Mike the Mad Biologist

A couple of weeks ago, I found a post, “Is HIV ‘fingerprinting’ junk courtroom science?“, which argues:

But calling the comparison of HIV strains’ genes “fingerprinting” — calling to mind the more-familiar matching of human suspects’ DNA to blood at a crime scene — is dangerously misleading, they warn.

“By calling such investigations HIV fingerprinting, scientists raise unrealistic expectations” about the method’s accuracy among juries and judges, the write. “Unlike for (human) DNA fingerprinting, where a likelihood can be calculated for a full match between the evidential DNA and the suspect’s DNA, there is never a full match between the RNA or the DNA of HIV in two samples, even within an individual.”

That is partly because HIV strains are constantly evolving, they note.

“Proper identification of the transmission source would require two major assumptions: that a phylogenetic tree can flawlessly reconstruct a true epidemic history and that strains from all patients ever infected with HIV are available as controls,” the authors write. “Both assumptions are unrealistic.”

Worse, since the full range of local genetic variation and the relatedness of local HIV strains are unknown, the probability that one individual’s HIV infection came from another specific individual simply cannot be quantified, the authors note.

“Because the full transmission tree is unknown, no likelihood can be attached to the a priori hypothesis of direct transmission,” they write.

I think there’s a far more serious problem, and it has to do with the rapid rate of evolution of the HIV virus (the virus that causes AIDS).

HIV evolves so quickly that most patients don’t have one virus, they have multiple, genetically distinct viruses. In other words, each patient has a population of HIV viruses that changes rapidly through time. So what is actually being reported is what we call the consensus sequence. To use a toy example, imagine that, using the omniscient powers of the Mad Biologist, we know that a patient has viruses with the following sequences–the number of sequences indicates their relative proportions in the population (these aren’t real sequences):

ACTGG
ACTGG
ACTGG
TCTGT

Due to how most HIV sequencing is done, we would report the consensus sequence as ACTGG. Now, suppose that patient infected another patient, but due to random factors, different population dynamics, or that TCTGT transmits to other patients better, that new patient has the following HIV sequences (again, known through my awesome superpowers):

ACTGG
TCTGT
TCTGT
TCTGT

The consensus is TCTGT, and looks completely different. But it gets worse. Sometimes, the consensus doesn’t even exist in the patient. How is that even possible? Imagine the following sequences:

TCTGT
TCTGA
ACTGC
GCTGC
CCTGG

Here, the consensus is TCTGC, and that sequence does not exist in the population. To eliminate that problem, we can use what’s known as 50% majority consensus, where we call those bases for which only 50% of the sequences yield the same base (i.e., here we would report NCTGN), but we lose a lot of information (since CTG is invariant, that doesn’t help us).

People are developing ways to sequence the population of HIV viruses, but that creates a whole new set of difficulties: populations of HIV can change rapidly, and, if there’s a response to the new patient’s immune system, that too can alter frequencies of individual HIV viruses. I don’t even know how you definitively in a legal context identify a source with that going on.

Having said that, HIV fingerprinting can work as an epidemiological tool, provided the samples are collected shortly after infection. But, outside of that situation, I think a good defense attorney could honestly raise issues that lead to reasonable doubt.

Comments

  1. #1 Paul Orwin
    February 21, 2011

    Couldn’t you use the diversity of the HIV in an individual to determine how long ago they were infected? I’m thinking of an “infection molecular clock”. I would presume that there are some parts of the viral sequence that mutate and diversify relatively freely (aren’t constrained by the infection process). This seems like a better way to do HIV forensics – of course, the converse (??) might also be true, a highly constrained site could be a good marker of strains that would allow tracking through populations…agree, of course, that consensus sequence is not the right approach with something like this. Always bad when you mix lawyers and science!

  2. #2 HappyEvilSlosh
    February 21, 2011

    Your description of consensus is generally not what I’ve seen done in determining if someone has infected someone else with HIV (although admittedly what I’ve seen may not be representative). Rather many HIV cells will be sampled and sequenced and the phylogenetic tree for these will be constructed, probably using something like splitstree so that errors possibly arising from lateral gene transfers can be spotted. Then it is a matter of observing whether the subtree consisting of the infectees HIV strains is a pendant subtree of the subtree of the hypothetical infectors HIV strains. This seems not unreasonable to me?

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    February 21, 2011

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  4. #4 Mark Panzarino
    February 22, 2011

    This is a well written article, and makes some very astute points. But could you not call it the “HIV virus”, please? It’s simply, “HIV”.

  5. #5 stdsingle
    February 22, 2011

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  6. #6 chloe
    February 25, 2011

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