Colonel Eli Lilly 1838-1898
Eli Lilly (July 8, 1838 – June 6, 1898)
Eli Lilly was an American soldier, pharmaceutical chemist, industrialist, entrepreneur, and founder of the Eli Lilly and Company pharmaceutical corporation. Lilly enlisted in the Union Army during the American Civil War where he recruited a company of men to serve with him in an artillery battery. He was later promoted to colonel, and was given command of a cavalry unit. Lilly was captured near the end of the war and held as a prisoner of war until its conclusion. After the war, he attempted to run a plantation in Mississippi, but failed and returned to his pharmacy profession after the death of his wife. Lilly remarried and worked in several pharmacies with partners before opening his own business in 1876 with plans to manufacture drugs and market them wholesale to pharmacies.
Lilly’s company was successful and he soon became wealthy after making numerous advances in medicinal drug manufacturing. Two of the early advances he pioneered were creating gelatin capsules to hold medicine and fruit flavoring for liquid medicines. Eli Lilly & Company was one of the first pharmaceutical firms of its kind, with a dedicated research department including numerous quality-assurance measures.
Using his wealth, Lilly engaged in numerous philanthropic pursuits. He turned over the management of the company to his son in 1890 allowing himself to continue his engagement in charity and civic advancement as his primary focus. He helped found the organization that became the Indianapolis Chamber of Commerce, was the primary patron of Indiana’s branch of the Charity Organization Society, and personally funded the creation of the city’s children’s hospital which was later expanded by the state to become the Riley Children’s Hospital. He continued his active involvement with many organizations until his death from cancer in 1898.
Lilly was an advocate of federal regulation of the pharmaceutical industry, and many of his suggested reforms were enacted into law in 1906, resulting in the creation of the Food and Drug Administration. He was also among the pioneers of the concept of prescriptions, and helped form what became the common practice of giving addictive or dangerous medicines only to people who had first seen a physician. The company he founded has since grown into one of the largest and most influential pharmaceutical corporations in the world, and the largest corporation in Indiana. Using the wealth generated by the company, his son and grandsons created the Lilly Endowment to continue Lilly’s legacy of philanthropy. The endowment remains one of the largest charitable benefactors in the world.
Eli Lilly was born the son of Gustavus and Esther Lilly in Baltimore, Maryland on July 8, 1838. His family was of Swedish descent and had moved to the low country of France before his great-grandparents immigrated to Maryland in 1789. The Lilly family moved to Kentucky, where Lilly first enrolled in public school. His family moved again in 1852 to Indiana, where he apprenticed to become a printer. Lilly grew up in a Methodist household, and his family was prohibitionist and anti-slavery; their beliefs served as part of their motivation for moving to Indiana. He and his family were members of the Democratic party during his early life, but they became Republicans during the years leading up to the Civil War.
Lilly became interested in chemicals at an early age. While on a trip visiting his aunt and uncle, he was taken to visit an apothecary, where he first witnessed the creation of drugs. In 1854, he served an apprenticeship to become a chemist and pharmacist under Henry Lawrence at the Good Samaritan Drug Store in Lafayette. In addition to learning to mix chemicals, Lawrence taught Lilly how to manage funds and operate a business. His parents enrolled him in pharmacology studies at DePauw University, then known as Indiana Asbury University, and he graduated after two years. In 1859, he took a position at Perkin’s and Coon’s Pharmacy in Indianapolis. Lilly became acquainted with Emily Lemen, the daughter of a local merchant, and the couple married in 1860. The couple returned to Greencastle, where Lilly opened his own drug store in 1861.
Lilly’s war recruitment poster
Lilly enlisted in the Union Army at the start of the American Civil War. Lilly actively recruited among his classmates, friends, local merchants and farmers, asking them to join him in forming a unit. He had recruitment posters created and posted them around Indianapolis, promising to form the crack battery of Indiana. His unit, the 18th Battery, Indiana Light Artillery, was known as the Lilly Battery and consisted of six 3 ordinance rifles (not parrott rifles as stated in Lilly’s recruiting poster) and 150 men. He mustered in at Indianapolis and spent a brief time drilling. His unit was assigned to the Lightning Brigade commanded by Colonel John T. Wilder in 1862 and Lilly was elected to serve as the commanding officer of his battery from August until the winter of 1863, when his three-year enlistment expired. His only prior military experience had been in a Lafayette Indiana Legion unit, and several of his artillerymen considered him too young and intemperate to command. Despite his initial inexperience, he became a competent artillery officer and his battery was instrumental in several important battles. He first saw action in the 1863 Battle of Hoover’s Gap, and he was later in the Second Battle of Chattanooga and the Battle of Chickamauga.
When Lilly’s term of enlistment ended, he reenlisted and was promoted to become a Major of cavalry and given command of the 9th Indiana Cavalry. During a mission in Alabama in the December 1864, he was captured by Major General Nathan B. Forrest and held in a Confederate prisoner-of-war camp until the end of the war in the spring of 1865, when he was paroled and returned home. He was granted the brevetted rank of Colonel before being mustered out of the army. In his later life he obtained a large atlas and marked the path of his movements in the war and the location of battles and skirmishes. He often used the atlas when telling war stories. His Colonel’s title stayed with him for the rest of his life, and his friends and family used it as a nickname for him. Lilly served as chairman of the Grand Army of the Republic, a brotherhood of Civil War veterans, in 1893. During his term he helped organize an event that brought tens of thousands of war veterans, including Lilly’s battery, together in Indianapolis for a reunion and a large parade.
After the war, Lilly attempted a new business venture and purchased a 1,200-acre cotton plantation in Mississippi. Shortly after moving to their new home, the entire family was stricken with mosquito-borne malaria, a disease common in the region at that time. Although Lilly and his son recovered, his wife Emily died on August 20, 1866. She was eight months pregnant with the couple’s second child; their unborn son could not be saved and was stillborn. The death devastated Lilly; he wrote to his family, I can hardly tell you how it glares at me – it’s a bitter, bitter truth – Emily is indeed dead. She was initially buried on the plantation, but later that year her body was disinterred and moved to Indiana to be reburied. Lilly’s return to Indiana following her death allowed the plantation to fall into disrepair and his crop to fail. His partner was unable to maintain the plantation because of a drought and then disappeared with the business’s remaining money. Lilly was forced to file bankruptcy in 1868. Josiah was sent to live with Lilly’s parents in Greencastle while he worked to resolve the situation on the plantation. He remarried in 1869, this time to Maria Cynthia Sloan, and began working for Pattison, Moore & Talbott, a medicinal wholesale company. The business was purchased by H. Daly and Company during his employment there.
In 1869, Lilly left Indiana and, with a partner, opened a successful drug store, Binford and Lilly, in Paris, Illinois. He soon sent for his son. The business was profitable and allowed Lilly to save money, but he was more interested in medicinal manufacturing than running a pharmacy. He formulated a plan to create a medicinal wholesale company of his own. In 1873, Lilly left the partnership and returned to Indianapolis, where he opened a drug store, Johnson and Lilly, with a new partner. Three years later, Lilly dissolved the partnership; his share of the assets amounted to several pieces of equipment, a few gallons of unmixed chemicals, and a small amount of money. He had previously approached a family friend, Augustus Keifer, to create a new partnership. Keifer and two associated drug stores agreed to purchase all their drugs from Lilly at a cost lower than they were currently paying. On May 10, 1876, Lilly opened a laboratory to manufacture drugs. The sign for the business said Eli Lilly, Chemist.
A photo of Lilly’s first laboratory building. Lilly and son Josiah K. Lilly, Sr. are on the right side of the doorway.
Lilly’s manufacturing venture began with three employees, including his 14-year-old son Josiah, who had quit school to work with his father. The elder Lilly had $1,400 ($29,575 in 2011 chained dollars) in working capital. His first innovation was gelatin-coating for pills and capsules. Other early innovations included fruit flavoring for medicines and sugarcoated pills, making the medicines easier to take. Following his experience with the low-quality medicines used in the Civil War, Lilly committed himself to producing only high-quality prescription drugs, in contrast to the common and often ineffective patent medicines of the day.
One of the first medicines he began to produce was quinine, a drug used to treat malaria, which became his best-selling medicine. His products gained a reputation for quality and became popular in the city. In his first year of business, sales reached $4,470 ($90,057 in 2009 dollars), and by 1879 they had grown to $48,000 ($1,105,200 in 2009 dollars). Sales expanded rapidly and he began to acquire customers outside of Indiana. Lilly hired his brother, James, as his first full-time salesman in 1878. James, and the subsequent sales team that developed, marketed the company’s drugs nationally. Other family members were also employed by the growing company; Lilly’s cousin Evan Lilly was hired as a bookkeeper and his grandsons, Eli and Josiah, were hired to run errands and perform other odd jobs. In 1881, he formally incorporated the company, naming it Eli Lilly and Company. By the late 1880s, he was one of the Indianapolis area’s leading businessmen with over one hundred employees and $200,000 ($4,775,556 in 2009 dollars) in annual sales.
An 1886 drawing of Lilly’s plant on McCarty Street
To accommodate his growing business, Lilly acquired additional facilities for research and production. He purchased a complex of buildings on McCarty Street in south Indianapolis. Other businesses followed, and the area began to develop into a major business section of the city. Believing that it would be an advantage for his son to gain a greater technical knowledge, Lilly sent Josiah to attend Philadelphia College of Pharmacy in 1880. Upon returning to the business in 1882, Josiah was named superintendent of the laboratory. In 1890, Lilly turned over the management of his business to Josiah, who ran the company for several decades. The company flourished despite the tumultuous economic conditions in the 1890s. In 1894, Lilly purchased a manufacturing plant to be used solely for creating capsules. Several technological advances were made by the company, and the capsule creation was automated. Over the next few years, they annually created tens of millions of capsules and pills.
Although there were many other small pharmaceutical companies in the United States, Eli Lilly and Company distinguished itself from the others by having a permanent research staff, inventing superior techniques for the mass production of medicinal drugs, and its strong focus on quality. At first, Lilly was the company’s only researcher, but as his business grew, he created a laboratory and employed a department dedicated to creating new drugs, hiring his first research scientist in 1886. The department’s methods of research were based on Lilly’s. He insisted on quality assurance, and instituted mechanisms to ensure that the drugs being produced worked as advertised, had the correct combination of ingredients, and that only the correct dosages of medicines were contained in each pill. He was aware of the addictive and dangerous nature of some of his drugs, and pioneered the concept of giving such drugs only to people who had first seen a physician to determine if they needed the medicine.
By the time of his partial retirement from his business, Lilly was a millionaire. He had been involved in civic affairs for several years and became increasingly philanthropic, granting funds to charitable groups in the city. Working with a group of twenty-five other businessmen, he had begun sponsoring the Charity Organization Society in the late 1870s and soon became the primary patron of its Indiana chapter. The society was the forerunner of the United Way and worked to organize charitable groups under a central leadership. It allowed the many organizations to easily interact and better help people in need by coordinating their efforts and identifying areas with the greatest need.
Indiana Soldiers and Sailors Monument in Indianapolis. The Colonel Eli Lilly Civil War Museumis inside it.
Lilly wished to encourage economic growth and general development in Indianapolis. He attempted to achieve those goals by supporting local commercial organizations financially and through his personal advocacy and promotion. He first became active in local civics in 1879. As a result of his proposal for a public water supply company to meet the needs of the city, the Indianapolis Water Company was created. In 1890, Lilly founded the Commercial Club and was elected as its first president. The club was the primary vehicle for his city development goals and was a precursor to the Indianapolis Chamber of Commerce. The group was instrumental in making numerous advances for the city, including city-wide paved streets, elevated railways to allow vehicles and people to pass beneath them, and a city sewage system. The companies were created through private and public investments and operated at low-cost; in practice they belonged to customers of the company who slowly bought each company back from its initial investors. The model was later followed in most parts of the state to provide water and electricity. The group also helped fund the creation of parks, monuments, and memorials, and successfully attracted investment from other businessmen and organizations to expand the city’s growing industries.
After the Gas Boom began to sweep the state in the 1880s, Lilly and his Commercial Club advocated the creation of a public corporation to pump the natural gas from the ground, pipe it to the city from the Trenton Gas Field, and provide it at low cost to businesses and homes. The project led to the creation of the Consumer Gas Trust Company, which was named by Lilly. The company provided low-cost heating fuel that made urban living much more desirable. The gas was further used to create electricity to run the city’s first public transportation venture, a streetcar system.
During the Panic of 1893, Lilly created a commission to help provide food and shelter to the poor people who were adversely affected. His work with the commission led him to personally donate enough funds to create a children’s hospital in Indianapolis to care for the many children of families who had no money to pay for routine medical care. Lilly’s friends often urged him to seek public office, and they attempted to nominate him to run for Governor of Indiana as a Republican in 1896, but he refused. He shunned public office and instead wanted to focus his attention on his philanthropic organizations. He did regularly endorse candidates, and made substantial donations to politicians who advanced his causes. Lilly became friends with former Governor Oliver P. Morton, who suggested that Lilly use his Commercial Club to advocate for the creation of a memorial to Indiana’s many veterans of the Civil War. Accepting the suggestion, Lilly began raising funds to build the Indiana Soldiers’ and Sailors’ Monument. Construction began in 1888, but the monument was not completed until 1901. The interior of the monument houses a civil war museum that was later named in honor of Lilly.
Lilly was an avid fisherman and built a family cottage on Lake Wawasee in 1887, where he had enjoyed regular vacations and recreation since 1880. In 1892, he built the Wawasee Inn on the lake. The site became a haven for the family, and his grandson later expanded the estate. He also owned a large home on Tennessee Street in Indianapolis, where he spent most of his time. Lilly developed cancer in 1897 and died in his Indianapolis home on June 6, 1898. His bier was held on June 9 and attended by thousands before he was moved to his burial site, a large sepulcher in Indianapolis’s Crown Hill Cemetery.
Colonel Eli Lilly (right) with son Josiah K. Lilly Sr. (left) and grandson Eli Lilly (center)
By 1898, Lilly’s namesake company had a product line of 2,005 items and annual sales over $300,000 ($7,736,400 in 2009 dollars). Josiah Lilly inherited the company following his father’s death, and continued to build the company before passing it on to his own sons, Eli Lilly and Josiah K. Lilly Jr. Josiah and his two sons continued the philanthropy practiced by Lilly and later established the Lilly Endowment that in 1998 became the largest philanthropic endowment in the world in terms of assets and charitable giving; it has since been surpassed but still remains in the top ten. The company played an important role in delivering medicine to the victims of the devastating 1906 San Francisco Earthquake. Lilly’s company has since grown into one of the largest pharmaceutical companies in the world, and under Lilly’s grandson’s leadership developed many new innovations, including the pioneering and development of insulin during the 1920s, the mass production of penicillin during the 1940s, and the promotion of advancements in the mass production of medicines. Innovation continued at the company after it was made a publicly traded corporation in 1952, and it developed Humulin, Merthiolate, Prozac, and many other medicines. According to Forbes, Eli Lilly & Co corporation and the largest charitable benefactor in Indiana.
Lilly’s greatest contributions were his standardized and methodical creation of drugs, his dedication to research and development, and the actual value of the drugs he created. He pioneered the modern pharmaceutical industry, and many of his innovations later became standard practice. His ethical reforms, in a trade that was marked by outlandish claims of miracle medicines, began a period of rapid advancement in the development of medicinal drugs. During his lifetime, Lilly had advocated for federal regulation on medicines, and his son continued that advocacy after his father’s death.
The Colonel Eli Lilly Civil War Museum, located below the Sailors’ and Soldiers’ Monument in Indianapolis, is named in Lilly’s honor. It opened in October 1999 and features exhibits about Indiana during the war period and the war in general.
Molecular Link Between Metabolism and Breast Cancer
Metabolic imbalance is often caused by elevated carbohydrate intake, which can lead to over-activating a molecule called C-terminal binding protein (CtBP). This over-activation, in turn, can increase the risk of breast cancer. It has been known, primarily through population based studies, that there is a strong link between obesity and cancer. But the mechanism behind this link has been uncertain. A previous study found that CtBP repressed expression of a gene associated with breast cancer (BRCA1) at an early age by sensing when the cell was in a high metabolic state; that, in turn, led to processing large amounts of carbohydrates in the body.
According to an article published online in Nature Communications (5 Feb 2013), a protein associated with conditions of metabolic imbalance, such as diabetes and obesity, may play a role in the development of aggressive forms of breast cancer. This early study suggested that obesity and weight gain may contribute to breast cancer by decreasing the level of the BRCA1 tumor suppressor gene expression in response to high carbohydrate intake. This may explain, in part, why women who have hereditary mutations of BRCA1 also experience an increased risk of breast cancer if they gain weight.
The study analyzed prior gene expression studies to determine if gene pathways, repressed by CtBP, were diminished in breast cancer patients who suffered from more aggressive clinical outcomes. The study began first with the human breast cancer cells in the laboratory where the association of CtBP and the genes it bound to in order to regulate expression were measured. The study combined this approach with genome sequencing to confirm how, and where, CtBP bound to genes associated with breast cancer. Next, the study integrated analyses with gene expression studies in cells in which they observed decreased the levels of CtBP by RNA interference (a process that inhibits gene expression), or by decreasing carbohydrate feeding of the cells.
The study found that, under conditions where the levels of CtBP were decreased, DNA repair increased and the cells developed stability and growth control. Results showed that gene pathways targeted by CtBP were also disrupted in more aggressive breast cancers. Moreover, patients with high levels of CtBP in their tumors had shortened survival. It was also shown that a small molecular inhibitor previously shown to bind to CtBP was able to reverse the gene-repressive effects of CtBP in breast cancer cells even under conditions of high carbohydrate feeding.
Increases in Risk of Certain Leukemias Related to Treatment
A new study published online in Blood (14 February 2013) describes the pattern of risk for one form of cancer, acute myeloid leukemia (AML), that has risen over the past three decades for adults who have previously been treated with chemotherapy for other forms of cancer, notably non-Hodgkin’s lymphoma. Although these findings were based on small numbers of patients, they are intriguing in light of recent changes in treatment practices for these cancer patients.
The authors noted that chemotherapy is often a very effective treatment for cancer, and the subsequent risk of leukemia is generally low for an individual patient. The authors indicated that the increased risk among NHL survivors could be due to prolonged survival in recent years for some lymphoma subtypes that are associated with multiple courses of chemotherapy.
Results showed that over the study time period, declining risks were observed among patients treated for ovarian cancer, myeloma, and possibly lung cancer. The decreased risk among patients with ovarian cancer is consistent with a shift from use of an alkylating agent called melphalan to platinum-based chemotherapy in the early 1980s. The authors also found evidence that the risk of treatment-related AML has increased since 2000 among patients treated for esophageal, prostate, and cervical cancer and since the 1990s among patients treated for cancers of the bones and joints and of the endometrium.
The study used data from NCI’s Surveillance Epidemiology and End Results (SEER) cancer registries to evaluate the risk of leukemia in more than 426,000 adults who had been diagnosed with cancer between 1975 and 2008 and who had received chemotherapy as part of their initial cancer treatment. Among these patients, 801 people were identified who subsequently developed AML. Because the data came from SEER cancer registries, information on specific drugs used to treat each individual patient was not available. A unique feature of the study was the ability to evaluate leukemia risks in a large number of patients treated with chemotherapy in the current treatment era (2001-2008).
The stated that it is important to identify patient groups that have the highest risks of treatment-related leukemia, particularly for patients with cancers that have favorable survival potential, so that efforts to prevent a return of the disease can be implemented where possible. The authors added that future studies are needed to gather information on the risks associated with specific chemotherapy agents, which could not be obtained from this study.
Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in Children
Prenatal folic acid supplements reduce the risk of neural tube defects in children, but it has not been determined whether they protect against other neurodevelopmental disorders. As a result, a study published in the Journal of the American Medical Association (2013;309:570-577) was performed to examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children.
The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008 and by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Analyses were adjusted for maternal education level, year of birth, and parity. The main outcome measure was a confirmed diagnosis of ASDs.
At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% had autistic disorder, compared with 0.21% in those unexposed to folic acid. No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use.
According to the authors, use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation.
TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.
FDA Approves First Bionic Retinal Implant for Adults with Advanced Retinitis Pigmentosa
Retinitis pigmentosa (RP) is a rare genetic eye condition that damages the light-sensitive cells that line the retina. In a healthy eye, these cells change light rays into electrical impulses and send them through the optic nerve to the area of the brain that assembles the impulses into an image. In people with RP, the light-sensitive cells slowly degenerate resulting in gradual loss of side vision and night vision, and later of central vision. The condition can lead to blindness.
The FDA has approved the Argus II Retinal Prosthesis System, the first implanted device to treat adult patients with advanced RP. The device, which includes a small video camera, transmitter mounted on a pair of eyeglasses, video processing unit (VPU) and an implanted retinal prosthesis (artificial retina), replaces the function of degenerated cells in the retina (a membrane inside the eye) and may improve a patient’s ability to perceive images and movement. The VPU transforms images from the video camera into electronic data that is wirelessly transmitted to the retinal prosthesis.
The Argus II system is intended for use in adults, age 25 years or older, with severe to profound RP who have bare light perception (can perceive light, but not the direction from which it is coming) or no light perception in both eyes, evidence of intact inner layer retina function, and a previous history of the ability to see forms. Patients must also be willing and able to receive the recommended post-implant clinical follow-up, device fitting, and visual rehabilitation.
In addition to a small video camera and transmitter mounted on the glasses, the Argus II Retinal Prosthesis System has a portable video processing unit (VPU) and an array of electrodes that are implanted onto the patient’s retina. The VPU transforms images from the video camera into electronic data that is wirelessly transmitted to the electrodes. The electrodes transform the data into electrical impulses that stimulate the retina to produce images. While the Argus II Retinal Prosthesis System will not restore vision to patients, it may allow them to detect light and dark in the environment, aiding them in identifying the location or movement of objects or people.
The FDA approved the Argus II Retinal Prosthesis System as a humanitarian use device, an approval pathway limited to those devices that treat or diagnose fewer than 4,000 people in the United States each year. To obtain approval for humanitarian use, a company must demonstrate a reasonable assurance that the device is safe and that its probable benefit outweighs the risk of illness or injury. The company also must show that there is no comparable device available to treat or diagnose the disease or condition.
The FDA reviewed data that included a clinical study of 30 study participants with RP who received the Argus II Retinal Prosthesis System. Investigators monitored participants for adverse events related to the device or to the implant surgery and regularly assessed their vision for at least two years after receiving the implant.
Results from the clinical study show that most participants were able to perform basic activities better with the Argus II Retinal Prosthesis System than without it. Some of the activities tested included locating and touching a square on a white field; detecting the direction of a motion; recognizing large letters, words, or sentences; detecting street curbs; walking on a sidewalk without stepping off; and matching black, grey and white socks.
Following the implant surgery, 19 of the 30 study patients experienced no adverse events related to the device or the surgery. Eleven study subjects experienced a total of 23 serious adverse events, which included erosion of the conjunctiva (the clear covering of the eyeball), dehiscence (splitting open of a wound along the surgical suture), retinal detachment, inflammation, and hypotony (low intraocular pressure).
Three government organizations provided support for the development of the Argus II. The Department of Energy, National Eye Institute at the National Institutes of Health and the National Science Foundation collaborated to provide grant funding totaling more than $100 million, support for material design and other basic research for the project.
Second Sight Medical Products, Inc. is based in Sylmar, Calif.
Crustless Broccoli Quiche
- Canola Cooking Spray
- 1 onion, chopped well
- 2 garlic cloves, chopped
- 1 teaspoon turmeric
- 1 teaspoon ground flaxseed
- 1 cup almond flour
- 2 Tablespoons cream sherry
- 2 tablespoons grated Parmesan cheese
- 1 large bunch fresh broccoli
- 1/2 package frozen whole kernel corn
- 1 cup grated soy Cheddar cheese (save a little to sprinkle on top)
- 1 carton (16 oz each) Egg Beaters® Original
- Pinch black pepper or grind to taste
- Preheat oven to 350?F. Spray casserole dish with cooking spray; set aside.
- Spray a small pan with the canola oil, and saut? the onion and garlic.
- In a small bowl, mix together the almond flour, grated Parmesan cheese, onion and garlic, black pepper, cream sherry, stir everything together and set aside.
- Wash and drain well, the broccoli and then steam it until it’s slightly cooked but retains its crispness. Break apart the florets into smaller pieces.
- Now, add all of the broccoli florets into the casserole dish.
- Next, add the corn kernels, stir slowly two or three times to combine the broccoli and corn.
- Into the flour-Parmesan mixture add the grated soy Cheddar cheese, stir slowly.
- Next pour the Egg Beaters into the flour-Parmesan-soy Cheddar mixture and stir slowly.
- Pour the cheese-egg beaters mixture evenly over the rest of the casserole. Help the cheese-egg liquid get in between the veggies, but don’t stir it.
- Sprinkle a little of the grated soy Cheddar cheese on top.
- Bake 18 to 22 minutes or until puffy and knife inserted in center comes out clean. Let stand 2 minutes just to set, before serving.
Serve this delicious low-calorie quiche for brunch, lunch or a light supper. The quiche will go well with your favorite tossed salad, warm French bread or rolls dipped in olive oil, and a beautiful fresh fruit plate sprinkled with sliced almonds. As for which white wine – we love icy Sauvignon Blanc or even some Champagne that you didn’t drink on Valentine’s Day.
Passion Flower: Andrew Zuckerman
What Makes Target Health Different From Other CROs?
CROs provide drug, device and biologics development services for the pharmaceutical, device and biotechnology industry. When Target Health was founded 20 years ago, a colleague told us that no matter what happens in the pharmaceutical industry, there will always be a need for data and expertise in regulatory affairs.
We took that advice seriously and as of today Target Health represents over 30 clients at FDA from Australia, Denmark, England, France, Germany, Israel, Korea, Sweden Switzerland, and the US. In addition, our data management team and software tools for the paperless clinical trial are the best in the Industry.
To put the icing on the cake, last year Target e*CRF, our eDC system, was used in 3 regulatory approvals (2 in the US and 1 in Europe) and we were directly involved in the planning and execution of 2 complete NDAs and the clinical design for a 3rd NDA. For the 4th approval in Europe, we did all the early development and program execution in the US until the company was purchased by an international pharmaceutical company.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com
American Civil War Medicine
Period painting of a US Civil War soldier, wounded by a Minie ball, lies in bed with a gangrenous amputated arm
Roughly three in five Union casualties and two in three Confederate casualties died of disease.
It has been said that the American Civil War was the first “modern war” in terms of technology and lethality of weapons, but that it was simultaneously fought “at the end of the medical Middle Ages.” Very little was known about the causes of 1) ___, and so a minor wound could easily become infected and take a life. Battlefield surgeons were under qualified and hospitals were generally poorly supplied and staffed. The most common battlefield operation was amputation. If a soldier was badly wounded in the arm or leg, amputation was usually the only solution. Surprisingly, about 75% of amputees survived the operation. Contrary to popular belief, few soldiers experienced amputation without any anesthetic. Heavy doses of chloroform were administered; in fact, a few soldiers died of chloroform poisoning, rather than their wounds. If wound produced pus, it was thought that it meant the wound was healing, when in fact it meant the injury was 2) ___.
In the war, both armies researched advancement in the development of battlefield recovery techniques. In the Union, a new medicinal wing was created under the jurisdiction of a “Medical Director of the Army”, the first field hospitals, small tents with a few tables or beds for the 3) ___, were developed, and a system of transport of the wounded to general hospitals was created, the first wooden ambulances which could hold at max around 4 wounded laying down, 1 or 2 medical officials, and a driver for the horses. The Confederacy advanced mainly by learning from Union camps they overtook, but generally had a less established medical service largely as a result of its more limited resources, vast rural areas, limited 4) ___ knowledge, and a much lesser amount of medical professionals available. The single most seen battle injury was simple flesh wounds that led to amputations of limbs due to lack of proper techniques in removing lodged bullets. Both of the armies used similar techniques in amputation – quickly drugging the soldier and removing the limb which was generally affected by the wound, or could be infected easily, effectively using skin from the extracted limb to cover the stub.
Before the Civil War, armies tended to be small, largely because of the logistics of supply and training. Musket fire, renowned for its inaccuracy, kept casualty rates lower than they might have been. The advent of railroads, industrial production, and canned food allowed for much larger armies, and the Minie ball rifle brought about much higher casualty rates. The work of Florence 5) ___in the Crimean War brought the deplorable situation of military hospitals to the public attention, although reforms were often slow in coming.
The hygiene of the camps was poor, especially at the beginning of the war when men who had seldom been far from home were brought together for training with thousands of strangers. First came epidemics of the 6) ___ diseases of chicken pox, mumps, whooping cough, and, especially, measles. Operations in the South meant a dangerous and new disease environment, bringing diarrhea, dysentery, typhoid fever, and malaria. There were no antibiotics, so the surgeons prescribed coffee, whiskey, and quinine. Harsh weather; bad water; inadequate shelter in winter quarters; poor policing of camps; and dirty camp hospitals took their toll. This was a common scenario in wars from time immemorial, and conditions faced by the Confederate army were even worse.
When the war began, there were no plans in place to treat wounded or 7) ___ Union soldiers. After the Battle of Bull Run, the United States government took possession of several private hospitals in Washington, D.C., Alexandria, Virginia, and surrounding towns. Union commanders believed the war would be short and there would be no need create a long standing source of care for the armies medical needs. This view changed after the appointment of General George B. McClellan and the organization of the Army of the Potomac. McClellan appointed the first medical director of the army, surgeon Charles S. Tripler, on August 12, 1861.
Tripler created plans to enlist regimental surgeons to travel with armies in the field, and the creation of general hospitals for the badly wounded to be taken to for recovery and further treatment. To implement the plan, orders were issued that each regiment must recruit one surgeon and one assistant surgeon to serve before they could be deployed for duty. These men served in the initial makeshift regimental hospitals. In 1862 William A. Hammond became surgeon general and launched a series of reforms. He founded the Army Medical Museum, and had plans for a hospital and a medical school in Washington; a central laboratory for chemical and pharmaceutical preparations was created; much more extensive recording was required from the hospitals and the surgeons. Hammond raised the requirements for admission into the Army Medical Corps. The number of hospitals was greatly increased and he paid close attention to aeration. New surgeons were promoted to serving at the brigade level with the rank of Major. The Surgeon Majors were assigned staffs and were charged with overseeing a new brigade level hospital that could serve as an intermediary level between the regimental and general hospitals. Surgeon Majors were also charged with ensuring that regimental surgeons were in compliance with the orders issued by the Medical Director of the Army.
In the Union, skilled, well-funded medical organizers took proactive action, especially in the much enlarged United States Army Medical Department, and the United States Sanitary Commission, a new private agency. Numerous other new agencies also targeted the medical and morale needs of soldiers, including the United States Christian Commission as well as smaller private agencies such as the Women’s Central Association of Relief for Sick and Wounded in the Army (WCAR) founded in 1861 by Henry Whitney Bellows, and Dorothea Dix. Systematic funding appeals raised public consciousness, as well as millions of dollars. Many thousands of 8) ___ worked in the hospitals and rest homes, most famously poet Walt Whitman. Frederick Law Olmstead, a famous landscape architect, (creator of NYC Central Park) was the highly efficient executive director of the Sanitary Commission.
States could use their own tax money to support their troops as Ohio did. Following the unexpected carnage at the battle of Shiloh in April 1862, the Ohio state government sent 3 steamboats to the scene as floating 9) ___ with doctors, nurses and medical supplies. The state fleet expanded to eleven hospital ships. The state also set up 12 local offices in main transportation nodes to help Ohio soldiers moving back and forth. Field hospitals were initially in the open air, with tent hospitals that could hold only six patients first being used in 1862; after many major battles the injured had to receive their care in the open. As the war progressed, nurses were enlisted, generally two per regiment. In the general hospitals one nurse was employed for about every ten patients. The first permanent general hospitals were ordered constructed during December 1861 in the major hubs of military activity in the eastern and western United States. An elaborate system of ferrying wounded and sick soldiers from the brigade hospitals to the general hospitals was set up. At first the system proved to be insufficient and many soldiers were dying in mobile hospitals at the front and could not be transported to the general hospitals for needed care. The situation became apparent to military leaders in the Peninsular Campaign in June 1862 when several thousand soldiers died for lack of medical treatment. Dr. Jonathan Letterman was appointed to succeed Tripler as the second Medical Director of the Army in 1862 and completed the process of putting together a new ambulance corps. Each regiment was assigned two wagons, one carrying medical supplies, and a second to serve as a transport for wounded soldiers. The 10) ___ corps was placed under the command of Surgeon Majors of the various brigades. In August 1863 the number of transport wagons was increased to three per regiment.
Union medical care improved dramatically during 1862. By the end of the year each regiment was being regularly supplied with a standard set of medical supplies included medical books, supplies of medicine, small hospital furniture like bed-pans, containers for mixing medicines, spoons, vials, bedding, lanterns, and numerous other implements. A new layer of medical treatment was added in January 1863. A division level hospital was established under the command of a Surgeon-in-Chief. The new divisional hospitals took over the role of the brigade hospitals as a rendezvous point for transports to the general hospitals. The wagons transported the wounded to nearby railroad depots where they could be quickly transported to the general hospitals at the military supply hubs. The divisional hospitals were given large staffs, nurses, cooks, several doctors, and large tents to accommodate up to one hundred soldiers each. The new division hospitals began keeping detailed medical 11) ___ of patients. The divisional hospitals were established at a safe distance from battlefields where patients could be safely helped after transport from the regimental or brigade hospitals.
Although the divisional hospitals were placed in safe locations, because of their size they could not be quickly packed in the event of a retreat. Several divisional hospitals were lost to Confederates during the war, but in almost all occasions their patients and 12) ___ were immediately paroled if they would swear to no longer bear arms in the conflict. On a few occasions, the hospitals and patients were held several days and exchanged for Confederate prisoners of war.
The U.S. Army learned many lessons and in 1886, it established the Hospital Corps. The Sanitary Commission collected enormous amounts of statistical data, and opened up the problems of storing information for fast access and mechanically searching for data patterns.
ANSWERS: 1) disease; 2) infected; 3) wounded; 4) medicinal; 5) Nightingale; 6) childhood; 7) sick; 8) volunteers; 9) hospitals; 10) ambulance; 11) records; 12) doctors
Florence Nightingale 1820 – 1910
Young Florence Nightingale
Florence Nightingale was a celebrated English social reformer and statistician, and the founder of modern nursing. She came to prominence while serving as a nurse during the Crimean War, where she tended to wounded British soldiers. She was dubbed “The Lady with the Lamp” after her habit of making rounds at night. Nightingale’s achievements are all the more impressive when they are considered against the background of social restraints on women in Victorian England. Her father, William Edward Nightingale, was an extremely wealthy landowner, and the family moved in the highest circles of English society. In those days, women of Nightingale’s class did not attend universities and did not pursue professional careers; their purpose in life was to marry and bear children. Nightingale was fortunate. Her father believed women should be educated, and he personally taught her Italian, Latin, Greek, philosophy, history and – most unusual of all for women of the time – writing and mathematics.
Florence Nightingale mentored Linda Richards, “America’s first trained nurse”, and enabled her to return to the USA with adequate training and knowledge to establish high-quality nursing schools. Linda Richards went on to become a great nursing pioneer in the USA and Japan.
Before the experiments of the mid-1860s by Pasteur and Lister, hardly anyone took germ theory seriously; even afterwards, many medical practitioners were unconvinced. However, in the early 1880s, Florence Nightingale wrote an article for a textbook in which she advocated strict precautions designed, she said, to kill germs. Nightingale’s work served as an inspiration for nurses in the American Civil War. The Union government approached her for advice in organizing field medicine. Although her ideas met official resistance, they inspired the volunteer body of the United States Sanitary Commission.
Florence Nightingale exhibited a gift for mathematics from an early age and excelled in the subject under the tutorship of her father. Later, Nightingale became a pioneer in the visual presentation of information and statistical graphics. She used methods such as the pie chart, which had first been developed by William Playfair in 1801. Indeed, Nightingale is described as “a true pioneer in the graphical representation of statistics”, and is credited with developing a form of the pie chart now known as the polar area diagram, or occasionally the Nightingale rose diagram, equivalent to a modern circular histogram. Nightingale used these techniques in order to illustrate seasonal sources of patient mortality in the military field hospital she managed.
In 1860, Nightingale laid the foundation of professional nursing with the establishment of her nursing school at St Thomas’ Hospital in London. It was the first secular nursing school in the world, now part of King’s College London. The Nightingale Pledge taken by new nurses was named in her honor, and the annual International Nurses Day is celebrated around the world on her birthday. Her social reforms include improving healthcare for all sections of British society; improving healthcare and advocating for better hunger relief in India; helping to abolish laws regulating prostitution that were overly harsh to women; and expanding the acceptable forms of female participation in the workforce.
Nightingale was born to a wealthy upper-class family, at a time when women of her class were expected to focus on marriage and child bearing. Unitarian religious inspiration led her to devote her life to serving others, both directly and as a reformer. Nightingale rejected proposals of marriage so as to be free to pursue her calling. Her father had progressive social views, providing his daughter with a well-rounded education that included mathematics and supported her desire to lead an active life. Nightingale’s ability to effect reform rested on her exceptional analytic skills, her high reputation, and her network of influential friends. Starting in her mid-30s, she suffered from chronic poor health, but continued working almost until her death at the age of ninety.
In her youth she was respectful of her family’s opposition to her working as a nurse, only announcing her decision to enter the field in 1844. Despite the intense anger and distress of her mother and sister, she rebelled against the expected role for a woman of her status to become a wife and mother. Nightingale worked hard to educate herself in the art and science of nursing, in spite of opposition from her family and the restrictive social code for affluent young English women.
In Rome in 1847, she met Sidney Herbert, a politician who had been Secretary at War (1845–1846). Herbert would be Secretary of War again during the Crimean War; he and his wife were instrumental in facilitating Nightingale’s nursing work in the Crimea.
Nightingale circa 1854
While traveling in Thebes, she wrote of being “called to God” while a week later near Cairo she wrote in her diary: “God called me in the morning and asked me would I do good for him alone without reputation.” Later in 1850, she visited the Lutheran religious community at Kaiserswerth-am-Rhein in Germany, where she observed Pastor Theodor Fliedner and the deaconesses working for the sick and the deprived. She regarded the experience as a turning point in her life, and issued her findings anonymously in 1851. The Institution of Kaiserswerth on the Rhine, for the Practical Training of Deaconesses, etc. was her first published work; she also received four months of medical training at the institute which formed the basis for her later care. On 22 August 1853, Nightingale took the post of superintendent at the Institute for the Care of Sick Gentlewomen in Upper Harley Street, London, a position she held until October 1854.
A print of the jewel awarded to Nightingale by Queen Victoria, for her services to British soldiers in the war
The territory of Crimea was conquered and controlled many times throughout its history. The Cimmerians, Greeks, Scythians, Goths, Huns, Bulgars, Khazars, the state of Kievan Rus’, Byzantine Greeks, Kipchaks, Ottoman Turks, Golden Horde Tatars and the Mongols, all controlled Crimea in its early history. In the 13th century, it was partly controlled by the Venetians and by the Genovese. They were followed by the Crimean Khanate and the Ottoman Empire in the 15th to 18th centuries. The Russian Empire conquered Crimea in the 18th to 20th centuries followed by Germany during World War II, then the Russian Soviet Federative Socialist Republic and later the Ukrainian Soviet Socialist Republic. Finally it was within the Soviet Union during most of the rest of the 20th century. Crimea is now an autonomous parliamentary republic, within Ukraine, which is governed by the Constitution of Crimea in accordance with the laws of Ukraine.
The Crimean war was part of a long-running contest between major European powers for influence over territories of the declining Ottoman Empire. About 250,000 men died on the Russian side and the same number on the British-French-Turkish-Austrian side – many of them victims to disease. The war did not settle the relations of the powers in eastern Europe. It made, however, the new Russian emperor Alexander II realize Russia was a backward country that had to sharpen up to compete successfully with other European powers. A further result of the war was that Austria, having sided with Great Britain and France, lost the support of Russia in central European affairs. Austria became dependent on Britain and France, which failed to support that country, leading to the Austrian defeats in 1859 and 1866 that, in turn, led to the unification of Italy and Germany.
The Crimean War (1854-56) developed because of an argument between the French and Russian religious fraternities over who should have access and right to holy areas in the Middle East, namely Nazareth and Jerusalem. The whole debate had been escalated to a level beyond all reason. The situation was compounded when the Russians, under the directive of Tsar Nicholas I, moved troops into the area, supposedly to shield the aforementioned sacred grounds, and positioned Russian troops in the Middle East, then a part of the Turkish Ottoman Empire. When the Russians upped the stakes by massacring a small fleet of Turkish boats, the Turks and their allies (mainly British & French) responded with war.
A tinted lithograph by William Simpson illustrating conditions of the sick and injured in Balaklava
A ward of the hospital at Scutari where Nightingale worked, from an 1856 lithograph
“Nightingale receiving the Wounded at Scutari”, a portrait by Jerry Barrett
Florence Nightingale’s most famous contribution came during the Crimean War, which became her central focus when reports got back to Britain about the horrific conditions for the wounded. On 21 October 1854, she and the staff of 38 women volunteer nurses that she trained, including her aunt Mai Smith, were sent (under the authorization of Sidney Herbert) to the Ottoman Empire. They were deployed about 339 miles across the Black Sea from Balaklava in the Crimea, where the main British camp was based. Nightingale arrived early in November 1854 at Selimiye Barracks in Scutari (modern-day Uskudar in Istanbul). Her team found that poor care for wounded soldiers was being delivered by overworked medical staff in the face of official indifference. Medicines were in short supply, hygiene was being neglected, and mass infections were common, many of them fatal. There was no equipment to process food for the patients.
After Nightingale sent a plea to The Times for a government solution to the poor condition of the facilities, the British Government commissioned Isambard Kingdom Brunel to design a prefabricated hospital which could be built in England and shipped to the Dardanelles. The result was Renkioi Hospital, a civilian facility which under the management of Dr. Edmund Alexander Parkes had a death rate less than 1/10th that of Scutari.
The first edition of the Dictionary of National Biography (1911) asserted that Nightingale reduced the death rate from 42% to 2% either by making improvements in hygiene herself or by calling for the Sanitary Commission. However, death rates actually began to rise to the highest of all hospitals in the region. During her first winter at Scutari, 4,077 soldiers died there, with 10x more soldiers dying from illnesses such as typhus, typhoid, cholera and dysentery than from battle wounds. With overcrowding, defective sewers and lack of ventilation, the Sanitary Commission had to be sent out by the British government to Scutari in March 1855, almost six months after Florence Nightingale had arrived. When the commission flushed out the sewers and improved ventilation, the death rates were sharply reduced.
After she returned to Britain and began collecting evidence before the Royal Commission on the Health of the Army, Nightingdale came to believe that most of the soldiers at the hospital were killed by poor living conditions. This experience influenced her later career, when she advocated sanitary living conditions as of great importance. Consequently, she reduced peacetime deaths in the army and turned attention to the sanitary design of hospitals.