Saturday, March 31, 2007

How does a scientist determine causation?


After talking it over with Mrs. Factician (who is also a molecular biologist), I realized that yesterday's post might not have made sense to everyone in the way it does to me. I would like conspiracy factory to be more than a place where scientists whine to each other that no one understands us. I'd like it to be educational to folks who don't do science every day. I'd like people like my Mom to come here and read it and find something useful for their day.

That said, I'm going to spell out the comic a little better. For those of you who are skeptics/scientists, this may seem a little like explaining a joke (if you have to explain it, it's not funny). But it should be educational, too. So go over, look at the comic, and come back if you have to. What does it have to do with autism? The joke is that scientists don't immediately assume causation if two events occur close together. The fact that the scientist gets zapped by lightning immediately after pulling the lever doesn't necessarily mean that the lever caused the lightning. (Granted, it may have caused the lightning, but until you've seen it multiple times under controlled conditions, you can't say for sure). Of course, doing an experiment that involves being shocked by lightning certainly wouldn't be performed by a scientist. It would be performed by her graduate student. ;)

What does this comic to do with autism? As it happens, the folks who claim that vaccines cause autism mostly rely on the fact that autism begins to show its ugly head around 2 years of age, right after children get a series of booster shots for their vaccines. Does this mean that vaccines cause autism? No. Especially once you realize that autistic children present with autism around 2 years of age whether they've had vaccines or not. It just happens that these things coincide in time with each other.

An experimentalist who wants to ask the question: "Do vaccines cause autism?" would examine a large group of children who get the vaccine and a large group of children who don't (who otherwise are living in similar circumstances) and see if a similar frequency of children get autism in both groups. As it happens, several groups have done this (National Academy of Sciences summarizes the studies here). And they do see similar frequencies. This pretty much kills the argument. (To further extend the analogy to the comic, this would mean that the scientist who pulls the lever a thousand more times would never get shocked again).

Digg!

8 comments:

Kathy Finfrock said...

I enjoyed the comic and immediately thought of my son-in-law who is neither a scientist or autistic. He's just all male. (lol)

Anonymous said...

NAS has never done a control study of un-vaccinated individuals because that would be unethical. Also epidemical studies neither proves, nor disproves causation. Since there is no defined pathology in the DSM criteria, there are no defined areas that must be affected for an ASD diagnosis. Also, like cancer, there is probably no one single agent or disorder that would increase the likelihood of being diagnosed with an ASD disorder.

The Factician said...

NAS has never done a control study of un-vaccinated individuals because that would be unethical.

Not true. The National Academies study that I link to above is a compilation of many experimental studies (they don't do experiments as a part of this study, they review everyone else's). They contain numerous epidemiological experiments that contain vaccinated and unvaccinated populations.

Also epidemical studies neither proves, nor disproves causation.

Strictly speaking, epidemiological studies can neither prove nor disprove that umbrellas cause autism. Nonetheless, the failure to find any link is extremely compelling. There has been a complete failure to link thimerosal to autism. Ergo, thimerosal almost certainly doesn't cause autism (the umbrella link hasn't been as well studied, so I'm not willing to make such strong statements about umbrellas).


Since there is no defined pathology in the DSM criteria, there are no defined areas that must be affected for an ASD diagnosis.

Beg pardon? I don't understand what you are trying to say here.

Also, like cancer, there is probably no one single agent or disorder that would increase the likelihood of being diagnosed with an ASD disorder.

If you mean there will likely be multiple causes found for autism, you are correct. If you mean that "we'll never really know, and we should keep thinking it's thimerosal" you are incorrect. Thimerosal has been extensively studied, and it almost certainly doesn't cause autism. If there is no link, why should we posit one?

Recently, a group has found that at least 10% of autism cases can be found to be caused by a de novo mutation. Read more here:

http://conspiracyfactory.blogspot.com/2007/05/on-cause-of-autism.html

Anonymous said...

De novo mutations does not cause any ASD, they may increase the probability of being diagnosed with an ASD. All de novo mutations do not contribute to ASD disorders.

Smoking cigarettes does not cause lung cancer but it does increase the probability of it. People are genetically susceptible to becoming alcoholic (my doctor quotes an 80% likelihood if both parents are alcoholic), yet people may limit their environmental exposure to alcohol and not become alcoholic.

You cannot prove causality to a subjectively defined psychological disorder with no objectively defined areas that must be affected. Applying scientific rigorous studies to a subjectively defined psychological disorder is foolish at best.

The Factician said...

De novo mutations does not cause any ASD, they may increase the probability of being diagnosed with an ASD. All de novo mutations do not contribute to ASD disorders.

You are incorrect. I suggest you read the Nature paper that I link to in my response to you above. It tells quite a different story from what you are representing.

You cannot prove causality to a subjectively defined psychological disorder with no objectively defined areas that must be affected. Applying scientific rigorous studies to a subjectively defined psychological disorder is foolish at best.

I think of this as the "this problem is to hard to study" gambit. Not true.

Epidemiologists (nay all scientists) who study autism have rigorous standards that they apply to defining autistic patients. Granted, they may miss patients outside of their standards, but they define the objective standards in their own publications. If you're interested in studying people that fall outside of traditional standards, by all means, do, just be certain to define them in your own publications.

Anonymous said...

What the study you site does is provide is a potential genetic cause to symptoms in 10-30% of the studied population. 10-30% does not prove causation for all ASD disorders, only a fraction as the paper explains. This genetic mutation would not explain regressive autism in which children loose communications and socialization skills in early development after birth. Even if this study does prove these mutations lead to ASD disorders, then is there an increase in de novo mutations and what might be causing them? Are we now back to a refrigerator mom or dad theory?

Epidemiologists (nay all scientists) who study autism have rigorous standards that they apply to defining autistic patients.

These rigorous standards are subjective in nature, just as diagnosing the criteria in the DSM-IV is subjective in nature. The actual diagnosis criterion in the DSM-IV has no objective measurements in it whatsoever. So how are they objectively diagnosing ASD because that approach should be applied globally?


This isn’t "this problem is too hard to study" gambit, it is a "this problem is not physiologically defined yet" gambit, which is true.

The Factician said...

10-30% does not prove causation for all ASD disorders, only a fraction as the paper explains.

You're absolutely right. But it does explain that fraction quite well.

Even if this study does prove these mutations lead to ASD disorders, then is there an increase in de novo mutations and what might be causing them?

There's two parts to your question, both of which I find interesting. The first is, "Is there an increase in autism frequency?". As you alluded to, depending on diagnostic criteria, you may find more or less autistic patients. So is the increase in autism frequency we've seen over time due to an actual increase in frequency of autism? Or due to an increase in our ability to diagnose it? I think this is a very difficult question to answer, but most autism experts think that it is merely an increase in diagnosis. Clearly a well-defined diagnostic protocol should be used over a long period on a large population to see if the frequency really is increasing.

The second part of your question: What is the cause of these de novo mutations? Also an interesting question, though the truth is, there might not be a preventable cause. Mutations occur at a certain frequency depending on the target and the context of that target. It may be this is just what that frequency is of this particular target.

These rigorous standards are subjective in nature.

You seem to be using subjective in the sense that there isn't a blood test. Is that your usage? I use the term objective to mean that anyone can use the same diagnostic criteria and come up with the same (or very similar) results. By this definition, the standards used in most papers are objective.

Anonymous said...

“So is the increase in autism frequency we've seen over time due to an actual increase in frequency of autism? Or due to an increase in our ability to diagnose it?”

You missed another possibility. Is it possible to change our diagnosis criteria and thereby change the diagnosis frequency? The answer to that has already been proven to be, “YES”. I also predict that the diagnosis criteria in the next edition of the DSM will be different, further confusing the current situation.

“I use the term objective to mean that anyone can use the same diagnostic criteria and come up with the same (or very similar) results. “

The problem is that any two different entities using the DSM-IVTR diagnostic criteria will not come up with the same (or very similar) results. Within a narrowly defined study with a team consensus diagnosis you can be objective. Observations between separate studies or studies using one individual diagnosing, or studies relying on pre-diagnosed ASD individuals are not objective.