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| My Photo of 1500 Owens St. San Francisco, CA |
Three months ago I had the unsuccessful, yet
fortunate, opportunity to interview for an internship at C--- Corporation in
San Francisco. Approaching the executive park I had no idea what to expect;
perhaps white walls, white ceilings, lab coats- you know, like Willy Wonka, but
super high tech, so maybe more like Area 51. As I approached the building with
profusely perspiring palms and pits, I realized I might have misconstrued the
rising biotech industry of the Bay. Yet, I was still shocked by the fourteen-story
glass monolith before me, just a stone's throw from the Bay.
Impressively, this gorgeous
building at the San Francisco branch is only one of nearly one hundred
locations sprinkled across 38 nations that cumulatively employ approximately 5000
people. This only seems appropriate
for a company like C--- whose mission is
dedicated to "delivering innovative
therapies to patients with unmet medical needs." Rather, it may seem that
5000 is not
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| Celgene Corporation's presence in 38 countries www.celgene.com |
enough as they race to produce, analyze, and sell the best cancer
and anti-inflammatory drug therapies on the market.
International
presence aside, however, I found that 2 features of this industry made it very
different from the scientific research that I have come to know.
"Profit." Throughout the day it became
evident that money was a primary consideration in all decisions, made on all
levels, of this Fortune 500 member. This is not to say, at all, that these are
necessarily bad companies. This is to say that many of these large companies are
publicly traded. They have investors, boards, steering commissions, federal
oversights and funding, and many other interests to consider when deciding to
pursue a potential drug or toss it down into a vast dustbin of unlikely
candidates.
In fairness,
investors have good reason to be interested in the decisions made; making the
right ones could lead to highly marketable cancer medications. Last year, the Economist
announced that Gleevec, Herceptin, and Avastin respectively grossed more than
4, 6, and 7 billion dollars in 2010. Avastin also costs $88,000 per year of
prescription. It is obvious that the pharmaceutical industry is a lucrative
business; it leads me to wonder.
The National
Cancer Institute says the 2010 national cost of cancer treatment was
$125 billion and is expected to rise to $150 billion by 2020 because of
expanding chemotherapy costs. Are these companies taking too
much? On the other hand, perhaps, the price tag may be justified by outputs that have been unmatchable by individual academics. These biotechnological companies for better, or worse, fulfill a very efficient niche. The development of successful
chemotherapies, and the success of the companies that manufacture them, depend
equally upon funding and efficiency.
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| Meet the Super Duncan Thermo Cycler. This one can cycle more than 120,000 PCR samples at once. And, if programmed right, will even cherry pick certain transfected bacterial colonies. |
Efficiency is a characteristic cherished
by most. Quite simply, wasted time is wasted money. When considering
the massive amounts of money being made by biotechnological, pharmaceutical
companies, it is important
to note that they are bringing an
unprecedented, corporate-level efficiency, never before seen in science.
Largely, this is due to the high volume of very expensive, extremely efficient
instruments that profits allow them to purchase. This is not to mention the
tremendous man-power and top-down corporate structure that allow directions to
be followed quickly. With these instruments, a single researcher can do work in 20 minutes that still would take most
individuals days or weeks to accomplish with smaller, simpler, machines that are still quite expensive. [Examples of these more expensive instruments are to the right and below. Think on the order of hundreds of thousands of dollars, if not, far more]
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| This is the main tool used for determining the IC-50 of many samples at once. It can quickly load and monitor well over 1,000 enzyme assays. FYI, it takes me to about 15 minutes to prepare one plate of 16 samples for my work. This guy is about 70x faster. |
Furthermore,
each branch of this business essentially has its own niche within the
company at a very specific point in drug development. A global version reminiscent
of Henry Ford's assembly line. The branch I visited in San Francisco was a small cog in a large system. At this point in the line, phase
III drugs that have been shown to treat cancers are blindly screened for
efficiency. Specifically, the fifty people at this step are all dedicated
to translational and molecular kinetics. They investigate the efficiencies of
drugs that inhibit histone deactylases that suppress the
expression of tumor suppressors.
At this San
Francisco branch, a team of MDs and PhDs is trying to answer the most critical
question about each medication: How well, and where, does the medication work? To address the first
question, "how well", researchers use relatively simple, yet very
efficient techniques. A given set of cells (stored in one of hundreds of freezers until needed) gathered from human tumors, will be treated in culture with
medicine X or Y, and medicine X + Y. After T, time, the cells are lysed and
analyzed by Western Blot and other immunologically based methods. At this step, the key piece of data they are looking
for is called "IC-50" (Inhibiting Concentration). This is similar to a "Km" value. It
tells doctors and researchers how much medication is needed to inhibit a
phenotype- say, tumor growth- in 50% of the cells. This is to be
compared to the toxic levels of the medication, based on clinical, or historical,
controls. [An example of the IC-50 for Gleevec (Imatinib) is below.]
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| IC-50 for Gleevec. Data are tested in the absence and presence of two anti-inflamatories (NSAIDs). (Wang et al.) |
Together, these data allows
doctors and researchers to decide, "will we kill them, if we need to give
this estimated dose?" I was reminded of the ultimate question: "would you give this to your
son?" Furthermore, answering the second question, "where it
works" could perhaps be the $100 billion question. By comparing different
cell lineages from different people and/or different tumors scientists can say,
this worked for Z% of colon cancers. The burning question remains: why does not
it treat the same symptoms in kidney cancer, for example? Perhaps, this could be answered by upcoming breakthroughs in high throughput genetic sequencing.
I have shared my
experience with you all to hopefully reveal what was shown to me. I was told
that if a medication does not show promising results after about two weeks, it
is more than likely thrown to the dustbin. I was also reminded that if a drug
flops on the market, or has unforeseen side-affects because of poor phase III
and IV screening, this may easily translate to a loss of public and private
confidence and investment. We still need academic
research: to pursue novel candidates and methods. Some one must make the phase
I suggestion. We need biotech to accelerate production.
As for Biotech,
we have a duty to question where all this money is going given the rising costs
of cancer healthcare. We have a responsibility to understand why the money is
necessary if we want the mass production of novel therapies to continue to
enable costs to drop. I truly believe this is a debate we need to be having.
Should these companies be subject to stricter regulations of disclosure and
profit? Should they be granted more access to patients than already is the
case, in order to expedite access and progress? Are they as efficient and
thorough as possible?
Most importantly
I wanted to highlight that while cancer is physically destructive, emotionally
tolling, it is also financially draining. These patients and their families go
through a tremendous amount of suffering on all levels. NIH reports that the
initial year of cancer treatment for chemotherapy, alone, can cost anywhere
between $100 and $30,000, on average, with insurance. We need to be sure that patients are
getting what they paid for, or at least the best possible.
* I highly recommend the article in the Economist listed below
- Drug companies in America: The costly war on cancer. The Economist. 5/26/11
http://www.economist.com/node/18743951
- http://www.cancer.gov/newscenter/pressreleases/2011/CostCancer2020
- Wang et al. Contrasting effects of diclofenac and ibuprofen on active imatinib uptake into leukemia cells. British Journal of Cancer.
- Title Photo: Harvard Business School Bulletin. June 2000. Online.
