Blood and Guts (13 page)

McBirnie had been assigned the job of catching groundhogs by
Wilfred 'Bill' Bigelow, surgeon and director of the Cardiovascular
Laboratory at the Banting Research Institute. Bigelow wanted to
understand hibernation. In winter, when the prairie was covered in
snow, groundhogs curled up in their burrows and hibernated.
During hibernation the animals' core temperature cooled down to
match their surroundings, their metabolism and circulation slowed,
as did their heartbeat, allowing them to withstand temperatures
only a few degrees above freezing. Bigelow had the idea of creating
a similar state in humans – inducing hibernation to slow down the
circulation. If he could reduce the amount of oxygen the body
needed, perhaps this would buy surgeons enough time to be able to
cut open the heart?

Bigelow had first got interested in studying the effects of cold in
1941, when he was a young surgeon at the Toronto General
Hospital. His shift involved having to attend to a patient who had
been drinking. The man had got so drunk that he passed out in the
snow and when he woke up a few hours later, his hands were badly
frostbitten. When he eventually got to the hospital there was not
much Bigelow could do other than amputate the poor man's frozen
(and now gangrenous) fingers. It was an unpleasant task, but the
gruesome experience made the surgeon realize how little doctors
knew about frostbite and the effects of cold. It inspired him to study
how the body's metabolism reacts to low temperatures. Three years
later he had published his first research paper on hypothermia.

After the war (and following a posting as a battle surgeon in the
Canadian Army Medical Corps) Bigelow trained as a specialist in
vascular and cardiac surgery. When he was working late one night
he had a flash of inspiration. He realized that he might be able to
apply what he had learnt about the cold to the problems of operating
on the heart. He started to experiment on dogs.

The researchers immersed anaesthetized dogs in tanks of icy
cold water to induce a state of hypothermia in an attempt to slow
down the animals' circulation. The first results were baffling: the
dogs were using up more oxygen when they were cooled than when
they were at normal temperature. Bigelow realized that the dogs
were shivering – even under anaesthetic. The muscle contractions
were using up energy, so the muscles required more oxygen. But
once the researchers switched to using ether anaesthetic – which
also worked as a muscle relaxant – the dogs' temperature could be
cooled by several degrees. With the animals' circulation and heartbeat
slowed, the organs needed less oxygen. A 7-degree (Celsius)
drop in temperature reduced oxygen consumption by half.

Bigelow was a generous man and openly shared his findings and
published his results. Some thought he was mad; others thought the
studies looked promising. The dog experiments had shown that the
animals could be anaesthetized, cooled and their hearts operated on.
When the dogs were revived, a good percentage survived and recovered
well with no signs of permanent injury. This same technique
might work with humans. Other surgeons started to take notice.

Meanwhile, Bigelow had a more ambitious goal in mind: he
wanted to go beyond hypothermia to crack the secrets of hibernation.
Could the research team find a chemical to slow down the
body – a hormone perhaps? He set about collecting groundhogs.
Or rather, because he was in charge, he made the (wise) decision
to delegate.

Despite McBirnie's initial difficulties, Bigelow's team soon
became adept at groundhog capture. They realized that the best way
to get the animals out of their burrows was to flush them out with
water. Three trucks moved from farm to farm, a line of spectators in
their wake, as farmers and other locals came to watch. It seemed
that this was the most exciting thing that had happened around
these parts for a long time.

The first truck was the scout car; the scout car team was responsible
for finding the groundhog burrows. The next vehicle was a
tank truck full of water. Bringing up the rear was the truck carrying
cages. Once the animals were captured they did everything they
could to escape – they chewed through chew-proof cages, they
escaped from escape-proof containers, the sharp-toothed little
brutes would bite researchers' hands as a matter of course. Some
members of the team began to dread the work. All of them came to
treat the animals with great respect.

Eventually Bigelow had enough groundhogs to establish the
world's first (and only) groundhog farm. A large, fenced-off field,
complete with luxury (in groundhog terms) ready-made burrows,
was home to some four hundred groundhogs. The burrows
consisted of tunnels leading into underground tanks that were
built into mounds of earth. From the inside these were ideal
groundhog homes. What the animals did not realize was that each
mound had a lid on it so that the researchers could reach them
while they were hibernating.

Once the groundhogs were settled in for their winter hibernation,
the scientists were able to open the lids of the burrows and pick
up the tightly curled balls of fur. Unlike when they were awake (and
to the great relief of the scientists), the groundhogs did not seem to
notice. For the first time, the animals could even be described as
cute. The researchers collected extracts of blood, fats, proteins and
steroids. They measured, analysed and recorded. The evidence
pointed to there being a chemical – some active substance – that let
the groundhogs hibernate without coming to harm. All the research
team had to do was find it.

But Bill Bigelow was not planning to wait until he had discovered
the elusive secret of hibernation. His hypothermia research on
dogs had already proved successful, and safe
^*
enough to try on
humans. Now the Canadian surgeon just had to wait for the right
patient. However, if he had been hoping to make it into the history
books, he was about to be beaten to it.

^*
Well, reasonably safe. Experiments had suggested that cooling the body too much could stop
the heart altogether.

University Hospital, Minneapolis, 2 September 1952

The green-tiled operating room was the modern equivalent of an
old Victorian operating theatre. Instead of a raked gallery surrounding
the operating table, spectators could observe from a room
above, through glass portholes in the domed ceiling. And today's
operation would certainly be worth watching.

Some of the brightest, most ambitious and daring cardiac
surgeons are working in Minneapolis. Today, F. John Lewis is leading
the surgical team. He is assisted by a young surgeon called
Walter Lillehei, a man who will come to epitomize the heart
surgeon: confident, resilient and, it will later become apparent,
something of a showman. Above all, these are men (and they are
all
men) who are not afraid to fail.

The patient is a thin, frail five-year-old girl named Jacqueline
Johnson. She has been diagnosed as suffering from a hole between
the two upper chambers (the atria) of her heart. Without surgery she
is unlikely to live much longer. Her heart is already swollen and she
is becoming weaker by the day. The anaesthetist puts her to sleep
(using a muscle relaxant to prevent her shivering) and the surgical
team wraps a special blanket threaded with rubber tubes around her.
They tie the sides of the blanket together with wide ribbons of cloth
and turn on the taps to allow cold water to pass through the tubes.

It is a slow process to gradually cool the girl down – it takes
twenty-five minutes before her temperature has dropped just one
degree. Eventually, after two hours and fourteen minutes, her body's
core temperature is down to 28°C – 9 degrees below normal. And as
the girl's temperature falls, so does her heart rate. Jacqueline's heart
is now beating at half the normal rate. According to calculations
based on Bigelow's research, if surgeons usually had four minutes to
operate on the heart to avoid starving the brain of oxygen, they now
have six. But is six minutes enough to cut open the girl's heart, repair
the defect and sew it back up again? Can those extra two minutes
make the difference between failure and success?

The surgeons untie the blankets and Lewis cuts open Jacqueline's
chest. Her heart is beating slowly as the surgeon prepares to clamp off
the girl's circulation. Lillehei starts his stopwatch.

The six-minute countdown begins.

Lewis works slowly and precisely. Unnecessary haste could be
fatal. He tightens tourniquets around the veins entering the heart
and the arteries leaving it. The blood stops moving around
Jacqueline's body, but her heart keeps beating. Lewis cuts into the
right atrium to expose the inside of the heart. Unlike closed-heart
operations, where surgeons operate in a river of blood, Jacqueline's
heart is practically dry. Lewis can clearly see what he is doing. The
defect is exactly as he had expected: a hole between the left and
right atrium. He begins to sew.

Two minutes left.

Lewis finishes sewing and pours some saline solution into the
heart to test the repair. There is a leak. He puts in another stitch and
tries the saline again. The hole is closed.

One minute left.

Lewis starts to suture together the thick muscle of the heart
wall. The muscle is still beating but the rhythm is becoming weaker,
the beat irregular.

Thirty seconds.

Lewis releases the clamps across the arteries and veins. Blood
begins flowing. The surgeon grasps the heart in his hands and
begins squeezing to help it back into its natural rhythm.

Time up.

He closes the girl's chest as quickly as he can and carries her over
to a bath of warm water (actually a watering trough ordered from a
farm catalogue). Her heartbeat becomes stronger. She is going to be
OK. Five-year-old Jacqueline Johnson leaves hospital eleven days
later. She will grow up to have two children of her own. It was an
incredible surgical advance: open-heart surgery had arrived.

Although Bill Bigelow did not get to perform the first successful
open-heart surgery on a human patient, he was undoubtedly
pleased that his theory had been proved right. Many patients,
particularly young children, would owe their lives to him.
Hypothermia bought surgeons valuable extra minutes – enough
time to carry out procedures that had previously been impossible.
Bigelow continued to work to improve the techniques of cardiac
surgery. He developed the first electronic pacemaker. He also
continued to study the groundhogs.

Bigelow's team had been collecting groundhogs for almost ten
years. The farm was thriving; the little bastards were still biting. Back
in the lab the doctors were taking extracts from the animal's brown
fat deposits – pads of fat that the researchers decided were the key
to hibernation. These samples were analysed and their chemical
composition checked. Finally, in December 1961, it appeared that
all the research effort had paid off – one of the tests revealed a
completely new substance. Could this be the mysterious chemical
that allowed the groundhogs to hibernate?

A small amount of the substance was extracted and injected into
some guinea pigs. The animals were then cooled down to low
temperatures – much lower than they had previously been able to
endure. There were no ill effects. This could finally be it. There was
great excitement among the team. A vial of the new chemical was
personally delivered to the National Research Council in Ottawa for
further tests. It was even given a name: Hibernin.
^*

^*
Its full chemical name was 1-butyl, 2-butoxy-carbonyl-methyl-phthalate.

The hospital appointed the finest patent lawyer, and Bigelow filed
a patent (no Minnesota surgeon was going to get his hands on the
product of his research this time). NASA made enquiries – perhaps
they could use this substance for astronauts on long-duration space
missions? A few journalists got wind that something was going on, but
the researchers kept their silence. One of them even delayed a promising
job offer so that he could spend more time with groundhogs.

They decided to try out Hibernin on patients. After all, the
guinea pigs had survived. The surgeons operated on two people
suffering from holes in the heart. The human guinea pigs were
hooked up to some tubing to enable Hibernin to be injected.
Bigelow found he could cool the patients down to around 18°C –
four degrees lower than anything they had achieved before – which
bought the surgeons much more time. Both operations were
successful. The only peculiar thing they noticed happened after the
operation: the patients were sleeping for much longer than usual.
They seemed groggy. It was strange, but the nurses in the recovery
room said it was almost as if they were drunk.

Now that Hibernin had been proved to work there was immense
pressure to publish the results of the trial. Everyone was lined up for
a major media event to make the big announcement. This would be
a significant achievement for Canadian science. Then Bigelow
received a letter from the patent office in Washington DC. The
letter said that the chemical had already been patented. 'Hibernin'
had been used for some twenty years as a plasticizer – employed to
make intravenous plastic tubes pliable. Bigelow was incensed. How
annoying that a biological extract from groundhogs turned out to
be the same stuff as an industrial chemical. Still, the team had better
do one final check as a scientific formality. Some clean plastic
tubing was cut up and placed in water. A few hours later the scientists
analysed the water. They extracted Hibernin.

Rather than having extracted a miracle substance from groundhog
fat, the surgeons had simply flushed out the plasticizer from the
tubing used in their research. The plasticizer was a potent form of
alcohol. This explained why the patients acted as if they were drunk
– they were. It says a lot about Bigelow and his management style
that he and his team were able to laugh about it. Ten years of visiting
the groundhog farm in the bitter winter. Ten years of groundhog
bites. Ten years of hard research work. Thank heavens they had
held back on the publication.