This week’s science news is a relatively old story with a new twist: in the journal Blood, scientists in Germany report a possible “cure” for infection with the human immunodeficiency virus (HIV), the virus which causes the disease acquired immunodeficiency syndrome (AIDS).
An American living in Germany became ill with the rare and unfortunate combination of AIDS and leukemia. Doctors carried out a standard, but radical and dangerous, therapy to treat the leukemia: they destroyed his native immune system and replaced it with a new one transplanted from another patient’s stem cells. As a result, it seems as though the HIV infection has been completely eliminated from the patient’s body.
Now that you’ve survived the jump, here’s some backstory.
The immune system is extraordinarily complex, but to simplify, there are two main kinds of cells that mount an immune defense.
The B cells are called “B” because they mature in the chicken’s bursa of Fabricius. Luckily, in humans, the equivalent of the bursa also starts with the letter B—bone marrow. These cells are born in the bone marrow and stay in the bone marrow to mature. They release a special kind of protein called an antibody that binds to invaders. Like Boys, they spit out these antibodies without regard to what happens to them; they just release their antibodies into the bloodstream on command.
The T cells (called this because they mature in the human thymus) are also born in the bone marrow, travel to the thymus to mature, and then travel the body to fight infection using cooperative methods. The T cells collaborate with each other by plotting, planning and scheming to destroy invaders.
This film shows a light-hearted treatment of how T cells are like the girls in the movie Mean Girls. (If you’re interested in the subject, there is a longer version with more information.)
There are several main types of T cells:
- T helper (more about these below)
- T suppressor (also called T regulator, “peacemaker” T cells), “Amanda Seyfried cells”
- T cytotoxic (i.e. “cell killing” T cells), “Lacey Chabert cells”
- T natural killer cells (Played by Lizzy Caplan. I call these “ninja” cells, because they talk invaders into dying.)
T helper cells direct the immune attack, and are the queen bees or quarterbacks of the immune system. They carry a surface protein called CD4, so these are also called “CD4+ cells”. These are the cells that are infected and destroyed by HIV, which renders the immune system leaderless and rudderless.
Leukemias are cancers of the immune system which cause uncontrolled division in one or more of these immune cells. The standard treatment is to kill off the entire immune system, then find someone else’s immune system to start over again. The problem is that the transplanted immune system wants to go out and attack everything in the recipient’s body, because it’s all foreign. This is called “graft vs host disease” and this, plus the other possible complications (e.g. the new immune system doesn’t “take root”, or an infection kills the patient while their immune system is incapacitated) means that only about half of the patients who undergo this treatment survive.
In the present case, the doctor who found a compatible immune stem cell donor found a donor whose cells were naturally resistant to HIV. So, the former AIDS patient not only got a new immune system, but his new immune system repelled any remaining HIV in his bloodstream and tissues.
Current estimates are that 33 million people worldwide and well over a million US citizens are infected by HIV. The problem is finding a compatible donor match and getting over the expense (in dollars and health) of such a treatment. Just for starters, there’s the extended hospitalization under absolutely sterile conditions; the lost time and health of the bone marrow donor; the cost of the “biologics“, drugs made from living organisms which are more expensive than synthetic drugs. For example, treatment for childhood respiratory syncytial virus (RSV) with the biologic palivizumab costs $5,000 per infant treated. Understandably, many have questioned the cost-benefit ratio, but if it were my infant, I’d pay for the treatment. The biggest problem with health care is that its pricing is what economists call inelastic.
Let’s say this treatment is improved to the point where it represents a “cure” for AIDS. An estimate of $1 million treatment cost per patient is not out of line. How are we going to calculate the cost-benefit ratio of such a treatment? In other words, how do we ration health care?
Each medical advance we make forces us closer to a point where we have to make this calculation. You can call them “death panels”, but someone has to make this decision. Right now, we ration health care based on who can afford to pay the bill, or who can manage to stiff their insurance company with a bill. Is that the fairest, or the best, system to ration health care?
Because of total inelasticity, the question is not whether to ration health care or not. The question is how that rationing is to be done.
- Report: Scientists finally cure HIV with stem cells? (hotair.com)
- Cure for HIV Claimed But Not Proven (livescience.com)
- Possible HIV infection cure reported (cnn.com)
Or, perhaps there’s another route…
The hematopoeitic stem cells (HSCs) used for the bone marrow transplant in this case had a mutation in the CCR5 receptor which is what gave the donor an immunity to HIV/AIDS, and that immunity was transferred to the recipient along with the bone marrow transplant that was intended to cure the leukemia.
Because bone marrow transplants are risky, costly procedures, and because people with the CCR5 mutation are relatively rare, perhaps a better solution would be to pursue some form of gene therapy that stimulates or mimics the same CCR5 mutation?
For the short term, we might be able to save a few patients at a million apiece with the transplant process, assuming we can find more donors with the same CCR5 mutation. But in the long term, it would probably be more efficient to have a synthetic means of generating the immunity, perhaps via a nanovirus or similar?
(OK, here’s where my biology/medical knowledge deteriorates… Anyone else know if there’s been any progress on the gene therapy front??)
I know, I’ve dodged the question about whether or not it’s worth a million dollars per patient to save each life and how to choose who gets the treatment(s). But sometimes, the question isn’t a simple either/or, and there’s a third option that gets overlooked. To my way of thinking, that’s the biggest problem with the hyperpolarization of our politics, is that everyone’s so busy staking out their positions in red vs. blue, that no one sees the rest of the rainbow. There are beautiful options in yellow, orange, purple, green, magenta, cyan, periwinkle, etc…
In the case of healthcare, I don’t know what that third option is, but I’m willing to bet it exists.
Amusing lesson on biology and the human imune system.
I have to admit though, I liked the version from Fantastic Voyage better.
This is great news, I hope it can be duplicated in other cases.
I think what one would do is to induce the double delta32 mutation before transplantation.
However, to answer your other question, gene therapy has been an abysmal failure in practice. The patients who have been treated have significant morbidity and even mortality, and what’s worse, we have no idea why. Clearly, there are things in heaven, earth, and gene therapy that are not dreamt of in our philosophies.
Well, let an old algorithms guy make a suggestion: what the DNA is, fundamentally, is a program which designs a human. It takes as inputs environmental cues, which modify its behavior, and adapts the specification to these inputs.
Biologists understand only dimly and imperfectly what particular sections of the program affect what particular parts of the design and have no real means of controlling the inputs to the program, yet, in gene therapy, they are attempting to modify the program.
This is analogous to modifying bits in the operating system of the computer while it is in operation and without the source code.
Ever watch the Stargate SG-1 TV series? There’s an episode in there where one of the characters gets a brain-boost from alien technology, and proceeds to reprogram the base computer system on the fly — in machine language (seemingly random patterns of bits…). I laugh every time I see that episode.
Until there is a far greater understanding of the mechanism by which the specification (DNA) is transformed into the design, gene therapy is going to be a game of Russian roulette with a pistol having several million chambers, almost all of them loaded with various forms of ammunition (armor-piercing, poisoned, bird-shot, etc).
If it really is that expensive, private pockets only and public funding in rare exceptions. Correct me if I am wrong, but I suspect a lot more patients could be treated with the cocktail at the cost of that one cure.
AIDS treatment is not my forte, but I’m pretty sure that when you calculate out the lifetime costs of the cocktails and lost time and quality of life, that $1 million is a favorable cost comparison. I would welcome someone who is capable of doing the math.
That still leaves the question of whether we can find compatible donors, and whether treatment modalities will be successful.
What would the “rare exceptions” entail?
DC knows this already, but I’m a huge believer in emergent properties.
Emergent properties are an important part of understanding cell biology. If I understand you correctly, that’s the right label for what you’re saying — that the interaction between complex systems becomes a system in itself.
The famous molecular biologist Gunther Stent (who I had the honor of knowing, once upon a time) put it this way in a 1973 paper, written long before we could imagine sequencing the human genome. His gedanken experiment was:
Imagine we could send the genetic code for a cat and instructions for reading that code to a civilization on a distant planet, light-years away, that had never seen a cat. Armed with this information, could they make a cat? (You might recognize this as the problem with Jurassic Park: if we don’t have a dinosaur, can we bootstrap one?)
Since no one wants to bite on the inelasticity of cost problem, let’s kick this one around. Could the Alpha Centaurians make a cat?
“Could the Alpha Centaurians make a cat?”
The question then arises as to whether the Alpha Centaurians would be allow themselves to be treated with such disdain as the typical cats treats most humans.
I think, personally, that anyone who wants badly enough to participate in the dangerous experiment involved in trying to cure aids by the method described should get the chance — and the public should pay for it. I’m pretty sure it would be a desperate gamble, and, sadly, I strongly doubt that individual has a long and healthy life to look forward to.
But it is only through experiment that science truly progresses, and medicine is a more messy science that most others.
As for whether the scientists on a planet orbiting Alpha Centauri could make a cat, that devolves into the question of “what is a cat?”. If a “cat” is a creature that can interbreed with other cats, then how would we know? If a “cat” is a creature with the DNA of a cat, then, perhaps, if they can somehow provide the “manufacturing plant” (AKA womb) which takes the DNA and allows it to replicate in the correct fashion.
I’d suggest that we send along with the DNA a description and video that will allow the scientists at the other end to have some idea as to what the end result should look like. It would be embarrassing — and possibly result in an interstellar incident — if they ended up with a 12-foot tall saber-toothed tiger with a huge appetite…
@Shortchain and @Max,
Oh, the epistemology!
I don’t want to hijack my own thread, yet, but the answer lies in genetics vs epigenetics, which is why Shortchain’s comments triggered the thoughts they did.
We understand the genetics quite well; what we don’t understand is the epigenetics.
can’t speak to who is right or not about cost of the cocktail, as for exceptions I was thinking along the lines of an Einstein.
That’s what I thought you meant. It sounds like rationing and “death panels” to me.
If private pockets had access then “government board approval” wouldn’t be needed.
A Blue Cross/Blue Shield “death panel” is better than a government “death panel”?
I’m not being flip; I’m honestly trying to wrap my mind around what sort of rationing mechanism you’re suggesting.
I’m trying to figure out how robert (or someone, whether it’s a private or government “death panel”) is going to identify “Einstein”-type individuals when they are young and can benefit from the procedure. He does realize, I hope, that, in Germany, even into the twenties, Einstein was not thought of highly in their academic/scientific community.
Indeed, not only don’t I understand epigenetics, but had never heard the word. Does epigenetics have an explanation for mama grizzly ~ just wonderin’ …
and damn, still trying to figure out Benford’s Law, although palin is quite familiar w/Murphy’s Law! 😀
Aww, Shiloh, it’s not that bad.
All it really means is that you can have all the DNA sequences you want (see: Human Genome Project) but unless you know how to read and process that DNA, it’s pretty worthless.
Or, in real world terms, a sperm cell (just a guided missle with a payload of DNA) is worthless without an egg. The egg is what decodes the sperm DNA and starts the program that becomes a human being when sperm and egg are united. The “stuff” that is inside that egg (except for its DNA) is epigenetics.
Thanx Monotreme ~ epigenetics appears to be a tad simpler than Benford’s Law as I’m still trying to figure out how you can put a diamond needle on a vinyl/plastic record and hear Chuck Berry singin’ Roll Over Beethoven and tell Tchaikovsky the news!
re: All it really means is that you can have all the DNA sequences you want (see: Human Genome Project) but unless you know how to read and process that DNA, it’s pretty worthless.
Or, in real world terms, a sperm cell (just a guided missle with a payload of DNA) is worthless without an egg. The egg is what decodes the sperm DNA and starts the program that becomes a human being when sperm and egg are united. The “stuff”
that is inside that egg (except for its DNA) is epigenetics.
This may be a dumb question (I’m not a scientist, just someone who troubleshoots corporate mainframe computer systems and the web-based overlays to those mainframes), but I’d like to know if the work being done by organizations such as http://www.nationalgeographic.com/genographic will ultimately add to the field of epigenics ?
Interesting question, but what they are doing with what they call “genographics” is really just applying old-fashioned genetics to determine how we are related to each other.
There’s some science behind it, and a fair bit of nonsense, but the science is all genetics.
Epigenetics is more like the question: how are identical twins alike and how are they different? They share the exact same DNA, but they may not have (for example) the same diseases or die at the same age because of epigenetics.
I recall a novel about this concept…
re: Epigenetics is more like the question: how are identical twins alike and how are they different? They share the exact same DNA, but they may not have (for example) the same diseases or die at the same age because of epigenetics.
So epigenetics is everything EXCEPT the DNA? Nevertheless, wouldn’t learning about your own family’s genetic background, even if you were not an identical twin, ultimately be a benefit – learning what and why you may have a genetic predisposition to certain diseases or the likelihood of dying at a certain age? Or perhaps instead learning that, because of your genes and what scientists have learned about your genetic background , that you do NOT have a predisposition to certain diseases?
Genetic research such as this definitely is taking the long term view, but what I’d like to ask you is – is it worthwhile research and worthwhile for someone to contribute their DNA towards learning something that may or may not be relevent to their own personal genetic background?
@DC: Yeah. It was a great novel, too. Still Life by D.C. Petterson. Available here.
@Jean: I see where you’re going. I have submitted a DNA sample to help trace my ancestry, so I’m down with that, but in terms of our understanding of the linkage between genetics and disease, the science is still in its infancy. Here’s what I tell my students: sure, we want to know the genetic bases for all kinds of diseases, and I think the Human Genome Project is worthwhile. But we’ve known the genetic basis for sickle cell anemia for over 60 years, and still kids die of it everyday. Knowing and knowing how to fix are two different things.
Therein lies my concern and question. As you say, “we’ve known the genetic basis for sickle cell anemia for over 60 years, and still kids die of it everyday. Knowing and knowing how to fix are two different things.” Yes, they are separate (unfortunately) but I agree.
My question is, would more folks voluntarily contributing their own DNA add to the general scientific knowledge that may actually SOMEDAY lead to learning how how to FIX the problem, whatever the problem may be? It may be in it’s infancy, but you have to start somewhere.
A fascinating question, and one that I might cover in a future article.
For now, there is a fairly well-studied example, that of genetic testing for Huntington Disease. This is a horrible neurological disease that killed Woody Guthrie and causes dementia (loss of memory and executive function), uncontrollable movements, and eventual death.
Children have a 50:50 chance of inheriting the gene from an affected parent. You would think that the availability of a genetic test would be a great benefit to these families. In the event, relatively few individuals at risk opted for testing. I don’t recall the exact number, but I believe it was less than 1/4. Rather, most children of Huntington Disease patients opted for voluntary sterilization so that if they were affected, there was zero risk of passing it along to their offspring.
Let’s say we refined the technology to the point where we could say, with certainty, that you would die at 54. As a 30 year old, would you want to know that? How would it affect how you live your life?
This just came out today and I thought it would interest you.
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