Siddhartha Mukherjee’s Emperor of All Maladies is a biography
of a malicious stalker of mankind which, throughout history, stalks men, women,
and children without distinction for age, class, or wealth. Mukherjee joins his fearsome biography of
cancer with stories of victims, survivors, researchers and physicians who
determinedly claw from the specter of cancer, the secrets necessary to banish
its malevolence.
In over five hundred pages Mukherjee
examines early attempts to treat cancer through mysticism, crude surgery, and
inexpert experimentation which grew to include large government and privately
funded crusades to end cancer by experimentation and research. Understanding of the disease progressed from
the balance of humors and fluids to cellular mutations and therapies to arrest
malicious cellular alterations. Mukherjee describes the quest to solve cancer
as driven by patient’s desire to survive the disease and the determination of
researchers, scientists, and doctors to make that desire a reality.
Mukherjee chronicles the passion of
those combating cancer, particularly those who seek to preserve the lives of
children. Breaking new ground meant
going beyond the expected and safe modalities of treatment to push forward
toward new treatments. Researcher and
doctor Min Chiu Li, in the mid 1950s, linked the use of antifolates used to
arrest bleeding from aggressive leukemia to reducing blood loss from
choriocarcinomas. Li started antifolates
in a young woman rapidly dying from blood loss due to ruptures of tumors in her
lungs. So successful was the treatment that
the patient appeared to be cured as her tumor shrunk to undetectable
levels. Common understanding of cancer
treatments declared the patient cured but Li, through persistent observation,
noted the minute yet continued presence of a cancer ‘marker’ hormone in the
patient’s blood. Li, contrary to
established protocols, determined the cancer, although unobservable, still was
extant in the patient’s body. He
continued to administer additional dosages of the drug until the hormone level
reached zero.
The
National Cancer Institute, despite Li’s apparent success in curing the patient,
accused Li of “experimenting on people” and fired him. Emil Freireich, a fellow researcher noted,
“Li was accused of experimenting on people, but of course all of us were
experimenting…we were all experimenters. To not experiment would mean to follow
the old rules-to do absolutely nothing.” Muckherjee reveals that decades later,
clinical trials would prove Li’s assertion that total eradication of the
disease required treatment until the cancer ‘marker’ was totally
eliminated. But, as Muckherjee would
observe, “[I]n 1960, oncology was not yet ready for this proposal”.
Because cancer is so indiscriminate
regarding the victims it afflicts and, because in most cases, the discovery of
the disease has few, if any precursor symptom’s, it is much as Mucherjee
describes, an entity who arbitrarily seizes upon its ‘prey’. Researchers and clinicians are often left
with hope rather than certainty as they attempt to heal their patients. The fear and anxiety of cancer victims drives
clinicians often to desperation and spurs innovation. However, often the passion of innovation is,
as in Li’s case, stymied by bureaucratic systems slow to adapt to new
technologies and alternative therapies and treatments.
The extensive delay in the drug
approval process conducted by the Food and Drug Administration (FDA) is a major
factor hindering the introduction of new drugs for the treatment of many
diseases including cancer. For example,
the FDA, in the past four years, increased the fees it charges drug companies for
generic drug approval in order to speed review.
The change in fees netted the agency nearly $1 billion dollars in
revenue. Regardless, the time to process
an application has risen from 30 months in 2011 to 48 months in 2014. David
Gaugh, Senior Vice President of the Generic Pharmaceutical Association
observes, “These delays contribute significantly to rising health care costs
and impact access to pharmaceuticals for millions of patients.”[1]
Delay in regulatory approval by the
FDA is but one factor, the cost to bring one product to market is often
staggering. While the cost of bringing a
product to market is impacted by many variables, the approval process can cost
more than $1 billion dollars. This
includes $50-840 million to bring treatments through basic drug development
trials and between $50-970 million to complete the various phases of clinical
trials.[2] Cost and delay significantly limit the ability
of researchers to both bring new treatments to market and increase access to
proven drug treatments through the production of less expensive generic
alternatives.
Another factor in adding to the cost
and time required to introduce a new treatment is the seemingly needless
duplication involving the necessity of obtaining approval by both American and
European regulatory agencies. As
mentioned before, the FDA depends upon its Center for Drug Evaluation and
Research (CDER) to supervise manufacturer’s clinical trials before a drug may
be introduced to the public. This
process may take several years. In
Europe, there are two paths which approval for medicines may be obtained
through the European Medicines Evaluation Agency (EMEA). A “centralized system”
which scrutinizes drugs for AIDS, neuro-degenerative conditions, and diabetes.
The ”decentralized system” reviews all other types of drugs. A drug may be approved by either process and
receive a marketing authorization but a manufacturer must then apply to each
country before selling its drug. There
is debate about whether the FDA or EMEA process is quicker. What is certain is that a drug may be approved
by one country’s regulatory body and not another.[3] Additionally, the clinical trial protocols of
one national agency are not accepted by the other requiring the expense and
delay of dual testing. A single international
standard testing regimen needs to be established to both reduce the expense and
delay of introducing treatments to the market.
If researchers and clinicians are to
fulfill the passion of defeating Muckerjee’s animated ‘cancer’ the drug testing
and approval process must be streamlined.
Patients, as in the case of Doctor Li, are deprived of new treatments because
bureaucratic malaise, needless duplication in approval processes, and an
inability to ‘keep up’ with lightning fast developments in technology have
delayed and acted as a deterrent to the development of new drugs aimed at
ending the terror of the disease which stalks among us.
