[acb-diabetics] Rediscovering the First Miracle Drug

[armando del gobbo]

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-classifier>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=nyt-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 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 < 
http://health.nytimes.com/health/guides/disease/type-2-diabetes/overview.html?inline=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?inline=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 
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 < 
http://topics.nytimes.com/top/reference/timestopics/organizations/s/supreme_court/index.html?inline=nyt-org>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 < 
http://health.nytimes.com/health/guides/symptoms/diarrhea/overview.html?inline=nyt-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 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 < 
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 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 < 
http://topics.nytimes.com/top/reference/timestopics/people/h/warren_g_harding/index.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 Hughes 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, 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 < 
http://topics.nytimes.com/top/reference/timestopics/organizations/m/memorial_sloankettering_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 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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