Promising Discoveries and Tweaked Results

This post will come in two parts. Mostly because I really would like to focus on the good in Sequenom's promising new discoveries in prenatal testing, but it's also important to see what happens when the self-interest of researchers, whether it be a few individuals or (god forbid) a company conspiracy, throws a wrench in the mix.

New Discoveries in Prenatal Testing
Aneuploidy in a developing fetus causes a wide variety of genetic disorders including the more common and well known trisomy 21, or down syndrome. Current testing for chromosomal disorders are limited to amniocentesis and chorionic villus sampling which are both invasive techniques requiring a puncture and removal of placental tissue or fluid. Data on the risks of these procedures seems random and inconclusive with associated miscarriage rate at anywhere between 1 in 200 and 1 in 1600. The non-specificity of this data is fairly surprising. You'd think that there would have been more conclusive studies if for no other reason than to calm the fears of mothers who are most likely already extremely concerned anyways--I'm pretty sure that allowing doctors to probe one's placenta to determine any genetic defects of the fetus constitutes a concerned mother. New methods as described by Dhallan et al are non-invasive and have been shown to be more accurate than current methods, which post a true positive detection rate of 64-94% and false positive rate of 5%. The idea behind the procedure is the analysis of free fetal DNA or RNA within maternal plasma. Sure, the idea is simple enough and appears to be a promising method, but up to this point, isolation of fetal genetic material from from the mother has proven to be fairly difficult. Considering the obvious similarities from mother to offspring, how does one go about this isolation? The answer: You don't! Analysis of the human genome has shown a trend in certain alleles to have single-nucleotide polymorphisms (SNP's) between individuals. By locating a few homozygous single-nucleotide polymorphisms between maternal and paternal DNA, a signal for fetal DNA has been generated, which will be heterozygous for the polymorphic alleles. One can quantify fetal DNA levels by merely looking at the proportion of DNA containing the parental polymorphism to maternal homozygous DNA. What's so convenient about this method is that a specific locus doesn't have to be targeted. SNP's just need to be located on the chromosome where we are trying to detect the aneuploidy. For example, a trisomy 21 indicator would be abnormally high ratios of the unique fetal allele signal to the combined mother and fetal allele signal quantified by SNP's on chromosome 21. The 60 person study conducted posted improved results from the traditional karyotyping methods with a true positive detection of 66.7% and false positives at only 1.8%. This initial study by Dhallan et al seems airtight. It's not perfect, but it is certainly an improvement from current methods and doesn't carry any of the associated risks to the fetus. This is where self-interest unfortunately starts to tear things apart. Sequenom is currently developing a modified version of the test called SEQureDX, which uses fetal RNA instead of DNA. Their company profile looks, or should I say looked, solid, and they have a few promising genetic tests in the pipeline. But when big money gets involved, funny things start happening...

Human Nature Delays Medical Advances
With investor sentiment high and stock prices sailing, it seems one or a few unscrupulous members of the R&D team decided to get a little creative with their results. I hope they at least got some kicks from tweaking their numbers, because whoever it was is likely out of work now. Management doesn't take kindly to employees who bring about class action lawsuits to the company. Oh and lest we forget Sequenom (SQNM) stock dropped $11 to under $4 a share literally overnight. I don't know whether to feel bad for or laugh at the authors of recent articles urging us to hop on the Sequenom bandwagon. Sure would have been one hell of a short though...

Sure, screwing your investors is bad enough, but the content of the issue raises moral questions outside the realm of the marketplace. By falsifying this type of data, researchers at sequenom have delayed the release of a service to the public that could vastly change prenatal testing procedures for the better. I'm not quite sure of the specific details of the data modified. I wasn't able to find the actual publication, most likely because they pulled it from print. Manipulation of data in any kind is not only unethical, it's unacceptable. This makes me question the integrity of an entire industry. Why can't we use our best judgement in these situations? Why do we work directly against the greater good? Money. Notoriety. Self-interest. Sequenom was on their way to releasing a successful test which would have certainly increased revenues and provided mothers access to a new, revolutionary, and safe test for their unborn child. Where does that leave us now? Mothers must continue to face the risks associated with current testing as Sequenom starts from square one, sifting through data from all of their current projects in an attempt to regain the trust of the public. At least in my eye, this casts a dark shadow over what I would like to believe is an industry working to improve our lives.