A Gene Therapy That Works … And the Ethical Dilemmas It Presents

 

769px-Autorecessive.svg Metachromatic leukodystrophy (MLD) is Alzheimer’s on speed. Children born with the most common form of the disease will die by age five, due to atrophy of brain tissue. The incidence in the general population is estimated to be 1 in 40,000 to 160,000 births.

Unlike Alzheimer’s, MLD has a known genetic cause. It has an autosomal recessive inheritance pattern, which means a child must inherit a defective, recessive gene from each of two carrier parents to be symptomatic. That suggests the frequency of carriers in the population is 1 in 200 to 1 in 400. But for couples who are both carriers, the odds of a child with MLD are 1 in 4.

Post-natal testing does not work on MLD. The enzyme test that reveals the disease has a 7-15 percent false positive rate due to other, less severe conditions affecting the same body chemistry. Unless a specific genetic test is done on the parents or the pre-natal fetus, the first time most affected couples will know is when their child exhibits unmistakable symptoms. By that point, the disease in untreatable and irreversible. And there are 1 in 4 odds that any future child of theirs will die the same way (see illustration).

There is hope. This is a case where post-natal gene therapy seems to be effective. An MIT Technology Review article describes a technique to modify extracted stem cells with a corrected gene and reinsert them in the child’s body, reversing the disease. As far as can be determined with a small sample size over a few years, it appear to be safe and effective: that is, a genuine cure. Amazingly, the whole development in an Italian clinic has been supported by national telethons and philanthropy. Huzzah for the Italians!

The MIT article raises several issues, but without pause or analysis. I extract two passages to frame the dilemmas:

…treatments have been purchased by British drug giant GlaxoSmithKline, which is pursuing commercialization of the therapies. By adding correct DNA code to cells, gene therapy has the potential to erase devastating illnesses with a one-time treatment.

On one hand, a GSK pickup means the therapy will no longer live on charity. But what will it cost? Remember, this is a cure, offering no recurring revenue stream from afflicted patients. The costs of conclusive clinical trials and manufacturing must be amortized across the limited number of victims, one time each. And, of course, who pays? And if not the individuals concerned, what onus is there on others to pay for a stranger’s care?

Mind you, this is a cure for the child’s lifetime only. It does not modify the germ cells. A child with MLD who survives to reproduce — which will now happen at far greater frequency — will pass a copy of the bad gene to every offspring. Good for the individual, bad for the human gene pool, creating further potential costs down the road. Some believe that tampering with the germline is ethically problematic, but this case demonstrates the down-side of not doing so. Is it counterproductive — is it ethical — to save the current suffering at the cost of more in the future?

…[the mother] also disagreed with the Italians’ advice to get a prenatal genetic test during her two subsequent pregnancies to learn in advance if the fetuses would be affected, as she wouldn’t consider abortion. She had four more children, three of them in 2014 when she delivered natural fraternal triplets (there are one-in-8,100 odds of that). One of them, Cecilia, also had inherited the MLD genes. The Italians accepted the second baby into the study and treated her…

The American couple in question now have eight children, three (one deceased) with MLD. They live on a single house remodeler’s income. They are a charity case. Luckily, the Italians stepped in, not just once but twice.

What are the chances such a family would be able to afford GSK’s cure in the future? Should they be subsidized if they continue to procreate, knowing there’s a 25% chance that their children will need care they cannot afford? Should society support this? Can an obligation be created to test and yes — abort — once the hazard is known? What can we say about the ethics of such parents, or, on the other hand, a societal decision to turn its back on children born in such a situation?

We are going to see a spate of novel and effective gene therapies in the near future, due to advances such as CRISPR, but having cures is not going to end the dilemmas of treatment.

Image Credit: en:User:CburnettOwn work in Inkscape.

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  1. Zafar Member
    Zafar
    @Zafar

    Sabrdance:

    If insurance companies today don’t cover it, why would a single payer government system?

    Bigger risk spread – i.e. Everybody.

    Wrt benefit – I’d have thought that one would not be arguable. ?? The treatment saves a very young life and allows an individual to go on and lead a full and productive existence.  It isn’t a matter of a couple more years, it’s a lifetime

    Single payer systems do take on significant ongoing costs – I’m thinking treatment for things like RA or HIV or Hep C – I don’t think this would be so different.

    • #31
  2. Sabrdance Member
    Sabrdance
    @Sabrdance

    Zafar:

    Sabrdance:

    If insurance companies today don’t cover it, why would a single payer government system?

    Bigger risk spread – i.e. Everybody.

    Wrt benefit – I’d have thought that one would not be arguable. ?? The treatment saves a very young life and allows an individual to go on and lead a full and productive existence. It isn’t a matter of a couple more years, it’s a lifetime

    Single payer systems do take on significant ongoing costs – I’m thinking treatment for things like RA or HIV or Hep C – I don’t think this would be so different.

    The risk isn’t spread out any more than for a normal insurance company of similar size (remember, US insurance companies dwarf the single payer systems of Europe).  Statistical value of a human life runs around $10 million.  What’s the treatment cost?  If we’re talking well south of that, then we’re back to “normal insurance companies could do it.”

    And insurance companies handle arthritis, HIV, and Hep C, too.  Single payer still doesn’t improve on that.

    The only area where government provision might help is in the case of a “high risk pool,” which is roughly equivalent to, say, flood insurance -with similar arguments.

    • #32
  3. Liz Member
    Liz
    @Liz

    Dynamic-range, welcome to Ricochet. I’m glad you joined! I can only imagine what the experience of your family has been throughout your children’s diagnoses and treatment. I hope you’ll be able to share more.

    @psychlynne, one reason some women avoid prenatal testing is because they know, should anything turn up on a test, they will face great pressure from the doctors to abort.

    • #33
  4. Merina Smith Inactive
    Merina Smith
    @MerinaSmith

    Liz:Dynamic-range, welcome to Ricochet. I’m glad you joined! I can only imagine what the experience of your family has been throughout your children’s diagnoses and treatment. I hope you’ll be able to share more.

    @psychlynne, one reason some women avoid prenatal testing is because they know, should anything turn up on a test, they will face great pressure from the doctors to abort.

    I second this–thanks for coming on DR.  My prayers are with you and I too would like to hear more about your situation.  My heart goes out to you, one Mom to another.

    • #34
  5. Saint Augustine Member
    Saint Augustine
    @SaintAugustine

    Locke On:

    Is it counterproductive — is it ethical — to save the current suffering at the cost of more in the future?

    Sabrdance:@saintaugustine and @rachellu are more qualified to opine on the natural law argument here . . . . If the child is born with the disease, we treat them too, and we move on with our lives.

    I don’t see a natural law issue here, actually.  Just some basic questions about consequences and moral obligation.

    I think the questions are pretty simple to answer.  It may be counterproductive, but it’s still ethical.

    Hypothetically, suppose a good case could be made that the harming (through medical action) of 5 future but currently non-existent people would outweigh the harming (through non-action) of 1 person currently living.  I think I’d still want to go through with it.  Those 5 people are only hypothetical, and they have a good chance of having access to this and better medical treatments.  Both they and their suffering are only possibilities, which another person (their ancestor) has to act to bring about; our medical actions today are not the cause of harm, so much as the enabling of someone who might later cause harm.

    Meanwhile, I know that that someone is here, alive, today, and suffering–heal him if he may be healed.

    • #35
  6. Zafar Member
    Zafar
    @Zafar

    Sabrdance:

    And insurance companies handle arthritis, HIV, and Hep C, too. Single payer still doesn’t improve on that.

    The advantage of single payer is that everybody is covered.

    The only area where government provision might help is in the case of a “high risk pool,” which is roughly equivalent to, say, flood insurance -with similar arguments.

    If insurance companies only take the low risk pool, with tax payers subsidising high risk individuals, then what’s the advantage of them over single payer?  What value does the private sector add when it comes to health insurance, as opposed to health care provision?

    This already sort of what happens with Medicare, isn’t it, with insurance companies covering (statistically more likely to be healthy) younger people and the Government stepping in at the age when medical expenses are likely to increase.

    It looks like a case of privatising profit, nationalising loss cost and calling it a free market.

    • #36
  7. Zafar Member
    Zafar
    @Zafar

    Welcome to Ricochet, @dynamic-range.

    Do you have any thoughts, from the front line, as to how insurance for things like MLD would be best structured?

    • #37
  8. Sabrdance Member
    Sabrdance
    @Sabrdance

    Zafar:

    The advantage of single payer is that everybody is covered.*

    This already sort of what happens with Medicare, isn’t it, with insurance companies covering (statistically more likely to be healthy) younger people and the Government stepping in at the age when medical expenses are likely to increase.**

    * Not relevant to the pricing question.  Extent of coverage doesn’t effect the price if the extents are the same.  If we can achieve the same without single payer (which even single payer doesn’t actually cover as many people as it sounds because every single payer system excludes patients who are such massive expenses that they don’t cover the treatments and let the die).

    **That’s… not even remotely how Medicare works.  Medicare is predicated on the idea that when you get old, you will need more medical care of specific types: hospitalization, surgical procedures, and prescription drugs (A, B, and D respectively -and Medicare also includes part C, Medicare Advantage, which is… private insurance to supplement what Medicare provides).  You pay premiums in youth as an insurance policy against old age.  Now, it’s horribly run, so in practice we take money from today’s young and healthy to pay for today’s old and sick, but that isn’t how it is designed.  It isn’t a high risk pool.

    What we call “high risk pools” are a euphemism for “100% risk.”  These people don’t need insurance, they need a financing plan.

    • #38
  9. Zafar Member
    Zafar
    @Zafar

    Sabrdance:* Not relevant to the pricing question. Extent of coverage doesn’t effect the price if the extents are the same.

    Put it this way – everybody pays into a universal insurance scheme, there are no opt outs by younger, healthier people – so the spread reflects the entire population rather than just the people who think it’s worth buying insurance (something which may correlate with getting older and more likely to need healthcare).

    …even single payer doesn’t actually cover as many people as it sounds because every single payer system excludes patients who are such massive expenses that they don’t cover the treatments and let the die).

    Single payer systems do cover everybody, just not for everything. That’s a fair issue to raise.

    Medicare is predicated on the idea that when you get old, you will need more medical care of specific types: hospitalization, surgical procedures, and prescription drugs (A, B, and D respectively -and Medicare also includes part C, Medicare Advantage, which is… private insurance to supplement what Medicare provides). You pay premiums in youth as an insurance policy against old age.

    Can you opt out of paying for Medicare A, B and D?

    Is there a flat levy, or is it a % of your salary/taxes?

    Does everybody get the same Medicare A, B and D coverage, no matter what they earned and paid in taxes? (Is it redistributive?)

    Could private sector schemes provide the same outcomes without disadvantaging the poor?

    • #39
  10. Midget Faded Rattlesnake Member
    Midget Faded Rattlesnake
    @Midge

    Zafar: Could private sector schemes provide the same outcomes without disadvantaging the poor?

    Medicaid doesn’t seem to serve poor Americans terribly well, though I’ve heard the argument that it would if rich people were also forced to use it. And yes, it’s true that, when no one is allowed to exit, the wealthier can still purchase more voice. But even if all Americans, including the wealthy, were expected to use Medicaid, the poor would still be at a disadvantage. Wealth means more resources to navigate and supplement the system. It does for Medicare, too.

    I doubt there’s a way to erase the advantage to health of wealth. Rather, making sure cheap medical care isn’t made artificially expensive (including unavailable entirely) may do the most for most of the poor. Charity cases — the very poor and very sick, or those poor because they have been so sick — I do sometimes wonder if the older way, where rather than “insurance” (that wasn’t really insurance) they just got care, was better.

    Mutual aid societies were once relatively successful at providing cheap care to their members, who could be quite poor.

    • #40
  11. Merina Smith Inactive
    Merina Smith
    @MerinaSmith

    Just to brag a little about Zafar, because he will never brag about himself–this is his field and he’s working on exciting new ideas in the Australian system.  We’re lucky to have him here to tease out some thoughts about this.  Obviously, our nation needs some serious work on medical insurance what with the Obamacare disaster.  Zafar, please volunteer your services to Paul Ryan!

    • #41
  12. Zafar Member
    Zafar
    @Zafar

    Ha! Merina (as usual) is too kind.  I am working for an Agency that administers a brand new universal disability insurance scheme – not healthcare – so I am currently in the mode of looking at how societies deal with random misfortune, and also how random misfortune affects not just an individual but their families and communities.

    • #42
  13. Phil Turmel Inactive
    Phil Turmel
    @PhilTurmel

    Zafar: …. looking at how societies deal with random misfortune, and also how random misfortune affects not just an individual but their families and communities.

    “Random misfortune” is the key phrase here, I think.  There’s a huge difference between treating the random car accident injury and treating acute heart disease.  The former hits all ages, but only a few.  The latter hits many, and largely the elderly.

    Even more divisive are the battles over ICU care decisions and similar high technology medicine when prognoses are poor.  Families don’t want to give up on one of their own, but they are asking society to pay for it with resources that the rest of us might want to spend elsewhere.  Our society has lost touch with mortality, and the need for balance between life extending treatments and all of the other needs of society.

    • #43
  14. The Reticulator Member
    The Reticulator
    @TheReticulator

    Phil Turmel:“Random misfortune” is the key phrase here, I think. There’s a huge difference between treating the random car accident injury and treating acute heart disease. The former hits all ages, but only a few. The latter hits many, and largely the elderly.

    Even more divisive are the battles over ICU care decisions and similar high technology medicine when prognoses are poor. Families don’t want to give up on one of their own, but they are asking society to pay for it with resources that the rest of us might want to spend elsewhere. Our society has lost touch with mortality, and the need for balance between life extending treatments and all of the other needs of society.

    I’ve sometimes heard people say, “a family should never have to make such a choice.”  Well, in my case it wasn’t a severe disability.  I once pointed out that I have bad teeth that never got straightened, but I’m glad my parents instead saved their meager amounts of  money and took us on travel vacations out west each summer.  Someone responded, “Parents should never have to make such a choice.”  Well, there are always tradeoffs, and I’d prefer that the family make them than have the government do it.

    It’s known as life.  It’s a terrible thing to live in a world where people are not allowed to make consequential choices. It leads to some nasty social pathologies.

    • #44
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