Perhaps this is a statement on my skills as a molecular biologist, but I always found bench science to be incredibly humbling. When I think back on what I was expecting to accomplish in any given experiment, it boggles my mind that anything ever worked.
I used to joke back in the day, when I also published the science humor magazine Aliquotes, that academic science was the only job you could ever have where a 95-percent failure rate was considered a good day.
But we persevered. We plunged forward in the eternal optimism that things would make a little more sense tomorrow than they did today. And another increment of sense the day after that.
As I was preparing for this month’s Special Report on Stem Cells, however, I realized just how humbling the science continues to be even when you’ve discovered something interesting and practical.
(Note: I got out with an M.Sc. that was neither interesting nor practical.)
I had the opportunity to speak with the team at Toronto’s Centre for the Commercialization of Regenerative Medicine (CCRM), whose goals include enabling breakthrough science to come to market and fostering Canada’s burgeoning regenerative medicine, cell therapy and gene therapy efforts.
Thus, they spend a lot of time meeting with and advising academic researchers who’ve found something interesting and want to explore that next step.
This is going to be amazing.
“Some of the groups we work with have spent a lot of time and energy developing really keen insights into the early stages of their work,” says Jana Machan, CCRM vice president of commercialization.
As CCRM engages with these researchers to provide the services needed to scale-up and -out their projects to make them commercially viable, she presses, there is a bridge that is inevitably crossed where the science that got the researchers this far needs to be re-evaluated.
“It’s not denigrating the work that was done and so much time invested,” she explains, “but there is such a different lens that they have to go through as you start thinking about what will matter if you do want to reach the clinic, if you do want to go commercial.”
“They often feel that they’ve invested a lot of time and energy and it works well in their lab,” Machen repeats, so why the need to retool?
But everything was working so beautifully.
It doesn’t mean they have to start from square-one, she explains, but it can sometimes feel like that.
At times, I find myself thinking we should be better at this, have a greater understanding of what it takes to move from bench miracle to clinical outcome.
There is so much focus on translating findings from animal cages to patient beds that it seems we forget the practical challenges, like translating cellular growth curves from culture flask to bioreactor, or the financial math of $600/L culture media during scale-up. And specs never get simpler.
But I had the details all worked out.
It can easily lead a poor researcher to question themselves and their findings, to question if they even know what success looks like. This may not be a completely bad thing.
Back in March, at the Cell & Gene Therapy Revolution forum, Triumvira Immunologics CTO Donna Rill suggested that academia is traditionally very loose on understanding the quality attributes of the products they are trying to move forward. She suggests that you always need to be asking yourself how well you understand those attributes—biological, biochemical, biophysical, mechanical, etc.—that led to your project’s success.
That can be a huge challenge for many projects, however, when in so few cases is there even a solid understanding of mechanism of action.
“The concept of potency is very complicated for cell therapy,” says Liz Csaszar, CCRM development manager. “You know they work, but they work in a very complicated way in conjunction with the body, and then you’re still trying to develop potency assays or release products on potency specs.”
And even if you had an inkling here, costs are another huge factor that immediately arise as you consider scale-up and manufacturing.
It forces a lot of simplification of processes, Csaszar says, and this may run counter to what researchers feel is appropriate.
But that changes everything.
“If it’s just not going to be cost-effective and you realize that early on, then you know changes will have to be made,” she says.
Rill acknowledges these challenges and suggests that this is perhaps the biggest area in which the education system has failed the field. There is a need, she says, to educate the next generation of specialists to think in these terms.
Why didn’t anyone tell me this stuff?
That’s where organizations like CCRM, Toronto’s Medicine by Design and Montreal’s Center for Commercialization of Cancer Immunotherapy (C3i) hit their stride.
“Here are the regulatory implications, here are the skill implications,” Machen says, describing a typical conversation. “You may want to think about maybe putting more in this direction.”
“That kind of commercialization-translation advice,” she reflects, “is a service that we have started to provide to the academic community, and appears to be greatly valued.”
So yeah, maybe we all need to be taken down a peg in our presumption of acumen and skill, but it’s good to know that the same people who humble us also offer help in achieving even greater things.
Randall C Willis can be reached at firstname.lastname@example.org