Breakthrough http://www.breakthroughthebook.com/blog Just another WordPress weblog Tue, 22 Mar 2011 22:54:56 +0000 en-US hourly 1 BREAKTHROUGH: “A Superb Book” http://www.breakthroughthebook.com/blog/2011/01/breakthrough-a-superb-book/ http://www.breakthroughthebook.com/blog/2011/01/breakthrough-a-superb-book/#respond Mon, 03 Jan 2011 18:05:30 +0000 http://www.breakthroughthebook.com/blog/?p=196 Continue reading ]]> Richard E. Epstein writes that BREAKTHROUGH is …

” … a superb book by Thea Cooper and Arthur Ainsberg called ‘Breakthrough: Elizabeth Hughes, the Discovery of Insulin, and the Making of a Medical Miracle.’  The title is not hyperbole … “

In the following post from the Hoover Institute blogRichard A. Epstein – a fellow at the Hoover Institute and professor at New York University and the University of Chicago – examines the path that transformed insulin from an idea to a mass-market drug, a process that took approximately three years.

Epstein questions whether the same could happen in today’s market. Does regulation prevent or delay “miracle” drugs like insulin from getting to the people? Or is regulation as it is today necessary to protect the public? Read the full post below:

January 2, 2011

defining ideas

The Tale of How Insulin Came to Market

by Richard A. Epstein

This inspiring story proves that medical innovation occurs in spite of, not because of, government regulators like the FDA.


One of the most pressing questions of modern biomedical research asks what the relationship between government regulation and scientific innovation is. Nothing is more common today than the plea that extensive government regulation, at every stage of the development process, is needed to protect innocent and uninformed patients and their families from exploitation by pharmaceutical companies, hospitals, and physicians. The underlying assumption is that good-faith government regulators can fill the void between ordinary people and the self-interested institutions that dominate our private lives. Indeed, filling this void is the purpose of the Food and Drug Administration (FDA), which supervises pharmaceutical companies.

Epstein

It was not always thus. Recently, I had occasion to visit the New York City Historical Society , which is featuring an excellent exhibit on the 1921 discovery of insulin by scientists Frederick Banting and Charles Best at the University of Toronto. That exhibit displayed a superb book by Thea Cooper and Arthur Ainsberg called “Breakthrough: Elizabeth Hughes, the Discovery of Insulin, and the Making of a Medical Miracle.” The title is not hyperbole. In fact, it behooves us to ask: could the same miracle be achieved today under the weight of our heavy system of regulation?

The Strange Path to Discovery

In 1920, diabetes was a condition ripe for research. For reasons that are not fully understood, some people from an early age find themselves unable to synthesize insulin, the hormone that breaks down a sugar called glucose. The result is the build-up of glucose in the bloodstream, which, if left unchecked, results in a grim death by diabetic coma.

Prior to the heroic work by Banting and Best, the standard treatment for diabetes was a relentless form of slow starvation that had been pioneered by one of the unsung early heroes of modern medicine, Dr. Frederick Allen. Around 1915, Allen discovered how to reduce the intake of food to levels so low that individuals could forestall an immediate death by diabetes for a slower death by starvation. Why make this grim choice? Allen realized that the ability to isolate and purify insulin was very much on the horizon. Diabetic children who might live just a few years longer could find themselves the recipient of a far better cure.

One child who won that bet was Elizabeth Hughes, daughter of Charles Evans Hughes. The senior Hughes sported an impressive resume that included items like Governor of New York, two terms as a Supreme Court Justice (the second as its Chief Justice), Secretary of State under Warren Harding and Calvin Coolidge, and much more besides.

Diagnosed with a serious case of diabetes in 1918 when she was eleven years old, Elizabeth endured 40 months of strict and unflagging adherence to the Allen diet until she was raised from the near dead in 1922, when she began to receive regular insulin shots that allowed her to live a normal life. She died, with her diabetes kept secret from the world, in 1981 at 73 years old.

Today, thanks to government regulators, the thought that the next insulin could move from successful synthesis to initial marketing in about a year’s time is a pipe dream.

If today’s regulatory rules were in place, Elizabeth would have died a horrific death before her sixteenth birthday. There are two truly impressive features about the discovery and commercialization of insulin: the speed of its discovery and the rapidity of its successful commercialization by Eli Lilly and Company.

As to the former, Frederick Banting, the driving force behind insulin, was something of a head case. In October 1920, as he was desultorily practicing medicine in London, Ontario, and in the midst of one of his chronic depressions, he dreamed up a way to isolate and purify insulin. By the spring of 1921, he was holed up in a ratty laboratory at the University of Toronto that the head of the Department of Physiology, John Macleod, had offered him. Macleod had mixed feelings, to say the least, about entrusting this project to so unstable a human being. But Banting enlisted the assistance of a young medical student, Charles Best, and together they went through a series of calamitous ups and downs, technical dead ends, and outright blunders, before they finally developed a method to isolate insulin. Amid the stench and the filth of the lab, the two men engaged in nonstop experiments to isolate insulin from the pancreas of dogs. Their grizzled experiments required that they kill one dog for its supply of insulin, which they promptly injected into a second dog whose pancreas had been removed.

Notwithstanding innumerable mistakes, frustrations, and setbacks, by the late summer of 1921, Banting and Best had progressed far enough in their work to produce a prototype of insulin that might work for human beings. As far as one can tell, their work was done without any government oversight. Two years later that work would garner Banting and Macleod a Nobel Prize for Medicine. Best was excluded because no one saw fit to nominate him. Macleod was a dubious winner given his indifference, which bordered on hostility, to the project.

Then lay the challenge of commercializing this new drug. Here, a stroke of good fortune brought Dr. George Clowes, head of research at Eli Lilly and Company, together with Banting. In December 1921, Clowes chose to attend a meeting of the American Physiology Society in New Haven. There, Banting made a ham-handed presentation of his basic research on insulin. With the blessing of the far-sighted and humane Josiah Lilly, President of Eli Lilly, Clowes made aggressive overtures to the University of Toronto to gain the rights to produce insulin for the United States market.

But there was a complication. The university’s own Cannaught Antitoxin Laboratories was pushing for the same rights, but without the resources or equipment that Lilly could bring to the venture. Eventually, though, a deal was struck where Lilly supplied the Canadian lab with a large fraction of its output, while also furnishing it with the state-of-the-art equipment it needed for key stages of the purification process.

Left to its own devices, Lilly put on a full court press to manufacture and market insulin, which it promoted under its brand name of Iletin. It achieved this feat astonishingly rapidly, given the logistical and technical obstacles that blocked its path. The only federal government involvement in this venture was, ironically, a temporary government order forbidding the use of pure alcohol in the company’s research—an offshoot of the Prohibition era. Fortunately, that order was lifted, allowing the remaining work, which was formidable, to go on.

In the days before gene cloning, insulin had to be isolated from countless pig pancreases, which necessitated a long-term supply contract with the Chicago-based Swift & Co., a meat packaging company. Once obtained, Lilly faced the major challenge of isolating insulin of sufficient purity and consistency for injection into human beings. They made lots of mistakes and some children died. No one sued.

In the beginning, there was barely enough insulin available to supply it to prominent diabetes specialists and the University of Toronto labs. It was there, at the University of Toronto, that Elizabeth Hughes began her recovery from the dead in August 1922. Her recovery was virtually complete by November of that same year.

Shortly thereafter, insulin took off in the market. As Cooper and Ainsberg report,

In January 1923 Eli Lilly and Company began to sell limited quantities of insulin to physicians through retail druggists. In June 1923, the Rockefeller Foundation chipped in $150,000 dollars to let 15 American and Canadian hospitals help spread the use of insulin. In October of the same year, Iletin was released for distribution directly through physician prescription. At that time it was estimated that 7,500 physicians were treating 25,000 diabetic patients with Iletin.

Lilly also took steps to ensure that in the early stages of commercializing the drug, physicians received free supplies of insulin for their patients. By 1924, an internal Lilly publication, which is currently on exhibit at the New York City Historical Society, shows Lilly reminding its sales agents to stress the company’s good works in the face of impending competition.

For its efforts, the company’s initial sales came to about $1,110,000, which is a tiny figure compared to the ultimate human benefit from the drug.

Modern Epilogue

Today’s constant denunciation of pharmaceutical companies looks weirdly out of place, considering this story.

From start to finish, it took about three years for the conception and commercialization of insulin to occur. The painful question is whether that track record could be repeated today. In one sense, it is impossible. The near-eradication of major scourges, like diphtheria and smallpox, in the first decades of the 20th century means that thankfully we do not have the same major opportunities for medical innovation today as we once did.

Beyond that, the thought that the next insulin could move from successful synthesis to initial marketing in about a year’s time is a pipe dream. Today, before a drug is released for general use, there is an endless cycle of FDA reviews that can take years to complete. Clinical trials, for instance, are a legal necessity. All sorts of animal studies, three stages of trials, strict warnings, and market restrictions both raise the price of treatment and slow down the process of introducing the drug to the market.

The uniform view among doctors and research scientists is that the FDA slows down medical progress by about three to five years.

Fortunately, the FDA of 1923 only had power to remove contaminated batches of drugs from the channels of interstate commerce and could do absolutely nothing to regulate the way in which Lilly ran its laboratories or production lines. But today, the FDA prohibits new and untested therapies on the market, even when a compassionate exception could be made, as in the case of desperate parents who are willing to try an untested cancer drug on their child.

It was, of course, just that frustration that led to the formation of the Abigail Alliance for Better Access to Developmental Drugs. In 2001, Frank Burroughs, who would later found the Abigail Alliance, could not secure the experimental use of Erbitux or Iressa in time for his cancer-stricken daughter Abigail, as advised by her team of oncologists at Johns Hopkins. The drugs did not come until she had already died.

The Abigail Alliance’s website notes that every drug for which it has sought approval in the past eight years is now on the market, which shows that the FDA’s risk aversion can kill thousands of people in the name of protecting them against “quack” treatment. The statist mentality that created and expanded the FDA is still very much in play in the courts, as the judicial effort of the Abigail Alliance to claim a constitutional right to receive experimental therapies was roundly rejected in the Circuit Court for the District of Columbia. Once again, state power dominates individual choice.

In a larger sense, the sorry role of the FDA is an outgrowth of the misguided progressive belief that benign government expertise can save ordinary citizens from abuse and misfortune. Unfortunately, it does not seem to work out that way.

I have attended countless meetings of doctors and research scientists in which the role of the FDA was discussed. The uniform view is that the FDA slows down medical progress by about three to five years. These doctors, however, are not willing to state this publicly for fear of administrative revenge. All of their simmering resentment travels below the radar for a simple reason. The best way to throttle free speech is not through punitive or criminal measures, but to ensure that individuals and firms who take on the government find that their FDA submissions are subject to innumerable administrative delays that are effectively unreviewable in court, except at the cost of still further delays. These regulators hold monopoly power, and they know it. They can use their routine power to stifle their critics.

The current regulatory regime needs a prompt reversal to the earlier status quo. If the comparisons between Abigail’s Erbitux and Lilly’s insulin tell us anything, it is that medical progress and innovation take place not because of government regulation, but in spite of it. It is time to change that mindset and that institutional reality.


Richard Epstein is the Peter and Kirsten Bedford Senior Fellow at Hoover. He is also the Laurence A. Tisch Professor of Law at New York University and the James Parker Hall Distinguished Service Professor of Law at The University of Chicago. His areas of expertise include constitutional law, intellectual property, and property rights. His most recent books are The Case Against the Employee Free Choice Act (Hoover Press, 2009) and Supreme Neglect: How to Revive the Constitutional Protection for Private Property (Oxford Press, 2008).

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BREAKTHROUGH Should Be On Your “Next-to-Read” List http://www.breakthroughthebook.com/blog/2010/12/breakthrough-should-be-on-your-next-to-read-list/ http://www.breakthroughthebook.com/blog/2010/12/breakthrough-should-be-on-your-next-to-read-list/#respond Thu, 16 Dec 2010 21:30:34 +0000 http://www.breakthroughthebook.com/blog/?p=191 Continue reading ]]>

“If you love to read history books, place this one as your ‘next to read.’ ” –Amy, Three Thirty Three

A review of Breakthrough: Elizabeth Hughes, the Discovery of Insulin, and the Making of a Medical Miracle was posted today on the blog Three Thirty Three.  Amy, the blog’s founder, discovered the book while researching Type 1 diabetes; her 10-year-old daughter Ellie was diagnosed with T1 in September of this year.

Amy sites some of her favorite moments from BREAKTHROUGH and writes how deeply she was affected by these passages.

Here is an example:

PROLOGUE: page 1

“In 1918 an eleven-year-old girl stands in the kitchen of her family’s elegant townhouse gulping water from a glass with such ferocity that it runs down the sides of her face. It is her sixth glass.”

::Thud:: (the sound of heart dropping down to my toes) At this point, only 38 words into the book, I wondered how far I would get. Tears were streaming down my face as I pictured Ellie standing in front of me clutching 2 water bottles just 3 months ago.

Girl injects herself with insulin, 1930

 

Read the full post here.

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Before Insulin, Elixirs Promised Over-the-Counter Diabetes Cure http://www.breakthroughthebook.com/blog/2010/11/before-insulin-elixers-promised-over-the-counter-diabetes-cure/ http://www.breakthroughthebook.com/blog/2010/11/before-insulin-elixers-promised-over-the-counter-diabetes-cure/#comments Wed, 17 Nov 2010 20:27:42 +0000 http://www.breakthroughthebook.com/blog/?p=180 Continue reading ]]>

Warner's Safe Diabetes Cure

As scientists in the early 1900s began to learn more about diabetes, their ability to diagnose the disease improved. But with more cases diagnosed, a real treatment remained elusive. Before the breakthrough discovery of insulin, many people, desperate to believe they could be cured, turned to elixirs to treat their diabetes.

Here’s an excerpt from BREAKTHROUGH: Elizabeth Hughes, the Discovery of Insulin and the Making of a Medical Miracle by Thea Cooper and Arthur Ainsberg:

By 1920, the death rate from diabetes would be double what it was twenty years before, and the number of diagnoses was rising. It appeared that medical research was losing ground.

The rise in diagnoses fertilized a burgeoning business of fad diets, patent medicines, and hope cures hawked by unscrupulous opportunists, hucksters, and self- described healers. The oat cure, the legume cure, potato therapy, lime water, sweet wine, rancid meat, high carbohydrates, low carbohydrates, high- fat diets, low- fat diets, horse back riding, abstinence from plant products, even opium— each had been heralded as a miracle cure for juvenile diabetes. (26)

The use of elixirs that promised to cure disease was not isolated to diabetes. A new article in the Atlantic examines the history of hawking “snake oil” and has a great slideshow of original bottles of patent medicine (including the one above)  from Smithsonian’s National Museum of American History patent medicine collection. You can link to the article here.

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Breakthrough: Diabetes History and the Experience of a Child http://www.breakthroughthebook.com/blog/2010/11/breakthrough-diabetes-history-and-the-experience-of-a-child/ http://www.breakthroughthebook.com/blog/2010/11/breakthrough-diabetes-history-and-the-experience-of-a-child/#respond Fri, 05 Nov 2010 18:47:25 +0000 http://www.breakthroughthebook.com/blog/?p=175 Continue reading ]]> Louise Mirrer, president of the New-York Historical Society, wrote a wonderful blog on the Huffington Post on November 5. She notes that the “experience of children can teach us volumes about our history.” One such child is Elizabeth Hughes, who, after being diagnosed with diabetes, became one of the first recipients of the newly-discovered insulin. Her story, chronicled in BREAKTHROUGH, is inspiring and eye-opening. 

Louise Mirrer writes: 

 The story of young Elizabeth Evans Hughes led us to think differently, as an institution organized around history, about the fight for life waged by medical patients almost a century ago and about the roles of science…” 

You can read the full post below or at the Huffington Post.  Also, be sure to check out the exhibit at the New-York Historical Society (also called Breakthrough) based on the book BREAKTHROUGH. 

Louise MirrerLouise Mirrer

New-York Historical Society president 

Posted: November 5, 2010 09:41 AM 

How the Past Changes

When It’s Seen

Through a Child’s Eyes

  

Think for a moment about a young boy in 1870s New York, born into an impoverished immigrant family, who is swept up in the movement to take destitute children away from their urban homes on “orphan trains” and send them to work in the West, on the farms of complete strangers. Or think about a newsgirl in the late 19th or early 20th century, struggling to make a living on the city streets and caught up in the movement to institute child labor regulations. 

The experiences of children can teach us volumes about our history–about education, religion, working conditions, warfare, domestic life, medicine and a multitude of other aspects of our past. But these experiences do not teach us volumes–because historians for too long have neglected to look into them. 

Fortunately, this situation has been changing, thanks to a new international trend in childhood studies. We are proud to be a part of that trend at the New-York Historical Society, where we are now in the midst of constructing our new DiMenna Children’s History Museum and Library. When this facility opens next year, as part of our overall renovation, visitors of all ages will see history as it was experienced by children like that boy on the orphan train, or that newsgirl on the street. 

Meanwhile, there is no waiting to relive the past through the experiences of yet another child–a famous one, as it happens–either at the New-York Historical Society or in a new book. The child, Elizabeth Evans Hughes, was the daughter of one of America’s most distinguished jurists and statesmen, Charles Evans Hughes. Her experience was a close brush with death, averted by a medical discovery that has since then saved countless lives. The book is Breakthrough: Elizabeth Hughes, the Discovery of Insulin, and the Making of a Medical Miracle by Thea Cooper and Arthur Ainsberg, and the exhibition (also titled Breakthrough) is on view now at the Historical Society, through January 31, 2011. 

Elizabeth Hughes, ca. 1923 courtesy of Thomas Fisher Rare Book Library, University of Toronto

 

In 1918, when Elizabeth Hughes was 11, she was diagnosed with diabetes. This was tantamount to a death sentence. She was not expected to live beyond her 14th birthday. At that time, the only known method of prolonging the life of a diabetes patient–a method practiced by Elizabeth’s physician, Dr. Frederick Allen, the period’s greatest specialist in the disease–was to put the child on a starvation diet. Elizabeth was still holding on, and weighed just 45 pounds, three years after her initial diagnosis. That’s when an extraordinary team from the academic world, government and industry discovered insulin and rushed it into use. Elizabeth was one of the first patients to try the new drug. She lived to be 74 years old. 

The story of young Elizabeth Evans Hughes led us to think differently, as an institution organized around history, about the fight for life waged by medical patients almost a century ago and about the roles of science, government, higher education, and industry in creating and distributing the life-saving drug. Although our exhibition (curated by my colleagues Jean Ashton and Stephen Edidin) goes beyond Elizabeth’s experience to explore a wider field, up to the present day, a large part of its impact lies in revealing to the public what it meant, in a different era from our own, to be a sick child.

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BREAKTHROUGH: The Miracle of Insulin http://www.breakthroughthebook.com/blog/2010/10/breakthrough/ http://www.breakthroughthebook.com/blog/2010/10/breakthrough/#respond Mon, 25 Oct 2010 20:21:16 +0000 http://www.breakthroughthebook.com/blog/?p=168 Continue reading ]]> Thomas Sullivan, in Policy and Medicine, praises the groundbreaking collaboration between researchers, physicians, and industry that made the discovery of insulin possible and changed diabetes treatment in his article discussing BREAKTHROUGH, by Thea Cooper and Arthur Ainsberg.

“While significant breakthroughs in medicine and innovation in science occur each day, ‘only once or twice in a generation does a miracle drug’ come about that changes the way humans live and physicians practice medicine.”

“‘As Thea Cooper and Arthur Ainsberg explain in their book “Breakthrough,”… what came [after the discovery of insulin] was a series of complicated questions that inevitably follow medical miracles: “Who will get the drug first? Who will pay for it? Who will make enough for everyone? And, of course, who will reward its developers as they feel they deserve?’”

 

Read the full article below:

The Miracle of Insulin

October 15, 2010  

Today, only 1 out of 5,000 to 10,000 chemical compounds makes it to the pharmacy, and this process can take between eleven and twelve years, and can cost on average $1.3 billion. While significant breakthroughs in medicine and innovation in science occur each day, “only once or twice in a generation does a miracle drug” come about that changes the way humans live and physicians practice medicine. We often refer to these products as “blockbuster medications.”

Yet with so many advances occurring so rapidly, the New York Times pointed out that we often forget the “birth of the first” blockbuster medication: injectable insulin, which was “finally isolated in 1921 by a team of squabbling Canadians.” Fortunately, the public will have a chance to relive the birth of injectable insulin starting this week when the exhibition “Breakthrough: The Dramatic Story of the Discovery of Insulin” opens at the New-York Historical Society, 2 West 77th Street, New York, and continues through Jan. 31, 2011.

The exhibition tells the story of how New York City’s death rate from diabetes in 1921 was estimated to be the highest in the country. When insulin was introduced, although it was not a cure, it turned “a brief, deadly illness into a long, chronic struggle.” As Thea Cooper and Arthur Ainsberg explain in their book “Breakthrough,” on which the exhibit is based, what came next was a series of complicated questions that inevitably follow medical miracles: “Who will get the drug first? Who will pay for it? Who will make enough for everyone? And, of course, who will reward its developers as they feel they deserve?”

“Breakthrough,” tells the story of how half a dozen different research groups in the first decades of the 20th century “were hot on the trail of insulin, a hormone manufactured in the pancreas but difficult to separate out from the digestive enzymes also made there.” This discovery was significant because “without insulin the body is unable to use glucose, its primary fuel.” As the Times explains, when there is a lack of insulin, “sugar and starch in the diabetic’s diet turn into poison, clogging the bloodstream with unusable glucose: the glucose is eliminated in sweet-tasting urine as the body’s cells literally starve in the midst of plenty. Insulin-deficient patients are both thirsty and ravenous, but the more they eat, the faster they waste away.”

Before insulin was available, doctors were forced to put diabetics on “salad- and egg-based diets devoid of sugar and starch, with only the minimum number of calories needed to survive.” While this caused patients to become “skeletal, the excess glucose disappeared from their blood and urine, and they survived far longer than untreated contemporaries.”

When insulin was finally isolated in Canada at the University of Toronto by Frederick Banting and his assistant Charles Best in 1921, everything changed. Their discovery came while they were experimenting on diabetic dogs, with only limited success until finally dog No. 92, a yellow collie, jumped off the table after an injection and began to wag her tail. This discovery was short lived for Dr. Banting because his mentor and lab director, Dr. John J. R. Macleod, took over the research and eventually won the Nobel Prize in 1923. Dr. Banting refused to attend the ceremony, for although he shared the physiology prize with Dr. Macleod, he would not share a podium.

Consequently, the team was having difficulty making enough insulin for more than a handful of patients. This created a problem for a number of children “who had to wait while the Canadians fought bitterly with each other over how to fairly distribute their tiny amounts of the lifesaving substance.” Eventually, Eli J. Lilly and Company, the Indianapolis pharmaceutical firm, won the right to mass-produce insulin. “It was the first partnership negotiated among academia, individual physicians, and the pharmaceutical industry.” If it were not for this partnership and collaboration, where would medicine for diabetes be today? How many people would have suffered without this partnership?  

As Dr. Kent Sepkowitz, an infectious disease expert at Memorial Sloan-Kettering Cancer Center in New York pointed out, getting miracle drugs like insulin and the AIDS drugs to go from discovery to production is a “big challenge.” Nevertheless, pharmaceutical companies like Eli Lilly overcame such obstacles by playing an innovative role in helping cover the cost and logistics of large-scale insulin manufacture. Because of their work, by 1932, the price of insulin had fallen by 90 percent. That decline shows the true value of medicine pharmaceutical companies provide.

Today, according to the American Diabetes Association (ADA), 23.6 million children and adults in the United States—7.8% of the population—has diabetes. Of that amount, 17.9 million people are diagnosed, and 5.7 million people go undiagnosed. Additionally, 57 million people have pre-diabetes like factors, and each year, 1.6 million new cases of diabetes are diagnosed in people aged 20 years and older.

If it were not for this first partnership between academia, individual physicians, and the pharmaceutical industry, 8% of our population would still be suffering today. It then seems obvious that any one of those 23.6 million children or adults would tell those who criticize such collaboration that these partnerships and relationships are essential not only for their present health and well being, but for the future as well.

As a result, people must recognize the impact this partnership has had in the daily lives of millions of Americans and in numerous other diseases and conditions. Those with diabetes and other illnesses that have benefited from this partnership must speak up and show their support for this collaboration that has saved their lives in some case, and made them healthier in others. Otherwise, if we continue down a path that stifles these relationships and chills the willingness of researchers and physicians to collaborate with industry, we may never find the cures and treatments to diseases the way Dr. Banting did over eight decades ago.

Posted by Thomas Sullivan on October 15, 2010 at 06:38 AM in Pharmaceutical and Device, Research, Science | Permalink

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BREAKTHROUGH: Riva Greenberg Review http://www.breakthroughthebook.com/blog/2010/10/breakthrough-riva-greenberg-review/ http://www.breakthroughthebook.com/blog/2010/10/breakthrough-riva-greenberg-review/#respond Mon, 25 Oct 2010 19:55:34 +0000 http://www.breakthroughthebook.com/blog/?p=165 Continue reading ]]> BREAKTHROUGH is reviewed by Riva Greenberg on her blog Diabetes Stories. Greenberg is also a blogger on the Huffington Post.

…the overall arc of the book conveys a true look at the drama of living with diabetes before insulin was discovered…

The full review as it appeared is below:

The discovery of insulin and how it effects one family

The first few patients to actually receive insulin back in 1922 make an interesting story in, Breakthrough: Elizabeth Hughes, the Discovery of Insulin and the Making of a Medical Miracle.

It all began at the University of Toronto with the discovery of insulin after two years of scientific research and experiments conducted on dogs.

The back story is really the story: the personal and professional struggles of the lead scientist, Dr. Frederick Banting, whose birthday has been taken as World Diabetes Day, November 14th. Banting did not have an easy slog through the myriad of academic regulations and competing researchers’ jealousies. 

Elizabeth Hughes, the daughter of an American diplomat, was one of Banting’s first patients after she managed to live for four years on a starvation diet – the treatment before insulin was discovered. Amazingly, perhaps she lived to be a ripe 77 years old.

While the authors, Thea Cooper and Arthur Ainsberg, guess at times at actual occurrences, the overall arc of the book conveys a true look at the drama of living with diabetes before insulin was discovered and shortly afterward.

Sep 27, 2010
Original posting can be found here.
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BREAKTHROUGH: Arthur Ainsberg Interviewed on NBC http://www.breakthroughthebook.com/blog/2010/10/breakthrough-arthur-ainsberg-interviewed-on-nbc/ http://www.breakthroughthebook.com/blog/2010/10/breakthrough-arthur-ainsberg-interviewed-on-nbc/#respond Wed, 13 Oct 2010 20:11:55 +0000 http://www.breakthroughthebook.com/blog/?p=152 Continue reading ]]> Arthur Ainsberg appeared on NY Nightly News with Chuck Scarborough Monday night! He discussed BREAKTHROUGH: Elizabeth Hughes, the Discovery of Insulin, and the Making of a Medical Miracle, which he coauthored with Thea Cooper. He also talked about the accompanying exhibition at the New-York Historical Society, based upon the gripping story of the discovery of insulin.

Follow the link below to watch the clip:

Arthur Ainsberg on New York Nightly News with Chuck Scarborough

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BREAKTHROUGH in The New York Times! http://www.breakthroughthebook.com/blog/2010/10/breakthrough-makes-the-new-york-times/ http://www.breakthroughthebook.com/blog/2010/10/breakthrough-makes-the-new-york-times/#respond Tue, 05 Oct 2010 17:17:42 +0000 http://www.breakthroughthebook.com/blog/?p=140 Continue reading ]]> “With insulin, dying children laughed and played again, as parents wept and doctors spoke of biblical resurrections.”
The New York Times

BREAKTHROUGH is on the front page of the October 5, 2010 Science section  in The
 New York Times!

The article explores the current exhibition at the New-York Historical Society, chronicling the discovery of insulin. The exhibition, which opens today, is based upon BREAKTHROUGH: Elizabeth Hughes, the Discovery of Insulin, and the Making of a Medical Miracle by Thea Cooper and Arthur Ainsberg, the dramatic and rivetting story of the discovery of insulin.

The full article, as it appears in the NYT, is below:

REDISCOVERING THE FIRST MIRACLE DRUG

By ABIGAIL ZUGER, M.D.

Every few months some miracle drug or other is rolled out with bells and confetti, but only once or twice in a generation does the real thing come along.

These are the blockbuster medications that can virtually raise the dead, and while the debuts of some, like the AIDS drugs, are still fresh in memory, the birth of the first one is almost forgotten. It was injectable insulin, long sought by researchers all over the world and finally isolated in 1921 by a team of squabbling Canadians. With insulin, dying children laughed and played again, as parents wept and doctors spoke of biblical resurrections.

Visitors to a new exhibition opening Tuesday at the New-York Historical Society will find a story made particularly vivid by dramatic visuals, for insulin’s miracle was more than a matter of better blood tests. As in Ezekiel’s vision of the dry bones, it actually put flesh on living skeletons.

But the miracle went only so far: insulin was not a cure. In 1921, New York City’s death rate from diabetes was estimated to be the highest in the country, and today the health department lists diabetes among the city’s top five killers. Now though, it is adults who die, not children. What insulin did was turn a brief, deadly illness into a long, chronic struggle, and both the exhibit and the book, “Breakthrough,” by Thea Cooper and Arthur Ainsberg, on which it is based highlight the complicated questions that inevitably follow medical miracles: Who will get the drug first? Who will pay for it? Who will make enough for everyone? And, of course, who will reward its developers as they feel they deserve?

In the first decades of the 20th century, half a dozen different research groups were hot on the trail of insulin, a hormone manufactured in the pancreas but difficult to separate out from the digestive enzymes also made there.

 Without insulin the body is unable to use glucose, its primary fuel. Most diabetic children lack insulin completely, while adults with so-called Type 2 diabetes often associated with obesity are resistant to the hormone’s action. Either way, sugar and starch in the diabetic’s diet turn into poison, clogging the bloodstream with unusable glucose: the glucose is eliminated in sweet-tasting urine as the body’s cells literally starve in the midst of plenty. Insulin-deficient patients are both thirsty and ravenous, but the more they eat, the faster they waste away.

Before insulin was available, doctors understood enough of this sequence to cobble together a stopgap treatment: diabetics were put on salad- and egg-based diets devoid of sugar and starch, with only the minimum number of calories needed to survive. Already thin, these patients became skeletal, but the excess glucose disappeared from their blood and urine, and they survived far longer than untreated contemporaries.

Dr. Elliott Joslin, whose Boston clinic was and remains a renowned diabetes center, recalled that before insulin one of his dieting patients was “just about the weight of her bones and a human soul.”

The other great authority on diet therapy was New York’s Dr. Frederick Allen, now long forgotten, who founded a residential hospital for diabetics, first on East 51st Street in Manhattan, and then in rural New Jersey.

It was to Dr. Allen that the eminent American jurist and Supreme Court justice Charles Evans Hughes turned when his daughter Elizabeth was diagnosed with diabetes in 1919, at age 11.

Elizabeth Hughes was a cheerful, pretty little girl, five feet tall, with straight brown hair and a consuming interest in birds. On Dr. Allen’s diet her weight fell to 65 pounds, then 52 pounds, and then, after an episode of diarrhea that almost killed her in the spring of 1922, 45 pounds. By then she had survived three years, far longer than expected. And then her mother heard the news: insulin had finally been isolated in Canada.

The unlikely hero was Frederick Banting, an awkward Ontario farmboy who graduated from medical school without distinction, was wounded in World War I, then more or less forced himself into a laboratory at the University of Toronto with an idea of how to get at the elusive substance. Over the miserably hot summer of 1921 Dr. Banting and his assistant Charles Best experimented on diabetic dogs, with only limited success until finally dog No. 92, a yellow collie, jumped off the table after an injection and began to wag her tail.

Meanwhile, Dr. Banting’s mentor and lab director, Dr. John J. R. Macleod, was summering in Scotland.

Dr. Banting never forgave Dr. Macleod for arriving back in the autumn, rested and refreshed, and taking over. His bitter hostility lasted years, long after the Nobel Prize ceremony in 1923 which Dr. Banting refused to attend, for although he shared the physiology prize with Dr. Macleod, he would not share a podium.

Meanwhile, mothers all over the globe were writing him heart-wrenching letters: “My dear Dr. Banting: I am very anxious to know more of your discovery,” wrote one, going on to describe her daughter’s case: “She is pitifully depleted and reduced.”

That was from Elizabeth Hughes’s mother, Antoinette. Charles Evans Hughes had by that time temporarily left the Supreme Court, and was serving as secretary of state in President Warren G. Harding’s administration. Dr. Banting, unimpressed, replied no, sorry, no insulin available — for, in fact, the team was having difficulty making enough for more than a handful of patients.

And then a few weeks later, Dr. Banting changed his mind.

Presumably higher powers had intervened, or perhaps Justice Hughes himself — a rigid, unsmiling man whom Theodore Roosevelt had nicknamed “the bearded iceberg” — had pulled strings. Either way, Elizabeth traveled posthaste to Toronto and the lifesaving injections.

It was the end of her journey, but only the beginning for many children without her connections, who had to wait while the Canadians fought bitterly with each other over how to fairly distribute their tiny amounts of the lifesaving substance.

Dr. Banting wound up giving one of his colleagues a black eye before it was all over, and Eli J. Lilly and Company, the Indianapolis pharmaceutical firm, won the right to mass-produce insulin. It was the first partnership negotiated among academia, individual physicians and the pharmaceutical industry.

When the first combinations of AIDS drugs proved to save lives in just the same seemingly miraculous way, Dr. Kent Sepkowitz, an infectious disease expert at Memorial Sloan-Kettering Cancer Center in New York, was moved to look up the old literature on the discovery of insulin and found many parallels between the two eras.

 “In some sense, the breakthrough is the easy part,” he said. “Then the real work begins.”

For both insulin and the AIDS drugs the big challenge was “getting it from here to there,” Dr. Sepkowitz said. The expense and logistics of large-scale insulin manufacture were initially daunting. But soon trainloads of frozen cattle and pig pancreas from the giant Chicago slaughterhouses began to arrive at Lilly’s plant. By 1932 the drug’s price had fallen by 90 percent.

Meanwhile, the notion of allowing patients to test their own urine for glucose and calculate their own insulin doses was outlandish to most doctors. Diabetes was the first illness which forced them to cede some medical authority to the patient, said Jean Ashton, one of the exhibit’s curators. With insulin, diabetics suddenly acquired both the right and the responsibility to maintain their own health.

Some of the children who were early recipients of insulin became diabetes advocates, speaking out for patients’ rights well into their old age.

But not Elizabeth Hughes: she ran in the other direction, far from the headlines that briefly made her the most famous diabetic child in the United States. Although she received an estimated 42,000 insulin shots before she died in 1981 at the age of 74, she systematically destroyed most of the material documenting her illness, expunged all references to diabetes from her father’s papers, and occasionally even denied she had been ill as a child.

Ms. Cooper, a writer, and Mr. Ainsberg, a Wall Street executive and amateur historian, show no compunction in making her the focus of their story anyway, creating dialogue for her, and even imagining a few pivotal scenes of which there is no historical record.

But Elizabeth forms only a small part of the exhibit, and a viewer suspects this is exactly what she would have preferred. The few dozen of her letters that survive from her six-month stay in Toronto, as she exuberantly regained health and strength, emphasize how desperately she wanted to stop being a patient forever.

 It was a great day when she injected herself with insulin for the first time: “I can do it perfectly beautifully,” she wrote to her mother. “Now I feel so absolutely independent.”

The exhibition “Breakthrough: The Dramatic Story of the Discovery of Insulin” opens on Tuesday at the New-York Historical Society, 2 West 77th Street, New York, and continues through Jan. 31, 2011.

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Washington Times: BREAKTHROUGH Told With “Energy” and “Vividness” http://www.breakthroughthebook.com/blog/2010/09/washington-times-breakthrough-told-with-energy-and-vividness/ http://www.breakthroughthebook.com/blog/2010/09/washington-times-breakthrough-told-with-energy-and-vividness/#respond Fri, 24 Sep 2010 21:28:22 +0000 http://www.breakthroughthebook.com/blog/?p=131 Continue reading ]]>

“Although this is the authors’ first book, they are adept at telling their complicated, multifaceted story with energy and vividness. Their account of diabetics’ treatment before the production of insulin is harrowing”

See the full Washington Times review of BREAKTHROUGH below:

The word miracle is one of the most overused in our language and so often engenders a skeptical reaction. But if ever there was a medical miracle, the discovery of insulin and its rendering into a form deliverable to human beings is up there. For not only did this conquer the hitherto universally fatal Type 1 form of diabetes, in which the pancreas no longer produces insulin, but it provided the paradigm for an incurable disease that could be managed so successfully that many of those suffering from it would live on to die eventually of something else.

In any story, medical or otherwise, it helps to have human faces, and the story of insulin has many, starting with those who waged the long struggle to identify just where it came from, immeasurably complicated by the fact that the pancreas is both an endocrine gland and an exocrine gland: the endocrine portions being islands within the larger organ – hence the name insulin for their secretion, from the Latin “insula,” meaning island.

The two main faces that emerge from “Breakthrough,” an enthralling account of the actual conquest of diabetes, are that of the rough-hewn Canadian physician Frederick Banting and Elizabeth Hughes, the privileged and precocious teenage daughter of Charles Evans Hughes, one of the most distinguished members of the American establishment in the 20th century. Not only do these two provide a study in contrast, but their luminous personalities dial up a text already alive with fascinating characters and incidents.

Although this is the authors’ first book, they are adept at telling their complicated, multifaceted story with energy and vividness. Their account of diabetics’ treatment before the production of insulin is harrowing. There was no other way to prolong the lives of those hapless folk, often children, except by essentially starving them to the point where sugar no longer appeared in their urine.

Many people thought that amounted to torturing the patients – as the authors write, it was a real example of the cure being worse than the treatment – but in the early 1920s, with the production of insulin just beyond the horizon, it might buy the patients the essential time. Elizabeth Hughes endured this torturous form of treatment for several years with fortitude – some might say heroism after reading the account in “Breakthrough.” But she was blessed with a sense of destiny. When she met Banting after nearly four years of starvation that had reduced her weight to about 50 pounds, he exclaimed:

“You look sick, but you don’t act sick. Why is that?”

“Well, I know that I’m going to get better,” she replied.

That she did. Although diabetic for the rest of her life, she lived to the age of 74, dying of heart failure. She had managed her diabetes by injecting herself more than 42,000 times with insulin in the previous six decades, sharpening her needles on a whetstone. (Just the kinds of details that abound in this book, making it so absorbing a read.)

But “Breakthrough” is not a fairy tale. It is full of stories of struggle and adversity, of mental and physical suffering. The role played by personality clashes and politicking (both in the groves of academe and in government itself) is related at length and is not a pretty story. By the time Banting won the Nobel Prize, the first Canadian to do so, who did – and did not – share it with him had become such a loaded issue that it poisoned the triumph for all concerned.

The role of Eli Lilly in producing insulin in sufficient quantities and at reliable levels of potency makes for more edifying reading: a symbiosis of enterprise and philanthropy mutually beneficial to both medical practice and research.

The authors are harsh in their condemnation of Hughes for making no effort to use her celebrity to raise money for diabetes causes or otherwise raise awareness of the disease. They postulate that her desire for secrecy might have been linked to feelings of guilt about, in effect, jumping the queue at a time when insulin was a rare commodity by using her father’s position as U.S. secretary of state, knowing that when she did so, another diabetic died.

But they also acknowledge the different zeitgeist that prevailed back then, when there generally was much less openness about disease in general. Still, they cannot help deploring that she did not play a part in eroding such attitudes.

A problematic aspect of “Breakthrough” is the authors’ description of specific scenes involving Hughes, her parents and the various physicians who treated her. They acknowledge in an afterword that these are sometimes composites, while others are just plain imagination or speculation on their part. Such scenes might sit more easily in a fictionalized version of events rather than embedded in what otherwise is a factual account. They certainly add to the vividness and texture of the story, but they may give some readers pause.

Although the insulin used on Hughes and the other pioneers was derived from cattle and pigs, the experiments that proved the drugs’ efficacy by injection was conducted on dogs, which were subjected to operations and to living the rest of their lives without pancreases.

This will appall anti-vivisectionists, but even they might have to acknowledge that Banting‘s canine experiments were of enormous benefit to mankind – particularly after reading the book’s account of Banting‘s sensitive euthanasia of a dog named Marjorie after she had rendered a particularly crucial service to his process. As he chloroformed her, he poured out a heartfelt torrent of gratitude to the dog. Hughes never ceased to remember and be grateful to her, either: Throughout the rest of her long life, all her beloved pet dogs were named Marjorie.

Martin Rubin is a writer and critic in Pasadena, Calif.

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Insulin in its Infancy: Dogs and Diabetes http://www.breakthroughthebook.com/blog/2010/08/insulin-in-its-infancy-dogs-and-diabetes/ http://www.breakthroughthebook.com/blog/2010/08/insulin-in-its-infancy-dogs-and-diabetes/#respond Tue, 31 Aug 2010 20:13:59 +0000 http://www.breakthroughthebook.com/blog/?p=127 Continue reading ]]> This Day In History: On August 31, 1921, in the early days of his research, one of Frederick Banting’s beloved test subjects died. Referred to in his notes as “Dog 92,” the collie provided Banting’s first real success during his research. The dog lived for twenty days without a pancreas, surviving with an extract Banti…ng and Best called “isletin.”
When Dog 92 died, Banting cried. He always loved and appreciated the sacrifice the dogs were making so that humans might live. “I shall never forget that dog as long as I shall live,” Banting wrote of Dog 92 in 1940, “…when that dog died I wanted to be alone for the tears would fall despite anything I could do.”

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