September 27, 2011 | 1
As the Head of Scientific Affairs for a young biotechnology company, I’m not the type to sign petitions or take up bleeding heart causes. But, that changed when I learned about the campaign: Scientists Against Sample Abuse.
I trained as molecular geneticist and spent many years at the laboratory bench before moving into management, so I have witnessed firsthand the multiple forms of sample abuse that can occur. I’ve seen beautiful young cells in tiny little vials left to languish in buckets of melting ice pools for hours at a time under the guise of proper incubation. I’ve seen freezer racks endure repeated temperature fluctuations as one graduate student after another opens and closes a freezer door with no single person responsible for the unrecognized damage to the samples within.
Indeed, I have probably been guilty of sample abuse myself, without even realizing it. That’s the insidious nature of the problem. We are trained as scientists to be rigorous in controlling so many variables of our experiments, to take extra care as we operate highly sensitive instruments and assays. We measure out microliter volumes and picogram weights with decimal point precision. We learn to perform blinded experiments to avoid investigator-driven biases, we learn to randomize.
But, we are human and so we do not always see the simple, yet critical experimental variables that we fail to treat with the same insight into the need for rigor. Think about cells in a standard laboratory 96-well plate, placed in a water bath. Are we treating them all equally? Are the cells in the middle exposed to the warmth as the ones on the end? And if the answer is no (which it clearly is), what are those differing temperature gradients doing to the proteins or genes we are interested in? Do we just have to live with this source of variability in our experiments? Scientists Against Sample Abuse says we can do something, if we work together.
So, full disclosure. Scientists Against Sample Abuse is, in fact, an awareness campaign that my company is sponsoring. We hope scientists will find humor in it (and of course we hope they will want to learn more about the products we have developed to ensure reliable sample handling). But, we also hope that biomedical researchers and clinicians will take a step back from their experimental protocols and re-think the sources of variability in their experiments.
The “post-genomic” era that we are living is full of promise that depends critically on the precision with which we handle biological samples. I will focus here on two areas: personalized medicine and regenerative medicine.
Implications for Personalized Medicine
Personalized medicine or molecular medicine is the idea that a disease that we call be a single name – e.g. breast cancer – is actually many different diseases on a molecular level. In order to optimally treat the disease, therefore, we need to know which molecular mutations are giving rise to an individual cancer. In the case of breast cancer, research has advanced to the stage where we have matched treatments to molecular markers in certain cases, e.g. Herceptin for the treatment of breast cancers that are overexpress a mutated form of the growth factor receptor HER2. But here’s the thing – HER2 is a thermolabile protein. So depending on how carefully you control the temperatures at which you handle the breast cancer biopsy sample before you measure HER2, you could fail to identify this critical molecular diagnostic.
Now, take a step back and think about the research that goes into identifying molecular markers associated with cancers in the first place. Biobanking is a key component to that research. Researchers with a particular hypothesis or a screen for disease targets rely on biological samples that have been extracted from patients and stored in repositories. But, are all samples handled equally from clinical site to clinical site, from biobank to biobank? The NIH has recognized the critical impact of this question on molecular medicine research by forming the Office of Biorepositories and Biospecimen Research (OBBR). OBBR’s director called the lack of high quality biospecimens the “number one roadblock in the progression of cancer medicine and research.”
Implications for Regenerative Medicine
Turning to regenerative medicine, we are still in the early stages of research and clinical development on the use of human pluripotent stem cells to treat disease. (Pluripotency refers to the ability of these cells to develop into the multiple types of cells that form our bodies). The first trials using human embryonic stem cells to treat disease got underway only in 2010. One of the big stumbling blocks for research and clinical development in this important field of biomedical research is the difficulty in storing and propagating these cells. Our “standard” protocols for freezing and thawing other cell types – even mouse pluripotent stem cells – don’t seem to fare as well for human samples. One study, for example, has found that standard slow freezing of human embryonic stem cells (hESCs) in the cryoprotectant DMSO resulted in almost complete loss of a critical protein marker for pluripotency – Oct4 – after thawing.
As a scientist, wouldn’t I rather think about what that critical protein marker – Oct4 – is doing in pluripotent cells and devise sexy experiments to figure that out? Of course. But without first working out the “boring” aspects of how exactly to freeze down those cells to begin with, there’s not much point in looking further.
Which is why Scientists Against Sample Abuse is so important. As individuals, we can feel overwhelmed by the problems of sample handling, but as a community, we can solve them.