Friday, June 1, 2012

Inside the Industry of Cancer: Pricey or Priceless?

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 
Celgene Corporation's presence in 38 countries
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.

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]

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.]

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

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.