Monday, March 5, 2012

Steve Jobs - To the Finish line #1


From the book "Steve Jobs" by Isaacson

The cancer always sent signals as it reappeared. Jobs had learned
that. He would lose his appetite and begin to feel pains
throughout his body. His doctors would do tests, detect nothing,
and reassure him that he still seemed clear. But he knew better.
The cancer had its signaling pathways, and a few months after he
felt the signs the doctors would discover that it was indeed no
longer in remission.

Another such downturn began in early November 2010. He was in
pain, stopped eating, and had to be fed intravenously by a nurse
who came to the house. The doctors found no sign of more tumors,
and they assumed that this was just another of his periodic
cycles of fighting infections and digestive maladies. He had
never been one to suffer pain stoically, so his doctors and
family had become somewhat inured to his complaints.

He and his family went to Kona Village for Thanksgiving, but his
eating did not improve. The dining there was in a communal room,
and the other guests pretended not to notice as Jobs, looking
emaciated, rocked and moaned at meals, not touching his food. It
was a testament to the resort and its guests that his condition
never leaked out. When he returned to Palo Alto, Jobs became
increasingly emotional and morose. He thought he was going to
die, he told his kids, and he would get choked up about the
possibility that he would never celebrate any more of their

By Christmas he was down to 115 pounds, which was more than fifty
pounds below his normal weight. Mona Simpson came to Palo Alto
for the holiday, along with her ex-husband, the television comedy
writer Richard Appel, and their children. The mood picked up a
bit. The families played parlor games such as Novel, in which
participants try to fool each other by seeing who can write the
most convincing fake opening sentence to a book, and things
seemed to be looking up for a while. He was even able to go out
to dinner at a restaurant with Powell a few days after Christmas.
The kids went off on a ski vacation for New Year's, with Powell
and Mona Simpson taking turns staying at home with jobs in Palo

By the beginning of 2011, however, it was clear that this was not
merely one of his bad patches. His doctors detected evidence of
new tumors, and the cancer-related signaling further exacerbated
his loss of appetite. They were struggling to determine how much
drug therapy his body, in its emaciated condition, would be able
to take. Every inch of his body felt like it had been punched, he
told friends, as he moaned and sometimes doubled over in pain.
It was a vicious cycle. The first signs of cancer caused pain.
The morphine and other painkillers he took suppressed his
appetite. His pancreas had been partly removed and his liver had
been replaced, so his digestive system was faulty and had trouble
absorbing protein. Losing weight made it harder to embark on
aggressive drug therapies. His emaciated condition also made him
more susceptible to infections, as did the immunosuppressants he
sometimes took to keep his body from rejecting his liver
transplant. The weight loss reduced the lipid layers around his
pain receptors, causing him to suffer more. And he was prone to
extreme mood swings, marked by prolonged bouts of anger and
depression, which further suppressed his appetite.

Jobs's eating problems were exacerbated over the years by his
psychological attitude toward food. When he was young, he learned
that he could induce euphoria and ecstasy by fasting. So even
though he knew that he should eat-his doctors were begging him to
consume high-quality protein-lingering in the back of his
subconscious, he admitted, was his instinct for fasting and for
diets like Arnold Ehret's fruit regimen that he had embraced as a
teenager. Powell kept telling him that it was crazy, even
pointing out that Ehret had died at fiftysix when he stumbled and
knocked his head, and she would get angry when he came to the
table and just stared silently at his lap. "I wanted him to force
himself to eat," she said, "and it was incredibly tense at home."
Bryar Brown, their part-time cook, would still come in the
afternoon and make an array of healthy dishes, but jobs would
touch his tongue to one or two dishes and then dismiss them all
as inedible. One evening he announced, "I could probably eat a
little pumpkin pie," and the even-tempered Brown created a
beautiful pie from scratch in an hour. Jobs ate only one bite,
but Brown was thrilled.

Powell talked to eating disorder specialists and psychiatrists,
but her husband tended to shun them. He refused to take any
medications, or be treated in any way, for his depression. "When
you have feelings," he said, "like sadness or anger about your
cancer or your plight, to mask them is to lead an artificial
life." In fact he swung to the other extreme. He became morose,
tearful, and dramatic as he lamented to all around him that he
was about to die. The depression became part of the vicious cycle
by making him even less likely to eat.

Pictures and videos of jobs looking emaciated began to appear
online, and soon rumors were swirling about how sick he was. The
problem, Powell realized, was that the rumors were true, and they
were not going to go away. Jobs had agreed only reluctantly to go
on medical leave two years earlier, when his liver was failing,
and this time he also resisted the idea. It would be like leaving
his homeland, unsure that he would ever return. When he finally
bowed to the inevitable, in January 2011, the board members were
expecting it; the telephone meeting in which he told them that he
wanted another leave took only three minutes. He had often
discussed with the board, in executive session, his thoughts
about who could take over if anything happened to him, presenting
both short-term and longer-term combinations of options. But
there was no doubt that, in this current situation, Tim Cook
would again take charge of day-to-day operations.

The following Saturday afternoon, jobs allowed his wife to
convene a meeting of his doctors. He realized that he was facing
the type of problem that he never permitted at Apple. His
treatment was fragmented rather than integrated. Each of his
myriad maladies was being treated by different specialists-
-oncologists, pain specialists, nutritionists, hepatologists, and
hematologists-but they were not being coordinated in a cohesive
approach, the way James Eason had done in Memphis. "One of the
big issues in the health care industry is the lack of caseworkers
or advocates that are the quarterback of each team," Powell said.
This was particularly true at Stanford, where nobody seemed in
charge of figuring out how nutrition was related to pain care and
to oncology. So Powell asked the various Stanford specialists to
come to their house for a meeting that also included some outside
doctors with a more aggressive and integrated approach, such as
David Agus of USC. They agreed on a new regimen for dealing with
the pain and for coordinating the other treatments.

Thanks to some pioneering science, the team of doctors had been
able to keep Jobs one step ahead of the cancer. He had become one
of the first twenty people in the world to have all of the genes
of his cancer tumor as well as of his normal DNA sequenced. It
was a process that, at the time, cost more than $100,000.
The gene sequencing and analysis were done collaboratively by
teams at Stanford, Johns Hopkins, and the Broad Institute of MIT
and Harvard. By knowing the unique genetic and molecular
signature of Jobs's tumors, his doctors had been able to pick
specific drugs that directly targeted the defective molecular
pathways that caused his cancer cells to grow in an abnormal
manner. This approach, known as molecular targeted therapy, was
more effective than traditional chemotherapy, which attacks the
process of division of all the body's cells, cancerous or not.
This targeted therapy was not a silver bullet, but at times it
seemed close to one: It allowed his doctors to look at a large
number of drugs-common and uncommon, already available or only in
development-to see which three or four might work best. Whenever
his cancer mutated and repaved around one of these drugs, the
doctors had another drug lined up to go next.

Although Powell was diligent in overseeing her husband's care, he
was the one who made the final decision on each new treatment
regimen. A typical example occurred in May 2011, when he held a
meeting with George Fisher and other doctors from Stanford, the
gene-sequencing analysts from the Broad Institute, and his
outside consultant David Agus. They all gathered around a table
at a suite in the Four Seasons hotel in Palo Alto. Powell did not
come, but their son, Reed, did. For three hours there were
presentations from the Stanford and Broad researchers on the new
information they had learned about the genetic signatures of his
cancer. Jobs was his usual feisty self. At one point he stopped a
Broad Institute analyst who had made the mistake of using
PowerPoint slides. Jobs chided him and explained why Apple's
Keynote presentation software was better; he even offered to
teach him how to use it. By the end of the meeting, Jobs and his
team had gone through all of the molecular data, assessed the
rationales for each of the potential therapies, and come up with
a list of tests to help them better prioritize these.

One of his doctors told him that there was hope that his cancer,
and others like it, would soon be considered a manageable chronic
disease, which could be kept at bay until the patient died of
something else. "I'm either going to be one of the first to be
able to outrun a cancer like this, or I'm going to be one of the
last to die from it," Jobs told me right after one of the
meetings with his doctors. "Either among the first to make it to
shore, or the last to get dumped."


To be continued

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