Understanding Cancer Part 2 – Telomerase, the Road to Immortality, and the Nobel Prize

Aging is a much more complicated kettle of fish. I can assure you that there is no simple relationship between telomere length and aging, even at a cellular level. At the level of an organism it's much more complicated: for example mice have long telomeres and short lifespans, we have short telomeres and a long lifespan. There is one thing that everyone in the field agrees upon, and that's that upregulating telomerase will not prevent aging (at least: everyone who doesn't already have a financial stake in the idea). It may be useful in other cases, such as the PNAS paper you linked to (marked 'Telomerase Does Not Cause Cancer'), where they were trying to extend the life of vascular smooth muscle cells taken from patients with a view to building up artificial veins and re-implanting them. You'll notice that at the end of the paper they're still not convinced by their own experiments and suggest that transient expression would be best (and I agree - some of their assays were a little iffy: who measures the doubling time of cells in culture as a measure of tumorigenesis? Who makes the conclusion that their cells are not predisposed to cancer by comparing with HEK293 cells (their positive controls) which have been in culture for like 30 years?). I'm afraid I didn't bother to read the other paper, but I assume it was similarly cherry-picked. It is very difficult in science to prove a negative (e.g. upregulating hTERT/telomerase DOESN'T cause cancer), because you have to be right every single time for anyone to believe you, and people will quite simply assume you just didn't find what you were looking for. It's even harder to convince people that telomerase doesn't cause cancer when proper in vivo experiments show that it does. For example this paper where they expressed mTERT in mouse basall keratinocytes (skin cells to you and me), and found an increased sensitivity to chemical carcinogenesis, and this paper where they created transgenic mice expressing mTERT in several tissues, and found tumours in those tissues.

Interestingly, TA sciences (who you appear to be speaking for, although my apologies if you're not) says that there IS a risk of cancer on their FAQ, although they brush it off as 'theoretical'. They have a very interesting website. There is excruciating detail about the purification of their product, TA-65 (N.B. a search for TA-65 doesn't find any results on PubMed), repeating over and over again how important and science-y it is, but as soon as it starts talking about the mode of action there's little asterisks after every claim. Ah! I thought when I first saw this, the footnote will be a nice reference to back up the claim! Unfortunately not. It reads:

**These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

After failing to find any evidence that it does what it's supposed to, I checked over at Geron.com, Geron being the pharmaceutical company that TA Sciences claims invented and tested TA-65, and there's no mention of it. Not to sound like a grumpy arsehole, but I don't like Geron either. On their telomere page (that dear Mr. Anonymous linked to too) they keep saying "We and our collaborators have shown that telomeres...are key genetic elements involved in the regulation of the cellular aging process", "Our work has shown that each time a normal cell divides, telomeres shorten" and "Our work and that of others has shown that telomerase is not present, or is present at very low levels, in most normal cells". Woah there sombrero, you can't take the all the credit for that you douche! You may have shown these things to be true, but I bet you weren't the first to do so so you can't claim these discoveries as your own.

Anyway, back to TA-65, it would only take a few days to isolate some primary cells, add TA-65, and do a western blot for telomerase. It's not like it would be difficult to get a bit of proof that your product does something interesting. That in itself would probably be publishable, and other telomerase researchers would probably be quite pleased, because then they can do their upregulating telomerase experiments twice: once by added a new telomerase gene by transduction, and once by using TA-65.

Oh, and one final note. The 'clinical trial' run by TA Sciences in 2005. No thanks. I tend to disregard the evidence of unpublished, unregistered (admittedly I only searched clinicaltrials.gov, but I get the feeling a longer search would have been fruitless) trials with groups of 6-12 self-selected participants with no mention of randomisation. Having reached this conclusion I decided to skim through the 'report' anyway and found, to my suprise that all due care had been taken to ensure that the statistics were as clean and relevant as possible with no possible way for anyone to accuse them of measuring lots of things and shaking the data until they found something with low p-values. Sorry. That was another paper I read. No, in this report they decided, upon looking at the numbers and finding that it made no difference whether the patients took 2 or 4 pills to put the groups together. Um...do they know that they're not allowed to do that? I don't know in what world they're living, but suddenly they're allowed to talk about p-values of 0.2 and 'trends' and p-values of 0.1 as 'significant'. WTF??. I dread to think what they mean by "We systematically took multiple approaches to the data set". Actually no, I know exactly what they mean. They mean that they pushed the data around an excel sheet until nice numbers popped up.

I think I may have gotten into a little bit too much of a rant there, but that's what happens when people are so confidently, blithely, mistaken