Send in the Orphans - A brief history of informed consent!

Most of us accept informed consent as routine and automatic. But given our track record in looking out for others outside our own intimate group, it serves us well to conduct a reality check on occasion.

Throughout history we can find numerous instances where the people in control have preyed on the weak or the powerless. Many people know the stories of the Nazi atrocities during the 1930s and 1940s and the experiments the Japanese conducted on the Allied POWs during World War II, but the use of uninformed or powerless individuals in medical experimentation has been going on for centuries. That still doesn’t make it right, but I have to say I have been more than a little fascinated as I learned just what we humans have done to others “for the greater good of the collective” throughout our history.

A Progressive Champion steps forward

When Smallpox was the scourge of the earth long before vaccination was developed, the practice of variolation was the accepted prophylaxis against Smallpox in much of Asia. Smallpox scaring and complications were common throughout Europe and the mortality rate was significant as well. Lady Mary Worley Mantagu is often credited for introducing variolation to Britain. Her husband was posted as Ambassador to the Ottoman Empire (Turkey today) and while stationed in Constantinople against her husband’s wishes she had their son variolated. Lady Mary was apparently severely scarred from Smallpox herself and in fact had no eyelashes as a result of her own illness and was determined her children would not suffer as she had. She also was instrumental in persuading many of her friends and family to undergo variolation for their children.

A Process is Born

King George and Princess of Wales Caroline, the reigning monarchs of England were intrigued about the success of the procedure and of course wanted the Royal Princesses protected. But first they had the Royal Surgeon make certain it was in fact safe for the young princesses. To insure the safety of the Royal Princesses the Royal Surgeon first had six condemned and jailed prisoners (male and female) variolated. He promised them amnesty if they survived. None of them died. This was good but not quite good enough for the Royal Highnesses. That was apparently a “Phase I” trial. Today clinical trials are often accompanied by catchy marketing generated names that resonate with the Pharmaceutical company or sponsoring entity and a lot of time and expense goes into choosing that catchy name and clever acronym. I think the most apt name for this next Phase II trial could have been “send in the orphans”.

Ten orphans from the St. James Orphans Asylum were selected and variolated. When they all lived The Princess Caroline decided the procedure was safe enough for the young Princesses. Still Variolation was not without problems, some studies show the death rate from the procedure to be as high as 5%, less than that of smallpox (15 – 20%) but not exactly odds that assured people.

The good doctor did what?

The celebrated Jenner vaccine protocol would have had certainly raised eyebrows today. Edward Jenner was a country doctor, but he was educated in London’s St. Georges Hospital under the famous surgeon of the day, Dr. John Hunter. Jenner was a keen observer of nature and was convinced of the prevailing theory of the time that people who recovered from the very benign illness of Cowpox never got Smallpox. When a local milkmaid named Sarah Nelmes came to see him with an obvious case of Cowpox sores on her hands Jenner saw his chance. Somehow he managed to convince a local farmer named Phipps to let him inoculate his son with Cowpox assuring him the boy would never suffer from Smallpox. Somewhat surprisingly the farmer agreed so Jenner inoculated young James who was six years old by making two cuts in his arm and pouring a vial of the Cowpox puss into the cuts. Young James came down with a mild case of Cowpox and quickly and quite nicely recovered.

Then came Jenner’s “Phase II” and if we were to name this study today it would be called “WTF RU NUTZ?”. Six weeks after pouring the cowpox into the kid’s cuts Jenner took puss from a dying Smallpox victim and again made an incision in young James arm and poured in the Smallpox puss this time. Whoa! Did the farmer sign up for this part of the experiment? Fortunately Jenner’s theory was right and young James did not come down with Smallpox. Had young James contracted Smallpox and died, Jenner would surely have faced a murder trial. If an IRB were to be presented with this proposal today their eyes would pop out of their head! The cynic in me actually can’t help but wonder if Jenner didn’t “have the goods” on the good farmer Phipps because I cannot imagine a father even considering such an action.

Meanwhile - back at the orphanage

Even after Jenner’s vaccine to prevent Smallpox was discovered we didn’t end the use of orphans as medical tools. The vaccine was effective, but how did it get manufactured? It was discovered that “arm to arm” inoculation was very effective. That meant once a person had the Cowpox virus inoculated into their body, it could then be extracted and inoculated into another person. Convenient since the only container for a human vaccine at that time was the human body. No such thing as a vial, ampoule or a syringe. Why orphans? It seems unbelievable today but orphans were considered to be the perfect solution. Society had fed and housed them, no one championed their cause. They were less troublesome than convicts (the other disposible group of the day).Usually you just had to have a nun watch over the orphans as opposed to guards, weapons and restraints for convicts.It really simplified that whole “chain of custody” process. Orphans, the perfect biological drug containers!

Not just an English practice

Next came the Balmis- Savony Expedition sponsored by another Royal House. King Charles IV of Spain had lost a son to Smallpox and announced that all the Spanish Colonies of America and Asia would in fact begin a vaccination program using the Jenner vaccine to wipe out Smallpox. The Balmis – Savony expedition was underway with orders to all civil and religious authorities to do what was necessary to insure vaccination of all the King’s subjects. Once again “queue the orphans”. A Royal edict was issued by Charles IV to take 20 children between ages 8 and 10 from La Coruna's Orphans' Home that had never had Smallpox. A plan was devised to pass the vaccine live, transmitting it from child to child as the skin lesions began to extrude lymph from Days 4 to 10 post-vaccination. The initial vaccination was performed in Madrid using 5 orphans who were sequentially inoculated on the way to La Coruna.

The ship was loaded with 21 orphans (along with one unlucky Nun) and the orphans were inoculated sequentially throughout the voyage to keep the vaccine alive until they reached their first stop – Puerto Rico and then apparently the orphans were systematically replaced with local orphans as the voyage worked its way through the Spanish colonies throughout the Caribbean and South American. Balmis picked up 25 fresh orphans in Mexico to transport the vaccine across the Pacific and ultimately on to Asia.

Fortunately we have less intrusive methods of transporting vaccines today. Syringes and vials immediately come to mind. Still, given our nature to take shortcuts and save costs as well as our tendency to use the subjects of convenience, I think history (ancient and recent) has provided us with a lot of good reasons for enhanced FDA oversight as well as a strong IRB process.

Regulations and regulators, considering our history, I am very much in favor of them!

A More Graphic Argument for Global Warming Concerns

Global warming. Nothing chills a room full of people quicker than when that topic comes up for discussion. The debate rages on. I have noticed a new tactic among many of the “deniers”. They have embraced a term that has entered the lexicon of late and made it their own. That term is “junk Science” and it tends to roll of their tongues just a little too easily and with ever increasing frequency. It is my observation that most people who use the term just don’t understand or like science. Since they have no use for it that they can see, they call it junk.

Many good people have tried many an effective means of trying to instill a knowledge or an appreciation of science where none exists. One of my favorite tools in this effort is the visual aid. One such as the following that starkly contrasts the past with the present.

You would think an image showing the early explorers arriving at the North Pole on foot with supplies pulled by dog teams displayed along side a present day picture of the North Pole would have some sort of impact. In 1909 it required a trek with a dog team to reach the North Pole and in 2009 you could send your parents there on a freestyle cruise ship. Something changed but this does not seem to cause worry amongst those so quick to dismiss the concept of global warming.

But I think I have just found something that might at least give them a moment’s pause. Scientists have shown us for years evidence of species relocating into new areas that were previously inhospitable to them because of the temperature or other climate restrictions. As the atmosphere warms, their ranges expand. We now have West Nile Virus endemic through the U.S. and it was never even reported there before 1990. We have seen Dengue Fever return to the U.S. for the first time in nearly a century. But this weekend I learned of a new pest that many people feel is moving closer to us. This one my denier friends you are going to want to hear about. You might even want to re-think your whole opposition to funding the Global Warming impact studies. I give you The Human Bot Fly.

Until this past weekend I had never heard of this insect. Trust me it will now be a long time before I forget it. This past weekend Juan Carlos asked me what I knew about Human Bot Fly infection. My response was, “Huh?”. One of his classmates had just posted on her Facebook page that she had recently returned from a vacation in the Yucatan and had contracted a Human Bot Fly infection that had just resulted in her having a larvae extracted from the back of her head. Once I gotten over the amazing revelation that there really are no boundaries as to what a person will post about themselves on a Facebook page we immediately went to Google for information and oh boy what we learned!

This fly is rather large and very distinctive looking in its appearance so problem solved, just avoid it. The more I read, the more I realized this is a nasty little creature. The female knows she must get her eggs into a host species if they are to survive. There are many different types of Bot flies. Some infect rodents, others cattle and there is a reason this particular one is called the Human Bot Fly. Yes, her eggs are destined for us. Because Bot flies realize they have no chance of installing their eggs into the unwilling host themselves, they have learned how to get others to do it for them. The female employs a process known as phoresis. Immediately after copulating she traps a mosquito or some other small blood feeding fly and she glues 50 or so eggs to their abdomen before she releases the captive. The relieved kidnap victim flies off and finds the appropriate host and when it begins to feed on the host the temperature sensitive eggs begin to hatch. The larvae then enter the host through the insect bite or even along a hair follicle. Some can even just burrow into the skin and they remain inside the host growing and developing until they are mature.

Once they have spent 5 to 10 weeks maturing they then work to the surface and drop to the ground where they molt and develop into an adult fly and repeat the process.

In Brazil the species that infects cattle has been responsible for millions of dollars damage to their milk and leather industries. The problem has been widespread for many years in South America but the Bot flies are now moving farther north. As temperatures increase so does their range. The orange area on the map shows their range as of 2002. Now they have been reported in Belize and Yucatan Mexico. Not just the cattle and rodent Bot flies but also the Human Bot fly.

I finally came to accept the Africanized (so called Killer Bees) bees got here and took over our hives and ruined our honey production in this country. I have made détente with the dreaded iguanas here in Florida but I am not ready to have alien possession of my subcutaneous tissues become a way of life. Check out the video below of the guy getting the larvae removed from his elbow following his Belize vacation.

Okay my Global Warming denying friends, don’t say we didn’t ask you to pay attention

http://www.youtube.com/watch?v=knQGq5V_cUs

Hallelujah its raining iguanas !!!‏

First my apologies to the Weather Girls whose disco and dance hit “It’s raining men” I just parodied, but that revered anthem just seemed to fit so well for those of us down here in South Florida. Here we were this past week trying desperately to heat our homes against freezing weather that they are not designed to face and being forced to play favorites and choose which of our tropical plants we could save after years of careful cultivation. We were being warned of icy doom by our weather forecasters who were delirious at being able to announce climatic disaster since they were all but deprived of a hurricane season this past year. The great freeze of a century had descended upon us and suddenly we are being warned “beware of falling iguanas” Huh? Falling what?

For my friends who do not live in South Florida let me tell you, we have a problem here. Nearly every plant, animal and annoying person on the planet strives to relocate itself to South Florida. We are in a constant state trying to rid ourselves of annoying exotic plants that choke out our native plants, annoying people who think they are exotic but actually are just whiners who complain incessantly about Florida while they are in Florida and then there is the iguana. We all usually overlook or excuse all but the meanest of the offending people and defend most plants but in general most of us unite in our mutual dislike of the iguana. It is our way.

How does a small green lizard become such a polarizing figure? First, they don’t stay small or green for long here in Florida where they have few competitors as they do in their native habitats. They begin to look less like a lizard and more like a dinosaur as they grow. Here a large number of them grow to as much as 6 feet in length. They range in color from green to brown to orange. They have large sharp claws for climbing and eating our plants and fruits and these claws work well at scratching if we try to capture them. They have sharp teeth that have been known to remove finger tips and leave stitch requiring bites as well. They have dug and burrowed and undermined our roads.

They are notorious for eating the blossoms of our orchids and hibiscus plants but as far as we can tell no plant is spared. My friend Rob in Fort Lauderdale was out on his hands and knees planting a border of impatiens in his yard when he looked back and saw an iguana was following him eating all the blossoms from his plants as fast as he was putting them in the ground. They eat any and all manner of fruit from berries to figs to bananas. They spare nothing.

As much as they eat, it is no comparison to the quantity they seem to poop. They are especially fond of pooping near water. As many of us have learned “near water” is defined as on our pool furniture, patios and decks and boats and boat docks. They poop everywhere and anywhere that they think will annoy us.

So when the weather man who usually screams for days in advance that a hurricane is eying us suddenly announces with the same glee “the iguanas are falling”, he has my attention. I needed to know more.

In their native countries they apparently have no need to exercise their ability to hibernate like our native reptiles do here, so they do so rather haphazardly. It never occurred to me that hibernation was a learned process. So like Cinderella at the strike of 12 on ball night, picture this. As soon as an iguana’s body temp hits 40 degrees, it just shuts down. Boom! It just goes to sleep wherever it is. At any given time the majority of them are apparently in a tree top and suddenly their claws just let go when their body hits the 40 degree mark and they faint and they fall. Thus we have “iguana drops”. Reports of iguanas going thud were all around us last week. They fell to the grass, they fell onto pool enclosures, they fell and dented automobiles and at least one reportedly hit a pedestrian. We had more reports of iguanas down than we did confirmed snow and sleet sightings in South Florida.

So I had to investigate further about this phenomenon. Hibernation as we learned in school is reversible, but they didn’t always teach us there is a caveat. In the case of these iguanas, if they stay frozen for three days or longer their chances of revival are dramatically decreased. This is good news. We all hate them but we all differ in how we “exclude” them. We all want to “repel” them which is a polite way of saying, “let’s just transfer the turd drop from my house to yours”. Not a good neighbor inducing solution. But when it comes down to it most of us just cannot actively participate in the actual killing of these nuisances. We want them dead, especially after finding a large deposit of poop on one of our Smith & Hawken poolside cushions, but still we had rather outsource the actual kill. Most of us will agree to allow them to be “culled” humanely. Humane as we have learned is very slippery to define. Even the most hardcore iguana haters among us felt bad when we saw the picture of a dead iguana with a cross-bow arrow protruding from it. But the approved humane way to kill them is to cut their heads off with one swift strike of a shovel. Oh yeah, that is a whole lot better than a cross-bow, right?

Still, I imagine by the time one has wrestled an iguana who is whipping you with his tail, snapping with his teeth while he claws you with all his might as you put him into the position for one swift shovel thrust is going to win at least half of those shovel execution attempts. Perhaps the shovel game makes the whole process more sporting but I find the prolonged freeze possibility a more palatable solution. If we are going to lose our hard worked gardens to the freeze some good just has to come from the event. Let it be the iguana culling by natural cryogenics.

Still it is inevitable, a number of us manage to screw this up. In Deerfield Beach a man supposedly began collecting the frozen iguanas from the ground in a large plastic hefty lawn bag which he threw into the back of his station wagon when it was full and as the story was reported he planned to take and dispose of them humanely. Unless someone can tell me where a drive up shovel execution squad is located in South Florida I will assume he was headed to an even more humane solution but the article did not elaborate. Still, he screwed up.

What happened next is why it is important to pay attention in science class. The bagged iguanas began to revive inside the lawn bag in the back of the station wagon and they were not happy. They began to claw their way through the plastic bag and startled the driver when one of the beasts climbed onto him as he was driving. Fortunately there was no accident. Apparently no one in South Florida is cursed enough to warrant being hit by a vehicle filled with unwanted reptiles. I don’t want to be called on to defend that assumption too strenuously. Not after the many stories we have heard about some of our citizens (especially politicians). I’m surprised it doesn’t rain toads down here yet.

Not only do we have these brainiacs trying to take iguana disposal into their hands, we had one guy in Pompano Beach who was so moved by the plight of the fallen frozen freaks of nature he actually cranked his truck up and began to thrown them into it to revive them in order to release them again into his neighborhood because he took pity on them. How special.

To all my friends who are dealing with the iguana poop I have an idea. If we can find where this guy lives I think I know a way we can rid him of his misplaced pity and his misguided need to be an iguana Samaritan. Start saving those poops and wait for instruction.

Meanwhile, I say we investigate doing to iguanas what the Texans used to do for unwanted rattlesnakes in Texas. Find a sponsor for an “Iguana Rodeo” and start promoting an “Iguana Cook-off”. I am betting there are some recipes out there we could use. Lets plan this quick before the population begins to re-build after this once in a century freeze opportunity.

Any questions or comments about my blog, send me an email at L.Lynam@theLynamGroup.com or visit my website at www.thelynamgroup.com. The Lynam Group - where Comprehensive Biotech Consulting Services Begin.

NEW - Pharma Guidelines re: Trade Show Giveways

Hi all,

Since the “no more pens and pads” rule has been put into place by PHARMA Guidelines many folks have been speculating on what is going to pass muster as give ways. Walking the exhibit halls at several recent shows including ICCAC in San Francisco, ISDA in Philadelphia, AABB in New Orleans and AASLD in Boston I was curious to see how different companies and organizations were treating the guidelines.

One observation that became quickly apparent is you can readily distinguish between which companies sold prescription drugs and which companies did not. If the companies were not promoting a prescription product they seemed to be carrying on business as usual and pens, pads and a whole array of branded trinkets were being handed out no problem. But, when you were at a booth where prescription drugs were promoted it was apparent that people are still coming to grips with how to proceed in this new environment. Not a pen or pad among them but there was an interesting array of alternative practices.

Beginning at ICAAC I noticed that the coffee / refreshment bars are still being provided and they certainly seem to be doing their job to attract people into the exhibit areas. I silently thanked God that some civility remained in this world and coffee had not been entirely banned. I noticed many companies had a small discrete but clearly visible sign that displayed the message if you are from Vermont, Massachusetts (and sometimes a third state that seemed to vary but New Hampshire and even California were often added to the sign) we …….

Insert one of several variations including

…. ask you not to partake of our refreshments as it is a violation of your state laws

… must inform you it may be in conflict of your state laws etc, etc

You get the idea but they generally politely fulfilled their obligation of making people aware of the laws they were complying with today.

But I did find that a few had managed to come up with a giveaway that had at least some perceived relevance. I collected a number of CDs that had animated mechanism of action videos. Schering was one I received at ICAAC that I thought was very well done and would be useful in educating medical team members and even patient and consumer groups. Pfizer was offering what they claimed to be very nice disease state photo collections and slide decks. They were nicely packaged and while they were what they claimed to be, they really were lacking in substance that I thought would be useful if I were a practitioner looking for a quick source of materials to put together for a balanced clinical presentation. The slides were of excellent quality on the Pathogen disk. But there were only 4 images, in several formats. Still they at least accomplished the goal of putting the Pfizer brand on a promotional piece that had just enough utility that it would survive the trip back from the meeting and into a place on the shelf or desk where it will be seen and recognized for years to come. Mission accomplished Pfizer!

All in all I think I was impressed with what several companies did to come up with as an item that will outlive the show and make it back to where it will be a subliminal reminder of a corporate commitment for years to come. Face it, most of us never get rid of our reference sources no matter how little the contribution or outdated the material. My perfect example that is despite having a current edition of all the reference texts I use in my work I still have shelves of outdated materials that I just can’t seem to part with yet. This includes a 1970 Human Blood Cell Morphology Chart put out by Abbott Laboratories back when the stem cell was still just a theory! Nostalgia, I hear it can be treated with intervention. I should possibly consider this. But promotions do live on, occasionally in infamy.

But when I got to AASLD I found there was a whole different way of handling the Pharma Guideline. Welcome to what I call “ Apartheid 2.0 - The Pharmaceutical Solution”. As I strolled the exhibits I walked into one booth that had lots of traffic going on inside its cleverly arranged stylish walls that were decorative on the outside but did not readily reveal anything about the company or give a clue as to what was going on inside that booth. I was greeted by a smiling representative standing between me and what was I judged by the contented and happy chatter carrying on behind her was a very amicable group of people being happily engaged in some sort of fun activity. She looked at me, smiled and said, I am sorry but this is only for non-U.S. attendees. She waved her arm to point to an empty booth down the corridor being manned by one rather bored woman sitting on a stool and playing with her Blackberry. She told me that was for the U.S. attendees.

As I walked away curious as to what was going on behind that wall that I was not privy to I knew one thing, I did not care if they were giving away coffee, massages or even a high colonic but I instinctively knew I had just been given the bum’s rush and I had no intention of stopping to visit with bored Miss Blackberry reader no matter what they were promoting. Note to companies taking this approach …… hello, do you not know a snub when you deliver one? I bet you recognize it when you receive one. Think about it, do you ever forget it. I know I don’t.

I did not go to AHA in Orlando but I just saw this one. Pfizer, I thought you were on the high road with those slide decks and educational material. They were at least something that had a chance to add a little value but come on now, how did you ever make the leap from “ Pens are bad” to “Poster size Photo of the Doctor is good”? Somehow the logic escapes me.

Stay tuned to see what the next show season of post new PHARMA regulations delivers.

Any questions or comments about guidelines or my comments, send me an email at L.Lynam@theLynamGroup.com or visit my website at http://www.thelynamgroup.com/. The Lynam Group - where Comprehensive Biotech Consulting Services begin.