NATURALLY DANGEROUS: Surprising Facts About Food, Health, and the Environment.
By James P. Collman, Professor of Chemistry, Stanford University
Chapter 4. Infectious Agents: are All Microorganisms Bad?
© James P. Collman, 2003. All rights reserved
DNA analysis of a young mother, unearthed from a 9,000 year old village showed that both she and her 1-year-old child had human tuberculosis. Recall that in Naturally Dangerous it is speculated that bacteria that infect humans is thought to have passed from domesticated animals such as cattle. These results indicate that bovine tuberculosis evolved after human tuberculosis, because cattle were not domesticated 9,000 years ago. (Science News November 8, 2008, page 12)
A small study of 14 infants by the Stanford Medical School is focused on the infant’s internal microbes. These researchers examined the stools taken from 14 newborn infants, including one pair of fraternal twins. All the infants except the twins were born without surgical intervention; the twins were delivered by caesarean section. All 14 infants were healthy full-term infants and were studied for a year. The gut of a baby starts out sterile; it has no inhabitants before birth but within days microbial immigrants inhabit their guts and develop a population that soon numbers 10 times the baby’s own cells. The same ratio is found with adults. The nature of the immigrant bacteria were discovered to fluctuate with time; in some cases the infants received antibiotics, which caused dramatic changes. DNA techniques were used to study these bacteria by analyzing a series of stools starting with the first one after birth. Less than half of the bacteria have been characterized. These “friendly bacteria” play critical roles in health: processing nutrients, defining the extent of body fat, and protecting against invading pathogens. Such studies are in an early stage; many more infants must be studied, but this is a messy business. The parents must agree to collect the baby’s stools and take them in for analysis. Little is known and much is to be learned. (Stanford Report, July 11, 2007, page 7)
On page 101 in Naturally Dangerous Chagas disease is described. Recall that
this incurable disease is transmitted by the "kissing bug", but
it can also be transmitted by blood transfusions from blood that is contaminated
with this parasitic infection that is common in Latin America, where donated
blood has been inspected for Chagas disease for many years. Finally, the US
is taking this long-overdue measure. About 100,000 people in the US are now
thought to be infected with the Chagas parasite and the chances of getting
this deadly disease from a blood transfusion in Los Angeles has risen from
one in 10,000 a few years ago to one in 2,000 at the present time. On the
13th of December, 2006, the Food and Drug Administration approved an antibody
test for Chagas disease. Blood banks say they will quickly adopt this test
and discard any blood that shows a positive test. A side effect of this test
will be to develop a more accurate measure of the extent of Chagas disease
infection in the US. From south of the US border to the tip of Argentina up
to 20 million people are thought to be infected with the incurable Chagas
disease, but most people don't realize that they are infected. Chagas disease
can fester in the heart and gut undetected for 10 to 30 years before it erupts
and suddenly kills its victims because of heart failure or a ruptured intestine.
Only two treatments for Chagas disease are the drugs: nifurtimox and benznidazole,
but these drugs have very unpleasant side effects and it is difficult to tell
if the treatment worked because antibodies for this disease remain in the
body. It is estimated that these drugs cure up to 95 percent of recently infected
children but less than 10 percent of adults who have been infected for a long
period and have been asymptomatic. The latter class of older patients will
probably not be treated with these unpleasant drugs. (New York Times 12/14/06,
The friendly bacteria in your stomach and intestines are important in digesting food and combating dangerous, disease-causing microorganisms that invade your body. The side effects from antibiotics, which can kill your friendly microbes are discussed in Chapter 4. Recent evidence now shows a possible connection between obesity and the types of microorganisms in your stomach. These studies involve both mice and humans and show similar results. Obese humans and mice were both found to have lower concentrations of bacteria called Bacteroidetes, but higher concentrations of another type of bacteria called Firmicutes. These findings suggest that the proportion of these different bacterial families may be linked to obesity or thinness. Firmicutes seem to be related to weight gain versus Bacteroidetes, which appear to be connected to moderate weights.
When lean mice had larger ratios of Firmicutes transplanted into their guts, they became twice as fat and took up more calories from the same amount of food compared with mice which had more Bacteroidetes. Similar dramatic results were found in a small study of twelve dieting people. Before dieting these subjects had only 3 percent of the “slim bacteria”, Bacteroidetes, but after dieting these now lean subjects had developed much higher levels, nearly 15 percent of Bacteroidetes.
These results are interesting and, if confirmed might lead to strategies to control one’s weight by adjusting the type of microorganism in one’s intestines. The effect of taking antibiotics on weight loss or gain could become an interesting issue. Remember that there are trillions of friendly bacteria of many varieties in our bodies. This is an important arena for future research. It is likely that these microbes may influence everything from personal height to incidences of diabetes and asthma, and perhaps medical problems that we have not yet associated with these bacteria. From Chapter 4 in Naturally Dangerous you may recall that infants develop microbes in their guts within days of birth. These friendly bacteria come from food, especially breast milk, but also formulas. Scientists need a deeper understanding of these friendly organisms and their influence on human health. (Associated Press, Dec. 20, 2006 )
There are interesting parallels between the current avian flu and the infamous 1918 influenza pandemic, which is thought to have killed between 40 and 100 million individuals. The current avian flu, still has not passed from human to human, and may never do so. But analysis of the 200 people who have so far died from contacting the avian flu shows that the highest death rate – 73%- is among patients 10 to 19. In the 1918-1919 epidemic, also thought to be derived from an avian retrovirus (based on an RNA core) the death rate for people between 18 and 30 started in the first year at 30 per 100,000 , and in the next year soared to 5,700 per 100,000 people. Far fewer older or younger victims died in either year from this 1918 “Spanish Flu”. These figures sharply differ from current annual flu, which tends to kill the very old and the very young, usually via secondary bacterial pneumonia. It appears that these deadly avian flues cause a “cytokine storm” by activating the immune system; the immune reaction floods the lungs with fluid. The difference in age group has been proposed to be caused by the powerful immune systems that are present in young adults.
There is an increasing awareness of a poorly diagnosed bacterium that thrives
in warm, humid environments: nontuberculous mycobactria. This ubiquitous bacterium
is found in soil and water, even potable water from municipal water sources.
But few people seem to become seriously infected: most victims are thin, postmenopausal,
white women, who have never smoked. There may be an unrecognized genetic disposition.
An indoor hot tub is a breeding ground for this disease; it can be acquired
by breathing the most air just above the hot water. In one instance an entire
family: the wife, the husband, and three sons, 14, 12, and 9 contracted this
disease from their indoor hot tub. These dangerous nontuberculous mycobacterial
infections are more common in hot, moist climates such as Hawaii and Florida,
but they are being seen across the country. A serious case can lead to lung
surgery, even to death. Diagnosis is difficult requiring sputum samples, and
chest X-ray or CT scans. Why are these infections increasing, or are there
better diagnoses? Lower temperatures in modern hot water heaters in homes,
hotels, and hospitals may be one explanation. Another possibility is that
in modern times, more people take showers than baths. Treatment involves a
cocktail of at least two antibiotics along with a steroid to suppress hypersensitive
reactions. (Jane Brody, New York Times, June 13, 2006)
Dr. Stanfley Falkow, professor of Microbiology and Immunology at Stanford University has discovered that some pathogenic (dangerous) microorganisms may have a beneficial side to individuals that are infected. The bacteria, Slmonella may cause a short-term infection, but long-term infection is usually innocuous. Salmonella can exist in the white blood cells of the immune system over the host's lifetime without ever causing clinical symptoms of infection. Different individuals may have different susceptibilities to microorganisms resulting in different susceptibilities to infection. The susceptibility is thought to have a genetic origin. Another bacterium, H. pylori, can cause gastritis, ulcers, and stomach cancer, but ninety percent of humans are infected with H. pylori and show only mild inflammation of the stomach lining. Only one percent of the infected people ever develop ulcers or gastric cancer. Do these pathogenic bacteria have beneficial effects similar to our friendly bacteria? Some statistical evidence suggests that H. pylori protects against esophageal cancer. There may also be some benefit in protecting against immune disorders? Much is still to be learned about the bacteria that inhabit our bodies. (Stanley Falkow, "Is Persistent Bacterial Infection Good for Your Health?" Cell 124, (Feb. 2006): 699-702.) ("Bacterial Pathogenesis: Friend or Foe?" by Chelsea Young and Nisha Gadgil, Stamford Scientific, Vol. IV, page 12, 2006)
Over the past year or so there has been an increasing fear that the current
bird pandemic from the avian flu virus, known as A(H5N1) or H-5 for short,
might undergo some mutation(s) such that it could develop into a human-to-human
disease resulting in a human pandemic like the 1918 flu, which killed well
over 20 million people. Previous human pandemics did involve H type viruses
that began in birds: H-1 in the 1918 flu, H-2 in the 1957 Asian flu, and H-3
in the 1968 Hong Kong flu. Scientists from Scripps Research Institute reported
that only two mutations might be needed to enable the H-5 virus to make the
switch to a receptor in the upper lungs. Both other scientists point out that
the H-5 virus has been present in humans since the late 1950's, but this virus
has not acquired the mutations necessary to set of human-to-human infection
and a human pandemic. Other scientists agree that such mutations enabling
a self-sustaining chain of transmission between humans is unlikely. Only people
who are exposed to large doses of the H-5 virus by sleeping in the same room
with chickens or eating raw poultry are likely to come down with the H-5 virus.
However, someday there will be another human pandemic derived from an avian
virus and we should prepare for that eventuality by developing antiviral drugs
and new, efficient methods to prepare vaccines. We are not currently prepared
for such a pandemic. (New York Times, March 23, 2006, page A16)
Most people have heard about mad cow disease, referred to by scientists as bovine spongiform encephalopathy, which has proven deadly to cattle and to some humans who ate beef from an infected cow. A cousin to mad cow disease is found in deer and elk: CWD or chronic wasting disease. Fewer people are aware of CWD, in spite of the fact that it has been devastating wild animals and herds of deer and elk on ranches in eight US states and two Canadian provinces. Recall that mad cow disease infected about 180,000 cattle in Great Britain and has been linked to 140 human deaths. This prion infection, which is discussed on pages 102 – 105 in Naturally Dangerous, raised havoc with the British beef industry and the discovery of one infected cow in the US, which was imported from Canada, caused serious economic problems in the US. Both diseases are referred to as TFEs, for transmissible spongiform encephalopathies. These prion are related to a rare human condition: the Creutzfeldt-Jacob disease, CJD. Only 1 in a million humans get CJD; most cases are in people between 50 and 70 years of age; these “sporadic” cases have no known origins except that 10 to 15 percent are inherited; if either of your parents had CJD, you have a 50-50 chance of getting it yourself. All prion diseases are fatal and the only reliable diagnosis is still only by autopsy of the brain. CDJ deaths are far less common than Alzheimer’s disease, by about twice as common at deaths from lightening strikes. Since CWD has become so widespread in the US, why has there not been more public discussion and concern over such a scary disease? After all there are 10 million deer hunters and 900,000 elk hunters in the US and in Michigan alone more than 500,000 deer are killed each hunting season. In the infected areas, up to 10 percent of all deer have been found to be infected with CWD. The reason that the public has not become alarmed is that there is no firm evidence that CWD can infect humans, although there is some circumstantial evidence that transmission of CWD to humans might have occurred. The risk of transmission of CWD to humans is considered to be low, but given the long incubation period and the large number of opportunities for transmission, this risk is by no means zero. Hundreds of thousands of Americans eat deer and elk meat from hunting carcasses to meat from slaughter of ranch raised deer or elk. CWD is very contagious among deer and elk and between deer and elk and this infectious agent is very resistant to decontamination. Hunters are advised: not to hunt in infected areas, not to hunt ill animals, handle carcasses with gloves, sterilize their cleaning knives, and not to eat the brains or nervous tissue from any deer that has not been certified as CWD free. Wisconsin has spent one third of their wildlife budget, about $7 million in one year trying to eradicate or control CWD in their deer population. The game authorities in Wisconsin hope to reduce their deer population density from75 in an acre to just 5. These attempts to limit CWD in Wisconsin have failed, as have Herculean measures to eradicate CWD from a research and testing facility in Ft. Collins Colorado. So far the CWD has not spread from elk or deer to cattle or to Buffalo, even though this disease easily spreads among deer and elk who simply pass over a field that has contained previously infected animals. So far 6 percent of the deer and 4 percent of the elk in Colorado have CWD. This situation has had a devastating effect on the nation’s 10,000 captive –deer farmers, who are forbidden to ship or sell their stock; it is estimated that billions of dollars have been lost. In restaurants that serve venison or elk meat, only that from New Zealand is available; that distant country is not infected: yet! (The Pathological Protein, Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases, Phillip Yam, Copernicus Books, New York, 2003, ISBN 0-387-95508-9)
There is a rare, naturally occurring form of the prion disease, variant Creuzfeldt-Jakob disease (vCJD), which affects roughly one person in a million. This spontaneous natural disease is of course related to the infamous Mad-Cow-Disease (BSE) and to other infectious prion disorders discussed in Chapter 4. Recall that these prion diseases are always fatal, but may take decades to develop after the first exposure. Now it has been found that there is a genetic susceptibility to vCJD. A particular genetic site: codon 129 on the gene coding for the normal prion protein seems to determine an individual’s susceptibility to acquiring vCJD. The most susceptible humans are those who have a pair of identical amino acids, methionine-methionine coded for at that site. Recall that DNA contains instructions for the sequences of amino acids in individual proteins. Only 33 percent of the U.S. population has this methionine pair, but in Japan 92 percent of the population has this characteristic genetic feature. Of course the Japanese are much more genetically homogeneous compared with the heterogeneous American population. There are still many things that are not known about the seprion diseases. (Chemistry & Engineering News, May 16, 2005, page 29)
A mild childhood virus, varicella zoster, causes chicken pox; many children suffer this mild disease, which seldom requires and treatment other than rest and isolation. But many years after its symptoms have gone, this virus can reappear in adults. The result is a much more serious, painful, and dangerous disease: shingles. The chicken pox virus was hiding in the patient’s body for many years; why, when, and whether shingles will develop is unknown, but shingles affects 20 to 30 percent of Americans sometime in their lives. Shingles results in a very painful rash; if treated immediately with an antiviral drug such as acyclovir, the symptoms will usually disappear. Sometimes, especially when untreated, shingles results in nerve damage and pain. This condition is called post-herpetic neuralgia (PHN), which is very painful, can persist for long periods (even years), and has few effective treatments. Geriatric patients have a risk of 50 percent or higher of getting PHN. There is recent good news. A new formulation of the chickenpox vaccine has been tested in adults. This vaccine, which is not yet on the market, appears to protect about two-thirds of patients from getting shingles. (New York Times, June 6, 2005, page D5)
Over the past four years 35 people in New York City, 22 adults and 13 children have gotten tuberculosis (Tb), apparently from eating contaminated cheese or raw milk. One infant has died from complications of Tb. All the infected adults were born outside the U.S., most of them in Mexico, but the affected children were born in the U.S. and apparently contracted Tb in this country. The F.D.A. has issued a warning against eating any raw-milk soft cheeses from Mexico, Nicaragua, or Honduras. Improperly labeled, or unlabeled cheeses have been found by health officials in Brooklyn and Queens. The bacterium that causes Tb, Mycobacterium bovis, is primarily found in cattle, and can be transmitted by drinking milk or eating milk products from contaminated cows. It is rare to find cattle in the U.S. that are infected with the Tb bacterium. In Latin America, it is common for cheeses to be made from raw, unpasteurized milk in Mexico, especially Quesofresco (“fresh cheese”) the soft cheese that is suspected to be a source of infection in the New York City cases. (New York Times, March 16, 2005)
In Naturally Dangerous Chapter 4 contains a large section describing “good bacteria”. The New York Times science writer, Jane Brody has recently written an informative article about these valuable, natural microorganisms and their use in warding off disease (New York Times, September 14, section D). There are 10 times more bacteria than human cells in our body: 100 trillion bacterial cells from 500 bacterial species. The vast majority of these friendly probiotics are harmless and many promote good health. We could not live a healthy life without these beneficial bacteria; animals who are raised germ-free are usually unhealthy; their immune systems are underdeveloped and they have vulnerable intestinal tracts. Friendly bacteria in a human’s digestive tract are acquired after birth; the first ones to take up shop become dominate. These air-sensitive probiotics aid in digestion, keep harmful bacteria in check, and stimulate our immune system. They seem to protect children from skin allergies such as eczema, and from dental cares, and diarrhea. In adults, friendly bacteria are speculated to lower cholesterol, and to ward off ear and bladder infections. Probiotics may even degrade carcinogens thus thwarting the development of cancers. If probiotics are so useful in promoting good health, can you install them by eating food such as yogurt containing such friendly bacteria? This might be useful after your own probiotics have been degraded from a treatment with antibiotics? Obtaining your probiotics from food is attractive, but this method is not very effective. Unpasteurized yogurt does not have a sufficient quantity of probiotics to restore your health. There are some seemingly effective probiotic products on the market, but most of these are sold overseas: Yakult in Japan for warding off bladder infections and VSL-3 in Italy, which contains eight different probiotics and may suppress Crohn’s disease, a serious inflammatory bowel disorder. Another overseas product is ProboTek from Denmark, sold in the U.S. by Bradley Pharmaceuticals as Flora-Q. This latter product, which contains four microencapsulated probiotic organisms, is designed to survive oral ingestion so that these friendly bacteria can reach the intestinal tract. Another probiotic product is Lactobacillus reuteri, which occurs naturally in the gut of many humans as the result of breast feeding. This substance is being tried in patients with H. I. V.
Molds sometimes introduce non-toxic natural chemicals into foods; the resulting flavors can be appealing or disgusting. For example, the blue streaks in Roquefort cheese impart a wonderful flavor to most food lovers, but the musty flavor and odor in a tainted wine cork repels wine drinkers. Neither mold product is a health risk, but our taste buds react differently to these natural substances, attracted to one and repelled by the other. The blue color and taste in Roquefort and related blue cheeses is deliberately introduced by “infecting” unpasteurized sheep’s milk or curds with mold spores that have been cultured in loaves of rye bread. This blueing process results from one of several strains of Penicillium rogueforti, a mold found in the Combalou caves under the village of Roquefort-sur-Soulzons in southwest France. The development of the blue color and probably of the flavor requires oxygen, which penetrates the cheese. In contrast, the undesirable musty taint and odor in wine corks comes from a mold product: TCA (2,4,6-trichloroanisole) This compound isn’t a health risk but it ruins the flavor of any wine, including expensive wines. Such wines are said: to be “corked”. Very sensitive individuals (such as professional wine-tasters) can taste TCA at 2 or 3 parts per trillion! TCA is reported to occur in between 1 and 10% of the corks sold to wineries. Partly for this reason, New Zealand wines are now caped solely with plastic stoppers. Once a winery becomes contaminated with TCA, cleaning up this problem can be time consuming and expensive. TCA is formed when chlorine bleach, used to remove stains from a winery’s cement floor, reacts with naturally occurring phenols in the wine. The product of that chemical reaction is then transformed into TCA by common molds. One solution to this contamination is for wineries to use a peroxide cleanser rather than chlorine. The TCA problem may not be completely solved by using plastic corks. TCA also occurs in polystyrene screw cap liners, again creating a corky wine. (Janet Fletcher, S. F. Chronicle, Fall 2003, page D1)
An accidental discovery suggests a plausible link between Alzheimer’s disease and ingestion of copper along with a high cholesterol diet. When feeding a high-cholesterol diet to rabbits, researchers observed that plaque-like structures that are associated with a protein called beta-amyloid accumulated in brain tissue. These plaques increased 50 percent more if the rabbits were fed water containing copper salts. Similar results were observed in two different laboratories: in West Virginia University and the University of Kentucky. Others working on Alzheimer’s disease are skeptical and more research needs to be done before this possible clue is followed up. Don’t throw your copper soufflé pans away quite yet. (Science Vol. 301, 15 August, 2003, page 905).
As described in Naturally Dangerous, many viruses are species-specific or even organ-specific. The species barrier has been called a biological Hadrian’s wall, analogous to the fortified rampart which was constructed by the Romans in ancient Britain to protect them from invasion by northern barbarians. But the agent that causes mad cow disease, a new variant of the very rare Cruetzfeldt-Jacob disease, is thought by most scientists not to be a virus, but this infectious agent is thought to be a misfolded protein called a prion. No one knows how or under what circumstances these prion diseases pass from one species to another. Even transmission within a species is not understood. Can cows infect cows, or humans infect humans; if so, how does the infection occur. Moreover, can different species infect another? For example can sheep infect cows (this seems likely), can deer infect cattle living in the same pasture (this does not seem to take place, but don’t bet against it). Do these infections occur through cannibalism or by eating the flesh of a different species? The mechanisms and circumstances by which prion diseases are passed from one creature to another are mysterious; often there is no plausible explanation of the mechanism, nor the time required for infection to manifest itself. The question is made more difficult since an autopsy of brain tissue from an infected animal is the only definite way to diagnose prion diseases. One rapid approach to carry out inter-species infection is to inject tainted brain material from a diseased animal into the brain of an uninfected animal. In this way cow to sheep and sheep to cow injections have lead to characteristic brain lesions. Mad cow disease has been passed to pigs and cats in this way. However, raccoons have been infected by injecting diseased mink or sheep brain segments, but not by injections from deer who have a prion disease referred to as “the wasting disease”. Sheep that receive injections from infected deer do get the sheep prion disease called “scrapie”. Many of the unsuccessful trans-species infections may actually take place, but because it often takes many years for a prion disease to develop, some species may not live long enough to develop symptoms, but such animals could be infectious if eaten by another animal.
Remember from Chapter 4 that a virus such as hepatitis A can survive in food. Viruses can hide in refrigerated foods and then kill or make ill people who eat this fresh food. Such was the case with a large outbreak of hepatitis A in western Pennsylvania, where patrons of a chain restaurant became ill after eating a salsa, contaminated with green onions from Mexico. Three people died and another 575 became sick from consuming salsa that contained chopped onions. These onions are thought to have become contaminated by child farm workers, who were infected but paid scant attention to their personal hygiene, or from sewage-containing fecal matter in water that was used either to irrigate the scallions or to make the ice that was used in shipping this produce. This episode was not the first time that scallions contaminated with hepatitis A have appeared in U.S. markets. Other earlier outbreaks in Tennessee and Georgia were traced to Mexican suppliers. Rinsing the scallions did not disinfect them, nor is it practical to wash this produce in chlorine water, which would ruin their flavor. The best advice is to avoid eating raw scallions, but when thoroughly cooked they are safe. International trade is creating health hazards that are difficult to monitor. (New York Times, November, 2003).
Some readers may remember reading about the Irish potato famine that occurred about 150 years ago. This fungus-like blight destroyed a staple food for millions of people over the World, caused the migration of many Irish to the U.S., and it is still present wherever potatoes are grown. The only solutions to this blight have been crop rotation or the use of unnatural, potentially toxic anti-blight pesticides. A strain of potato that is resistant to the blight has long been known, but all attempts to interbreed this blight-resistant strain with commercial potatoes have failed. Now scientists have used genetic engineering to transfer the gene, which confers blight resistance into a commercial variety thus producing a transgenic blight-resistant potato plant. This new genetically-modified potato could be field-tested within a year and shortly thereafter potatoes could be grown without using troublesome, expensive pesticides. One can bet that some activists that are against genetically modified foods of any sort will fight this new environmental improvement. (Science News, 07/19/03, page 35)
According to Dr. Gabriela Chavarria, a director of the National Wildlife Federation, “people who insist on owning wild or exotic pets clearly have more money than common sense”. Table 7, on page 119 in Naturally Dangerous, lists common human diseases that originated from domesticated animals; bacterial and viruses harbored by wild animals can be very dangerous, because humans have little immune resistance to them. Ninety percent of reptiles such as iguanas, snakes, lizards, and turtles are infected with salmonella, which contaminates their feces. It is estimated that each year in the U.S. nearly 100,000 cases of human salmonella infections can be traced to reptiles, mostly pets. Between 80 and 90 percent of macaque monkeys, the most common pet monkey, carry herpes B and simian B viruses; the latter can be fatal to humans. Indulgent parents should resist allowing their children to become infected by a whim. Visit such pets in a zoo. (New York Times, 7/8/03, page D4)
An interesting, but puzzling article by Sandra Blakeslee (NYT, June 3, 2003, p. D3) describes the current knowledge about jumping species barriers while contracting various classes of “prion diseases”. Recall from pages 102 Š 105 in Naturally Dangerous that these fatal diseases are thought to arise from a misfolded form of a natural protein, called a prion, resulting in lethal sponge-like holes in the brain. These diseases occur in several different species and have been given diverse names: new variant Creutzfeld-Jacob disease in humans, scrapie in sheep, mad-cow disease in cattle, and chronic wasting disease in deer and elk. All of these fatal brain diseases are very similar, and in many cases are thought to result from eating the remains of a different infected species (mad cow from cattle eating infected sheep) or from eating tissue from their own species (for example, Kuru in humans practicing cannibalism). An important question concerns how and under what circumstances a prion disease can jump from one species thus infecting another species. For example, can elk bearing the wasting disease infect humans, or could pigs carry an undetected (subclinical) prion infection and pass it to humans who eat sausage? Other possibilities are that the recent case of mad-cow disease in Canada might have come from elk infected with the wasting disease or that bison could become infected from contact with deer, elk, or cattle. Any of these possibilities would have dire economic and/or psychological consequences. Although several probing experiments have been performed, presently there is no understanding as to why an infectious prion agent does or does not pass from one species to another. The pioneer of the prion hypothesis, Nobel laureate Stanley Prusiner admits that “We don’t understand what is happening”. Among the complications are that detection of a prion disease is done by autopsy and the incubation periods are long and seem to vary with the species. Several types of experiments have been performed. In the first type of experiment, two different species of animals are confined in the same pen: one is infected and the other is not. So far cattle have not been infected from dear or elk in this fashion over several years. But, in a second type of more rapid experiment infected brain tissue from one animal is injected directly into the brain of a different animal. In this manner mad-cow disease was spread to sheep (who appeared to develop scrapie) and to pigs and cats! But attempts to infect cows from deer were inconclusive; however, sheep were infected from deer, and elk became infected with wasting disease by injections from sheep that have scrapie. A third approach has used “transgenic” mice, which carry prions from humans, cows, sheep, ordeer in place of normal mouse prions. These mice are then injected with prions from brain tissue derived from different infected species. The results are confused and follow no clear order. Diverse types of prion diseases are observed in these mice. A fourth type of experiment was performed that would have no analogy in the normal transmission of prion diseases: in these experiments prions are studied in test tubes by combining them with prions from other species. Prions from chronic wasting disease slowly transform normal prions from sheep, cattle, and humans into “infectious states”. This situation should be watched; eventually this important subject may become clarified.
On page 92 in Naturally Dangerous there is a discussion of a viral disease called monkeypox in Africa and the possibility that it might become a threat to people who have never been vaccinated for its infamous cousin, smallpox. Now monkeypox has been found in Wisconsin, Indiana, and Illinois and possibly New Jersey. This monkeypox infection has been traced to rodents imported from Africa by pet stores, where the virus spread to other rodents. For example, prairie dogs were apparently infected by contact with the African rodents. Children were subsequently exposed to monkeypox from their pet prairie dogs. This situation is a potentially serious health problem because this viral disease is dangerous, especially to children who have never been vaccinated for smallpox. The last routine smallpox vaccinations in the U.S. were in 1970, before these children were born. Fortunately health authorities now have smallpox vaccine on hand because of a possible terrorist attack. Smallpox vaccine is about 85% effective against monkeypox. Adults could be less susceptible to monkeypox, because smallpox vaccinations are now thought to have a longer lasting effect, although that claim is controversial (Science News, May 31, 2003, p. 340) Person-to-person infection of monkeypox has been reported in Africa, but this disease is not considered to be as infectious as small pox. Symptoms include a rash and blisters; a fever above 99.3 degrees, various aches; swollen lymph glands, and a sore throat. The death rate of monkeypox is lower than its cousin, smallpox: 10 percent versus 30 percent. The monkeypox problem could become endemic and thus very dangerous, if any of the infected prairie dogs escaped into the wild, spreading the virus to wild prairie dogs. It is very difficult to eradicate any species of wild animals. Recall that a persistent rabies infection exists in Raccoons in the eastern U.S.
An important clue to the possible origin of SARS has been reported from China where the SARS virus was discovered in three animals: the civet, a badger, and a raccoon dog. All were in a live animal market in southern China. The major infected species is the masked palm civet cat, a nocturnal, tree-dwelling animal considered a delicacy in Chinese culture. A major question is whether wild civets have SARS or whether these animals contacted SARS from food or feces within the market. The former possibility is dreaded, because SARS could not be eradicated from wild animals, but farmed animals could be slaughtered. The genetic map from SARS in these animals is slightly different from that obtained from human patients, but this difference may not be significant. Other live animal meat markets have not yet been tested for SARS. Although, as mentioned in Naturally Dangerous, viruses can be transmitted by eating infected meat, this is not considered likely in the present situation because the meat from civets is well-cooked. It seems more probable that the SARS virus may have been transmitted to the meat handlers. The possibility that household cats could become infected with SARS is also disturbing.
Strokes are the third-leading cause of death in the U.S. Each year 750,000 people have a stroke and approximately 20% die as a result. A recent study showed that the same bacterium that causes stomach ulcers is probably responsible for strokes that originate in plaque-congested artery walls in the neck and the brain. One particular strain of Helico-bacter pylori, releases toxic substances, called cytotoxins, which induce inflammation, thus setting up conditions for a stroke. One can speculate that a vaccine will be developed to protect against this bacterium.
As more information becomes available, the calculated death rate from SARS has increased to 15%. For many reasons this number is subject to change. Diagnosis remains slow and still depends on antibody measurements. Information from China, the most infected country and the place SARS originated may not be complete. Another factor that confuses average death rates is that these vary with age groups. The death rate from people over 60 is about 50%; but for young children it is about 1%. As of this date over 7000 people have been reported to have SARS, and over 500 have so far died. This mortality is far greater than the infamous 1918 “Spanish flu”, which had a death rate between 2,5 and 4% and killed many more than 20 million. Recent studies of the genetic makeup of the SARS virus indicate that it is only mutating slowly. This is both good and bad news. A slow mutation rate means a vaccine may be easier to develop. However, this means that the virulence of SARS may not attenuate.
As discussed in Naturally Dangerous, the first recognized version of “mad cow disease”, was kuru, a fatal neurodegenerative disorder that killed almost 10% of a New Guinea tribe of cannibals called the Fore. It is believed that the Fore became infected with kuru by eating human brains. A similar, very rare disorder, the Creutzfeld-Jakob disease (CJD), occurs spontaneously in humans. Both brain disorders are thought to be derived from deformed proteins referred to as prions. These contorted prions are believed to cause the prions that naturally occur in the brain to misfold, clump up, and kill brain cells. Other versions of these “prion diseases” are known as mad cow disease, scrapie in sheep, and the wasting disease in deer and elk. Now genetic studies have found a connection between the genes that code for prion proteins and susceptibility towards the human prion diseases, kuru and CJD. Those people having two identical copies of this gene are more susceptible to developing CJD than people having two different variations of this gene. It is believed that natural selection has resulted in a higher than expected percentage of people who have the two different versions of this gene and thus some protection against prion diseases. It is speculated that this situation might have come about because ancient people practiced cannibalism! This “politically incorrect” idea offends some anthropologists. (Science, April 11, 2003, Vol. 300, p. 228)
News about SARS gives some perspective. This virus is based on RNA. As mentioned on page 90 of Naturally Dangerous, RNA viruses are fragile and tend to mutate more rapidly than those containing DNA; such mutations change the virusÕs protein coat. The immune system and vaccines use this protein coat to recognize a virus. SARS is an entirely new corona virus; its genetic RNA sequence has been analyzed, which should help formulating a rapid diagnosis and finding effective drugs. The good news is that unlike many corona viruses, SARS has been cultured, facilitating drug evaluation and possibly development of a vaccine, but obtaining an effective vaccine is well over a year away. So far there is no rapid test for SARS; antibodies are still used and a reliable antibody test requires a minimum of 17 days and two blood tests. This means it is very difficult to verify new SARS cases, adding to the uncertainty about how many cases exist and the death rate. WHO (the World Health Organization) now estimates that 333 people have died from 5000 cases of SARS. This translates into a death rate of about 6.6%. Will the World ever be rid of SARS? Probably not, because it seems to have come from a yet to be identified animal species in Southeastern China, and jumped the species barrier infecting humans. According to antibody analyses from blood banks, SARS was not previously known in humans. If an animal reservoir exists for a virus, it is nearly impossible to eradicate that virus, because it would be necessary to exterminate or vaccinate all of those animals. Flu viruses are a good example of this problem; these viruses reside in birds, pigs, horses, and even ferrets. There are many developing controls on air travel in attempts to limit the spread of SARS. One interesting, non-intrusive method now being used in Singapore is employ infrared cameras to survey travelers before they are allowed on a plane. These subjects who show an elevated temperature according to the infrared scanner, are made to sit down for 30 minutes to cool off before their temperatures are taken a second time, more precisely. A body temperatures over 100 degrees Fahrenheit, is a primary symptom of SARS. (New York Times, April 27, 2003, Week in Review, page 1) (Wall Street Journal, April 28, 2003, page B1)
As summer approaches you will be hearing more about the West Nile virus. It has now spread to alligators in a Florida alligator farm. Its human mortality rate seems to be rising; during 2002, out of 2,300 people known to have been infected in the U.S., more than 4 percent died! The death rate for birds can be much worse; for American crows, the estimated rates are between 30 and 50 percent. This virus has infected at least 186 wild and captive birds as well as17 other vertebrate species from skunks to alpacas. Because of these widespread virus pools, it will never be eradicated. The virus has been spread by means other than mosquito bites: blood transfusions, birds eating infected flesh or infected mosquitoes, perhaps between migrating birds, and possibly from mother’s milk. Will eating meat transmit this virus? This has not been discussed and is probably not a problem, but read page 90 in Naturally Dangerous about the rabies virus. The West Nile virus has now spread to at least 48 continental states (with the possible exception of Nevada and Oregon, but they will surely become invaded). So far, Hawaii, with its exotic birds, has escaped, but for how long? The deadly West Nile virus is firmly established in the U.S., as it has been in the warmer parts of Europe and Asia for sometime. Avoid mosquito bites and hope for the development of an effective human vaccine; there is one for horses. (Science News, March 29, 2003, Vol.163, p. 203). (see another piece on West Nile Virus)
Like Dr. Jeckyll and Mr. Hyde, good and evil, Botox, the toxin from botulism, a microorganism found in soil has a wide range of uses. The application of Botox to remove wrinkles is described in Chapter 4. Now many other medical applications of this deadly toxin are being explored. At the same time it is feared that this botulism toxin, perhaps the most poisonous natural substance known, might be used by bio-terrorists. A single gram, the weight of a paperclip, if properly dispersed could kill up to 1 million people!
Botox is now being tested to treat a wide range of disorders, with very encouraging results. These include infant clubfoot, stroke paralysis, migraine headaches, facial tics, stuttering, lower back pain, incontinence, carpal tunnel syndrome and tennis elbow! Several trials on these new uses of Botox are nearing completion with the Food and Drug Administration. For example the toxin’s use to mitigate migraines is in final stages of clinical trials, but it is not known how this application works! These medical uses involve very tiny quantities of the toxin; nevertheless they are fairly expensive (about $400 per vial). Botox acts only where it is injected; the treatment lasts for months, but it is reversible because the effect does wear off. In over 25 years therapeutic Botox has harmed very few patients. (NY Times, March 2, 2003, page 1)
In the 1930’s this poison nearly wiped out the U.S. canning industry. As described in Chapter 4, such microorganisms are alive and can multiply in humans or in a food. Therein lies the danger and the possible use of a microorganism or its toxin product as a bioterrorism tool. So far botulinum toxin has not been successfully used as a weapon, although in the 1990’s, the Japanese cult, Aum Shinrikyo, tried to disperse it with aerosols at least three times. But introducing this readily available microorganism into a food during processing could produce a very dangerous situation and induce panic. For example, it could multiple while a food such as milk was being stored in a large tank. Bioterrorism officials are very concerned about this possibility. (CNN.com/HEALTH, March 25, 2003)
The contrast between the beneficial and terrorist uses of Botox is interesting and instructive in the context of the general theme discussed throughout Naturally Dangerous. Natural things can be both useful and dangerous, depending on the circumstances.
There is a gathering storm of reports regarding SARS (severe acute respiratory syndrome), which Canadian scientists have shown to be an unprecedented corona virus. The characterization of this virus’s genetic code should facilitate a test for SARS, and rapid diagnoses of new cases. There are many uncertainties about this dangerous virus for which there are as yet no effective medicines. SARS seems to have originated in the Guangdong province of southern China a notorious melting pot where humans, swine, and domestic birds in close contact can exchange DNA to produce novel viral strains. This life-threatening respiratory disease was first recognized in November 2002 as it spread through Hong Kong, Singapore, and elsewhere in Asia. Carried by high-speed jet airplanes, SARS has now been reported in many other parts of the World. Can SARS be contained, or could SARS become another example of the notorious 1918 pandemic flu, which killed over 20 million people. Much is unknown about SARS. How is SARS spread and how infectious is it? SARS spreads by person-to-person contact, but it appears to require closer contact than influenza does and face masks seem to protect doctors and nurses. However, before this simple protection was recognized, many medical staff members were infected and several died. In fact, Dr. Carlo Urbani of Italy, a director of infectious diseases in WHO, the World Health Organization, died at the age of 46 on March 29, a month after he saw his first SARS case. There is circumstantial evidence that SARS can be spread through contaminated objects such as doorknobs, water, and sewage. Scrubbing one’s hands is deemed an important precaution. Hong Kong officials have speculated that cockroaches and even healthy human carriers could spread this disease.
What is the death rate from SARS? That is also uncertain. WHO estimates that world-wide mortality is only 0.5%, but this varies widely from country to country. In Canada mortality is 10%, in Hong Kong 3%, but no deaths have yet been reported in the U.S. Madeline Drexler, author of a recent book on emerging infections, “Secret Agents”, estimates the death rate from SARS to be 3.5%, which she says is higher than that of the 1918 pandemic! At this time there is not enough good data to be certain; moreover, it may be that older people are at higher risk from SARS. It is curious that the infamous 1918 flu seemed more lethal to healthy young adults that the remainder of the population.
Beware of SARS; avoid travel to Asia and contact with people who have recently traveled there. It seems likely that a vaccine will be developed for SARS, but that will require more than a year now that this virus is being grown in cultures. In the interim, many of us will be at risk and without any protection except our immune system. The U.S. government has added SARS to diseases for which individuals may be forcefully quarantined.
Secret Agents: The Menace of Emerging Infections by Madeline Drexler is an engaging book that focuses on emerging bacterial and viral infections and ends with a frightening discussion of the potential dangers of bioterrorism. The book starts like a detective novel tracking the puzzling appearance of the west Nile virus in NY City. The emergence of drug resistant bacteria partially resulting from overuse of antibiotics is another frightening theme in this “mustread” book.
Newcastle disease is a highly contagious, deadly avian virus that infects both wild and domestic birds. Like the foot-and-mouth virus, Newcastle disease can be carried by humans, although it does not make people sick. As discussed in Chapter 4, viruses are usually species specific. Newcastle disease can be transmitted at cockfights and bird shows and by migratory birds. The symptoms are: sneezing, weight loss, lethargy and eventual death! The only treatment is to kill all the diseased animals as well as any that might have come into contact with them and then quarantine the premises. Both commercial flocks and pet birds (parrots, peacocks, ostriches, etc.) must be killed if they have been exposed. In 2002, more than 8,000 birds were killed by federal agriculture officials in Southern California. In the early 1970’s 12 million birds were killed when Newcastle disease devastated California’s poultry industry. (October New York Times, John M. Broder, 2002)
So far scientists have been unable to isolate and characterize the deadly 1918 “Spanish flu”, that killed over 20 million, mostly young adults worldwide. However, they have concocted some pseudo 1918 viruses by incorporating several genes from the lethal Spanish flu into an influenza strain that infects mice. Two recently approved classes of flu drugs were shown to successfully treat this pseudo 1918 virus, provided that the mice were treated within the first six hours! Perhaps the medical establishment will be prepared, if this deadly disease shows up again? (Science News, September 28, 2002, p. 196)
The first cases of West Nile virus were reported in New York in 1999; since then it has been detected in 35 other states and is expected to spread throughout the United States. By late 2002, West Nile virus infection had struck about 2000 people and had killed 98. This amounts to an epidemic, but it is less dangerous as the common flu. Symptoms are often mild: fever, headache, body aches, skin rash, and swollen lymph nodes. Some severe cases progress to encephalitis, a potentially fatal swelling of the brain. Spinal cord damage can result, reminiscent of polio, a virus disease common in the United States before vaccinations began in 1955.
West Nile virus disease is generally transmitted by mosquitoes, but blood transfusions appear to have infected some people as, as yet there is no test to detect this virus in the blood supply. Mosquitoes spread West Nile virus to people, birds (especially crows) and horses. Birds migrate and contribute to the spread of the virus when other mosquitoes bite the infected bird and then bite and infect people. A dead crow is a sign of a possible West Nile infection, because crows are normally very robust birds.
Given favorable warm, wet conditions, such as those in Louisiana, a single pair of mosquitoes can produce over 800 million progeny in 3 months. Because birds can be vectors, West Nile virus does not die off in cold climates; it appears again when warm weather returns and infected birds migrate. The spread of this virus draws attention to the need to control mosquitoes. Mosquito borne diseases are not new in the United States. Malaria struck more than 1 million soldiers during the Civil War and malaria was endemic in several parts of the United States such as the San Francisco bay area. Mosquito borne diseases can be reduced with pesticides, drained wetlands, and treating still water mosquito breading grounds. There is already a vaccine to protect horses from West Nile virus, but it will take time to develop an accepted vaccine for humans and vaccines also carry a risk. The public may become more accepting of insecticides because of their fear of the West Nile virus.
Recall that viruses called phages are bacteria’s natural predators and have been used as antibiotics. These therapeutic viruses are now being evaluated in the United States by a company, Intralytix, which is exploring approval from the FDA. Another company, Exponential Biotherapies Inc. (EBI), is also trying to rescue this old Soviet-era antibiotic therapy. Phages may be used in livestock, and to protect food-stuffs, before they are applied to humans, where they may find important applications in treating antibiotic resistant bacteria
These minuscule smart bombs are very specific with respect to the bacteria that they attack. Moreover, these antibacterial viruses are the most abundant life forms on Earth. Another advantage is that phages multiply in their bacterial host targets and thereby gain potency. Moreover, phages have few side effects. Why then aren’t American companies rushing to produce these cheap, amazing antibiotic alternatives? There are several drawbacks to phage therapy. Firstly, our immune systems attack and destroy phages that are infused into the body. Another problem is that phages come in two flavors: “lytic”, which are ideal for therapy, and “temperate”, which integrate their DNA into their hosts. The temperate phages can produce pathogens, because they can carry genes for the toxins that are released by bacteria such as diphtheria and cholera! The dangerous temperate phages can wreak havoc by integrating bad bacterial genes into the host undergoing therapy. Companies making therapeutic phages must be able to ensure that their phages remain stable in the lytic form and do not convert to the dangerous temperate form. If these problems can be solved, phages may become an important antibacterial therapy. (Science, October 25, 2002, Vol. 298, p. 728)
Helicobacter pylori is the bacterium that is responsible for ulcers and gastritis and is correlated with the development of certain types of stomach cancer. Scientists have recently shown that this pathogen can use hydrogen in their metabolism. Recall that hydrogen gas is produced by fermentation in the colon of some individuals and diffuses throughout the body. About 14% of the intestinal-produced hydrogen is exhaled in our breath. H. pylori infections may rely on hydrogen gas as an energy source because these pathogenic bacteria live in energy poor environments such as gastric mucosa. It is speculated that other human pathogens may also use hydrogen gas produced in the lower intestines. (Science, Vol. 298, November 29, 2002, p. 1788)