September 30, 2020

The Niche

Knoepfler lab stem cell blog

From Point A to Point Z: thinking outside the box about stem cells

What is the best way to get new stem cell-based therapies to the millions of patients who need help?

I would argue that this is the key question in the field of stem cell biology and regenerative medicine.

Sometimes I think it is easy for folks to lose sight of that and fall into traps.

*One trap is linear thinking. In a recent post I used a car analogy to compare different types of stem cells and asked a question about getting from ‘point A to point B’. What I meant behind ‘point A and point B’ was getting us from where we are now to a future point where we have FDA approved stem cell therapies that can help patients.

As I have thought more about that analogy, I think a better way to phrase it would have been ‘from point A to point Z’.

Getting stem cell therapies to patients is no one step process. It is not a linear path from point A to point B. There are many steps in between, both scientific and also regulatory. There are also landmines, trapdoors, and even political opponents to deal with along the way. The apparently fastest road is not always the best and certainly not the safest.

Point A in all regenerative medicine must be an idea, a hypothesis. I would argue it all starts with basic science. For example, without understanding embryology there would be no mouse or human embryonic stem cells. Without embryonic stem cells there would be no iPS cells. Without ideas and basic research, there would be no adult stem cell therapies under study. Even for developing or enhancing technologies, it all starts with ideas.

William Caldwell, CEO of Advanced Cell Technology (ACT) was quoted in the Nature Blog Great Beyond as saying that CIRM really should have devoted all its funding to 3-5 ‘low-hanging fruit’, meaning those with the most apparent clinical promise. Presumably, he would have not funded basic research and he would have put ACT’s research in that elite group of 3-5, but can anyone be sure what the handful of best candidates really are? Going with tunnel vision at the apparent low-hanging fruit is linear thinking. Sometimes the best ‘fruit’ are in fact a bit higher up on the tree or maybe they aren’t even on trees, but are underground like truffles.

ACT is doing wonderful work and I am hopeful they may have the stem cell-based tools for treating different types of blindness on their hands, but I do not see how having their CEO publicly chastise CIRM with linear oversimplifications achieves any purpose. Mr Caldwell, your own company would literally not exist without the stellar basic research of Robert Lanza.

*A second trap is ‘groupthink’. As human beings we are prone to being influenced in our thinking by the thinking of the group around us. No one is immune to this during the course of his or her lives and it affects scientists as well. Shinya Yamanka broke apart one very long period of groupthink that had assumed that cellular differentiation was a one-way street. We are probably in the midst of other types of groupthink and we do not even know it. To break these traps we need creative basic research of the kind that Dr. Yamanaka conducted that changed the world of biomedical science.

*A third trap is binary thinking. Paradoxically, groupthink can also turn people with similar goals into adversaries. One group over here thinks one way and by definition thinks differently than another group over there. For example, some adult stem cell proponents appear to think that they must by definition also be opponents of embryonic stem cell research. To victims of binary thinking, the world is all or nothing, black and white. There is no gray area. There is no uncertainty. When of course science is all about questions and about not knowing. Science is inherently gray.

I read an interview in the WSJ with James Sherley, the scientist behind the lawsuit against federal funding of ES cell research. According to Sherley, the statement ‘life begins at conception’ is a fact and anything else is a lie. That’s a good example of binary thinking. The reality is that the issue of when life begins is a matter of opinion, not fact. Different peoples around the world have dramatically different views on when life begins. Probably a lot of people agree with Sherley’s notion in this regard, but billions have other ideas and the majority of Americans would appear to disagree with him.

What to do?

I think the best way to get from point A to point Z, to get stem cell-based therapies to the millions of patients who need them is to fund a variety of types of research of different levels of risk and creativity as well as all different kinds of stem cells, just as CIRM has done.