Perfect Storm

I am currently trying to model antimalarial drug behavior in order to understand the spread of drug resistant malaria. Generally speaking, malaria strains are more or less tolerant to a drug depending on the quantity of drug that is necessary to kill an infection. In theory, a totally resistant infection will survive any treatment, a totally susceptible one will only require small levels of drug to be cleaned.

I see the word drug used in two different ways (for the readers of this blog that are specialists, in some form, on issues regarding drugs, particularly pharmacokinetics, if you see any thing particularly wrong, please do inform me): For instance, SP (Fansidar) is a drug, composed of two drugs (Sulfadoxine and Pyrimethamine). I will use drug for SP and compound for S and P (as active compound seems to be used).

Antimalarial drugs work mainly in the blood stream against asexual parasite forms.

In the blood, compounds have a certain concentration. With time, the body gets rid of compounds (thus the concentration of a compound goes down with time). The concentration of compounds is normally (but not always) modeled using an exponential decay function, being the fundamental parameter the half-life, i.e, the time that it takes for the concentration of a compound to drop to half.

Two other important concepts for drugs that are not taken intravenously (like cheap antimalarials which are oral), are

1. Bioavailability, i.e. the fraction of the compound that actually reaches the circulation. It seems that one of the problems with counterfeit drugs is low bioavailability. Bioavailability is normally discussed in terms of AUC (Area Under the Curve. Being the curve related to the plot of drug concentration against time). I will model it in terms of maximum concentration, half-life and the time it takes to reach maximum concentration in the blood, which by the way is the next concept…
2. The time it takes to reach maximum concentration in the blood, i.e. the time from ingestion to circulation in the blood at maximum concentration. I suppose this time frame has a technical name, but I don’t know it (if you know, drop me an email our comment, please).

Now, back to computational modeling:

A big objective is declarative programming. Preferably a program that can be read by domain specialists (biologists, MDs, biostatisticians, …), with that in mind…

Currently, a computer program in Scala to model drugs look like this.

Compound create "Sulfadoxine"
Compound abbreviation "S"
Compound half_life 116 //hours
Compound bio_availability 408 //1mg to nanoM
val Sulfadoxine = Compound prepare
 
Compound create "Pyrimethamine"
Compound abbreviation "P"
Compound half_life 83 //hours
Compound bio_availability 34 //1mg to nanoM
val Pyrimethamine = Compound prepare
 
Drug create "SP"
Drug includes Sulfadoxine quantity 500
Drug includes Pyrimethamine quantity 25
val SP = Drug prepare

Discussion:

• I am using the “object companion” pattern a lot. The idea is that all “stateful” mess is stored “prepared” in the object (which is the DSL source). When the prepare method is invoked in the object a class (with only immutable vals, very lovely for those of you who are functional programming enthusiasts) is created.
• Notice the dependence on operator precedence on Drug includes quantity (there is not really one, strictly speaking, but assume there is). I would really like to have, per class the ability to define operator precedence, other than not based on dictionary order (à la Prolog).
• I don’t like the val SP = Drug prepare. It is too verbose and too geeky. I would prefer just Drug prepare. I believe that this is possible in Scala as at least at the interpreter level (as the Scala interpreter does it), but I still don’t know how. The idea would be that a val named SP would be added to the local scope in some way. For those computer inclined readers that think that I am being too pedantic and nit-picking, I just have one thing too say: I am really trying to make the system the most pleasant possible to non programmer types, and I think my proposal does not sacrifice elegance and generality (although I would recognize the non-explicit name creation is “strange” - but, hey, the Scala interpreter already does it!)

Caveat emptor, big one: Although drugs (compounds) are discussed in terms of half-lives, bioavailability, etc… these properties are actually not of the drug but of the interaction between the drug and the individual. Making them drug properties only is a “cognitive abuse”, although it has its uses. For instance, my advisor, after looking at the language, was talking about bioavailability for counterfeit drugs, for children between 2 and 5 years. A great example that they are not properties only of the drugs but also, at least, of individuals (and not only that, for instance many drugs are more bioavailable if there are taken in conjunction with, say, fatty foods).

A proper, precise, computational modeling of drugs would be a gigantic undertaking. I have a different approach: Modeling as close as possible to the average domain discourse and hook, in some way, the necessary precision, should the need arise. It is worth noting that “incorrect”, “imprecise” modeling is enough for many tasks.

2 Comments to "Modeling drugs in Scala"

• Robin Message said: On 11/01/2007 at 2:34 pm

  >I don’t like the val SP = Drug prepare. It is too verbose and too geeky. I would prefer just
  > Drug prepare. I believe that this is possible in Scala as at least at the interpreter level

  Sadly the interpreter is not the same as the compiler so you can’t add to the local scope. What you could do is a have a hash table of drugs and compounds. Then Drug prepare and Compound prepare would add those things to the hash table, under the names you have already given them. All code would then simply need to refer to the hash table instead of local variables. Only problem I can see is you’d have to quote compound names in the drug, would that be an acceptable compromise?

• tiago said: On 11/01/2007 at 2:42 pm

  The problem with quoting names would be that I would loose strong typing (i.e. I would be passing Strings around, not Drugs or Compounds).

  But, one possibility that I am contemplating, and that you refer, is working on an interpreter level: For the simplified syntax the interpreter would be needed. If one would want to compile then the full verbose syntax would be used. But I would suppose that anyone compiling code would be more than capable of understanding “val X =…”.

  Thanks for your comment!

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