Life Science Development as an Unending Comedy of Delays

September 7th, 2018 Permalink

Few things are as satisfying to behold as a neatly formatted Gannt chart for a life science study; all of the interlocking pieces of modern biotechnology as it is practiced; the ordering of reagents and mice, preparation of cells, management of equipment, scheduling of researchers, and so forth. It is usually the case that a considerable amount of reading, discussion, and negotiation goes into the preparation of a study and its accompanying schedule. There is the feeling of having accomplished something to get to the end of that planning and have the proposal represented in Gannt form. Which is fair enough - planning can be hard work. Just don't for a moment imagine that in reality things will happen as neatly as is described in the proposal on the screen.

Firstly there is the ordering, whether reagents, cells, mice, or equipment. A surprisingly large fraction of orders cross international borders. Anything involving DNA, such as viral plasmids, has some chance of being held up at those borders, for no apparent reason, for days or a week or more. There is nothing much to be done but wait. This can happen to equipment as well, and that is even before the question of whether the vendor schedule slips on their side. It is a bad idea to place oneself in a situation in which materials absolutely must arrive by a given date, in order to prevent other work and materials from being discarded and redone. Set up the potential for that problem to occur, and it will happen.

For example, many mouse models require significant setup time, from HIV models to atherosclerosis models, and following that setup their useful study lifespan is limited, sometimes dramatically so. There is always the obvious incentive to run manufacture and ordering in parallel to the mouse setup - but then one risks the materials arriving late enough to compromise all of the expense invested in the mice.

Next, cells are unpredictable beasts. It can take weeks to vet a simple, how-could-they-get-this-wrong cell line from a new vendor when it fails to show the expected surface markers during quality control. Is the literature misleading? Does the vendor have quality control tests that sound good at first glance, but are actually inadequate for this particular cell type? Is the problem in one's own assessment and equipment? Testing one's way around an issue with cells failing to behave as expected is a laborious affair, and can swallow days.

Lastly, the combination of machinery and consumables, while allegedly reliable, can turn out in practice to be just as ornery as cells. Does the preparation of plasmid DNA fail in strange ways, with some quality assurance passing and other tests failing? Is it the DNA, the test, the preparation process, the machinery to run the process, the consumable kits, or user error? It will usually take at least a few days to answer that question for the strange behavior of even simple, regularly performed processes. It might be easier just to switch vendor to use another kit, or try again rather than diagnose. All of which still consumes time. What happens when complicated processes that take a week fail in this sort of manner? One is lucky to lose only a week.

The bottom line to all of this is that delays of this nature will occur in every project. It is inherent to work in the life sciences. Absolute reliability is a mirage, studies are complex undertakings, and delays will take place far more often than anyone would want or expect. When time is critical, as is usually the case when wages and rent are being paid, it can make a lot of sense to structure a study to have fallback options and parallel paths - to be more robust to failures and delays. Culture one's own cell line from mice as well as ordering cells from a vendor; buy viral plasmids from two vendors; and so forth. It winds up being a good insurance policy, and almost always costs much less than the delay caused by the failure or unexpected postponement of a critical component.