Poison or Medicine—Toxin or Drug?

Jack W. Dini
Livermore, California

“Poison surrounds us. It’s not just too much of a bad thing like arsenic that can cause trouble, it’s too much of nearly anything. Too much vitamin A, hypervitaminosis A, can cause liver damage. Too much vitamin D can damage the kidneys. Too much water can result in hyponatremia, a dilution of the blood’s salt content, which disrupts brain, heart, and muscle function,” reports Cathy Newman. (1)

However, more and more research studies are revealing that a little bit of some poisons can be quite helpful to human health. Examples include botulinum, carbon monoxide, hydrogen sulfide, and epibatidine, the toxic that native Indians use to make poison darts.

Botulinum

Botulinum is one of the most poisonous substances known (see Table 1 for comparisons). A gram of botulinum toxin, if dispersed and ingested could kill 20 million people (1). Yet, do you know anyone who has had Botox treatment to remove wrinkles? This is botulinum in extremely dilute form. Other applications include relief of migraines, a cure for crossed eyes, and a treatment for the spastic conditions of multiple sclerosis and cerebral palsy. Researchers in Britain report that the combination of botulinum, and a protein from the Mediterranean coral tree could provide a treatment for the chronic pain that afflicts millions of people, including cancer patients. (2)

Leon Fleisher, one of the world’s premier concert pianists became afflicted with focal dystonia, a misfiring of the brain that causes muscles to contract into abnormal, and sometimes painful positions. This career threatening disorder often strikes those who depend on small motor skills: musicians, writers, and surgeons. After treatments with botulinum toxin, Fleisher is performing and touring again, and recently released his first two-handed recording in 40 years. (1)

Table 1- Hold a nickel in your hand. Here’s how many lethal doses
equal that nickel’s weight*

Thallium 5
1080 Rat Poison 7
Cyanide 25
Strychnine 50
Nicotine 111
Botulinum 100,000,000
Anthrax 500,000,000

*Cathy Newman, “12 Toxic Tales,” National Geographic, 207, 2, May 2005


Carbon Monoxide

Carbon monoxide is an example of a ‘pollutant’ that is important for human existence. This deadly gas that kills thousands each year offers potential help for a number of medical conditions. (3)

Although carbon monoxide inhalation can be lethal, our bodies make the molecules naturally in small amounts when an enzyme called heme-oxygenase-1 (HO-1) breaks down a portion of the blood protein hemoglobin. (4) Ventilator-induced lung injury (VILI) is a major cause of morbidity and mortality in intensive care units. The stress-inducible gene product, HO-1 and carbon monoxide, a major by product of the oxygenase catalysis of heme, have been shown to confer potent anti-inflammatory effects in models of tissue and cellular injury. Tomas Dolinay notes, “The data from this work leads to a tempting speculation that inhaled CO might be useful in minimizing VILI.” (5)

Small amounts of carbon monoxide might alleviate symptoms of multiple sclerosis, a study in mice suggests. The finding may offer a treatment for MS, which strikes when a person’s immune system damages the fatty sheaths that protect nerve fibers in the brain and spinal cord. (4)

Other studies of laboratory animals suggest that carbon monoxide in small doses can prevent injury to blood vessels caused by surgery. In this study, rats that inhaled carbon monoxide-laced air for 1 hour before angioplasty had much less subsequent artery blockage than did rats not receiving the gas. Rats that underwent a vessel transplant also fared significantly better if given carbon monoxide before and after the surgery. (6)

Hydrogen Sulfide

Hydrogen sulfide, the compound that gives rotten eggs their odor, can be lethal at high concentrations. Yet researchers in Seattle reported that exposure to hydrogen sulfide gas can lower the heart rate, metabolism, and body temperature in lab mice. (7) Mice in the study revived and appeared healthy when exposure to the gas ended. This is one step in helping researchers understand about hibernation and torpor in animals. (8)

Why is this of interest? Some animals regularly slow down their metabolic rates, or the speed at which their bodies function. Every day, certain types of hummingbirds go into a state called torpor where their heart rate drops, breathing slows, and body temperature plunges. Bears go into a similar type of hibernation for entire seasons. This type of suspended animation could offer protection for humans after a heart attack or stroke, and it could help people survive while waiting for an organ transplant. (9)






Epibatidine

Epibatidine is the toxic chemical which a tropical frog arms itself against its predators. Not only is epibatidine very toxic, and the reason it is used by native Indians to make poison, but it also turns out to be a superb painkiller. Its two hundred times stronger than morphine.(10)

The chemical formula for epibatidine is C11H13N2Cl. Notice that it contains chlorine, which makes it an organochlorine compound. Bad stuff, let’s get rid of it, say many environmentalists. Jonathan Adler notes, “The campaign to phase out the use of chlorine, a staple of modern industrial chemistry, perhaps best illustrates environmental groups’ absolutist approach to risk assessment and their success at building political support. The anti-chloride crusade was a fringe campaign initiated by Greenpeace, but it has attracted adherents from throughout the environmental community.” It’s endorsed by varying degrees by the National Wildlife Federation, Environmental Defense Fund, Natural Resources Defense Council, Sierra Club, US Public Interest Research Group, National Audubon Society, Citizens for a Better Environment in Chicago, and World Wildlife fund.” (11)

Since epibatidine comes from frogs, what do you do to get rid of this chlorine product? As John Emsley points out, “Epibatidine is an organochlorine compound, which confounds somewhat environmental activists’ belief that organochlorines are entirely manufactured chemicals that cause disease and damage the environment. Epibatidine is highly dangerous, but it is perfectly natural. It would seem a little unfair on the frogs to eradicate them because they are making a dangerous organochlorine molecule.” (10)

The epibatidine story is only just starting. As Emsley notes, “It might well end a better painkiller, or a pill that smokers can take if they want to stop smoking. It might even result in a pill that will enhance learning or improve our enjoyment of intellectual pursuits.” (10)

Summary

Edward Calabrese of the University of Massachusetts-Amherst is a strong proponent of hormesis, a scientific term that means low doses help and high doses hurt. He’s concerned that if researchers don’t begin regularly probing the effects of agents at very low doses, scientists will continue to miss important health impacts—both good and bad of pollutants, drugs, and other agents. Janet Raloff points out that regulatory agencies don’t require scientists to evaluate a poison at exposures below that at which no harm is apparent. This dose is referred to as the NOAEL, for ‘no observable adverse effects level.’ (11)

Two obvious benefits can accrue from testing effects at low doses: 1- medical help might be found from material otherwise known to be toxic and 2- if traces of certain pollutants are not as dangerous as previous estimates had suggested, perhaps some overly stringent regulations could be changed. Dream on…

References

1. Cathy Newman, “12 Toxic Tales,” National Geographic, 207, 2, May 2005

2. James Randerson, “Botulinum toxin soothes chronic pain,” New Scientist, 178, 14, April 19, 2003

3. Liz Geltcher, “Life’s a Gas,” New Scientist, 172, 39, November 24, 2001

4. Nathan Seppa, “Good Poison?” Science News, 171, 53, January 27, 2007

5. Tamas Dolinay, et al., “Inhaled Carbon Monoxide Confers Antiinflammatory Effects Against Ventilator-Induced Lung Injury,” American Journal of Respiratory and Critical Care Medicine, 171, 1318, 2005

6. Nathan Seppa, “Carbon monoxide may limit vascular damage,” Science News, 163, 126, February 22, 2003

7. Eric Blackstone, Mike Morrison, and Mark B, Roth, “H2S Induces a Suspended Animation-Like State in Mice,” Science, 308, 518, April 22, 2005

8. “Putting a Mouse on Pause,” http://www.sciencenewsforkids.org/articles/20050427/Note2.asp

9. Ben Harder, “Perchance to Hibernate,” Science News, 171, 56, January 27, 2007

10. John Emsley, Molecules at an Exhibition, (Oxford, Oxford University Press, 1998), 84

11. Janet Raloff, “Counterintuitive Toxicity,” Science News, 171, 40, January 20, 2007