Another year has gone by, and in a few short weeks, we celebrate
National Cancer Survivor's Day. When this day arrives I am always taken
back and remember those who never had a chance to celebrate this day.
Having
practiced medicine for more than three decades, as physician I was
deeply involved with the care of little children. As a hospitalist, I
saw my fair share of childhood diseases. I can gladly say I was allowed
to save many lives with help from others on the medical teams I worked
with, and of course the cutting edge technologies afforded those of us
who are privileged to practice medicine in the United States. It is
interesting, the things in life which will push a man toward an
education and prepare him for the great profession of medicine. One of
those things was an event in my childhood in the early 1960s.
When
I was a boy, I had many friends in school and outside of school alike.
Growing up on a ranch in Nebraska, it was not unusual to have many
friends who lived in other towns come to visit. One of my friends
outside of school lived in a nearby town, but came over often. David and
I were both eight years old. I remember fondly of playing "army" with
David in the yard, and board games with him when he would come to visit.
I liked him. He was friendly and got along with my sister and little
brother too. We were both Cub Scouts but in different troops. You would
always hear about how much David loved Scouting.
Soon though, the
visits became fewer and fewer. David seemed to look frail and discolored
to me as time went by. The color thing really bothered me. I asked Mom,
"What's wrong with David?" Mom said, "He's sick, honey. He has cancer
of the blood. It's called leukemia". As you can imagine, this was a
little difficult for an eight year old to take in, but as time went by, I
learned more and more.
David's parents were good friends of my
parents, so we saw each other as families often. After he became ill, we
saw less and less of them. Very rarely did I get to see my friend.
David had an ever advancing condition of weight loss, bruising, sore
joints, infections, was easily brought to tears, and I thought his hair
looked funny. How does an eight year old process this inevitable plunge?
As children, David, his sister, my brother, my sister and I, we were
not emotionally mature enough to process this whole thing.
At home
we would get the occasional phone call that he was back in the
hospital. My parents were great. When we would get these calls, Mom and
Dad would sit with us and try their best to explain this thing called
leukemia. Understand, this was 1961, and leukemia was known as an
unrelenting killer of children. There were no cures. Not even a good
treatment. The medical community was desperate for a foothold.
One
night we received a phone call from David's father. David had passed
away at the young age of eight. I remember, it was really the first time
I heard those words, "passed away". It was also the first funeral I
went to for a friend. Friends are not supposed to die when you are kids.
It caused me to take pause, and realize, that we are mortal. I know, I
was just a child. I had seen two grandfathers buried, but I was very
quiet and overcome by this intense event. All of these grownups I knew
as strong, would breakdown and start to cry. I never the less watched in
a surreal world of sadness, my parents' good friends bury my buddy,
David.... And that image which is still so clear.... My friend, asleep
in his Cub Scout uniform.
All the while I was there, I remember
thinking David might come running out from behind that marble stone, but
he never did. Why had this happened? I seemed to feel a pull even then,
"The Calling", so many of us drawn to "medicine" and trained as healers
will occasionally and quietly talk about.
Time went by, but I
often thought of David and how unfair it had been for him and his
family. The early 1960s saw almost all children die who had leukemia.
The five-year survival rates of children then were only one in ten. All
families could do, was wait and watch while their babies died in agony.
He never had a chance, I often reflected. A sweet kid, taken from his
family at such a young age. He never got the chance to do anything after
he became sick. Never got to be an Eagle Scout, play baseball, be cool
at school, or fall in love. How scared he must have been.
Time
marched on and while in high school, I would hear of small advances in
the fight against cancer and leukemia. Then, in the early 1970s, when I
was in college studying chemistry, we began hearing about a new drug, a
drug with great promise in the fight against leukemia. It killed
leukemia cancer cells by attacking their ability to process folic acid
for DNA synthesis. Called Methotrexate, I remember thinking....
Damn!.... it's a little late, but in less than ten years they came up
with a weapon.
I had grown up with kids who had polio, but now, it
was gone. Diphtheria was gone. Small pox was all but vanquished.
Psychiatric hospitals were giving way to more advanced neuroleptic
drugs, allowing former patients to re-enter society and become
productive citizens. They had just invented the CAT Scanner. They had
started to use lasers in ophthalmology. And, I thought, even William
DeBakey is transplanting hearts with Denton Cooley down in Texas of all
places! Things were really happening, and I wanted to be on the inside
not the outside. It was an epiphany. Already a man of science, I
realized then, that I was going to become a physician.
As time
went by, more of these antimetabolite drugs became available and we
started to see a real dent in childhood mortality from leukemia. Soon
after, in the late 1970s, when I was a biochemist and starting my
medical career, a drug from a flower called, "The Rosy Periwinkle",
which only grows in the rainforests of Madagascar (go figure) gave us a
new drug called Vincristine. A drug that could only be brewed in mother
nature's kitchen, this was a monumental discovery. Never before had we
been able to reach for a drug that could stop mitosis in cancer cells
directly by shutting down their ability to pass through telophase.
That's right, Vincristine and its sister, Vinblastine, destroy
microtubule formation, so cells can't make spindles, resulting in the
inability to replicate.
Then, when I was a resident in medicine,
we discovered a way to perform bone marrow transplants, exchanging
cancerous white cells for fresh, normal white cell precursors. You
guessed it. We were now seeing cures and not just remissions. Lives were
now being saved in this war.
My friend David had what we call,
"Acute Leukemia". There are many types of leukemia, but there are two
well-known leukemias that prey on children. They are Acute Lymphoblastic
Leukemia, ALL, the one David had, which generally seeks out kids two to
ten years of age, and Acute Myelogenous Leukemia, AML, which generally
hunts down our babies under 1 year of age.
The acute leukemias are
proliferating bone marrow tumors of cancerous precursor white cells
still in the immature blast cell phase. The cells do not work like
healthy white cells to combat infection. They multiply wildly, creating
havoc in the body, literally consuming the patient to death, a condition
we call "cachexia". Patients have intense bone pain, anemia,
infections, swollen lymph nodes, enlarged spleens and livers, and, for
some, meningitis, strokes, heart attacks, and renal failure. Without
treatment, they are dead in a few weeks to a few months.
We still
do not have a full grasp on their cause. Most are caused by oncogenes,
which are mutated cancer inducing genetic codes for programming
carcinogenisis and disrupting programmed cell death we call "apoptosis".
What causes this, is the head scratcher. Many of us feel it is
radiation exposure, or certain viruses. Perhaps environmental toxins, or
even cosmic radioactive bursts. And of course, man-made toxins are
obvious suspects.
By the early 1990s we were seeing cure rates in
both ALL and AML of fifty percent and remission rates in the eighty
percent range. What a leap. In just 3 decades we saw a paradigm shift in
the treatment and outcomes of our children with leukemia, moreover, a
shift in therapies which utilizes a team approach to protect our
children from the acute depression and other collateral illness which
accompany these frightening diseases.
Newer drugs like
Daunorubicin have accelerated these therapies to even better outcomes.
Although this drug is very effective, it is extremely cardio toxic and
not generally used in children. However, it should be noted that we are
now seeing ninety five percent remission rates and sixty percent cure
rates in our children with ALL, and AML, a true shift in mortality that
could only be dreamed about just thirty five years ago.
The drug
Methotrexate is still at the heart of leukemia therapy, and is used in
combination with other drugs. Unfortunately, there has been a recent
shortage of this drug due to decreased production, and the drug makers
asking for more money and charging outrageous prices. This is an
unethical practice, and shameful in my opinion. It has been treated much
in the press of late. Hopefully attitudes will shift and our lobbying
campaigns to continue cost-effective production will be fruitful.
But
now, what treatments are on the horizon for leukemia? There is a new
drug. This drug arrived on the cancer chemotherapy shelves about a
decade ago, but shows outstanding promise even outside of cancer
therapy. Used mainly for Chronic Myelogenous Leukemia, CML, a leukemia
which is seen mostly in older adults, it is highly effective. Rendering
oncogenetic codes for cancer cell induction dead in their tracks, it is a
target directed drug aimed at a specific chromosome translocation
defect which exists in more than 90% of CML patients, called the
Philadelphia Chromosome. The drug, Imatinib, was built from a rational
drug design based on biochemical research already in place regarding the
specific allele the Philadelphia Chromosome codes for, and shuts down
the production of a protein called tyrosine kinase which induces
cancerous breakdown of normally functioning white cells.
Imatinib
has been used as therapy for other leukemias including refractory Acute
Lymphoblastic Leukemia, and Myeloproliferative Disorders (chronic bone
marrow cancers generally seen in the elderly) with outstanding success.
But what is also very interesting is its experimental applications which
are currently being investigated.
Imatinib has been touted as a
treatment for pulmonary hypertension, a rapidly fatal form of high blood
pressure in the lungs. It has been shown to reduce outcropping we call
smooth muscle hypertrophy and hyperplasia of the pulmonary vascular
tree. In systemic sclerosis, the drug has been tested for potential use
in slowing down pulmonary fibrosis. In addition, current laboratory
investigations show promise in stopping the progression of
atherosclerotic vascular disease in mice. Yes, a treatment for coronary
artery disease and heart attacks.
At Emory University in Atlanta,
there are promising studies suggesting that Imatinib could be used as an
antiviral against smallpox. Why is this important? Although this
disease has been wiped off the face of the earth with the remarkable
efforts of the World Health Organization, and no case has been
identified in almost thirty years, We continue to believe a weaponized
form of small pox launched from a rogue nation is possible.
Studies
also suggest that a modified version of Imatinib can bind to the
protein which increases the production and accumulation of amyloid
plaques in Alzheimer's disease, rendering it inert. Yes, a treatment for
Alzheimer's induced dementia.
But with all of this in our doctor
bags, there is still a dark and ominous specter. Although great strides
have been made, and I was privileged to meet and take care of children
with leukemia, and even watch them overcome the illness and move on with
their lives, one patient stands out.
I was working the Emergency
Department one night in 1995. It had been relatively quiet that evening,
when at approximately two in the morning a man walked in carrying his
teenage son. We acted quickly and helped him get his son to a gurney in
an open bay.
The staff and I immediately recognized the man's son
as Eric, a well-known high school football star. The father said he
found his son crawling on the floor trying to get to the kitchen to get a
drink of water. Eric looked awful. There was that damn color again.
Eric was delirious with fever, weak, and poor to respond. We went to
work on him immediately. His dad said that he was fine just a month ago,
but had developed a sore throat at about that time, and was seeing one
of our local doctors who just kept giving him antibiotics. We managed to
get young Eric stabilized. Just as we were settling him in and making
his father comfortable, I received a call from the laboratory. The lab
tech asked me to come down to the lab. I ran to the laboratory. When I
got there the tech was shaking her head as if to say, "this is really
bad". I looked at the blood count machine's screen. "my God", I said to
the tech. "His white count is seventy thousand". I looked in the
microscope, "blast cells". I knew right away we were looking at an acute
type of leukemia, but couldn't recognize it.
When I dashed back
to the Emergency Department, Eric was coming around a little. I spoke
with him and reassured him. But the look on my face when I turned to his
dad, could not be masked. He knew I didn't have good news. We talked at
length, then, I called in Eric's regular doctor. They talked while the
team and I continued to work on Eric. I called in the helicopter, spoke
with the hematology fellows at the university, returned to Eric and his
dad, made sure they knew what we were doing and flew them both to
University Hospital. All eyes turned to the Hematology Oncology Service
with hope that they could help young Eric.
One week later, while
seeing patients in my office, the Hematology service at the university
telephoned me to say that Eric had "passed away". You sit by yourself
and reach for introspection when these things sting you as a healer. I
wondered. How does a robust young athlete get sick with leukemia, fail
in health so quickly, and die in one month? As it turned out, Eric
contracted a type of AML, called Promyelocytic Leukemia, one of the most
deadly forms of AML, one which preys on teenaged children, and takes
them away from us with stealth and quickness. So you see, our job is not
done. I am reminded as to why we call it a "practice".
Our
knowledge of the genome, stem cell technology, oncogenetics, and
nanotechnology races onward. Our ability for rational drug design is
extraordinary, and the technical savvy to produce these great magic
potions has been nothing short of miraculous. In just four decades, we
have all but squashed the disease that took my friend, David. But as you
can see with Eric, we are not finished. I still think of David fifty
years later, and how his death stirred in a young boy, the spark of
becoming a physician. If I was educated only to save but one human
being, it was all worth it.
We already have at our fingertips two
technologies that must be placed into motion. Stem cell research has
already given us the ability to crush this killer, and should never be
interrupted. And, the science to manipulate the oncogenes so responsible
for the fuel that drives these diseases is already available. My hope
is that with our new technologies, in the near future, we will not need
any drugs for leukemia. We will simply turn off the genetic machinery of
bone marrow cancer and not allow leukemia even to exist, and therefore,
never threaten our children again.
