Wakefield and the colostrum nostrum

[Rolfe]

Rolfe, have you seen any of these?
http://www.ncbi.nlm.nih.gov/pubmed/11098887
http://www.ncbi.nlm.nih.gov/pubmed/8993773
http://www.ncbi.nlm.nih.gov/pubmed/6100889

I have 2 of the 3 (on order for one) but haven't read them thoroughly yet.

Este

Woo vanity publishing, by the look of these journals. The author of the second link is Fudenberg, Wakefield's collaborator, the person who was using his own bone marrow to treat autistic children.

This is all I could find relating to transfer factor. Quack promotions. There's no actual immunology relating to the term at all.

Rolfe.

 

[Capsid]

Woo vanity publishing, by the look of these journals. The author of the second link is Fudenberg, Wakefield's collaborator, the person who was using his own bone marrow to treat autistic children.

This is all I could find relating to transfer factor. Quack promotions. There's no actual immunology relating to the term at all.

Rolfe.

Right, the term transfer factor is not a term I recognise either (being an immunologist).

 

[Rolfe]

It's fairly mindboggling that Wakefield seems to indicate in the patent application that he isn't certain these nebulous "transfer factors" are antigen-specific, and yet it's the assumption of that very specificity that underpins the entire house of cards.

Rolfe.

 

[tsig]

Trolling a few antivax forums was something I had in mind, actually. However, there are two approaches.

If one simply takes the line that the preparation is just an ultrafiltrate of goat colostrum, which is likely to contain nothing of any immunological benefit and nothing of what was actually injected into the goats (which is likely to be true), it's a bit like debating homoeopaths. Your medicine has nothing in it! Oh yes it has, look at the great benefits I see from it! Goat milk as such is likely to be viewed as fairly innocuous, and about all you could really do would be some scaremongering along the lines I was indicating regarding the neonatal pancytopenia and bone marrow toxicity seen in cow colostrum.

On the other hand one could monster the preparation by going on about the things it's made from - tissues from dead mice, and measles virus, and human bone marrow. Of course there's none of that in the goat milk, but then there's no aborted human foetus or chick embryo or whatever in normal vaccines either, even though they may be made using cells ultimately derived from such sources.

I'm not sure if Wakefield is actually treating children with this stuff in the USA but I strongly suspect he is. However, even on the basis of "this is what this man wanted to inject into your children", it's something I doubt the antivaxers have considered.

Rolfe.

Maybe you could take quotes from the patent application and put it on some autism webs without attributing it to Wakefield till after the explosion of indignation that's bound to occur.

 

[Rolfe]

Rolfe, I don't think it would be unusual for someone at the Royal Free to hold a Home Office Licence to do the animal work (mice and goats).

I was forgetting that the Royal Free actually knew at least some of what Wakefield was up to, and apparently because it smelled money, was apparently happy to go along with this. I don't imagine any of the people who supported him at that point had any idea the science behind what he was claiming was so wacky.

http://briandeer.com/wakefield/falk-pharma.htm

It also appears that Wakefield was putting the Royal Free on the patent applications as well as his own name, though the Dean seems later to have said he didn't know about this. They gave up any claim to the patents when they realised how quacky it all was, at about the time Wakefield left. I'm getting the impression that at the same time the admin and finance people were loving him for his patents and potential money-making ideas, and the clinical people were expressing concerns about the ethics of what was going on.

The letters in that link do suggest the Royal Free was explicitly supporting the "transfer factor" proposals at the outset, though as I said I imagine the finance people involved had no idea it was quackery. So maybe the animal house and so on were all on board with the mice and even the goats. I'd still like to know, though.

I'd especially like to know what happened to the kids, because if they were killed at birth to allow the nannys' colostrum to be harvested, this is something the public would not be at all happy about.

Also, Wakefield left the Royal Free in about 2003. He may have been using stored product after that, if he was using it, and any further production taking place in the USA. I'd still like to know!

Rolfe.

 

[Rolfe]

Capsid, I was looking a bit further into the relationship between transfer factor and cytokines, and it's a bit hazy. Cytokines are, I believe, peptides, proteins or glycoproteins. The peculiarity of Wakefield's description of transfer factor is that he talks about "RNA bases attached to small peptides". I don't know what that would make this, but as far as I know, cytokines don't have nucleic acids in them, do they?

My suspicion is that in the 1940s and 1950s, Lawrence was transferring cytokines (not identified or named then, as far as I know) between individuals, and wrongly assumed he had identified something antigen-specific. He believed he had found a way to transfer CMI between individuals and so apparently confer active CMI immunity to the second individual without actually exposing him to the antigen.

Am I right in saying that cytokines are however not antien-specific, therefore the idea that transferring cytokines from one individual to another would not confer CMI to a particular antigen on the second individual? So the whole idea is completely wrong?

As I said, I suspect Lawrence had noted some non-specific effect of transferring cytokines, and interpreted in wrongly. It seems as if he himself was regarded as a bit of a maverick even at that time, and nobody appears to have followed up on his research. It all petered out in the 1960s I think.

Then if looks as if it was rediscovered by quacks in the 1990s, possibly Fudenberg himself, though I haven't looked into that, and Wakefield has become attached to the people promoting the idea.

I can just imagine the conversations at the Royal Free when someone actually looked into the details of what was on these patent applications, and got the real immunologists to comment. I'd like to have been a fly on the wall. No wonder they washed their hands of the patents, as well as Wakefield.

So, if "transfer factor" is anything, it's cytokines. A crude extract, inevitably containing an awful lot of different molecules. Wakefield never seems to have attempted to isolate his alleged active ingredient. If the preparation also contains RNA fragments, that might explain his description of it as contaiing both RNA bases and peptides.

What do we know about cytokines?

Correct, what went wrong with that drug trial disaster was a "cytokine storm" caused by the antibodies that were injected into the volunteers. Again, that's a very different situation to what Wakefield was doing, but would the parents of autistic children be pleased to learn that the "transfer factor" Wakefield is giving is likely to be composed of the same cellular regulators as were responsible for that incident?

Capsid, do you have any thoughts on this?

Rolfe.

 

[Estellea]

Rolfe, I found this. They are the umbrella organisation for DAN!s and it appears as though they are using it. I also found this on Thoughful House's site. They are careful about what they say but that was Waker's home in the U.S. until recently and they appear as though they, at the very least, endorse it. These fools are still using secretin for crying out loud.

Este

 

[Deetee]

I dropped BD an email.

 

[Rolfe]

Again and again, I come across press claims that Wakefield had patented a "single measles vaccine". No, he really hadn't. Whatever "transfer factor" is (crude preparation including a mix of cytokines?), it's not a vaccine. It doesn't deliver an antigen for the immune system to recognise.

When Deer accused Wakefield of having such a patent, Wakefield angrily denied this, claiming that transfer factor was a treatment for autism, not a vaccine. This is undoubtedly technically correct. However, Deer is also correct where it matters, in that the patent applications themselves refer to the product as "a combined vaccine/therapeutic agent which is not only most probably safer to administer to children and others by way of vaccination/immunisation, but which can also be used to treat IBD [....]" Similar statements appear several times throughout the application. Even though it wasn't a vaccine, he was intending to market it as a vaccine.

Nevertheless, the persistent description of this product by the media as a "single measles vaccine" seems to have obscured the sheer depths of the quackery involved. It portrays Wakefield as some sort of genuine hot-shot immunologist who could actually develop a vaccine and (implicitly) get it through the product regulation process.

Er, no.

Rolfe.

 

[Capsid]

Capsid, I was looking a bit further into the relationship between transfer factor and cytokines, and it's a bit hazy. Cytokines are, I believe, peptides, proteins or glycoproteins. The peculiarity of Wakefield's description of transfer factor is that he talks about "RNA bases attached to small peptides". I don't know what that would make this, but as far as I know, cytokines don't have nucleic acids in them, do they?

Correct.

My suspicion is that in the 1940s and 1950s, Lawrence was transferring cytokines (not identified or named then, as far as I know) between individuals, and wrongly assumed he had identified something antigen-specific. He believed he had found a way to transfer CMI between individuals and so apparently confer active CMI immunity to the second individual without actually exposing him to the antigen.

. you will get an effect by injecting cytokines into someone such as lymphoproliferation which could be confused for an immune response but it won't be antigen specific.

Am I right in saying that cytokines are however not antien-specific, therefore the idea that transferring cytokines from one individual to another would not confer CMI to a particular antigen on the second individual? So the whole idea is completely wrong?

Correct. The only way to transfer antigen specific CMI is to transfer the lymphocytes but that doesn't work because a graft vs host reaction results unless the cells are completely matched for their MHC.

As I said, I suspect Lawrence had noted some non-specific effect of transferring cytokines, and interpreted in wrongly. It seems as if he himself was regarded as a bit of a maverick even at that time, and nobody appears to have followed up on his research. It all petered out in the 1960s I think.

Then if looks as if it was rediscovered by quacks in the 1990s, possibly Fudenberg himself, though I haven't looked into that, and Wakefield has become attached to the people promoting the idea.

I can just imagine the conversations at the Royal Free when someone actually looked into the details of what was on these patent applications, and got the real immunologists to comment. I'd like to have been a fly on the wall. No wonder they washed their hands of the patents, as well as Wakefield.

So, if "transfer factor" is anything, it's cytokines. A crude extract, inevitably containing an awful lot of different molecules. Wakefield never seems to have attempted to isolate his alleged active ingredient. If the preparation also contains RNA fragments, that might explain his description of it as contaiing both RNA bases and peptides.

Maybe they did some crude analysis of the culture supernatant and found nucleic acid in it, which if course they would have done.

What do we know about cytokines?

Correct, what went wrong with that drug trial disaster was a "cytokine storm" caused by the antibodies that were injected into the volunteers. Again, that's a very different situation to what Wakefield was doing, but would the parents of autistic children be pleased to learn that the "transfer factor" Wakefield is giving is likely to be composed of the same cellular regulators as were responsible for that incident?

Capsid, do you have any thoughts on this?

Rolfe.

I think you have summed it up pretty well. The cytokine storm of the TGN trial works by a very specific method. I can't say it's different from what Wakefield filed a patent on as I don't think any method or mode of action was determined by Wakefield anyway.

 

[Rolfe]

I've emailed Brian Deer myself, as he's said (on the BMJ rabid responses) that he doesn't agree it's time to forget Wakefield.

I predict Wakefield intends to go to ground for a little to let the hue and cry die down (he surely has enough money to be going along with, what about that £2 million house he was selling), then to continue practising as a SCAM practitioner, still pushing the colostrum nostrum. In America of course, where such things are easier, and a long way from the GMC, Channel 4 and the Sunday Times.

Rolfe.

 

[Safe-Keeper]

I heard from a conspiracy theorist that no, we haven't heard the last from him, because now he's finally free to preach his gospel without having to abide by Big Pharma rules.

As if he ever did.

 

[tsig]

I was forgetting that the Royal Free actually knew at least some of what Wakefield was up to, and apparently because it smelled money, was apparently happy to go along with this. I don't imagine any of the people who supported him at that point had any idea the science behind what he was claiming was so wacky.

http://briandeer.com/wakefield/falk-pharma.htm

It also appears that Wakefield was putting the Royal Free on the patent applications as well as his own name, though the Dean seems later to have said he didn't know about this. They gave up any claim to the patents when they realised how quacky it all was, at about the time Wakefield left. I'm getting the impression that at the same time the admin and finance people were loving him for his patents and potential money-making ideas, and the clinical people were expressing concerns about the ethics of what was going on.

The letters in that link do suggest the Royal Free was explicitly supporting the "transfer factor" proposals at the outset, though as I said I imagine the finance people involved had no idea it was quackery. So maybe the animal house and so on were all on board with the mice and even the goats. I'd still like to know, though.

I'd especially like to know what happened to the kids, because if they were killed at birth to allow the nannys' colostrum to be harvested, this is something the public would not be at all happy about.

Also, Wakefield left the Royal Free in about 2003. He may have been using stored product after that, if he was using it, and any further production taking place in the USA. I'd still like to know!

Rolfe.

Maybe he didn't use any colostrum at all.

 

[Rolfe]

Maybe he didn't use any colostrum at all.

I just had a short but quite fascinating email from Brian Deer, and yes, he did use colostrum. Mr. Deer appears to be well up to speed on all these issues, and says he even knows "the man who paid for the goats".

I think Brian Deer knows most of what we've been speculating about. It's an area I'm very very interested in, but I'm not sure if he's going to do a feature about it or not.

Rolfe.

 

[TsuDhoNimh]

As I said, I suspect Lawrence had noted some non-specific effect of transferring cytokines, and interpreted in wrongly. It seems as if he himself was regarded as a bit of a maverick even at that time, and nobody appears to have followed up on his research. It all petered out in the 1960s I think.

I remember hearing about transfer factors in immunology classes in the mid to late 1960s. It was presented as "if it worked as described, it could be useful, but no one has been able to make it work except the guy who claimed discovery."

Then if looks as if it was rediscovered by quacks in the 1990s, possibly Fudenberg himself, though I haven't looked into that, and Wakefield has become attached to the people promoting the idea..

I don't think the idea was completely forgotten - the idea that drinking colustrum from cows will help humans is still floating around, and has been since it was discovered that colustrum contained immune globulins.

ADDING: The notion got its start after "cellular transfer of delayed hypersensitivity in guinea pigs" was discovered. Make one guinea pig hypersensitive to something, transfer some cells, and the recipient will acquire delayed hypersensitivity. This is an accepted, repeatable phenomenom, and you can even make it happen with no cells. But guinea pigs are not humans.

Dr. William Smith Tillett - a medical big gun in the 30s and 40s, encouraged Lawrence to begin his career by determining whether this sort of cellular transfer could be accomplished in man using viable white blood cells.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC416355/ (My professors!)

http://www.ncbi.nlm.nih.gov/pubmed/13233344 (Lawrence, making something work in humans)

Note that this is a direct transfer - a long way from the convoluted process described by Wakers of immunizing mice, harvesting lymphocytes, running it through cell cultures, then into pregnant goats, and extracting who knows what from the colustrum.

 

[Rolfe]

I remember hearing about transfer factors in immunology classes in the mid to late 1960s. It was presented as "if it worked as described, it could be useful, but no one has been able to make it work except the guy who claimed discovery."

That seems to fit with all the rest!

I don't think the idea was completely forgotten - the idea that drinking colustrum from cows will help humans is still floating around, and has been since it was discovered that colustrum contained immune globulins.

But that's a non-sequitur. As far as I know, Lawrence didn't say anything about colostrum. He was working with filtration fractions of lymphocytes. Colostrum doesn't transmit CMI - as you say, it transmits immunoglobulins.

Of course, immunoglobulins are useless to anyone except a neonate of the appropriate species less than a couple of days old (at most). Only at that stage of life is the intestine able to absorb the immunoglobulins intact and functional. If you miss that window, you can feed the calf all the colostrum you like, it will do no good. The proteins will merely be digested.

It's amazing the silly ideas some people get. The idea that bovine colostrum could be at all beneficial to humans is silly. The idea that caprine colostrum will contain a peptide that will confer immunity to measles if you inject the goat with a fraction of a lymphocyte preparation that has been exposed to the measles virus is insane to the nth degree.

Rolfe.

 

[Capsid]

Can I say bizarre again?

 

[Eos of the Eons]

From what I've managed to compute in my tired addled brain is that colostrum won't cause the immune system to build up any permanent immunity anyways, since it needs to react to actual antigens anyhow (hence real vaccines work, and we know why). So, this whole complicated process using this methodology to come up with colostrum to inject is completely useless to even meddle with?

 

[Mike!]

Not all parents of autistic children think highly of Mr. Wakefield, some of us think of him as "The Bastard Wakefield". He's done far more harm than any fraction of good from his B.S. research. He does need his head served up on a platter.

 

[Rolfe]

Well, you've got his head, platter and all. Though he seems quite unrepentant, and will probably still manage to net more money from all this than you or I could dream of in our entire careers.

I think what amazes me about the colostrum thing is the window it opens into Wakefield's thought processes. Here is someone in a research post in a teaching hospital, and yet he goes to a lot of trouble to take out patents on something which is complete, 24-carat nonsense. It's difficult to overstate the silliness of the entire concept. Commentators have tended to state that he had a patent on "a competeing single measles vaccine", because that clearly illustrates the conflict of interest involved. But of course it was no such thing.

How could anyone with even the most rudimentary knowledge on immunology and pharmacology imagine that pills made out of goat's milk with no defined active ingredient could become an accepted treatment for anything, or an alternative even to a single measles vaccine? It was going nowhere, and it was always going nowhere.

Pace the surgeons on here, but this is something I see in a lot of surgeons. Perhaps it's a side-effect of the degree of self-confidence needed to take patients apart on the operating table and put them back together again. They come to imagine they know everything about everything, and can pontificate just as authoritively on biochemistry or molecular biolody or immunology as they can on their own subject. Even when they know approximately bugger-all about it.

The patent applications are very badly-written as far as I can see. The Lancet trial is covered in just about as much detail as it is in the actual paper, but important things such as what transfer factor actually is and how you produce it are glossed over. It's pretty much Walter Mitty. It's just weird to see it from someone with an FRCS, rather than someone like ShareCures.

Rolfe.