Saturday, February 13, 2010

The start of a journey: reflections on the gene discovery

Real science is encroaching on stuttering research and stuttering is now being cornered from two sides: the symptoms and the genes. Mark asks the very crucial question that every sane person must now ask: How does a failure in a lysosomal transfer protein affect speech production? Genes are physical objects. No more hiding of your sloppy thinking behind the curtains of abstract psychological concepts. You can point with the finger to them, and they deliver the instructions for the cells on how to build proteins. Three mutant genes were identified in people who stutter. Such a mutant gene results in the failure to produce a standard lysosomal transfer protein. If you have one, you very likely stutter.
Let's re-examine those glorious statements of early intervention in the lights of kids with one such mutant gene. How exactly should that work? Behavioural work à la Lidcombe or parental work lets them fully recover? Oh, I once dared to ask the question on how such therapy can work if there is a neurobiological basis. The answer was of course: Brain Plasticity. The magic word, yet again a curtain to hide behind your sloppy thinking. Let's be clear: How can early intervention change the mutant gene or provide the body with the right lysosomal transfer proteins. The answer is very clear: It cannot. The damage is done, and the brain of the kids are damaged.
Tell me that you try to install new behaviours and cognitive schemes in the young children in order for them to better cope with a life-long neurobiological deficit. Great, I wish you would have worked with me as a kid. But don't tell me that early intervention makes more kids recover fully. You are being fooled by the natural
recovery rate and slow relapse rate. And don't blame natural recovery on your abilities.
I also throw the gauntlet to those who are scientists. We need to come up with an over-arching framework on how to build theories on stuttering. We need cause-specific models, e.g. a model on how the found mutations lead to stuttering. But we also need an effective model that explains us the diversity of symptoms and their situation dependency. We need the commonality to all cause-specific models. I would argue for a jam in the language-to-speech areas common to all subtypes of stuttering. Honestly, I have very little confidence in the modeling abilities of the eminent scientists, most of them are experimentalists and their modeling attempts are naive at best.
I also challenge the stuttering community not to chase into the gene-neurobiological corner. Conditioning and cognitive beliefs are very clearly responsible for the modulation of the symptoms, its frequency and severity, and so is the well-being of the person. Yes, I cannot blame you for having a neurobiological deficit (or the mutant gene). However, I can tell you that a decrease of your symptoms and an increase of your well-being is within your control. And yes it's not easy. It is very tough. And I have failed so far on the symptom side. Am I just too lazy, do I just don't listen, do I have the wrong personality or is my brain too messed up? I don't know. But I do know that my well-being has considerably increased with regards to my speaking.
We are at the start of a real scientific journey. Let's take it together.


Dave Rowley said...

Great post, Tom. I think one of the most interesting developments will be to see if anyone can account for natural recovery within this framework.

Anonymous said...

Can you please try to explain why 80% of kids spontaneously recover from stuttering and the unequal gender ratio?

Just try and take a wild guess...

Tom Weidig said...

Good question Anon.

It has to do a lot with the genetics. Females have extra genes as far as I know. Females are more "stable" across the board, and males suffer more from developmental disorders.

Maybe Mark can add to the details of this...


Anonymous said...

Hi Tom,

great post! But I`m not sure if your statement “If you have one, you very likely stutter. And two mutants will kill you at the end of the day.” is correct. Kang et al. write in the discussion: “None of the mutations we observed in GNPTAB and GNPTG have been identified in persons with mucolipidosis type II or type III.” I think the same genes are affected but by different mutations.


Tom Weidig said...

Thx Benjamin,

that might well be the case. It did not look into this about in great detail. My main messages are not affected by a change.

Best wishes,

Kanstantsin said...

Scientists still do not have enough experimental data to explain the mechanism of stuttering.
Speech pathologists still can not develop an adequate stuttering treatment without knowing the mechanism of disease.
PWS keep on suffering from stuttering.

Anonymous said...

When are you going to award the Crackpot to Jane Fraser and her SFA Group for "WE CAN PREVENT STUTTERING WITH EARLY INTERVENTION" lie???

Mark B. said...

Anonymous #1:

"Can you please try to explain why 80% of kids spontaneously recover from stuttering and the unequal gender ratio?"

It is not known why so many kids recover spontaneously. One study, by Ambrose, Cox and Yairi, showed evidence for recovery or persistence being genetically influenced. Their data also suggest that persistent and recovered stuttering has the same genetic cause, with a different genetic cause for the difference between persistence and recovery.

So maybe there's one gene variant that can set off early childhood stuttering that is overcome with greater maturity, and a second gene that, when added to the first, prevents the natural recovery.

Regarding the sex ratios: the sex ratio of stutterers starts at about 2:1, and rises to about 4:1 after the natural recovery period passes. So we know that more females than males recover. We also know that females mature about a year ahead of males in many ways, including language acquisition. This suggests that the maturing female brain can somehow eliminate stuttering before it becomes permanent.

Mark B. said...

Anon #2:

To clarify. One gene can have many alternate versions in a population (in this case, humans). The "stuttering version" of these genes (GNTPAB, GNPTG and NAGPA) are likely to produce a functionally different protein from the standard version of the gene.

It has been shown in the past that mutations in two of these genes - GNPTAB and GNPTG - are associated with inherited lysosomal storage disorders mucolipidosis types I and III, respectively.

In the case of the two latter disorders, the mutation causes either a serious disruption of the related protein or its total absence. With either a severely degraded or absent protein, the lysosome can't do its vital job, and it plays havoc with the body.

So the mutation that is associated with stuttering is not the same that causes serious illness. I stayed away from that topic because I didn't want to scare people.

Anonymous said...

I can't see how you can dismiss brain plasticity completely and be so sure that early intervention cannot work.

ig88sir said...

I have read that women are less lateralized then men. If there is stuttering due to an abnormal left hemisphere speech production area (from genes or damage etc.) there is more space to compensate than a male has (the right hemisphere). Recovered male stuttering children compensate by neighboring left hemisphere regions. So males have less space available than women.

I am bilingual and started to speak at 2 years old. I have read that bilingual stuttering children have significantly less odds of recovering. Each language actually takes its own space in the brain so there is less space to compensate. Is this a naive simplification? Is a child’s brain just like a computer hard drive? Please correct me if I am wrong. I am no expert...

Mark B. said...

There is a study that claimed that bilingual children have a lower recovery rate. This would need to be verified by more work. I don't know if space is the issue - perhaps more the demand on the system at a time of sensitivity.

My mother grew up in a Swedish-American family, and learned conversational Swedish as a child. She remembered reading the Swedish-language newspaper to her grandmother, but could not remember how she learned to read the written language - she was never "taught." The brain of a child is a remarkable thing.