Wednesday, December 12, 2012

Positive genetics

Ken and I spend a lot of time here on MT writing about what's wrong with human genetics.   We feel that too much money is being spent on approaches that don't and won't work, for reasons that should be obvious to all.  But, vested interests rule, not us, so there's no stopping the train.

But nothing in life or in science is black and white, and even when correctives might be due (or overdue), it would be wrong to suggest that there are no successes or that the claims are always exaggerated.  So, it's good to see a rare good genetics story, on the front page of the New York Times (and our local newspaper).  A girl from Phillipsburg, PA, just down the road from us here in State College, has been one of the first people to benefit from a new genetically driven approach to treating leukemia.

Emma Whitehead developed leukemia several years ago, at age 5, and was treated with chemotherapy in the traditional way, a treatment that is beneficial 85% of the time, but she was one of the 15% for whom it wasn't.  So, her parents sought and found an experimental treatment at the University of Pennsylvania that had been tried on a handful of people, including adults with a different form of blood cancer.

The treatment has had mixed results, for different reasons, some known and some not, but because it has worked so well for some patients the method is seen has having great potential.  So much so that, to the surprise of the researchers, Novartis, the drug company involved has committed to building a research center at Penn to advance the work.  Presumably they envision widespread application, and profit, even though the therapy must be individually produced for each patient.

The idea, described in the New England Journal of Medicine in August 2011 (no paywall) is to enlist the patient's immune system to specifically target his or her cancer cells by training his or her own T-cells to do the job.  Researchers remove T-cells from the patient, introduce cancer cell-specific antigen receptors into them with a lentivirus vector which inserts the receptor, and itself, into the cell's DNA (in this case, it's an inactivated HIV) and then reintroduce these treated T-cells into the patient.

When all goes well it seems to eliminate all cancerous cells, at least for some time -- in Emma Whitehead's case, 7 months so far, and in another case, also described in the NYT, over a year.  It's too early to declare patients cured, their doctors say, but some have gotten their lives back.

The case of the crossing-guard
Ken clearly remembers serving as a 'safety patrol' with a crossing-guard when he was in elementary school.  The guard regularly reported on a child living in her neighborhood who had been diagnosed with leukemia.  She reported seeing the child (of Ken's age) marching daily up and down the street happily engaged in day-dreams ....until one day the child did not appear.  He had died.

So, some anonymous little person simply disappears from the earth.  It was a poignant moment etched forever in Ken's memory, but that tiny, passing event was an unimaginable tragedy for the person and his family.  Every instance of such a thing that can be avoided should be avoided.  If striving towards such an end doesn't give a biomedical scientist's life meaning, it's hard to know what would.  Indeed, the piece in our local paper, a story by reporter Heather Hottle, ends with this quote from Emma's doctor:
“I’ve shown (Emily’s) picture when I’ve given talks internally at Penn and a couple times when I’ve given talks outside ... and every time I show that slide, I have a hard time getting through without choking up,” he said.
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Decades later, it had become clear that some chemotherapeutic approaches to leukemia worked better in children than in adults, and in fact had achieved substantial success.  We remember sitting next to a pediatric geneticist from Penn State's medical school, at some rubber-chicken dinner a few years ago, and he explained that this better result in children was due at least in part to their ability to withstand much more intensive dose levels than adults could tolerate.  So the cures were coming at a price, and in addition, they were based on the sledgehammer nature of much of cancer chemotherapy: if you kill all dividing cells, you'll kill all the cancer cells, and if the patient is still alive you can stop the therapy and the healthy cells will start dividing again.

More refined, specifically targeted approaches have problems (such as immune resistance to the therapy, and indeed in this case, the elimination of B-cells and thus the need for regular gamma globulin injections to prevent infection) but clearly are better both conceptually and in practice.  So this therapeutic approach serves as a heartening example of exactly the kind of application of genetics that Ken and I advocate all the time -- a problem like this for which a genetic approach can actually make a difference.  The treatment described here isn't genetic in the usual sense of inherited disease, but it does take advantage of knowledge about genes to produce a result.  While caution is still due this fledgling approach, it seems to have promise.  Yes, spend the money. 

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