Daniel Engber on The Use of Animals in Research - Part 2

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Daniel Engber on The Use of Animals in Research - Part 2

Man Cuts Dog.
Pepper arrives at a laboratory in the Bronx.

Here's one way to give a dog heart block: Anesthetize it, flip it over, and make an incision along the midline of its chest. Crack open the sternum and pull apart the bone and muscle. It's best to use a dog of medium size, with short hair and a long torso—like a Dalmatian. You won't be able to accomplish very much while the dog's heart is full of blood, so tie off the venae cavae with a tourniquet to block the flow into the right atrium. Remember to move quickly, as the dog can endure only a few minutes in this predicament. (You can buy some extra time by presoaking the animal in a basin of ice water.) Disrupt the heart's conduction mechanism by sewing a single, black silk suture between the tricuspid valve—which separates the right atrium from the right ventricle—and the coronary sinus. Now untie the tourniquet to restore the flow of blood, and you're done. If all goes well, the dog will have lost the ability to pace its own heart.

Every year, 200,000 Americans, and more than 500,000 people worldwide, receive a permanent cardiac pacemaker as a treatment for heart block, bradycardia, or another heart-rhythm disorder. The ubiquity of the pacemaker has a lot to do with the elegance of the procedure now used to implant it: The whole operation takes just an hour or two, it can be performed under local anesthetic, and patients are sent home the next morning. The safe and simple technique—in which doctors make a small incision near the collarbone, open a vein, and slide the pacing leads directly into the heart—was invented more than 50 years ago by Seymour Furman, a young resident at Montefiore Hospital who was spending his afternoons in the dog lab.

Early versions of the pacemaker were crude devices that attached to the external surface of the heart or the front of the patient's chest. A Boston physician named Paul Zoll installed one of the first modern devices in 1952. He wired up a pair of hypodermic needles and plunged them directly into a patient's skin. The pulse generator was a large, external box plugged into the wall. In 1957, an open-heart surgeon at the University of Minnesota started attaching the pacemaker leads directly to the cardiac muscle. This allowed the device to work at a much lower voltage—jolts from the earlier machine had sometimes blistered the patients' skin—but the electrodes were unstable, and it took major surgery to implant them.

Seymour Furman's great insight was to combine the new field of cardiac pacing with a medical procedure that had only recently become mainstream, cardiac catheterization, in which a thin tube is inserted into a blood vessel and advanced into the heart for diagnostic testing. The cardiac catheter had earned its inventers a Nobel Prize in 1956, and one of its early practitioners—Doris Escher—was Furman's mentor at Montefiore. With her guidance, he hoped to pass an electrode through the venous system to the right atrium, where he could pace the heart with more stability and less current than ever before. This would also eliminate the need for chest-cracking, open-heart surgery.

In the fall of 1957, Furman set to figuring out the details of his new procedure in the dog lab. The canine anatomy turned out to be perfect for the experiment: The dog's external jugular vein was large and easily accessible, and provided the catheter with a straight shot into the right ventricle. But before Furman could test the dogs with his new catheter leads, he'd have to open their hearts and induce an artificial block. That procedure proved to be dangerous: Of the 16 dogs assigned to Furman, only four survived.

Bill Miller arrived with his truck at Montefiore Hospital on Thursday, July 1. He'd spent several days carting two goats and 18 dogs across Pennsylvania and New Jersey, and had already sold most of the live cargo to medical centers in Manhattan. He unloaded the remaining animals that afternoon in the Bronx and set off for home.

One of the animals carted into the clinic that day would later be identified as Pepper, the adult, female Dalmatian who had recently disappeared from the Lakavage family's 82-acre farm near Slatington, Pa. While her former owners searched for her in vain, it's likely that Pepper was being stowed in a kennel on the roof of the hospital. It's also likely that her vocal cords were severed when she arrived, leaving her unable to bark and howl in her final hours.

Pepper spent just one night in the Montefiore kennels. Sometime on July 2, she was brought down to the dog lab, anesthetized, and prepped for surgery. A hospital spokesman later told the newspapers that she'd been scheduled to receive an experimental pacemaker.

By the summer of 1965, Seymour Furman had already worked out the basics of transvenous pacing. His technique enjoyed a significant following overseas, and the American medical device company Medtronic had just introduced its first commercial pacemaker with catheter leads. But there were plenty of problems still to be solved. Batteries died, pulse generators would fail, and patients had to make frequent return visits for follow-up surgeries. That year, the Atomic Energy Commission would start work on a durable, nuclear-powered pacemaker. (The first of these was implanted in a dog in 1969.) When Pepper arrived at Montefiore, Furman was hard at work developing his own, more permanent device, and he needed animals for testing.

On that Friday, Pepper's chest would have been opened like the other dogs, her sternum separated, and her venae cavae tied off to empty her heart of blood. It's not clear when or how the procedure went wrong. Perhaps the surgeons couldn't finish the operation in time to restore her circulation. Or maybe the induced heart block was too severe. Whatever happened, the experiment was a failure: Pepper died on the table.

The loss of a single Dalmatian meant little to the pacemaker program at Montefiore. The new prototypes would be tested on another dog, and another, and many more; Furman's research yielded plenty of discoveries in the years that followed. (To name just one: In 1967, he devised a way to check the function of an implanted device automatically over the telephone.)

Not even the doctors who were performing these experiments understood just how important the new inventions would soon become. Heart disease was already America's leading cause of death in 1965, as it had been since about 1930. But few cardiologists at the time had ever seen a case of heart block—most of its victims were elderly people with modest access to medical care, and they were dying before anyone could make a diagnosis.

That all began to change with the invention of Medicare. On July 9, less than a week after Pepper's death, the Senate voted to make health insurance universal for elderly Americans. Nineteen million patients enrolled in the program the following year, and it soon became obvious how many adults were suffering from slow heartbeats in their old age. Now, for the first time, there was enough money to treat them all.

The particulars of Pepper's death scarcely mattered to the revolution in cardiology. But her final moments on the operating table do carry their own historical resonance: Medical science as we know it today—constructed on a framework of experimentation, observation, and reason—had begun in much the same way a few centuries before, with a dog laid on its back, its breast cut open, and its heart snipped in two.

What might easily be called the founding experiments of modern medicine were conducted in the first decades of the 17th century, by English physician William Harvey. His crucial discovery that blood circulates in a closed system began with a series of gory demonstrations on the bodies of living animals. For one, he would expose the beating heart of a dog, horse, or other creature and puncture its left ventricle. The geyser of blood that erupted with each contraction suggested that the motion present in the arteries and veins wasn't mere sloshing about, as had been the theory, but rather the result of a "forceful systole" of the heart.

Those skeptical of Harvey's conclusions opened the bodies of living dogs to see for themselves, and according to historian and philosopher of science Rom Harré, the dog soon became a standard instrument for the study of circulation. By the mid-1660s, Christopher Wren had devised a method for the intravenous injection of chemicals—opium and Spanish wine, to start with—into the bloodstream of a dog, and Richard Lower had performed the first successful blood transfusion by using a chain of quills to connect the artery of one dog to the jugular vein of another.

The dog remained a vital tool in biomedical research for more than 300 years and was the vehicle for a remarkable run of medical breakthroughs. Ernest Starling's research on dogs led him to declare the existence of "hormones" in 1905. In 1921, Canadians Frederick Banting and Charles Best discovered insulin as a treatment for their colony of dogs with surgery-induced diabetes. In 1923, George Whipple used a Dalmatian-English bulldog cross to create a model of pernicious anemia, then cure the disease with supplements of iron. And shortly before Pepper's death, a stray mutt plucked from the streets in Moscow became the first animal to be launched into orbit. Though that dog died from stress and overheating only a few hours into the mission, the feasibility of human spaceflight was reported around the world.

By the 1960s, Furman and his colleagues at Montefiore Hospital were using a few hundred dogs for research every year, while larger institutions went through as many as 9,000. Rep. Joseph Resnick, the upstate lawmaker who attempted to intervene on behalf of the Lakavages on the very day that Pepper was killed, would later assert to the newspapers (and his fellow members of Congress) that the annual number of dogs used in federally funded research had reached 1.75 million.

But the dog-napping of Pepper marked the beginning of the end of canine experimentation. Outrage over her demise, and the theft and killings of other family pets, would soon turn public opinion—and federal law—against the use of dogs in biomedical research. Meanwhile, the rapid growth of American science after World War II had already created a new industry in purpose-bred, standardized lab animals—and the thriving trade in stray mutts and stolen pets would soon be replaced by an assembly line of laboratory flies, rats, and mice. Pepper's death in the summer of 1965 signaled the end of an era.

Go on to Part 3 - Pepper Goes to Washington
The most important animal-welfare law in America began with a stolen dog.

*****

Entire Series:

Part 1 - Where's Pepper?
In the summer of 1965, a female Dalmatian was stolen from a farm in Pennsylvania. Her story changed America.

Part 2 - Man Cuts Dog.
Pepper arrives at a laboratory in the Bronx.

Part 3 - Pepper Goes to Washington.
The most important animal-welfare law in America began with a stolen dog.

Part 4 - Brown Dogs and Red Herrings.
Or, why we no longer experiment much on dogs.

Part 5 - Me and My Monkey.
The confessions of a reluctant vivisector.

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