Explaining how antibodies work

As part of the fundraising effort on Indiegogo was a blitz through the various pet-centric blogs and websites KA found on the wide world of the internet. PER, KA, and i all took a set of websites and wrote directed emails to ask for help spreading the word of the fundraising to a broader audience. Of the dozens of blogs/websites i have written to, i've gotten two replies thus far (the writing begun around Christmas, we are now 5 days into the New Year). One reply was a request to remove the recipient from our mailing list, and the other was an offer to help along with directed questions about the work and drugs that CanFel is trying to bring to veterinary medicine, specifically, questions about antibodies and how they work.

So, over a rapidly cooling mug of coffee, the following is what i wrote back:

One good way of thinking about antibodies is this. 

First, some ground rules. Antibodies are designed to target cellular proteins and, through the binding of the cellular proteins, affect the cellular protein's function in one of three ways: activate the protein, inhibit the protein, or do nothing. Obviously, the do nothing antibodies are not much good for therapeutics 8). However, the activating or inhibitory antibodies are of therapeutic usefulness, as they can be used to tip the biological balance of cells. 

Second, cellular proteins are outside in signal transducers in the most part. They tell the cells they are on what is going on outside and if the cell should grown, arrest growth, or even self-destruct (a very important biological function actually, but that is for another time perhaps). Aside from signal transduction, some cellular proteins also act to stabilize cells on whatever surface they are sitting on, or act as treads so a cell can have "traction" as they move, or act as tension modifiers to govern how rigid a cell is.

Third, cellular proteins are actually highly mechanical in form and function. For one protein to interact with another protein, there must first be compatibility in form, a lot of time, the interaction of the tumblers in a lock and the key designed for the lock is used to illustrate the importance of form in protein interaction. After the compatibility in form is satisfied, the proteins interact, and the interaction will then send a signal into the cell. This signal is generally triggered by a secondary mechanical event. This second event could be a clustering of proteins, assembling a macro-molecule that is now capable of signal transduction, or a physical change in the protein's shape so that a previously hidden part of the protein is now accessible for function.

So, here is where the antibody comes in. An antibody is also a protein, so it is designed to interact with its target in a specific way. When an antibody is, for example, interacting with a protein in the region of the protein important for that protein's interaction with other proteins, the antibody can effectively block the protein interaction by acting like a piece of gum stuck into a lock and blocking the key's entry or something more subtle, like padding a few tumblers so they are stuck in one position or move too much or too little and jam the lock. The antibody can also bind to a protein in such a way that it acts as a clamp, so when the protein is activated to undergo a mechanical change to transduce a signal, the antibody - as a clam - has restricted the ability of the protein to undergo mechanical change.

So now, lets go to a real world example. Take the lights in your house. They are operated by a switch. The switch is a binary function, on or off. Your house, in essence, is like a cell. When it is tumorous, it has all its lights on. When it is normal, some lights are on, some lights are off. So, how do you go about preventing the lights from all coming on? Well, you can terminate the electricity. That is a very efficient way to kill the lights (as it were), but then you will be in the dark. An antibody, in essence, gives you a tool that allows you to disable certain switches. For example, you can have an antibody that is specific to a circuit breaker - shutting off entire set of switches - or antibody to a specific set of switches - shutting off only certain lights. These antibodies would behave in such a way that you can't physically turn on the switch or it will disable the wires to which the switch goes so that, even if the switch is flipped, no electrical signal is sent.

An accidental career...

In life there are accidents, some of them happy, many of them sad. My career, what of it there is, begun on a happy accident. That accident, after 22 years, has found me here, neurotically monitoring the Indiegogo campaign and hoping that there are, out there, other visionaries and pet lovers like CanFel principles.

It was about halfway through the semester in 1992. i was a Sophomore majoring in English and Biology (soon to be just majoring in Biology) and finding it difficult to make it to my Cell Biology class due to personal laziness and a dire hatred for the professor teaching the Cell Biology session i was in (the class was taught by two professors, Dr. M and Dr. H, i had Dr. M). That all changed after a string of events beginning with a rather uninspiring day and a night of college boredom. One of my floor mates, a Chinese fellow who was on the Pre-Med track (who, of Chinese ancestry, wasn't on a Pre-Med track?), came into my room at Myles Standish (3rd floor, overlooking the undertakers across the street) asking if i wanted to accompany him up to the 8th floor to be "moral support" as he asks out a gal who caught his eye in Japanese class. Suffering from utter boredom and needing a more concrete excuse to not study, i happily agreed and jogged up the stairs with him. What unfolded next was the happy accident that set out the course of life which resulted in me, sitting here, tapping out these words.

The empty 8th floor hallway was lit a sickly yellow green by the overhead lights reflecting off the thick - sometimes slightly tacky - white wash that covers everything in the building. A door was knocked upon by my floor mate, and we waited quietly. The door opened, revealing a darkened room. An image that shook my very core appeared in the threshold, frame by the alluring, captivating, enchanting darkness. She, also of Chinese ancestry, was a super Pre-Med, being in the 7 year MD program. She was, in my life at the time - yet perhaps still strangely so - the most beautiful and wondrous person i have ever set eyes on. Then she spoke. It was as if golden melodies shattered the staid world i had lived in so far. Hell, i think even the drab Myles Standish hallway brightened and beautified itself in my eyes.

She was also a Sophomore, she was also taking Cell Biology, but she was in the 8 AM session taught by Dr. H (i was in the 5 PM session taught by Dr. M and regularly found myself unable to get up early enough for it).  All this information i found out by hook and by crook. Then one morning, i saw her leave the building. Three more days confirmed her normal departure time for me (yes, i was stalking her). That led to my first visit to the main library on campus. Which led to me sitting in on Dr. H's Cell Biology class. Which led to my continued attendance of Dr. H's Cell Biology class and a visit to the registrar's's office to officially change sessions. Which led to my realization that, yes, MRK may have been the impetus that drew me to her Cell Biology session, but i've been, through Dr. H's energetic lectures and passion for the subject, made a Cell Biology convert. My innate interest for biology was revived and glowed brightly next to my absolute adoration and love for MRK as i sat there in Dr. H's Cell Biology class.

That love for cell biology resulted in me taking every high level biology class the university had to offer (though at the same time i neglected my non-biology classes - addictive personality, what can i say). It led me to volunteer my time (sans pay) in Dr. H's lab, where i would begin days dissecting three dozen eggs to harvest embryonic chicken retinas and then head off to Mal's for the "Country Breakfast" and the three mugs of coffee that comes with it. My time at Dr. H's lab reinforced my love for bench research, MRK's continued education for her MD after University gave me reason to stay put and land a job in the lab of CAP. CAP would become my mentor and surrogate father, and his kids my siblings. CAP would be one of my few friends who i would continually keep in touch with and sought out for advice in my times of need. CAP would also instill in me my love for human neutrophils and the beauty of the epithelial tight junction. MRK's return to CA would drive me to ask CAP for help getting me placed into a job in CA, and, though MRK and i ended up splitting up a mere week after my accepting of the job, i couldn't find it in myself to renege on a job i have committed to. The job led to my return to CA, resulted in my meeting of JPM and PER and, most importantly, my wife. Meeting JPM and PER resulted in my dedicating 10 years of my life to what i still consider to be one of the finest biotech ventures i've ever seen. Leaving JPM and PER allowed me to meet KAT, who i consider to be a dear friend and who facilitated me sitting here today writing this blog in front of my computer as my PCR reactions crank away in a Bio-Rad PCR machine.

All this, from one happy accident of me, being bored, in 1992 saying "yes" to a a request for "moral support".

So thank you, my Chinese floor mate who's name i cant' recall.

January 1st, 2013

Begun like the past handfuls of first of Januarys. In the warm house of R&C, surrounded by tipsy friends, hoisting crustal flutes of champagne as we all bade everyone a happy new year. Then comes the accounting of the remaining wines and R and i setting to work so that we "waste not want not". The year of 2013, the Year of the Snake in the Chinese zodiac.

The thought of it being the Year of the Snake, i recall, struck me as rather odd, having being born in the Year of the Rat. i remember thinking to myself, does this mean that the year will simply consume me, digest me, and excrete me with barely a thought? Would i be a nourishing meal? Would i be remembered for a particular taste? Possibly my high fat content? Or will i be forgotten, ingested like the millions of Big Macs served world wide?

2013, it turns out, was a strange year, a strange year where i walked out on a perfectly good job because of my personal idiotsyncracies, "principles", and an exaggerated sense of self worth. Where i discovered exactly how unremarkable my set of skills were in the biotech marketplace and was taught a lesson of humility over how common a non-degree'd grunt like me really is. Where i began a side career as a consultant and was aghast at the world of Contract Research Organizations and Contract Manufacturing Organizations. Where i then got horribly lucky, due to a very dear friend, to land my current job. Though, instead of being grateful to her, i've pestered her exceedingly with daily emails and requests for dinners. Yup, Year of the Snake.

Yet, it was still a year where i gained more than i have lost, and to that i am grateful to the slithering bugger of a Year.

Though i still don't know what kind of a meal i was... but i guess, it really doesn't matter. There are only so many more years left in me, and i doubt the ol Snake will get a chance at a second bite in twelve years.

Happy New Year all, onward to the Year of the Horse.