Here I am in Philadelphia attending the 2015 American Association for Cancer Research (AACR) meeting to imbibe the latest basic and translational science about oncology. So what am I doing in my non-conference time? I’m holed up in my hotel room near Rittenhouse Square writing a DoD Grant and this post. Fortunately, my grant is nearly done with the grant, with nothing I can do until I receive one last letter of support from a person who, as much as he’s my bud, is incredibly annoying and always makes me sit on pins and needles waiting for his letter of support. (Those of you who’ve applied for a lot of grants know what I mean.) Then tomorrow I will have to assemble the PDF package to get to my grants office two days before the deadline, which is pushing it to make sure they get it uploaded to Grants.gov in time. Fun times.
With the Stanley Cup playoffs just getting under way (complete with the ugly faux “Stanley Cup” made out of garbage cans our next door neighbor’s son puts on his lawn every year, bathed in red light for the Red Wings), it’s also the perfect time to revisit a story I’ve written about a couple of times before right here on this very blog. I’m referring (this time) to the story of hockey legend Gordie Howe and news stories of his “miraculous” recovery from a serious stroke suffered back in October due to treatment at a dubious Mexican stem cell clinic back in December. Of course, when I looked into it, there were a lot of holes in the story and clearly a lot of hype on the part of several parties: Howe’s son Murray Howe, whose love for his father apparently blinded him to some rather obvious issues with the care that his father was receiving and whether it was responsible for his recovery; Stemedica, the American stem cell company based in San Diego that sells its stem cells to a dubious Mexican stem cell company, Novastem, for use outside its U.S. clinical trials; and, of course, the credulous sports media, led by that most credulous of the credulous (with respect to Gordie Howe), Keith Olbermann, who was none too pleased with a certain not-so-pseudonymous “friend” of SBM and completely embarrassed himself in the process of attacking anyone who questioned whether stem cells caused Howe’s recovery. The whole story did have one salutary effect, though. It introduced me to a real stem cell scientist, Paul Knoepfler, who did a guest post for us.
It’s been a couple of months since I last paid attention to what was going on with Gordie Howe’s recovery. Fortunately, our very own Scott Gavura tweaked me by sending me a story by Avis Favaro & Elizabeth St. Philip that appeared over the weekend in the Toronto Star, entitled A closer look at the startling recovery of Gordie Howe. Accompanying the story is a broadcast on CTV’s W5 entitled Gordie’s Comeback. (See part 1, part 2, part 3.) Also accompanying all of this is a press release discussing how a Canadian stem cell researcher visited Novastem and left unimpressed.
The news story is better than the TV version, the latter of which falls prey to a lot of the same boosterism and lack of skepticism that previous news reports I complained about did. Indeed, it starts right out with Gordie Howe’s sons describing his recovery as a “miracle,” with the reporter helpfully asking them who was the first to use the term “miracle.” So I’m going to start with the news story and press conference. Let’s just put it this way. This is something that should have been done in December, but, even so, it’s clear that the TV story is a carefully managed puff piece. It has all the elements: the “miracle” claims, an old interview with Howe in which he was portrayed as fighter and fierce competitor, as well as a family man. His survival after a severe brain injury suffered in a Stanley Cup game.
Let’s start with what Dr. Duncan Stewart, a Canadian stem cell researcher from the Ottawa Health Research Institute, has to say about his trip to Novastem and its Clínica Santa Clarita stem cell clinic, where Gordie Howe received his stem cell therapy:
During the trip, Dr. Stewart had a chance to speak with people involved in producing and administering the stem cells, and view their facilities, documents and procedures. He was particularly interested in the regulatory framework for producing and administering the stem cells. In Canada and the U.S., any drug or cell therapy that will be used in humans must be produced in a carefully regulated manufacturing facility. In addition, experimental therapies can only be administered to humans through carefully regulated clinical trials that are designed to protect patient safety and produce meaningful results. The regulatory framework in Mexico is quite different, however.
“The good news is that the stem cells that Mr. Howe received were produced in a facility in the U.S. that complies with appropriate regulations, so we know that these were high-quality stem cells,” said Dr. Stewart. “I was also encouraged to see that the licensing agreement between the stem cell production facility in the U.S. and the clinic in Mexico requires that the stem cells be administered through clinical trials.”
“The bad news is that the clinic in Mexico is not in a position to perform clinical trials that meet Canadian and U.S. regulatory standards,” added Dr. Stewart. “This means that it is not clear whether meaningful results will be collected and whether patient safety will be adequately protected. It is also important to remember that this is not a research facility – it is a for-profit business.”
“Although they are using high-quality stem cells and have some of the trappings of clinical research, this is still a form of stem cell tourism,” said Dr. Stewart. “Without more rigorous research, we will probably never know if Mr. Howe truly benefited from stem cells or if his recovery was due to chance or other factors.”
This is, of course, very much like what I wrote about at the end of December, when seemingly I was the only one other than Bradley Fikes, a reporter for U-T San Diego, who took a skeptical view of the treatment. Back then, I reported based on my own distant investigation that there is in essence no meaningful regulation of stem cell use in Mexico. I pointed out that Novastem is a for-profit business and that their “registered” clinical trial just meant that the Mexican government gave them permission to use stem cells. Once that permission is given in Mexico, physicians can administer stem cells to whomever they wish for whatever indication they wish.
I also described how the physicians at Novastem are utterly unqualified even to safely administer stem cells to a patient, much less to conduct high quality clinical trials that will give a scientifically meaningful answer to the question of whether stem cells are useful for strokes. I also examined the clinical trial documents in depth and concluded that the “clinical trial” that Gordie Howe was enrolled on could not possibly answer the question it was supposedly designed to answer. Again, if you want the details, go back and read my post, which is lengthy even for me. Basically, I could have told Dr. Stewart everything he discovered about Novastem and Clínica Santa Clarita.
Yes, I’m a bit annoyed. All of what Dr. Stewart found (“The clinic says it is conducting a ‘clinical trial,’ but according to Stewart the study lacks proper follow-up to provide the data required in Canada and the U.S.“) could have been found back in December or January if anyone had bothered to look.
But what about the < em>Star story? What interested me about this story was that finally the Howe family had granted access to Gordie Howe to a camera crew, reporters, and a neurologist. For the first time that I can recall, Gordie’s son Murray actually gave some medically relevant details about Gordie’s stroke:
“He had an acute hemorrhagic, left thalamus stroke,” recalled his son, Murray Howe, a radiologist in Toledo, Ohio. He and other members of the family spoke to W5 in exclusive interviews.
“He couldn’t talk. He really couldn’t use his right leg and his right arm at all.”
A hemorrhagic stroke occurs when there is a bleed into the brain, referred to as an intracerebral hemorrhage (ICH). This is in contrast to an ischemic stroke, which occurs when a blood vessel supplying part of the brain is blocked, usually with a clot, leading to death of brain tissue (cerebral infarction, or CI). ICH is much less common than CI, representing only 15% or so of strokes but are more immediately deadlier than CI, whose victims have a better chance of survival. However, paradoxically, those who survive ICH tend to have better functional recovery over the long term than those who survive CI, perhaps because much of what causes damage is increased intracranial pressure and the neurons are better able to “bounce back” after the pressure is relieved. Knowing that Howe had an ICH could well go a long way towards explaining why he did as well as he did.
In any case, it was about a month after Gordie Howe’s stroke that Dr. Maynard Howe (CEO) and Dave McGuigan (VP) of Stemedica Cell Technologies contacted the Howe family to offer to have Howe treated in Mexico. The reason they did that was because Howe was not eligible for Stemedica’s clinical trial using its stem cells for stroke because the trial required that the potential subject entering the trial have had neurologic stability for at least six months, which Howe clearly did not have. At the time, I pointed out just how unethical it was to do this, in particular to offer to treat Howe for free just because he is a celebrity. As much as I understand Murray Howe’s desperation to help his father combined with his now unshakeable belief that the stem cell treatment is what made his dad better, I also pointed out that his statements indicated that he was oblivious as to why such an offer was unethical and seemed to see nothing wrong with his father being given special treatment that a normal joe on the street who suffered a stroke would never have been granted. Like many physicians, he also seemed unable to admit to himself that gifts influence; he was understandably grateful to Stemedica and became its greatest ambassador. We see this in the Star story and the W5 report. We also see the Star story note that Howe received a $30,000 treatment for free without noting the ethical problems with such a gift, as does the W5 report. Again, as I’ve said time and time again with Stanislaw Burzynski’s antineoplastons, it is ethically dubious at best to charge patients to be on a clinical trial, and trials for which it can be justified are few and far between.
The most interesting part of the Star story was to me that a neurologist was allowed to examine Gordie Howe:
W5 was given unprecedented access in Lubbock, where Gordie is undergoing rehabilitation, and the program was allowed to bring a U.S. stroke expert to assess him: Dr. Steven Cramer, a neurologist at University of California Irvine.
Cramer examined Gordie after a therapy session. Gordie’s grip is strong and his ability to move his feet near normal, he said. Gordie signed an autograph with his right hand, paralyzed only months earlier. He wrote slowly but the famous name is legible. Cramer’s conclusion: the recovery is “impressive.”
“It is a remarkable degree of motor improvement for anybody with that severe a stroke and when you mix in the fact that it was toward the end of his ninth decade, it’s all the more remarkable,” he said.
Cramer says physical and occupational therapy could have played a role or there may have been a spontaneous improvement, which happens sometimes during the first three to six months. But Gordie’s recovery may be due to the so-called “piss-and-vinegar gene” — a fighting spirit or drive that Gordie has in abundance, Cramer said.
It’s also possible stem cells could have helped. The fact Gordie’s recovery came so soon after the stem-cell treatment is an interesting “coincidence,” but Cramer is cautious.
“You have to be very careful about drawing any firm conclusions from what we see here. However, what we see here has some exciting potential,” said Cramer. “If his improvement is in anyway attributable to these stem cells, it’s very exciting. It raises hope.”
That’s why clinical trials are needed. Howe might very likely have recovered to the point where he is now thanks to, as Dr. Cramer noted, his intensive physical therapy and his motivation to get better. As Steve Novella has pointed out to me in discussions in the matter, determining if a given treatment improves stroke outcomes is difficult because of these very issues. Indeed, in the W5 report, Gordie Howe is shown in December struggling in his wheelchair even though he couldn’t move his right leg. Reading between the lines of what Gordie’s sons Murray and Mark were saying in the W5 interview, it sounds as though Gordie started getting better before the offer from Stemedica came in. The two sons talked about how seeing him refuse to give up led them to believe that there might be hope that he would survive. According to the accounts of Howe’s own sons, something had clearly changed for the better before Maynard Howe called the Howe family.
Which brings me back to the W5 story, which for the most part plays like a commercial for Stemedica, a story of a “miracle cure” that glosses over the issues with what Stemedica and Novastem did. As I’ve said before, I can’t help but see this relationship as a highly convenient one, where Stemedical puts patients on trials when it can but shunts patients across the border to Novastem, which purchases Stemedica stem cells. So, either way, the patient gets Stemedica stem cells. Indeed, if I were cynical, I could wonder whether it’s actually better for Stemedica if patients go to Novastem because that way it gets paid for its product, whereas in an FDA-registered clinical trial in the US Stemedica has to provide its product for free.
Be that as it may, the second part of the W5 report is basically a testimonial of a “miracle cure.” The Howes, who had not to this point released any but a single video of Howe playing hockey with his great grandson, suddenly decided to release multiple videos documenting Howe’s recover to show. True, the reporter keeps saying that scientific evidence is “limited” or “there is not much evidence” for the claims being made by Stemedica yet, but the overall message is that, hey, it’s Gordie Howe and he’s doing well. Yes, the reporters acknowledged the criticism of Stemedica, but then it showed Maynard Howe making what has to be the most disingenuous claim I’ve seen in a very long time, namely that he had offered to have all the doubters come out to Stemedica to see for themselves, but they all said no. Yes, Maynard Howe did offer to have me come out to Stemedica in one of our e-mails. He did not, however, offer to pay for it, and I’m not spending what would likely end up being over $1,000 of my own money to fly out to San Diego for a couple of days for that. So I make Maynard Howe a counteroffer: Pay for my travel, lodging, and food, and I’ll consider coming out. Of course, he probably won’t do that now because he already got one stem cell scientist to bless his stem cells as being real stem cells. Of course, I never questioned whether Stemedica’s stem cells were “real” stem cells. I questioned the ethics of what it is doing through its affiliation with Novastem, whose business, according to the W5 report, is booming, thanks to Gordie Howe’s “miracle.” Meanwhile, we learn from this report that the Howe family has purchased stock in Stemedica, giving them a financial conflict of interest to go along with their emotional investment in Stemedica.
The last part of the W5 story shows Gordie Howe in rehab, Dr. Stewart visiting Stemedica and Novastem, and Dr. Cramer examining Gordie Howe. Dr. Cramer, of course, couldn’t attribute Howe’s improvement to the stem cells and declared that it could be within the normal range of recovery after a stroke, pointing out that a single anecdote tells us little.
Predictably, both Dr. Stewart, who wouldn’t be a stem cell researcher if he didn’t think that stem cells as a treatment don’t hold great promise, and Dr. Cramer, who is also enough of a stem cell booster that he’s thinking in wake of the Gordie Howe story of starting up his own stem cell trial for stroke using Stemedica stem cells. I say “predictably,” but that’s not to disparage either doctor, but rather to point out that it would be surprising if either of them didn’t call for more research. In fact, for all my misgivings about Stemedica and Novastem and in particular what I see as an unethical gift of an unproven treatment by Stemedica and the incompetence of Novastem at doing basic clinical trials, if Gordie Howe’s story inspires more funding for stem cell research and more legitimate, well-designed clinical trials of stem cell treatments, that would be a good thing. Unfortunately, as this report shows, what Gordie Howe’s story has inspired first are more desperate patients to flock to Mexico to lay down $30,000 to Novastem for unproven stem cell treatments. Whether more high quality scientific research, if it ever occurs due to this story, is worth that price, I really doubt. The Gordie Howe story, alas, has been far more about marketing of Stemedica’s stem cells than science, and it has been a great success in that.Stem cells versus Gordie Howe’s stroke, part 3 David Gorski