production of prostaglandins (PGs) from arachidonic acid. Since PGs are essential for normal gastrointestinal, renal, and platelet function, as well as mediating the inflammatory process, inhibition of cyclooxygenase has both beneficial and deleterious effects. The beneficial effect, obviously, is inhibition of the inflammatory process, while the harmful effects comprise an increased incidence of upper gastrointestinal toxicity (ulceration, perforation, and bleeding) as well as possible renal and platelet dysfunction. In the late 1980s, it was discovered that two isoforms of cyclooxygenase existed (COX-1 and COX-2). COX-1 represents a constitutive form that is expressed in most tissues. In contrast, COX-2 is induced at sties of inflammation and also occurs under normal circumstances in the brain and renal tissues. Since COX-2 levels increase dramatically during acute and chronic inflammation, it was hypothesized that the COX-2 inhibitors might offer significant antiinflammatory qualities with reduced toxicity and may have utility in central nervous system mediated conditions other than peripheral pain, including dementias such as Alzheimer's disease and headache, specifically, migraine headache.

Old Yet New—Pharmaceuticals from Plants

Plants or their crude extracts have been used since prehistory to treat human ailments. Plants are still used in this way in many parts of the world, but Western scientific medicine has tended to isolate active compounds, or make derivatives of them, for use as drugs. Compounds produced by the plant have been important pharmaceuticals since the isolation of morphine almost two hundred years ago and new naturally occurring compounds such as paclitaxel are continually being introduced commercially. Bioactive molecules may also be produced from chemicals found in plants by chemical modification using synthetic chemistry or microorganisms (as in the production of steroids). A third major contribution of plant chemicals to drugs is their utilization as templates for the design of new compounds made by synthesis (e.g. the discovery of aspirin and related compounds from substances in willow bark). New pharmaceuticals from plants are being discovered by examining traditional medicines and by large-scale bioassay ...

Strategies and practice for use of nonsteroidal anti-inflammatory drugs.

Many nonsteroidal anti-inflammatory drugs (NSAIDs) have been developed and marketed since the discovery of aspirin in 1897. These agents frequently are prescribed for the management of arthritis symptoms, including joint pain and inflammation. Despite their therapeutic benefits, NSAIDs are known to be associated with serious gastrointestinal side effects, including ulceration, hemorrhage, and perforation. Thus, one of the main reasons for the continued development of new NSAIDs is the hope of of finding a drug with improved efficacy or safety. To date, clinically meaningful differences in the therapeutic efficacy of different NSAIDs have not been reported. However, recent studies have indicated that differences do exist in the gastrointestinal safety profiles of individual NSAIDs. This article reviews these studies and discusses strategies for NSAID use based on efficacy, safety, and cost issues.