September 26, 2020

The Niche

Knoepfler lab stem cell blog

Perspectives on uncritical NYT coverage of cardiac mitochondrial transplant trial

One of the reasons I’m a scientist is that I find biology fascinating and admittedly novel biomedical science can really catch my eye, but more recently as a somewhat grizzled researcher, I’ve become increasingly skeptical about some “sexy” research and media coverage of it.

mitochondrial transplant for heart

A small red flag went up for me as I was reading a new piece on mitochondrial transplants by Gina Kolata of the New York Times (NYT) yesterday. The article is focused on some researchers experimenting with investigational autologous mitochondrial transplants for patients, including babies or young children, with cardiac damage. Right from the get-go, the NYT article title raised great expectations with a definitive statement, “Dying Organs Restored to Life in Novel Experiments.” 

Restored to life?

In my train of thought there was a kind of “uh-oh” moment both from reading that title and then some more as I got deeper into the piece.

The title initially reminded me of some of the hype over certain as yet unproven stem cell approaches for various conditions including heart disease. You can see more on the big picture of stem cells for heart disease here. There may be promise of stem cells for heart diseases, but that subfield has been a rollercoaster of ups and downs.

What else specifically gave me concerns about the NYT article and the mitochondrial transplant technology?

First, some things about the technology struck me as ranging from puzzling to improbable. For instance, it is suggested that the donor mitochondria taken from healthy skeletal muscle elsewhere in the same patient, are simply infused into heart tissue or into coronary arteries to make the heart healthier. As a biologist I’m thinking to myself, “If these folks are right, how do the new mitochondria get inside the damaged cells?”

I’m not an expert in mitochondria, but I never heard of cells simply drinking up extracellular mitochondria, and even if they did, could they do it efficiently enough to make a real difference? Also, can mitochondria really “survive” (i.e. stay functionally intact) outside of cells for more than a few moments? What about when suddenly injected into the blood? I can’t imagine.

And from a single mitochondrial infusion into flowing coronary blood the researchers get new mitochondria inside enough heart cells to make a meaningful functional difference for the whole heart? And heart function then overall improves noticeably within 10 minutes in some cases? It seems improbable at best, but maybe I’m wrong. I further wondered if in the damaged heart cells once they got new mitochondria (again, assuming that happens) wouldn’t the damaged cells possibly be a toxic new home for the new mitochondria?

A search on PubMed didn’t find a whole lot that convinced me, but I confess I only skimmed through a few articles. Notably, I did see one review article proposing both intra- and extracellular mechanisms for purported benefits from mitochondrial transplants so maybe the mitochondria don’t have to always get inside target cells to help them? Hmm…

(Note that this mitochondrial transplant technology is entirely different from the 3-person IVF/”mitochondrial DNA transfer” in experimental human reproduction that is hoped to help parents-to-be with mitochondrial disease in the family have healthy children, but has been controversial.)

Second, this research is very preliminary. The data are basically anecdotal case report kind of stuff, which lack needed controls and statistical analysis. There’s nothing wrong with that per se and it is stated as such in the NYT piece, but this reality makes the reported positive human patient outcomes highly speculative and I wonder whether they will be reproducible. These issues and the points above together make me also wonder — how did this become a high-profile NYT science piece?

Finally, some aspects of the NYT piece itself are concerning and it feels unbalanced overall. Unless I missed it, the article has no unbiased quotes from outside experts such as cardiologists and/or mitochondrial experts uninvolved in the work. The piece also does not delve into the biomedical science very deeply to get at key issues such as assertively questioning how the mitochondria get inside the target heart cells nor did the lack of a plausible mechanism raise doubts in the NYT piece on the overall research. I think there should have been more healthy skepticism in the piece in general.

The tone of the piece is too generous and/or uncritical in my view too. Here’s an example of language in it that to me seemed over the top (emphasis mine):

“More recently, Dr. Emani and his colleagues have discovered that they can infuse mitochondria into a blood vessel feeding the heart, instead of directly into the damaged muscle. Somehow the organelles will gravitate almost magically to the injured cells that need them and take up residence”

Another “uh-oh” moment for me as the reader.

When I see science/medicine referred to in terms related to “magic” I automatically start asking even more questions. As to the claims in this particular quote, are there data to back this up, particularly in humans?

A PR piece by the hospital involved in this research makes some even bigger claims about these experiments as well and claims a life already saved. I don’t know enough about this to thoroughly address that claim, but it’s a big one to make about a small trial.

Because I’m not a cardiologist, I reached out to well-known cardiologist (and geneticist) Dr. Eric Topol of Scripps for comment on the science here and the NYT piece. He felt even more strongly than I did:

“I think it’s ridiculous; it makes no sense whatsoever. Unpublished, anecdotal, unreal. Outrageous that Kolata and NY Times published this piece.”

I emailed back and forth a bit with Kolata about her article, and she pointed out, “The article is part of our “the healing edge” series in surgery. Those articles are supposed to be about methods that are on the cutting edge, not necessarily proven but exciting and possibly transformative.” Maybe articles in that series should include a clearer heads-up kind of statement for readers about the context of the type of high-risk research covered and that it could often ultimately not be successful?

It can be a challenge to find the right balance between reporting on cool new research to appropriately convey the associated excitement and at the same time to keep asking the needed probing questions, but the bottom line is that there are concrete risks from science coverage that doesn’t take a sufficiently critical eye to sexy, new biomedical research. How many times have we seen that in the stem cell field?

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