In May, the Wall Street Journal published an article that describes a new breakthrough in the field of immunology. The breakthrough is that antibodies work inside of cells as well as outside of them. This discovery has huge implications for antiviral treatments and gene therapy treatments. Included below is the full text from the article.
It isn’t often that an entire field of medical science gets turned on its head. But it is becoming clear that immunology is undergoing a big rethink thanks to the discovery that antibodies, which combat viruses, work not just outside cells but inside them as well. The star of this new view is a protein molecule called TRIM21.
Dissident researchers have sparked a big rethink in the science of fighting infection. Yarek Waszul
Until recently, the conventional wisdom was that the body fights off infection in two separate ways. First is the adaptive immune system, which works outside the cell. It generates antibodies to intercept specific invaders, locking onto them like a tracking missile and preventing them from entering the cell. A second line of defense, the innate immune system, operates within the cell; it is like an expansive air-defense network, blasting away at all invaders.
Three years ago work by Leo James, William McEwan and their colleagues at the Laboratory of Molecular Biology in Cambridge revealed that this understanding was incomplete. They found that the neutralization of adenoviruses (common viruses causing colds and other infections) by antibodies was happening mainly inside the cell, not outside, and by an unexpected mechanism.
Their announcement—a challenge to the entire field of immunology—elicited a predictable immune reaction of its own from the establishment. Sure enough, leading journals rejected the Cambridge group’s paper, sometimes without even reviewing it, while key funding agencies turned down the group’s grant applications.
Gradually, though, the authors have won the argument. New papers from the group have pinned down what is going on. They describe a potent detection mechanism that links the antibodies outside a cell with its innate immunity, somewhat dissolving the distinction between the two.
Dr. James’s team has shown that if an adenovirus enters the cell with antibodies attached, those antibodies will attract TRIM21 molecules, which pull the virus into a disposal system and send danger signals to put the whole cell in a state of antiviral alert. This explains the hitherto baffling finding that just one or two antibody molecules can neutralize a virus 1,000 times their size.
The significance of the group’s finding is just sinking in. It gives medicine a whole new angle on infection, and it just might crack the hitherto almost insuperable problem of how to cure viral infections, rather than just prevent them by vaccination. Though treatments do exist for viruses such as HIV, they are neither as common nor as effective as antibiotics for bacterial infections. No effective remedy exists, for example, for the many kinds of common cold, whatever your grandmother says.
Perhaps the new knowledge that TRIM21 and other molecules like it are key antiviral defenders will lead to a true antiviral therapy, though if it was as easy as turning up the volume of TRIM21, then cells would surely be doing it. And it’s worth noting that some viruses (including HIV) use a tactic for getting into cells that allows them to evade TRIM21.
The discovery may aid vaccine design and begins to explain why gene therapy has often run into trouble. Such therapy uses adenoviruses to carry new genes into cells, but frequently this provokes a strong native-immune response. TRIM21 possibly plays a part in this. Finally, there is a chance that TRIM21 will help to explain autoimmune diseases, in which the body attacks itself. TRIM21 itself is a target of autoantibodies in autoimmune conditions such as lupus.
In short, we will be hearing more from this molecule.
Matt Ridley
May 24, 2013
Wall Street Journal
Negative News for Multivitamins: Are There Reasons to Question Conclusions from the Media?
My readers know that in my view, nutrition is everything when it comes to general health and wellness (well nearly everything). Globally there is population evidence suggesting that people who eat a diet emphasizing vegetables and fruits (and thus high density micronutrient/antioxidant food sources) have lower incidences of virtually any disease you wish to look for. We know that vitamins are essential to proper cellular function and energy metabolism- that’s why we call them essential vitamins. Without them, chemical cellular activities necessary for life cannot run.
We know also that eating protein throughout the day results in faster metabolism and lower central obesity. Clearly nutrition and lifestyle are critical to health. So why do the media and a large part of the medical community want to toss out conversations and studies looking at the role of nutrition and supplements on our health? I think it is because it is very hard to control for broad variables like multivitamins and food sources. Doctors are not well versed in nutrition- I recall being told dogmatically in medical school that “vitamins are a waste of money” with very little support of that dogmatic statement. This thinking hasn’t really changed. It is easy to attack things you are ignorant of.
Those that want to tout the benefits of supplements have plenty of water to carry as well. Scientists that have done vitamin studies do a poor job controlling for the supplements used. Good study design is critical for decent science. The supplement industry fails to do good studies and this is convenient for the industry (and equally convenient for the doctors to stay dogmatic). I say it is high time some folks put their money where their mouths are. Meanwhile we consumers have to do our best to eat optimally if we are interested in staying well. The decision to supplement is personal. Based upon the current literature no one should anticipate their insurance carrier paying for vitamins.
The media blitz that preceded two publications in the Annals of Internal Medicine (December 17th 2013 volume 159 Number 12) highlights how the medical community at large enjoys pooh-poohing supplementation of vitamins for diseases. In fact, the editorial provided in the same journal was titled: Enough is Enough: Stop Wasting Money on Vitamin and Mineral Supplements. Below I provide an analysis of the two trials from a doctor’s perspective.
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