Bite Point

Switching Gears

When I'm cycling and face a steepening hill, or, worse, a headwind, I have two choices.

Most of the time, it's a good strategy to shift gears, to downshift and reduce the effort that it takes to keep moving. It's appropriate. After all, I have to get up the hill, have to force my way into the wind. I'll slow down, but my workload stays the same.

Sometimes, though, that choice just seems like I'm giving in. Sometimes, I stay in gear.

And work harder. Smarter.

When you face a challenge, do you downshift, or stay in gear? Every situation calls for its own answer.

 

 

Postscript:

 

We can't change the hill that we face.  Wind resistance is going to be there, and the faster we go, the more resistance we face.  What can we control?  We can keep ourselves in shape.  And- we can reduce friction by keeping the bike clean.  Clean, well-lubricated moving parts perform their functions effortlessly, with very little friction.  This makes the hills and the headwinds easier to deal with.

 

So it is with ourselves and, may I suggest, our businesses.

Phage Therapy. Look Who's Coming To Dinner...

I am a member of the Philadelphia Academy of Stomatology, a dental continuing education society founded in 1894.  And, no, I was not a founding member!  We have four scientific meetings each year with a formal discussion session after each presentation.  My colleague Joe Greenberg DMD and I currently share the duties of Essay Chair, where we arrange the lectures.  (In case you were wondering, "Stomatology" derives from the Greek word "stomos", meaning "mouth".  A fine example of this word is in the name of Saint John Chrysostom.  Reknowned for his eloquence in public speaking and preaching, he was given the surname chrysostomos, meaning "golden mouthed".) 

Last October I invited Gary Pasternak MD PhD to speak on the subject of bacteriophages and their use in medicine and, perhaps, in dentistry.  He is a principal with Intralytix Inc., a Baltimore-based biotech company.  Dr. Pasternak is former Director of the Division of Molecular Pathology at Johns Hopkins Medical School, and a scientist with significant biotech/industry experience.

http://intralytix.com/

From the Intralytix website:

"Bacteriophages (or phages for short) are viruses that infect bacteria. The name was coined by one of the discoverers of bacteriophages (Felix d’Herelle), by combining the Greek “phago” meaning “to eat” or “to develop at the expense of,” and “bacteria.” Phages are the most numerous organisms on Earth, and they can be found – often in prodigious numbers – in every living ecosystem. Phages are highly specific for bacteria, and they can not infect eukaryotic cells; i.e., those of humans/animals and plants. Moreover, one phage can only infect a subgroup of strains within the same bacterial species, without affecting strains of other bacterial species."

This last bit is extremely important to understand before we go on.  Phages have evolved for millions of years to target specific bacteria, and unlike viruses that can harm us such as influenza, these little vixens do not pose any threat to us at all.  As a matter of fact, there are probably about a trillion of them on each of our bodies right now.  Dr. Pasternak pointed out that if our immune system tried to fight them, we wouldn't have any energy left for anything else!  So, they leave us alone, and we leave them alone.

Again from the Intralytix website, here's how phages work:

"Intralytix’s phage technology is based on the philosophy that naturally-occurring bacteriophages provide one of the safest and most environmentally-friendly, targeted approaches for dealing with bacterial infections in a variety of settings. Phages are “Nature’s way” of controlling bacteria on this planet, and they have played and continue to play a critical role in maintaining (via a well-balanced predator-prey relationship) microbial balance in every ecosystem where bacteria are present. Thus, Intralytix’s philosophy is to use this natural approach to control pathogenic bacteria in limited, specific settings where those bacteria may cause human illness or other problems."

What a phage does to earn its living is, when it comes into contact with the correct bacterium, it attaches onto the outer cell wall and then injects its DNA into the bacterium.  The phage DNA carries instructions to make more copies of itself, often about 20.  Phages basically take over the cellular machinery of bacteria for their own purposes.  When the new phages are assembled, they lyse the bacterium- which means that they explode it, releasing the new phage copies into the environment, only to start the process over again.

Here's a graphic and Scanning Electron Micrograph of phages attached onto the bacterial cell wall:

 

 

(File pic from the Wikipedia Commons: http://en.wikipedia.org/wiki/File:Phage.jpg )

So, here are some advantages of phages over antibiotics in medical uses:

-Phages are more natural.  They are everywhere; treatments simply consist of concentrating three or four strains of phage that attack the germ in question and then delivering them to the wound or other site. 

-There is a tremendous and developing problem with bacterial resistance to antibiotics; resistance to phages is minimal; recall that they have evolved for millions of years to do what they do and overwhelming germs with several kinds of phage at once is very effective.

-Antibiotics must be dosed every few hours to make up for the decreasing concentration as the body metabolizes the drug.  Bacteriophages multiply themselves by 10 or 20-fold each generation, which takes less than a few hours.  They basically increase in number until all the target bacteria are dead, then they go inert- since there's nothing left to do.  (Most biologists don't really consider them "alive" at that point).

According to Dr. Pasternak, this type of medical treatment will probably always be a "niche therapy".  It is most effective when the phage solution can be applied to an external surface like a wound.  Yet consider the advantages in certain situations- multi-drug resistant MERSA, multi-drug resistant ear infections, delayed wound healing.  He showed cases of impaired wound healing caused by bacteria (in those pesky biofilms, of course!)- after the topical application of phage solutions the healing was rapid and complete.

In dentistry we have found that one specific germ, Strep mutans, has a direct and key role in the formation of cavities- see "The Resurgence of Dental Caries".  It may be a promising preventive or treatment strategy to make a "phage cocktail" against tooth decay.  Periodontal disease is more complex in terms of the germs involved but we do know the main players here too- see my post "Gum Tissue Is The Issue".  Phage may be useful in treating this chronic disease as well.

A final and intriguing use is in the food industry.  If Salmonella or other food-borne pathogens become established in food processing facilities- and, really, how could they not?- then surface and equipment decontamination with bacteriophage is an excellent and already proven strategy.  Again, that magnification of numbers is unstoppable- far better than using exotic and toxic chemicals that are fear today, gone tomorrow.

Finally, I know that thinking of so many of these little beasties on and around is is kind of freaky.  It helps to remember that they are not really "alive" when they're dormant, which is at all the times that they are not attacking the bacteria that are their prey.  Also, there's a whimsical side to all this- you can buy Phage t-shirts on cafepress.com, for one:

A Plasma Torch For Dental Treatment. Really.

Once again, it's all about the biofilms.  Recall that these are habitats that bacteria set up for themselves, made of a polymer matrix of various substances, and the little nasties do this in and around our teeth, every chance they get.  Bacteria in such a film are harder to kill than isolated individual ones.

For example, in root canal treatment, we currently open up and clean each canal all the way to its end, and then use irrigants to kill the germs and dissolve as much debris as we can.  There are always bacteria left behind in the millions of tiny channels that exist in teeth; the idea is to entomb them, wall them off so that they become inactive through lack of a food source.

This strategy fails too often because of two issues.  One is that the commonly used root canal filling material, "gutta percha", cannot be bonded to,  there's always a weak seam between the gutta percha and the cement that seals it in, and bacteria can travel along this seam.  The other cause of trouble is that in conventional techniques the biofilm on the root walls has not been broken down.  Again, germs can survive better in a biofilm than they can on their own.

Great progress has been made with improving both the technique and the filling material.  My friend Martin Trope BDS (http://www.tecendo.com/index.html)is the principal inventor of "Resilon", a material that, like composite resin tooth restorations, bonds to the walls of the roots into which it is placed.  No weak, open seam.  In using this material we also treat the walls of the roots much more rigorously and deal with the biofilm more effectively.  This material and the associated techniques comprise a major advancement in root canal treatment.

Yet wait until you hear what's being studied now!  Dr. Chunqi Jiang, a physicist at the University of Southern California, have been experimenting with a possible new method of cleansing the interiors of infected teeth: a dental plasma torch.

I know, I know.  I can already hear the script that's going through your mind:

"Captain!  The Romulan vessel is targeting a plasma torpedo directly on... on your upper right first molar, Captain!"  (brief pause)  "Shields!  Fire photon torpedos and phasers!  Hit 'em with everything we've got!  And- hurry!"

I promise- it won't be like that!

Plasmas are gases in which the molecules have been stripped of their electrons to create positively charged ions.  Normally a great deal of heat is involved, and high temperature plasmas are what we think of when we hear about exotic physics experiments, or when we see images of the Sun with those massive and beautiful solar flares.  Dr. Jiang, however, has designed a device that uses very short pulses of electricity to ionize air to create a cool plasma jet that is rich in oxygen ions.  It's purple, by the way.  The special benefit of oxygen ions is that they are extremely destructive to bacteria and biofilms.

Progress so far?  Dr. Jiang and her team report in Plasma Processes and Polymers that when their Purple Plume of Plasma was aimed into the root canal systems of infected teeth, it succeeded in clearing up said infections completely.  The plasma flows and penetrates so well that it disinfects even in the hardest-to-reach areas of the interiors of teeth.  Also, "non-thermal plasma" appears to be safe to surrounding tissues.  Here is a very nice scanning electron micrograph of the results of the plasma treatment in an extracted tooth:

-All of those squiggly lines on the upper right portion of the photo are bacteria, and on the lower right we see clean "dentinal tubules", the microscopic channels that are supposed to be there; these are normal structures inside teeth.

This approach may turn out to have many other applications in dentistry, such as in treating gum disease, and also in medicine overall; wound infections definitely involve biofilms.

Whatever the outcome of this particular line of research, it is becoming clear to me that in the 21st century, dentistry is going to be about managing the biofilms.  Cavities, periodontal disease, root canal infections- patients can be freed of much of these ills if we become extradinarily skilled at this kind of manipulation.

After all, the old joke is that dentistry is the only business that is constantly trying to put itself out of business- through prevention.  I suppose that's still true.