The Complexity of Care in the 21st Century

Posted on March 15, 2011


Recently, a friend sent me a text message with a rather conservative back-of-the-envelope calculation putting the number of lecture slides we’ve seen since October 2009 at roughly 41,000.  Talk about PowerPoint Hell.  That got me thinking:  how many questions have I answered in that same time period?

Here’s the conservative estimate, not including quizzes, workshops, and miscellaneous other goodies:  with roughly 100 questions per exam, an average of an exam every 3 weeks, and accounting for a few weeks off, that puts us at about 1,500 test questions.  But to prepare for each exam, we (or at least, I) complete multiple practice exams – about 2 per exam, averaging probably 50 questions each – now we’re at 3,000.   Add another 3,000 from my USMLE Step 1 practice materials & online question bank, and I’ll have answered about 6,000 questions by the time I take my exam on May 5th.

Now, you’d think that would make me one hell of a physician-to-be, but the truth is this is pretty average for a US medical student.  Worst of all, we struggle daily with our perceived (and actual) incompetence in the face of the insurmountable knowledge medicine has accumulated, mostly in recent decades.  Science has given us insight that has made the study and practice of medicine simultaneously easier and more difficult.

Ars longa, vita brevis.

I spend some of the scant free time that I have reading health news, and I don’t have to look hard to find a fellow reader lamenting the fact that we haven’t cured cancer, or that we have the cure for diabetes but doctors stand to profit by keeping their patients on insulin for life.  But cancer isn’t a single process (there are enough variations of cancer to make your head spin – just ask a med student), and diabetes is a progressive disease exquisitely intertwined with diet and lifestyle.  We’re still struggling to wrap our minds around these and many other diseases on the molecular level.  We read of breakthroughs and potential cures often – treatments look promising, but may only reveal a new stumbling block or even stalemate with a disease process.

central dogma

Modern medicine, step 1: the central dogma of molecular biology. Figure by Bruce Fouke (2006).

I’d like to help people understand how we approach disease in modern medicine – it goes way beyond the history and physical exam that you’re used to suffering through at your doctor’s office (but continue to humor us, please, when we ask you how much you smoke and if it’s possible you may be pregnant – it’s important).  The practice of medicine has surpassed the levels of the person and the cell, operating now at the level of the protein (or its blueprint, the gene).

I’ll use Multiple Sclerosis as an example – take a look at an actual slide I dug up from a past lecture:

Multiple Sclerosis pathway

Proposed pathogenesis of multiple sclerosis

In English, the immune system inappropriately targets “self” proteins in people who develop MS.  A logical approach is to use immunosuppression – corticosteroids to shut the entire process down (like driving a thumbtack with a sledgehammer), or more targeted approaches, as we’ve discovered using molecular medicine.  That alphabet soup you see above is a collection of cell signals (called cytokines) involved in the process of inflammation.  As the mentor I quoted in a previous post taught, we must choose a point in the pathway to block.  Here are a couple:

Natalizumab (Tysabri) is a manufactured antibody that targets a specific protein (called an integrin) white blood cells need to cross from the blood into an organ.  It was a breakthrough drug – the first of its kind.  Natalizumab was (and is) employed in the treatment of MS, but carries a grave risk – some patients on long-term therapy developed a debilitating and fatal condition known as Progressive Multifocal Encephalopathy (PML), as a result of the immunosuppression.  The drug was removed from the market, but returned, and is still in use because it is believed the benefits outweigh the risks – and though controversial, for some, they do.

Rituximab (Rituxan) is another drug that works by specifically targeting the protein CD20 on the surface of B-cells.  It can completely decimate your mature B-cell population, leaving other cells untouched (pretty impressive).  You may have heard of it in the context of Rheumatoid Arthritis treatment, because it works rather well (recently, Rituxan has also been implicated in the development of PML, though fewer cases are documented).  Not long ago, however, it was discovered that Rituxan may help people who suffer from MS.

Now, it was believed that T-cells, not B-cells, were the main culprit in MS – but just because we don’t yet understand how or why a therapy works doesn’t preclude its use – welcome to the world of “off-label” use.  There are literally hundreds of examples of treatments we are close to clueless about, but are used because they work predictably – need an example?  Tylenol (and it wasn’t until the 1970s that we began to understand how aspirin works).

So there you have it – two examples of less-than-perfect treatments in the context of one disease.  It takes immense amounts of money, research, and testing (and more money) to bring new treatments to market.  This isn’t Advil for a headache – this is the big leagues.  The next time you witness someone complaining about the lack of progress in modern medicine, politely remind them that it’s more complex than even the best of us know, and that progress will continue to be slow and painful with respect to many diseases.

“Knowing my own limitations and those of medicine in general, I will make an effort to cure, when possible, and always comfort.”

Taken from a modified Hippocratic Oath

Posted in: Health, Medicine