Sadly, it’s not spam mail requesting to deposit gold into our bank account.

A law firm is gathering information about adolescent JUUL users. The law firm is based in New York. On their landing page for this - let’s call it a ‘scoping out operation’ - is a list of potential issues with vaping. The list is a decent length and highlights possible problems with vaping, including the now infamous popcorn lung. In over 10 years of e cigarettes being available there has not been one case of popcorn lung recorded as a result of vaping. Even the UK Government have popcorn lung down as a vaping myth to be debunked.

The initial reaction to this news was, well, lawyers are not dissimilar to vultures, they’re circling because they can smell a possible carcass and an astronomical amount of money. Somebody has sensed the climate, perceived a financial opportunity, so set out their placard.

Legal 2

Which means we – vapers - now have the FDA gunning for JUUL, we have an Attorney General gunning for them, and now we have a legal firm.

The firm involved state morality and ethics as their mission behind their actions: “we strongly believe that product manufacturers, pharmaceutical companies, and health care providers have a moral and legal duty to look out for the best interests of their customers and patients. When these parties are negligent and hurt our clients, we work to hold them accountable in court for their actions!”

Perhaps they should read our last post about flipping the script and go after the anti-tobacco lobby and their negligence? On their landing page the legal firm state their case and as one would expect, they refence some of their statements. If we look at one research paper they are offering up to entice people to submit evidence, it’s quite an interesting read.  

They quote this paper: Nicotine and the adolescent brain, based on rodent studies as the basis for claims that nicotine damages the teenage brain. This is science comparing complex teenage brains, to those of teenage rodents.  The researchers believe that nicotine is in fact a gateway drug to substance abuse, and conclude the abstract by stating, “We argue that nicotine exposure, increasingly occurring as a result of e-cigarette use, may induce epigenetic changes that sensitize the brain to other drugs and prime it for future substance abuse.”

They begin the body of the paper:

“Although relevant clinical work is discussed, this review focuses primarily on adolescent rodents, which exhibit many of the same physiological and behavioral changes as human adolescents (Spear, 2000) and are more appropriate experimental models for drug studies. We argue that the rapidly changing, immature adolescent brain has differing sensitivity to drugs such as nicotine and tobacco, and drug exposure during this time can lead to long-term changes in neural circuitry and behavior.”

They then go on to state though, that actually no one can agree when adolescence starts or ends, because it appears it could be part social construct on a moveable scale?

 “However, defining the boundaries of this period and what it encompasses is contentious. Some report that changes signaling its onset emerge as early as age 10 in humans or P21 in rats (Sturman & Moghaddam, 2011; Hollenstein & Lougheed, 2013; Burke & Miczek, 2014). Similarly, maturation may not be complete until the mid 20s in humans or around P55 in rodents (Laviola et al. 2003; Burke & Miczek, 2014). Since adolescence as a whole has no obvious events to signal its beginning or end and individual as well as sociocultural differences influence the timing and duration of this period, its boundaries remain a grey area.”  (emphasis ours)

Plus, in one of the research paper referenced in the one linked above – they state rat adolescence could be P28 to P42.  (P referring to the number of post-natal days alive). So, no one can agree on the start or end of adolescents in either rats or humans.  

The paper continues: 

 “Moreover, the relatively rapid changes in neural systems involved in emotional and reproductive function that occur during puberty do not match the maturation of other cognitive systems that extend further into the adolescent period (Dahl, 2008).” Meaning we can’t really use puberty as a marker either, because: “Pre-pubertal increases in neuroactive adrenal steroids, such as the androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), have also been associated with neurobehavioral changes of adolescence in humans and non-human primates, but corresponding effects are not seen in rodents”

This is all getting a tad confusing…

Are we then to understand, that rat studies, based on adolescence, that we are not sure when it starts or ends, and parts of it may or may not be in the rats but maybe in humans, are then going to be translated and applied to humans?

As we said, it’s confusing.

But then we have it, right at the end of the paper:  The very reason for the research and the inclusion on the legal landing page.

With increasing evidence that aberrant activation of nAChRs during adolescence triggers lasting changes in neuronal signaling, use of drugs containing nicotine may have potentially severe consequences for teen addiction, cognition, and emotional regulation. Thus, not only tobacco but also e-cigarettes must be considered as serious threats to adolescent mental health. E-cigarettes were initially introduced as a promising tool for smoking cessation. However, lack of federal regulations and a wide selection of flavors make e-cigarettes not only accessible, but also appealing to young people (Grana et al. 2014). Indeed, emerging clinical evidence reveals that more teenagers currently use e-cigarettes than tobacco (Dutra & Glantz, 2014; Wills et al. 2015).

The holy trinity of anti-vaping : Flavors, lack of regulation and teens.

Let’s now look at rodent studies from another angle.

Why is it not a good idea to use rodent studies?

We suggest you sit down for this answer, provide by Epidemiologist Carl V Phillips. He explains how scientists calculate the dose to give to a rat when conducting rodent research.  He uses the example of cancer studies.

With cancer, however, the whole megadose methodology is based on a theory known as LNT (linear, nonthreshold). Basically it says that each quantity of a possible carcinogen, divided by the weight of the body that is exposed to it, always causes the same probability of cancer. So if a 70 kg human is exposed to X per day for a year, the risk is the same if a .07 kg rat is exposed to X/1000 per day for a year. Moreover, the theory says that to model the risk for that human’s exposure for 50 years, you just need to multiply the rat’s dose by 50. Since no one wants to run the experiment for a full year, though, they cut it down to 2 months and increase the exposure by another factor of 6. Also, they do not want to use 100 rats to represent the risks for 100 people, so they increase the dose by another factor of 10 so each rat has the collective risk of 10 people.

According to LNT, that 3000-fold overdose means that each rat, over the course of 2 months, has the same probability of getting cancer as at least one of 10 humans who vapes for 50 years.” (emphasis ours)

We kid you not.

But to ensure you understand the deeper criticism of rodent studies, not the initial – wtf??? Carl Phillips explains further: “The estimates from that model are incorrect not because the dose is unrealistically high (the simplistic criticism) but because the LNT model for converting the effects of that high dose is known to be badly wrong.  

To summarize, the risk from cancer (and even more so, for other diseases) is not linear across the dosage, the time over which that dose is accumulated, or body weight. Also there is apparently usually or always a threshold (i.e., until you get up to some minimum dosage level, there is no risk), models might produce some positive estimate of cancer risk when there is actually zero risk. In addition, there is the problem that mice are not just little humans. Carcinogenicity in mice is not even a very good predictor of carcinogenicity in rats, let alone in humans. Again, biology is complicated.”

He continues:

To summarize, animal toxicology models are useful for a few applications, but they have almost no useful application to vaping exposures.

In this one post – we have shown that one paper, regarding nicotine and the adolescent brain, taken from studies on rats, is interesting to say the least. We have also shared information about the LNT method of calculation during rodent studies. Was the LNT method used in the rodent studies to observe changes in the adolescent brain, because if it was, wouldn’t this have skewed the results? The researchers mention high doses of nicotine, and bearing in mind what we now understand about the LNT – what does high doses mean? One would hope that it wasn’t used, and all that we have is interpretation and application, based on possibilities, because this is the only interpretation we have. One wonders though how much this application of rodent to human has been questioned and challenged?

We fully understand the reasoning behind rodent studies and that it would be considered unethical to study the adolescent human brain while the owner of said brain was using nicotine, but can these findings, that will probably be used in a court of law, truly be translated to the complex world of teenagers in the 21st Century?  No matter what many of us think of teenage offspring, they are far more complex than rodents.

Here’s a closing thought. What if adults responded to the legal landing page, and gave their experience of vaping, and how it is an adult product, and how it has changed their lives for the better; it would certainly make interesting reading for our ambulance chasers.