Last week it was announced extensively in the press that the so called "transfer factor", a hemoderivative product that has existed in Mexico for many decades, developed and sold by the Escuela Nacional de Ciencias Biologicas-IPN under the trade name "Transferon", is going to be used to treat patients with COVID19.
The thing is not registered as a "medicamento" at the national drug regulatory authority: it used to have one back in 1994 when you didn´t have to submit proof of safety and efficacy to get it.
I have no idea what twisted politics have allowed them to keep making and selling the thing and have a clinic for that: maybe it is under the auspices of the Homeopathy School or maybe is because the CEO of Transferon-FT is friends with many people in COFEPRIS and they have kept putting the file on the bottom of the pile. She argues that the registry database is not up-to-date and they of course have a permit. However she refuses to give the number and the boxes and bottles of Transferon do not have any "Reg.No XXXXXX- SSA" printed, as required for every legal drug. Aaaanyway, that is another story.
What I would like the hive-mind to help me with is to critically analyze the publications that have been made over the years using Transferon in vivo, in vitro and in patients.
I've been digging them and they are...um, interesting.
The product is question is obtained by repeated freeze-thaw of leukocyte concentrates obtained from material discarded in blood banks. The material is then dialyzed through a 12 kD filtration membrane, so what is left is a mixture of leukocyte-derived... stuff. Probably peptides and glycopeptides, pieces of nuclei acids, nucleotides, sugars...
This mixture is then liofilized and 2 mg of it are resuspended in 5 mL of sterile water (400 mg/mL). Each 5 ml flask is sold at around $500 MXN and people are prescribed between 1 and 7 dosis a week. Patients with what? Asthma, allergies, cancer, herpes zoster, sepsis, fibromyalgia, multiple sclerosis... It does not matter if they are adults or children either. And until recently the administration route could be any: intravenous, intramuscular, oral. Lately they recommend that people just drink it.
So, what do you say?
Do I put the papers here one by one?
I can also put them in PubPeer and those interested can stop by and check them out and comment. It is like a virtual journal club where the comments get registered for everyone to read and comment in turn: it even has the option to comment with your name or under a pseudonym. We could decide to write in Spanish or English too.
Honestly I have heard about the thing for many years and had filed it under "oh well, some people read horoscopes and pay to get the tarot read to them" but then I found one paper where they reported they had given the thing to 15 children, between 0 and 5 years of age, that were in intensive therapy for sepsis: 7 of them died. But the paper claims that Transferon is "a promising therapy as an immunoregulator that can prevent sepsis"...because 8 kids did not die. The authors do not mention informed consent or a bioethics commitee and the introduction states that the thing is approved as a drug. I mean, give me a break. And now they are going to immunorregulate COVID19 (just google "IPN Transferon COVID").
Let me know.
Irma
That's an issue of "Academic dynasties" , almost as old as the mexican immunology.
I know but the new generation of scientists is under no obligation to allow the lies and the sloppy science keep going!
Hey, I am not naïve, they have tentacles everywhere: commitees, CONACYT, COFEPRIS...
But maybe now is the time to sistematically take their claims down, one by one?
Like, the attached figures from Article CD80 Expression Correlates with IL-6 Production in THP-1-Lik...
A better title could be "Transferon does absolutely nothing (but if you add LPS the LPS does stuff)"
Maybe use them to train students about how to read papers and spot bad science?
I also suggest PubPeer. Another way of looking these publications is to check for their impact, that is, to look for the number of citations these studies have (obviously excluding self citations) and if these reports have been replicated elsewhere and by who. What is noticeable is the evident conflict of interest, as the Escuela Nacional de Ciencias Biologicas-IPN is the first to gain if they "demonstrate" that Transferon "works".
PubPeer it is then!
Article Dialyzable Leukocyte Extract (Transferon™) Administration in...
https://pubpeer.com/publications/91A78A7D767A58C3BFD8F7ABACF507
I used it when my son was very sick of respiratory infections, almost every week he wa sick until my pediatric doctor recomended the transference factor. And he improved his condition. Best regards.
Indeed, there are always cases in which the temporal relation between treatment and improvement suggest effectivity. Treatment, then improvement.
BUT
This is not enough, not even repeating the experience numberless times.
The real question to answer is, how do I knoe that the improvement was CAUSED by the treatment. A possibility to rule out is that the child would have improved by himself anyway or via a miracle. Who nows!
Fortunately, there are ways in which we can answer this question.
1.- Lets get similar children with similar recurring respiratory infections.
2.- Lets divide them at random to two groups.
3.- Then let's give group a the THING, and let's give goup b a same amount of the carrier (saline solution, a tablet) (volume, if liquid, weght if solid) in the same presentation (tablet, injection, enema, you name it) WITHOUT the THING.
4.- I love group b. It tells my troubled mind what percentage of children get better by themselves (Nature wins, pray God).
5.- If the proportion of healed children in group a (receiving the THING) is really bigger than the proportion in group b, the THING is working.
BUT, we have to make sure this result was not the result of mere chance (as my troubled existence),
Well, there are plenty statistical tests that tells us the probability of getting this result if proportions in group a and b are actually very overlapping (mostly the same). And humans agreed that a probablity of less than 5% (0.05) tells you that, well, the results HAD to differ between groups. This probability is known as the p value.
6.- Since these awesome tests use probability, you need a minimal number of children per group according to the size of the effect you see. Let's say, "more than 75% of children getting THE THING heal and only 10% of the other, miserable children". AND THIS IS NOT BY CHANCE, given the number of children in each group, then you have a remedy. A treatment!
ONLY THEN
7.- Let's add mystery to the finale. How do you know this miracle of sorts is gonna work everywhere at any time, with any child. Well, we cannot be absolutley sure. However, thanks to statistics, we can also calculate the number of children studied to be comfortable about the future performance of our THING in the market. And we must abide with that number, if you don't want cyborgs stalking you forever at any scientific forum or network. Boo!
Best regards, Mirza Romero-Valdovinos
Hello Dr. Mirza Romero-Valdovinos ,
I am a mother too. It is awful when kids are sick and the cough doesn´t go away.
It is great when it finally does and one wants to believe that it was due to the last thing we tried: bouganvilea tea, orange juice, chicken soup...
But most of the times the improvement is due to the immune system working on its own.
That's the dishonest trap that Transferon inventors use: they claim that the magical liquid tells the immune system what to do, sometimes activate, sometimes deactivate towards particular things. That therapeutic mechanism, is which is 1) ridiculous and 2) not proven to happen either in vivo, in vitro or in people.
I have been digging all their publications and reading them. The only thing that they have managed to maybe gather evidence about is that in vitro their magic potion maybe activates leukocyte receptors that get activated by cellular debris. But only at a concentration that is 1000 times what you would get by drinking it.
This activation is not surprising either, because the mixture they sell, if they in fact make it as they say, contains leucocyte debris. And EVERYTHING obtained from a living thing contains cellular debris and would activate those receptors. If you freeze and thaw bouganvilea flowers or a chicken nugget you'll get cellular debris. And if you put that chicken nugget juice to cells in culture they would activated PAMP receptors too.
And that is the only "positive" finding they had been able to get.
Did you look at the graphs I posted in my message above? When they measure meaningful things, say macrophage activation, it is clear that the product does not cause any response. None. Zero. It could be used as a great negative control.
Also, the inventors of Transferon have NEVER published results that show that the stuff works in people. They sell it to over 4000 people a year in their "clinic". If it worked they could have all those supporting data, right? If they were serious investigators they would try to do that. They don´t try. They just want to sell the thing to sick and vulnerable people including parents worried about their sick children. They hope placebo effect and some informercials would be good enough to keep the sales going.
But they have failed to convince medical authorities and that's why they only sell it (illegally) inside the IPN.
My personal favorite is that they also say that it can be used to try depression. I am not making it up. The same drops that "cure" long colds in children can also cure episodes of major depressive disorder in adults: "...it has been specifically proved to be effective as a coadyuvant to conventional therapies of certain diseases...such as major depressive disorders". They published that phrase in the introduction of this 2019 paper Article Validation of a Cell Proliferation Assay to Assess the Poten...
The funny thing is that after that phrase they cite a study they ran in collaboration with honest researchers outside their group , immunologists and psychiatrists, Article Effect of Selective Serotonin Reuptake Inhibitors and Immuno...
, That study concludes that the administration of the product had NO clinical effect. Specifically, it says "the total scores of the Hamilton Depression Rate Scale (HDRS) showed no significant changes between treatments".The ENCB people KNOW that the product is useless but they don´t care. It sells. It gives them fame and fortune, screw scientific evidence.
Hurting patients economically with a miracle product is bad enough. But in my opinion the whole Transferon phenomenon is additionally toxic because it hurts us too, the honest biomedical community, it corrodes the trust that Mexican researchers are able to do good science, it stains the rigorous work of many dedicated, real immunologists, both basic and clinical.
That the Transferon gang are able to convince even a medical professional with postgraduate training like you is indicative of how deep the problem is.
They are lying intentionally to enrich themselves. It is evil. We have to stop it.
saludos
Irma
If you really want to get the info and eventually to stop or to get clarification most probably you have to find a serious journalist and persuade them to pursue the matter. Otherwise by your self make a publication in a press paper. Then you are going to get an answer. Probably contact La Jornada or some like that.
This problem requires Science, not Journalism.
Of Journalism, we have aplenty.
Pues ahora dos de su artículos ya están siendo cuestionados en PubPeer
Uno es en el que supuestamente demuestran efectos sobre activación de macrófagos. Article CD80 Expression Correlates with IL-6 Production in THP-1-Lik...
Los cuestionamientos a los resultados y el análisis de ese manuscrito están aquí: https://pubpeer.com/publications/F652D5A2B3E986B327EC193923944D
Otro es una intervención clínica con su producto en el Hospital 20 de Noviembre (los médicos que lo administraron dicen que es un medicamento aprobado por las autoridad sanitaria en México seguramente porque les creyeron a los creadores). Se lo dieron a algunos de los niños admitidos a la terapia intensiva con sepsis y según ellos encuentran que la pócima es buena.
Article Dialyzable Leukocyte Extract (Transferon™) Administration in...
Los cuestionamientos a su diseño y a las conclusiones están aquí:
https://pubpeer.com/publications/91A78A7D767A58C3BFD8F7ABACF507
Son buenos ejemplos para enseñarles a los estudiantes lo que no se debe de hacer, tal vez se pueden usar como ejercicios de análisis crítico en "journal club" :)
Wow, ResearchGate just happened to recommended to me a Letter to the Editor/minireview titled "Transferon in 2020", published in both English and Spanish a electronic journal not indexed in PubMed
Article REVISTA BIO CIENCIAS Letter to the editor/Carta al Editor *C...
I find amusing how the authors cite as "evidences" of biological effect and therapeutical usefulness two recent papers that are being questioned in PubPeer.
This one that reports in vitro assays in immune cells https://pubpeer.com/publications/F652D5A2B3E986B327EC193923944D
and this one that reports a not-quite clinical trial on children with sepsis
https://pubpeer.com/publications/91A78A7D767A58C3BFD8F7ABACF507
What they don't cite in their review/letter, however, are the historical retractions of David Dressler, both in PNAS and the Annals of Internal Medicine back in 1975, which undoubtedly ended the existence of the "transfer factor" as a thing that merited any attention by serious immunologists.
Article Transfer Factor: Warning on Uncertainty of Results
Article Authors' statement: the existence and nature of "transfer factor/be/
I am attaching to this post two newspaper articles about the scandalous story of the "transfer factor" back in the 70s. It is a fascinating story, as far as science fabrication stories go.
(I sometimes wonder if the inventors of Transferon don't *know* about all this and they just want to believe in a mirage. But then I think about all the immoral fame and fortune they get by ilegally selling their product, which they *know* does nothing whatsoever to cure anyone...)
What is your opinion on this review and the articles that it cites?
Oh wow. This is a treasure! The references include a lot of unpublished works with Transferon: a thesis dedicated to the potion being given to patients with osteosarcoma.
Every new finding shows the Transferon team is worse than I previously thought!
Thank you so much for this chapter, what book is it?
I'll read it very carefully and post my comments here.
I'm glad you found the chapter useful Irma, I'm looking forward to reading your comments. The book from which I took the chapter is called "Immunotherapy: Myths, Reality, Ideas, Future". Here is the link if you want to check it out: www. intechopen.com/books/immunotherapy-myths-reality-ideas-future.
Problem in Mexico (and likely in other places) is the fact that there is a vast void of knowledge between what constitutes scientific evidence and what constitutes an evidence-based clinical recommendation. People will tell you Transferon has PLENTY of scientific evidence which avails its clinical use (then you ask for a simple double blind placebo controlled RCT for ANY of the wide array of conditions they claim it successfully treats). People lack knowledge of the steps to take towards leaping from basic sciece to clinical trials, and also funding is pretty non-existent for these costly studies outside the private initiative (which has no interest in conducting phase III RCTs for transferon). So, people continue to pursue it, authorities do nothing and the cycle goes on. Same thing for many other "miracle" products, i.e. immunocal. Sad, but true.
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