Re: Rediscovering the First Miracle Drug

October 11, 2010

Good article, Pat. And what a statement in the article:

" ...adults who die, not children. What insulin did was turn a brief, deadly

illness into a long, chronic struggle... "

Insulin is the first rung on a long, long ladder. Once you're on the ladder, on

the first step, it's a life-long journey upward, a rung at a time, one day at a

time, for as long as we are alive. That is, unless that allusive cure happens to

come along some time soon....

Dave

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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 <

http://health.nytimes.com/health/guides/disease/aids/overview.html?inline=nyt-cl\

assifier>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 <

http://health.nytimes.com/health/guides/disease/diabetes/overview.html?inline=ny\

t-classifier>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 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 <

http://health.nytimes.com/health/guides/disease/type-2-diabetes/overview.html?in\

line=nyt-classifier>Type

2 diabetes often associated with <

http://www.nytimes.com/info/obesity?inline=nyt-classifier>obesity

are resistant to the hormone's action. Either way, sugar and starch in the

diabetic's <

http://health.nytimes.com/health/guides/specialtopic/food-guide-pyramid/overview\

..html?inline=nyt-classifier>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

<

http://health.nytimes.com/health/guides/nutrition/diet-calories/overview.html?in\

line=nyt-classifier>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.

< http://www.joslin.org/about/elliot_p_joslin_md.html>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

, 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. that the eminent American jurist and <

http://topics.nytimes.com/top/reference/timestopics/organizations/s/supreme_cour\

t/index.html?inline=nyt-org>Supreme

Court justice turned when his daughter was

diagnosed with diabetes in 1919, at age 11.

was a cheerful, pretty little girl, five feet tall, with

straight brown hair and a consuming interest in birds. On Dr. 's diet

her weight fell to 65 pounds, then

52 pounds, and then, after an episode of <

http://health.nytimes.com/health/guides/symptoms/diarrhea/overview.html?inline=n\

yt-classifier>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 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. 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 <

http://topics.nytimes.com/top/news/science/topics/nobel_prizes/index.html?inline\

=nyt-classifier>Nobel

Prize ceremony in 1923 which Dr. Banting refused to attend, for although he

< http://nobelprize.org/nobel_prizes/medicine/laureates/1923/>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 's mother, Antoinette.

had by that time temporarily left the Supreme Court, and was serving as

secretary of state in President <

http://topics.nytimes.com/top/reference/timestopics/people/h/warren_g_harding/in\

dex.html?inline=nyt-per>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 himself

a rigid, unsmiling man whom <

http://topics.nytimes.com/top/reference/timestopics/people/r/theodore_roosevelt/\

index.html?inline=nyt-per>Theodore

Roosevelt had nicknamed " the bearded iceberg " had pulled strings. Either

way, 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 <

http://topics.nytimes.com/top/reference/timestopics/organizations/m/memorial_slo\

ankettering_cancer_center/index.html?inline=nyt-org>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 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 : 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. , 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 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.

October 11, 2010

It sure makes me thankful that insulin is so readily available, now. Vicky