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?

12 thoughts on “Perspectives on uncritical NYT coverage of cardiac mitochondrial transplant trial”

  1. This is just one of many different teams who are reporting the same sort of results with other organs, including lungs and spinal column.

    And yes it appears cells do “drink up” free floating Mitochondria. From an evolutionary perspective, this makes perfect sense. Trillions of mitochondria are set free daily due to apoptosis. They are packaged up carefully in vesicles. Why would this be done, if not so they can be recycled?

  2. A naive question: Could not mitochondria (under some conditions) recall that they are rickettsia?
    Regardless whether this is real or not, I would prefer to spend some tax money on testing this rather than e.g. on pretending that deletions are homologous recombinations.

  3. I don’t fully understand the mechanism by which the mitochondria get into the cell, and I’m skeptical that injecting naked mitochondria into the bloodstream would actually get them widely distributed into the heart, but if they saved lives then fingers crossed it holds up in a larger cohort of patients. The general concept of mitochondrial replacement I think is sound, but the hype and ‘magicalness’ of the results need to be taken with a dose of caution until the findings are more robustly tested.

  4. A very ignorant article; James McCully has performed mitochondrial transplants on hearts from sheep, pigs and other advanced animal models and achieved the type of results that were described in the NYT article. All his results have been replicated and passed peer review which you would know if you bothered to do your homework before posting your rant.

    The work described in the NYT article was performed by one of the world’s finest and reputable hospitals, do you think they’ve suddenly decided to lie and harm their institution out of the blue? Or perhaps the families of the infants are making it all up? Do you think your blog has more credibility than a hospital that has won nobel prizes and enjoys an affiliation with harvard?

    It was indeed a small trial but thats because the transplants were a desperate attempt to save the lives of near death infants and the doctors had no other option other than mitochondrial transplants. McCully and his associates are going to conduct a much larger trial with elderly patients next year with all federal approval and supervision. Either you’ve stumbled onto a vast conspiracy involving a nobel prize winning institution and families of disabled infants or you screwed up and didn’t do enough research: I know which one seems mostly likely.

    When you dismiss research you don’t understand out of cynicism you’re not being a skeptic, you’re just wallowing in lazy thinking that’s the direct inverse of rational inquiry.

  5. Thanks for sharing this article. This reminds me of the recent interest in extracellular vesicles for cardiac transplantation, which is a super hot topic right now. By looking at the review article you sent, it seems there are several published papers (albeit from the same group) demonstrating actin-dependent endocytosis as a means of uptake of mitochondria by cardiomyocytes. Obviously more research is needed to confirm, but seems there is a plausible mechanism. The notion that mitochondria could provide a benefit to a beating tissue that requires lots of energy doesn’t seem too far-fetched. The NYT article does at least say that a randomized trial would be needed to prove this. Seems like the mitochondrial isolation procedure is straight-forward. Wouldn’t it be easy for Topol or other cardio people to quickly see if they can get uptake into cardios? That these transplantations occured is a fact, not sure why it should be considered outrageous that they are reported. But I agree as scientists we want to see more skepticism. I’m not a cardio person, maybe this has been around the field for many years and already robustly debunked. Or maybe this NYT article will stimulate more scientific interest in this area.

  6. Thank you for your time and consideration. Your critical feedback is essential in making sure citizens get quality information when it comes to complex scientific research and findings.

  7. Lisa: Exactly. I remember the cancer pieces well, and hoped that her embarrassment about being conned would encourage her to be more cautious about hype. I keep wondering if she actually knows any scientists who she can ask about these things, like mitochondria magically getting into cells – if she asked, any biologist could have told her that was a silly idea.

    1. I too had never heard of mitochondrial uptake until I read this blog post. And yes I agree with the problem of using the word magical: we’ve seen too many claims like this from rogue stem cell transplantation, which Paul has done a great service commenting about here on this blog. But I wonder if you would like to comment on this paper about mito uptake? It is from the same group doing the transplants.

  8. This brings to mind Gina Kolata’s article in 1998, printed on the front page of the New York Times, about Judah Folkman and his company Entremed, claiming that inhibiting tumors’ blood supplies was the answer to cancer, and a quote from Jim Watson (famous cancer expert) that cancer could be cured within two years. Entremed’s stock shot up something like 100-fold after that. Hmm.

    1. Judah Folkman was a visionairy and his work was precursor to a whole field that led to development of useful drugs such as avastin

      Shameful that you are putting him in the same bucket as these mitochondrial guys

      Thomas ichim

      1. Thomas,
        You completely misunderstood the point I was making, which was to echo the concern voiced in the original post here, which is that responsible journalism should portray a balanced and realistic view of scientific results.

        Of course, there’s no doubt that inhibiting angiogenesis eventually proved to be one approach to cancer treatment (and other diseases). Maybe you are not aware of the fact that the New York Times and Gina Kolata got a lot of criticism for publishing a long article about Folkman and Entremed, on the front page, quoting Nobel prize winner Jim Watson as saying that cancer would be cured in two years based on the strategy of inhibiting tumor angiogenesis. Scientists who’ve been around the block would have known that, even though this was an exciting new approach, the claims that were made in the article were exaggerated. However, the lay NY Times reader would not necessarily have that perspective. If had been a lesser publication, it might not have had such an impact, but the NY Times is one of the most respected newspapers in the country. As I recall, shortly after this article was published, the price of Entremed shot from around $3 to in the hundreds of $.

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