Category: Science-Biology/Chemistry/Physics

The Antidote

The Book of the Week is “The Antidote” by Barry Werth, published in 2014. This suspenseful saga is about the public drug company, Vertex.

Vertex has created the core substances in drugs that treat niche diseases, such as hepatitis C and cystic fibrosis. It has partnered with various other drug companies to use their resources.

Unconventionally, in the 1990’s, Vertex’s employees were organized into teams working on protein targets rather than those working on different diseases. The company’s teams were demoralized when they failed month after month to come up with a successful molecule.

The cost of American drugs is so high not just because the drugmakers are greedy, but because their employees feel entitled to a large reward for creating an effective product that does minimal harm to patients. They take tremendous risks– acquire pricey, extensive educations in organic chemistry and such, working long daily hours, suffer loads of stress from dealing with grant applications, patent disputes, licensing issues, doctor-insurer issues, undergoing the rigorous process of seeking FDA approval after laboring months or years on a drug substance– possibly applying for approval at the same time as another company with a competing product, and face the possibility of being laid off anytime. This is why life-saving, life-prolonging medicines are astronomically expensive. However, the drugs would not exist, but for the necessary evil of a greed machine that raises the funds to pay for the price of creating them.

Vertex posted a “profit” of more than $2 million in the fourth quarter of 1993, even though it had yet to sell even one pill. Its financial arrangements with its partners allowed it to claim that its income exceeded its expenses. By the end of the 1990’s, however, there were still no actual drugs produced, and the company was likely many years and hundreds of millions of dollars from the market. It was thus a likely takeover target. Some of Vertex’s scientists and lawyers became avid day-traders of the company’s stock in the autumn of 2000, after a deal with Novartis.

Trading rumors fly all the time, and one influential analyst at a big-name investment bank might downgrade a drug company’s stock, causing a selloff. In the early 2000’s, there was an SEC accusation of insider trading against Vertex’s house counsel. Ironically, it is common practice for panel members of the FDA to receive financial support in research-funding from many pharmaceutical companies.

Those companies that are public must answer to Wall Street. Unsurprisingly, at numerous medical conferences, their executives spout cliches such as “…We believe it’s a matter of time before we break this disease wide open and make a really big difference for a lot of people.”

Read the book to learn about actions Vertex took in research, development and finance in order to stay in business twenty years while accumulating losses of more than $1.5 billion; the causes of its high turnover of executives; how it became more geared toward finding commercial applications with its research results, and how it had fared product-wise and financially by autumn 2013.

Genius on the Edge – Bonus Post

This blogger skimmed “Genius on the Edge” by Gerald Imber, MD, published in  2010. This long book describes the career of Dr. William Halsted.

Halsted was born in 1852 in New York City. There was still much ignorance about medicine in his generation. Fatal diseases, such as malaria, yellow fever and tuberculosis were rampant. He developed a passion for medicine at Yale University. The most prominent doctors of his age included Pasteur, Lister, Morse, Hunter, Wells, Koch, Morton, Young and Warren. They spurred progress in sanitation, anaesthesia, and the collection of new information and techniques for treating patients.

In the 1870’s, Columbia College, Physicians and Surgeons didn’t require undergraduate degrees for entry because it was seeking revenue from student tuition. The three-year program was all lectures– no labs, no interaction with patients. In the 1870’s, during Halsted’s internship at Bellevue Hospital, many personnel didn’t wash their hands before operating, and smoked.

In late 1884, Halsted started using cocaine as a local anaesthetic in dentistry. He displayed, “…hyperactivity, rambling speech, inattention, and suspended decision-making ability.” Medical students and their teachers started using cocaine as a pick-me-up. They became addicted. “The drug was readily available in Europe, through Merck, and there was no stigma associated with its purchase.” In late 1886, Halsted went to work at Johns Hopkins Pathological– the “Bell Labs” of medicine. He went to Baltimore because his addiction had wrecked his career in New York. He substituted morphine for cocaine.

It is unclear how much better Halsted could have performed were it not for his addiction. He did have a brilliant career, but there were bouts of irresponsibility, socially and teaching-wise. He missed classes, started surgery at 10am instead of 8 after a while, failed to show up for meetings, and retreated to his country home for almost half the year. One positive side effect of his addiction was that Halsted delegated complete patient care to residents when he had morphine withdrawal symptoms. So the residents got a golden opportunity they would not have had otherwise, to learn their craft.

Side Note (There’s nothing new under the sun.): “As a group, they [nurses] felt themselves underpaid and overworked.” The Training School taught them to cook and clean. They were required to wear brown Oxford shoes.

Halsted experimented on dogs on and off for a couple of years, between months-long stints in drug rehab. He began seeing human patients for surgery in early 1889. He pioneered the medical-school residency program. He instituted the training of surgeons to train other surgeons. Three other doctors at Johns Hopkins who wrought major change in medicine in the U.S. were William Osler, William Welch, and Howard Kelly. Halsted specialized in surgery for breast cancer and inguinal hernia.

Johns Hopkins wanted to remain on the cutting edge of medicine by opening a medical school but it needed money to do so. Female heirs of prominent, wealthy families raised the money and placed conditions on the school’s opening, requiring gender equality. After much controversy, it opened in the fall of 1893.

Read the book to learn how medicine in America changed through the years of the late 19th into the 20th century, and how, according to this book, Johns Hopkins led the way.

The Cure

The Book of the Week is “The Cure” by Geeta Anand, published in 2008. This ebook tells the emotional, suspenseful story of how a family coped with three disabled children, two of whom were suffering from a genetic disease for which a cure is yet to be found.

In the late 1990’s, John Crowley’s daughter and son were both diagnosed with Pompe disease, a muscle disorder. Patients, with varying severity, “have imperfectly produced acid alpha-glucosidase enzyme” which results in paralysis, obstructed breathing, and, if left untreated, death before the age of five.

Even though Crowley possessed the personality, talents, skills, education and privileged background that one would think would allow him access to a life-saving enzyme to save his children, he had to face numerous obstacles. The father naturally fell into the role of entrepreneur to do so. His wife provided invaluable emotional support and around-the-clock care of the children with the help of nurses; not to mention the running of the household.

Nevertheless, lots of genetic and environmental luck determines whether patients become fully cured and/or whether the quality of their lives improves significantly, or whether they die– even when they are sufficiently fortunate to take part in a trial of a new life-saving medicine. Death would be inevitable without the medicine.

Every patient is different. There are many different criteria the U.S. Food and Drug Administration considers when deciding whether to approve particular medical products for sale. Money plays a major part in whether a new product ever sees the light of day. A young medical research company raises funds through venture capitalists, and because the whole operation carries extremely high risks, if the company achieves success– the rewards, fittingly, are also extremely high.

Scientists must do years of preclinical testing on animals to make sure a new medicine works sufficiently well before even considering administering it to humans. In the United States, possible deadly consequences and possible future litigation motivate the scientists to act with integrity by performing tightly controlled experiments, so as not to have to fudge research results.

Another aspect of drug development, is avoiding a conflict of interest such as that in Crowley’s situation. He played a pivotal role in the race to bring a medicine to market; it appeared he was doing it to get the medicine for his own children.

The estimated annual expense of the enzyme for each child was $200,000, and $1 million for all future annual medical expenses, including the enzyme, plus wheelchairs, nurses, ventilators, catheters, etc.

Read the book to learn of the Crowley family’s experiences with American biotechnology.

All Creatures Great and Small

The Book of the Week is “All Creatures Great and Small” by James Herriot, published in 1993. This is a lighthearted account of Herriot’s training as an aspiring rural veterinarian in 1930’s England. A crotchety yet experienced character showed him the ropes. The author gradually developed confidence in curing the afflictions of pigs, cows, horses, etc. The job was suitable for neither the squeamish nor faint of heart.

The Emperor of All Maladies

The Book of the Week is “The Emperor of All Maladies, A Biography of Cancer” by Siddharta Mukherjee, published in 2010. Through this tome, the author, an attending cancer physician, researcher and assistant professor of medicine, discusses the history of cancer– how it came to be named, treated and researched through the centuries, and how it develops on the cellular level. He also talks about how cancer statistics can be manipulated to give people the impression that the illness is more common than it really is (to scare people into getting tested and treated), or– that treatment (including drugs and surgery) is more effective than it really is.

In ancient times, cancer was rare because lifespans were short. Several other diseases (tuberculosis, dropsy, cholera, smallpox, leprosy, plague or pneumonia) killed people before cancer would. More prevalent cancer testing has also made cancer a more common culprit in the cause of death, rather than, say, the labels, “abcess” or “infection.”

In modern times, specific factors, (like smoking and changes in public hygiene and diet) have increased the incidence of some kinds of cancer, and reduced the incidence of others.

The author points out the difficulties in determining whether detecting cancer early, helps save lives. Some cancers are quick-killing and others are slow-growing. If someone is diagnosed with an early stage of quick-killing cancer. whose treatment is rigorous and unsuccessful, is that a better situation than one in which someone has the quick-killing kind without knowing it, but goes about blissfully living his life, and dies quickly once he is diagnosed? Perhaps the former person lived six months longer, but given his lack of enjoyment of life after diagnosis, he might as well have died sooner.

The  author also writes regarding testing, “Using survival as an end point for a screening test is flawed because early detection pushes the clock of diagnosis backward.” Say we have the hypothetical scenario of cancer patients A and B. They both developed the exact same kind of quick-killing cancer at the same time. Say patient A’s illness was diagnosed in 1985 and she died in 1990. Patient B’s illness was diagnosed in 1989 and she died in 1990. But since doctors diagnosed A’s cancer earlier, it seems, falsely, that she lived longer and that the screening test was beneficial.

In 1976, a highly regarded mammography study was done on 42,000 women in Malmo, Sweden. The results showed that a significant number of women 55 years and older benefited from breast cancer screening– the lives of one fifth of them were presumably saved than otherwise. “In younger women, in contrast, screening with mammography showed no detectable benefit.” Many additional studies thereafter reinforced this conclusion by 2002: “In aggregate, over the course of fifteen years, mammography had resulted in 20-30 percent reductions in breast cancer mortality for women aged fifty-five to seventy. But for women below fifty-five, the benefit was barely discernible.”

Mukherjee also describes a moral issue that can arise when it comes to the testing of cancer drugs. A company was reluctant to spend hundreds of millions of dollars to do further testing on what appeared to be a promising new drug for a rare kind of leukemia that might (or might not) benefit only thousands of people. Thousands is considered a small number, compared to millions of individuals whom a drug might help in the long run. The company could spend the same amount of money helping millions. Patients for whom all other treatments had failed, aggressively pushed to be included in the drug trial, arguing it could save their lives. The company did eventually agree to test the drug, but on a small scale. The drug was wildly successful in its first decade for those few who were treated with it. However, a few years later, cancer cells had become resistant to the drug. A next-generation drug had to be developed to continue to keep those patients alive.

The author tries to explain why, even with all the resources currently poured into research for a cancer cure and improving treatment, many cases are still fatal even in industrialized countries. Nevertheless, he points out– there are pitifully few resources being thrown into prevention. I suspect it is just not as lucrative as research and treatment.

An Unquiet Mind

The Book of the Week is “An Unquiet Mind” by Kay Redfield Jamison, published in 1995.  This autobiography tells the story of someone with bipolar disorder (also called manic-depressive illness) who had gone undiagnosed until, ironically, she started working on her PhD in psychology.

Jamison was showing symptoms in high school– hearing music in her head, clear as a bell, and staying up all night, sometimes more than one night, energetically completing schoolwork. Sometimes she spoke too fast for people to understand her. A little later, she went on credit-card spending sprees and could not remember them afterwards. She also fell into periods of extreme depression. Each continual up-and-down cycle lasted about three days. She theorized that she had inherited the disorder from her father.

When Jamison got to graduate school, she was given a questionnaire on symptoms of her condition. That was the first time she got an inkling that she was mentally unbalanced.  Read the book to learn how she dealt with this revelation.

To Know A Fly

The Book of the Week is “To Know A Fly” by Vincent G. Dethier, published in 1962.  This thin, little paperback book discusses how scientists attempt to understand the behavior of a fly.  Those who pull off the legs or wings of flies either come to a bad end or become biologists.

“The [required] college education not infrequently is as useful for acquiring proficiency in the game of Grantsmanship as it is for understanding biology.  No self-respecting modern biologist can go to work without money for a secretary, a research associate, two laboratory assistants, permanent equipment…” a car, books, animals and their accompanying accessories, etc., and a vast quantity of money (called overhead) “to the university to pay for all the transcribers hired to handle all the papers and money transactions that so big a grant requires.”

There is much to be said for the fly as an experimental animal.  The author describes in detail some clever experiments involving the fly’s eating habits and capacity to learn.  “To know the fly is to share a bit in the sublimity of Knowledge.”