Try and beat this one, alties!

I’m not going to lie to you. This post contains some actual science. WAIT! Don’t click away! I’ll make it palatable, I promise!

It’s just that this is such an interesting story, and I can’t help sharing it. It is a shining example of one of the great successes of modern medical science, and stands in such stark contrast to the unfulfilled promises of the cult medicine crowd, with their colon cleanses and magic pills. This is the story of a real magic pill.

It starts back in 1960. A couple of researches at the University of Pennsylvania were looking at chromosomes in the blood cells of patients with chronic myelogenous leukemia (CML), and one stood out. This unusal chromosome was named the “Philadelphia chromosome”. In 1973, another researcher was able to piece together the precise genetic defect that creates the Philadelphia chromosome. In 1998, Peter Nowell, one of the chromosome’s discoverers, and Janet Rowley, the later scientist who discovered the exact defect, were awarded the Lasker Award for their work.

The significance of this work is that a particular chromosomal defect was associated with a particular cancer for the first time. This not only allowed for increased understanding of how cancers work, but also opened the door on how to fight them.

CML isn’t terribly common–it probably kills about 500 people per year in the U.S. But these numbers hide an amazing success story. Back to the science, and a little background in biology.

Chromosomes are large clumps of DNA (and protein), and the strings of DNA in them are instructions for making proteins. We call these instructions “genes”. These proteins are the structural and functional components of our bodies, and include enzymes that control when cells will or will not divide. Cells that divide in an uncontrolled way become cancers, so the start and stop mechanisms for these proteins are quite important. Control mechanisms exist on several levels. Sometimes they control when a gene will and will not make a protein, sometimes they determine when a protein will or will not function. A problem with any of these mechanisms can be quite bad.

The Philadelphia chromosome is a problem. It contains a gene called “BCR-abl” which produces a protein called a “tyrosine kinase” (TK). This particular TK is not present in normal cells. When it is present in certain white blood cells, it is stuck in the “on” position, and causes a cell to keep dividing in an uncontrolled manner. These abnormal white blood cells keep dividing, producing the condition we call “leukemia” (“white blood”).

In the 20th century, the 5-year survival rate for CML was somewhere between 32-50%, and didn’t improve much. Then this guy named Drucker came along.

Brian Drucker is a doctor and researcher who happened to be interested in TKs. He helped figure out how the Philadephia chromosome caused these white blood cells to turn cancerous. He teamed up with a drug company (which eventually became Novartis), to develop a compound that would inhibit the TK that was stuck on in CML.

Most cancer therapies traditionally were “cytotoxins”, that is, they killed cells. This is good—they killed cancer cells. But they also killed normal cells, giving chemotherapy a bad reputaion as a miserable thing to go through. If a compound could be found that turned off only this one little protein that caused CML, it had the potential to stop the disease without hurting healthy cells.

In the late 90’s, they found it. It was called STI-571, and not only did it seem to turn off the TK enzyme, it also came in a pill.

It went through the usual phases of clinical studies. I remember as a medical resident on a busy cancer ward one of my professors working hard to get access to this as yet unproven drug, as it seemed so promising. Patients were scrambling to enter research trials.

Well, the trials are done. Reported at the end of 2006, the 5-year survival rates for CML patients taking Gleevec (the commercial name for STI-571) is about 90%. Ninety percent!

This is an incredible story. It follows almost 50 years of hard and brilliant work by many researches named and unnamed, as they discover the cause of a disease, and it’s treatment.

It stands in stark contrast to the promises of the “alternative medicine” crowd. They proclaim loudly, “Buy my book! Take my enemas! Infuse my vitamins! I will cure you!” Of course, they cure no one, because they are lazy. They don’t understand science, and don’t care to. They prey on fears and hopes, and don’t deliver. They should be ashamed.

The rest of us can be proud and hopeful as medicine learns from it’s successes and failures, and marches on.

References (not otherwise linked above):

Brian J. Druker, M.D., François Guilhot, M.D., Stephen G. O’Brien, M.D., Ph.D., et al for the IRIS Investigators. Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia. NEJM Volume 355(23):2408-2417, December 7, 2006. http://content.nejm.org/cgi/content/full/355/23/2408

Comments

  1. #1 Boris
    May 4, 2008

    Some folks are allergic to reality.

  2. #2 azqaz
    May 5, 2008

    Boris,

    It is a stupidamine reaction.

  3. #3 FullFrontal
    May 5, 2008

    This is a great story. In peds we look to Acute Lymphoblastic Leukemia (ALL) as a similar success. Thirty-five years ago, ALL killed almost every kid that fell ill. Now we see cure rates approaching 90%. When the scientific method is applied to a problem and the information gleaned is then shared around the globe, good things happen.

  4. #4 Dianne
    May 5, 2008

    Eh, it doesn’t work for T315I mutations. Or cure in most cases (although a few apparent cures have been documented.) So calling it a magic pill seems a little much.

    On the other hand, that 10% mortality rate is an absolute mortality rate on a population that averages about 60-65 years in age. Some people with CML are now dying of something else unrelated to their disease so in that sense imatinib is even better than it looks. And it works in GIST, a previously essentially untreatable tumor, too.

    Which demonstrates the underlying difference between altie claims and real medicine. Alties will claim that their treatment always works for essentially everything from cancer to male pattern baldness. Yet their brilliant cures never seem to impact survival on a population level. Real medicine’s claims are more modest. Imatinib only works for a few diseases and doesn’t work 100% of the time even then. But it has made CML a truly chronic leukemia and has made GIST a slightly less horrible diagnosis to have. And it works even if you don’t believe in it.

  5. #5 TheNerd
    May 5, 2008

    Score one (per each life saved) for Science!

  6. #6 CanadianChick
    May 5, 2008

    three cheers for REAL science leading to REAL medicine!

    (says the girl who is very happy that biologic response modifiers for arthritis were discovered…)

  7. #7 Another Anonymous Poster
    May 6, 2008

    I remember back in 2000 or ’01 when Druker came to UVa to give a dinner talk to us. I just remember thinking ‘this is a guy who found a cure for cancer. How awesome is that’. I can’t wait to see how the other TK antagonists start working once we use them a bit earlier, now that they’re starting to hit the market.

  8. #8 Sally Church
    December 14, 2009

    It is a wonderful story from bench to bedside in cancer – how many others can claim this outside of stem cell transplant? But as someone involved with the drug’s development, I’m probably highly biased.

    To correct a few comments expressed here, the average age of CML patients is actually nearer 50-55 not 60-65, so most are still young and fairly active.

    How do you define a cure?

    60-70% of patients on imatinib attain a complete cytogenetic response in around 18 months and now live 7-10 years+ compared to 2-4 years on interferon, which also had nasty side effects. 20% of people die from transplant related mortality, assuming they have a matched donor and many transplant patients suffer side effects over the long term. Given the choices, what would you honestly choose?

    Imatinib is now approved for 10 different diseases, after CML and GIST, granted the others are fairly rare.

    Alternative medicine is no better than taken Hydrea or Busulphan and probably does even less for the patient. To even consider would be plain non-sensical in this case.

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