- The Washington Times - Monday, December 24, 2001

Fred's First Law of Research says that if you put smart people in a room with enough glassware, they'll probably do something clever. For example, they might make a large step toward getting rid of sickle-cell anemia by means of gene therapy. Some folks at Harvard and the Massachusetts Institute of Technology, funded by the National Institutes of Health, and colleagues elsewhere just have. It's kind of neat.
How it all works: Hemoglobin is what red blood cells have in them, and it carries oxygen from the lungs to wherever needs it. Bone marrow makes red blood cells, which manufacture the hemoglobin. It consists of a core with some protein chains attached to it. If you have sickle cell, as one in 400 blacks does, a chemical mistake in the chains causes the molecules to stick together. This makes them gummy and causes the red blood cells to adopt the shape of a sickle. It's painful, debilitating, and generally not a good thing.
So what to do about it?
There is a form of hemoglobin chain, found in fetuses, that counteracts the sickling effect. That is, when the anti-sickling form is present in a blood cell, it doesn't sickle. So, thought the ever-crafty scientists, what if we got the bone marrow in sickle-cell patients to make the anti-sickling chain? Ha.
Now, genes control the manufacture of protein. It's pretty much all they do. So if you could get some countersickling genes from fetal hemoglobin, and somehow get them inside of the bone-marrow cells of sickle-cell patients, then the marrow would make anti-sickling protein, and that would be that.
How do you get anti-sickling genes into a bone-marrow cell? Not with an ice pick or power drill. It doesn't work.
First, you have to take marrow out of the patient (i.e., now, the mouse). Then you have to add the desired genes, and put the marrow back. But how to add the genes? They don't work unless they're inside the cells.
What the researchers did was to attach the new genes to a weakened form of an HIV-like virus (I know: Makes you want to try it right now.) Anyway, the virus goes into the cell and leaves the genes. The cell starts making the desired proteins.
These days, viruses are regularly used to get things into cells. They know how to get into a cell so they can do bad things. Cripple the virus so it can't misbehave and it will take whatever you attach to it into the cell. It's like mailing a letter.
So they took bone marrow from mice with sickle-cell anemia, sent the virus in to carry the desired genes into the cells, and then put the marrow back in the mice. (First they had to engineer mice with sickle cell, so they could cure them. It doesn't always pay to be a mouse.)
It seemed to work. Ten months after trying the experiment on mice with sickle-cell anemia, or something close to it, the mice were making bunches of anti-sickling protein. One mouse didn't have any residual sickling at all. Sometimes grant money is well spent.
An enormous advantage of this new treatment is that you use the patient's own marrow. The immune system therefore doesn't reject it. You don't have to look for compatible donors. We are all compatible with ourselves.
So is sickle cell now a thing of the past? No. It's getting ready to be a thing of the past. I talked to Dr. Greg Evans, of the National Heart, Lung and Blood Institute at NIH. He says estimates run from two to five years before actual patients can be treated, and maybe more if some unexpected roadblock occurs. Work needs to be done first on larger and more humanlike animals. You know, pigs, monkeys and such.
Two major problems remain, says Dr. Evans. First, the weakened HIV virus isn't supposed to be able to reproduce, but may a little bit. This has to be figured out very carefully. Curing a patient of sickle cell by giving him AIDS is not therapeutically optimal. (Nor, on the other hand, is the medical use of a dangerous virus unusual. Many vaccines are made of weakened viruses.)
The second problem is that killing off the patient's original bone marrow, so you can put in the re-engineered marrow, involves risks. Such as death. Doctors are against this. Patients aren't enthusiastic either. The problem, however, is probably solvable, think scientists.
Says me, we've got big things coming down the pike in the life sciences. This, I think, is one.
* Fred Reed can be reached at [email protected]

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