Scientists are accustomed to the fickle nature of research, but sometimes it can get to even the most seasoned researcher. One especially poignant example – the Cancer Genome Atlas – starts with the completion of the Human Genome Project in 2003, an amazing achievement that many thought would not be possible, certainly not in their lifetimes. In record time the hard work was over and the rewards were just around the corner! Cancer researchers in particular were eager to put the knowledge gained in the Human Genome Project to good use in the development of novel cancer treatments. Riding the wave of optimism prompted by this achievement, in 2005 the National Institutes of Health (NIH) announced the launch of the Cancer Genome Atlas pilot project.
Their plan was to collect and analyze 1,500 tumor samples obtained from designated biorepositories. What followed next was the stuff of nightmares. “About a third of the way into the study, they told all their investigators to stop sending in their samples, because in a majority of them, they couldn’t recover enough of the DNA to actually do the sequencing,” explained Stephen Schwartz, CEO, Brooks Automation, a global provider of automated sample storage solutions. The Cancer Genome Atlas pilot project had halted, not because of a problem with the science or technology, but because of poor collection and storage of the promised source material.
Standardize, standardize, standardize
After the Cancer Genome Atlas debacle, “Biorepositories focused on developing stringent protocols for sample collection, transport, and storage,” said Schwartz. When operating properly, most follow complex operating procedures and rigorous quality assurance, ethical and legal standards. According to Schwartz, “Standardization and consistency is an industry driver. And the reason for that is it’s critical to the end results.”
Although much has been achieved by the burgeoning industry, there is still much to do. As recently as May 2014, Fay Betsou, president, International Society for Biological and Environmental Repositories (ISBER) commented in the ISBER News, May 2014, that “…biobanks have been accumulating and continue to accumulate millions of unused – and in many cases unusable – samples.”
Rolf Ehrhardt, president/CEO of BioCision, a provider of biomaterial handling products, agrees: “There’s a big need for making preanalytical sample handling more reproducible and more standardized. If you don’t standardize sample handling, you end up comparing apples and oranges.”
Cells in biospecimens are exquisitely sensitive to changes in their environment (eg, temperature). As soon as a biospecimen is collected - and even prior to its removal - the cells can start to take on new characteristics if their environment changes, which can lead to inaccurate determinations of molecular and physical characteristics during subsequent analysis.
Total cold chain management
A key environmental driver of biospecimen quality is temperature, which becomes a factor in biospecimen quality early in its lifecycle. The temperature of the room in which the sample is collected, the method and rate of freezing, and the temperature during storage, transport, analysis, and re-stocking (return of unused samples to storage) can alter a biospecimen’s characteristics.
Take the process of thawing the biospecimen for analysis. “What happens when you thaw cells for research or cell therapy?” asked Ehrhardt. “There are a lot of different methods out there, from thawing cryopreserved cells in a water bath at different temperatures, under your arms, in your hands or letting them sit on the bench. Some people we heard even use hot water, let the sample thaw under running hot water. In other instances, we heard that researchers use microwaves. It’s a little bit the wild West out there. It really is asking for standardization.”
Schwartz added, “There’s now the clear recognition that total control of cold chain management is as important as any individual step within the workflow. And if there’s a break anywhere within it, it can compromise whatever you’re analyzing. Total cold chain management is really a focus of the industry right now, and it’s in its very nascent stage.”
That said, let’s hope that the biorepository industry continues to mature. “It’s important that we start working like other parts of the industry with standardized operating procedures,” concluded Ehrhardt.