534 
THE CORAL TRIANGLE: HEARST BIODIVERSITY EXPEDITION 
means to administer the drugs beeause we eould use diazepam or lorazepam for this same route of 
administration. 
During this time, I perused (in the literal sense of thoroughly searching) the medical literature 
for research related to pre-hospital administration of nasal drugs, including those for seizures and 
neostigmine, as well. Nasal sprays and aerosols are used all the time to treat asthma and other lung 
diseases. Nasal sprays are used as decongestants and to deliver steroids for asthma and allergies 
and as cold remedies. To my amazement, nasal spray neostigmine had been used for the treatment 
of myasthenia gravis, a fairly rare cause of muscle weakness and fatigue, by a group of Italian neu¬ 
rologists in the late 1980s and early 1990s [11-13] . . . but never reported in the literature for use 
in anesthesia or snakebite or any other type of envenomation for that matter. 
Some months later I really got a bee in my bonnet about testing this idea and two things hap¬ 
pened. The fu st was that I mentioned the idea to friend, colleague and mentor. Dr. Phil Bidder, and 
he gave it some thought. Phil is an anesthesiologist at UCSF with a PliD in comparative anatomy. 
He has heard and (appeared to) seriously consider many of my wildest ideas over the years, but he 
was definitely paying attention when I mentioned this one. He didn’t say much, just, “let me talk 
to John Feiner and Tom Heier.” I had never met Tom Heier, but had heard of him. John, like Phil, 
is a friend and mentor from my UCSF days. 
A short time later, Phil and I were commuting into San Francisco and he said that Tom and 
John had a research protocol that could be easily adapted to test my idea [14]. By this time, I had 
become familiar with the epidemiology of snakebite from a global perspective and appreciated that 
the idea of developing a needle-free, heat-stable kit had repercussions far beyond the occupational 
hazard of scientific expeditions, and my goal was to ‘’beat the monsoon.” The monsoon is the peak 
of snakebite season in India. It is estimated that as many as 35,000 to 50,000 people die each year 
in India, alone, as result of snakebite [15,16]. Of those deaths, the vast majority occurring during 
the 3 or 4 months of rainy season — a death toll approaching 10,000 a month — staggering, yet 
invisible. There are, additionally, an estimated 5,000,000 snakebites each year, resulting in up 
tol25,000 deaths [17,18]. This makes snakebite one of the leading causes of accidental death 
worldwide, but is a largely invisible epidemic in North America where there are fewer than a dozen 
snakebite related deaths in any given year and an abundance of emergency care facilities. 
The fall and winter of 2012-2013 were dedicated to designing the experiment and gaining 
approval from the UCSF Committee on Human Research (CHR) to actually do it. Even the most 
mundane human research requires arduous review, including language that is as much directed 
toward the protection of human research subjects as it is to protectmg the university from lawsuits 
should anything happen or be alleged to have happened. In this case, the reviewers were carefully 
scmtinizing the protocol — one requiring the attending anesthesiologists to awake-paralyze one or 
more human subjects and test if a neostigmine nasal spray could counteract the paralytic agent. The 
protocol was submitted several times and returned several times until finally being approved on my 
birthday in late Februaiy. 
The idea of the experiment was to weaken the subject sufficiently that he or she could not 
move, but was still breathing. This requires careful titration of the paralytic agent and the ability to 
reverse it should the paralysis go too far. The shortest acting paralytic agent was used — mivacuri- 
um. Mivacmrium is a derivative of curare. 
Weakness induced by curare has long been recognized to have clinical similarities to cobra 
venom and, in fact, cobra venom is called a “curare-like” venom. The similarity between cobra 
toxin and curare was described, in detail, by Sir Joseph Fayrer in the 1870s and his experiments 
were neatly summarized in several treatises, “On the poison of venomous snakes and the methods 
of preventing death from their bite.” [19-21]. In 1935, Mary Walker described the use of a neostig- 
