The bane of biofilms: Bacteria bound together in a protective matrix tend to resist viral attack. But Lu’s virus produces an enzyme that breaks up these biofilms. When it infects the bacteria on the biofilm’s surface, they burst and release viruses that infect those underneath, soon exposing even deeply embedded bacteria to infection. Graphic Credit: Bryan Christie Design

MIT Technnology Review, August 25, 2010 — At Harvard Medical School, many of Timothy Lu’s patients were being attacked by carpets of microbial goo. They had “really bad infections,” Lu says. “Patients with cystic fibrosis, people getting infections in their catheters. All caused by biofilms.”

Lu, age 29, who is now an assistant professor at MIT, began researching how to destroy biofilms. But unlike those who had previously attacked the problem, he took advantage of the new tools of synthetic biology. He engineered a type of virus, known as a phage, to destroy biofilms and sabotage their defenses against antibiotics. His accomplishment could produce synthetic biology’s first big commercial success by attacking the biofilms that infest industrial equipment.

When bacteria settle on a surface, they spew out molecules that bind the entire population together and cover it in a protective shield. Bacteria in these biofilms are up to 500 times more resistant to antibiotics than free-floating microbes are. Normally, viruses have a hard time penetrating the dense layers of a biofilm. But Lu stumbled across an enzyme produced by oral bacteria that can break up biofilms. He inserted the gene for the enzyme into a phage called T7 so that when the virus infects a microbe, it makes as much of the enzyme as possible.

When the engineered T7 is unleashed on a biofilm, it invades the top layer of bacteria. These bacteria soon burst open, spilling out enzymes and new phages. Aided by the enzyme, the viruses then penetrate the next layer of bacteria, repeating the cycle until the biofilm is destroyed. Lu and his colleagues have also found other ways to turn phages into effective weapons against biofilms, such as creating versions that can shut down the genes that bacteria use to defend themselves against antibiotics.

Last year Lu cofounded Novophage (now called Ascendia Biotechnology) to develop commercial applications for the phages. The company is initially concentrating on biofilms that Lu says can corrode water pipes and block heat transfer in heating and cooling systems, decreasing energy efficiency by up to 80 percent. Conventional industrial attempts to deal with biofilms have involved scrubbing pipes, applying chemicals, or exposing the films to ultraviolet light, but these treatments are not very effective, can damage piping, and are toxic to humans and the environment. A small injection of phages into a water pipe, however, could clean an entire system, with the phages replicating themselves as they consume the biofilm. –Carl Zimmer

The bane of biofilms: Bacteria bound together in a protective matrix tend to resist viral attack. But Lu’s virus produces an enzyme that breaks up these biofilms. When it infects the bacteria on the biofilm’s surface, they burst and release viruses that infect those underneath, soon exposing even deeply embedded bacteria to infection.
Credit: Bryan Christie Design

Visit Dr.Timothy Lu’s lab to see how he destroys biofilms using engineered viruses.

Silky sensor: A biosensor made from silk and gold can pick up tiny signals from proteins and chemicals in the body. Researchers patterned gold over a silk film and wrapped it into a capsule shape to form a small antenna.   Credit: Hu “Tiger” Tao

 

 

MIT Technology Review, August 24, 2010, by Jennifer Chu

  A prototype silk biosensor could someday alert doctors to signs of disease.

Silk and gold, usually a pairing for the runways of Milan, are now the main ingredients for a new kind of implantable biosensor. Researchers at Tufts University have crafted a small antenna from liquid silk and micropatterned gold. The antenna is designed to spot specific proteins and chemicals in the body, and alert doctors wirelessly to signs of disease. Scientists say the implant could someday help patients with diabetes track their glucose levels without having to test themselves daily.

According to Fiorenzo Omenetto, professor of biomedical engineering at Tufts University, silk is a natural platform for medical implants–it’s biocompatible, and while it’s delicate and pliable, it’s also tougher than Kevlar. Implanted in the body, silk can conform to any tissue surface, and, unlike conventional polymer-based implants, it could stay in place over a long period of time without adverse effects. Omenetto has previously taken advantage of these properties to mold silk into tiny chips and flexible meshes, pairing the material with transistors to track molecules, and with electrodes to monitor brain activity.

Now Omenetto is exploring the combination of silk and metamaterials–metals like gold, copper, and silver manipulated at the micro- and nanoscale to exhibit electromagnetic characteristics not normally found in nature. For example, scientists have created metamaterials that act as “invisibility cloaks” by manipulating metals to bend light all the way around an object, rendering it invisible.

Omenetto and his colleague Richard Averitt, associate professor of physics at Boston University, used similar principles to create a metamaterial that’s responsive not to visible light, but rather to frequencies further down the electromagnetic spectrum, within the terahertz range. Not coincidentally, proteins, enzymes, and chemicals in the body are naturally resonant at terahertz frequencies, and, according to Averitt, each biological agent has its own terahertz “signature.”

Terahertz science is a new and growing field, and several research groups are investigating specific protein “T-ray” signatures. A silk metamaterial antenna could someday pick up these specific signals and then send a wireless signal to a computer, to report on chemical levels and monitor disease.

To engineer the responsive end of such an antenna, the team first created a biocompatible base by boiling down silk and pouring the liquid solution into a centimeter-square film. The researchers then sprayed gold onto the silk film, using tiny stencils to create different patterns all along the film. Each area of the film responds to a different terahertz frequency depending on the shape of the gold pattern. The team then wrapped the patterned film around a capsule to form an antenna.

To test its performance, Omenetto and Averitt subjected the antenna to terahertz radiation and found that the antenna was resonant at specific frequencies. Going a step further, the researchers implanted the antenna in several layers of muscle tissue from a pig, and still detected a terahertz signal.

“We’ll try to sense something next and maybe put the antenna in contact with something we’d like to detect, like glucose,” says Omenetto. “We’ll see if we can replicate a proof of principle, and try to add some meaning to the resonance.”

Rajesh Naik, a materials science expert at the Air Force Research Laboratory at Wright-Patterson Air Force Base, says the research has great practical potential.

“Proteins and other molecules can be entrapped within silk films, allowing one to monitor in-vivo chemical reactions,” says Naik. “Similar resonating structures can be patterned onto other polymeric materials, but silk has an added advantage of being biocompatible.”

FORBES.com, August 24, 2010, by Andy Greenberg  —  As the privacy controversy around full-body security scans begins to simmer, it’s worth noting that courthouses and airport security checkpoints aren’t the only places where backscatter x-ray vision is being deployed. The same technology, capable of seeing through clothes and walls, has also been rolling out on U.S. streets.

American Science & Engineering, a company based in Billerica, Massachusetts, has sold U.S. and foreign government agencies more than 500 backscatter x-ray scanners mounted in vans that can be driven past neighboring vehicles to see their contents, Joe Reiss, a vice president of marketing at the company told me in an interview. While the biggest buyer of AS&E’s machines over the last seven years has been the Department of Defense operations in Afghanistan and Iraq, Reiss says law enforcement agencies have also deployed the vans to search for vehicle-based bombs in the U.S.

“This product is now the largest selling cargo and vehicle inspection system ever,” says Reiss.

Here’s a video of the vans in action.

The Z Backscatter Vans, or ZBVs, as the company calls them, bounce a narrow stream of x-rays off and through nearby objects, and read which ones come back. Absorbed rays indicate dense material such as steel. Scattered rays indicate less-dense objects that can include explosives, drugs, or human bodies. That capability makes them powerful tools for security, law enforcement, and border control.

It would also seem to make the vans mobile versions of the same scanning technique that’s riled privacy advocates as it’s been deployed in airports around the country. The Electronic Privacy Information Center (EPIC) is currently suing the DHS to stop airport deployments of the backscatter scanners, which can reveal detailed images of human bodies. (Just how much detail became clear last May, when TSA employee Rolando Negrin was charged with assaulting a coworker who made jokes about the size of Negrin’s genitalia after Negrin received a full-body scan.)

“It’s no surprise that goverments and vendors are very enthusiastic about [the vans],” says Marc Rotenberg, executive director of EPIC. “But from a privacy perspective, it’s one of the most intrusive technologies conceivable.”

AS&E’s Reiss counters privacy critics by pointing out that the ZBV scans don’t capture nearly as much detail of human bodies as their airport counterparts. The company’s marketing materials say that its “primary purpose is to image vehicles and their contents,” and that “the system cannot be used to identify an individual, or the race, sex or age of the person.”

Though Reiss admits that the systems “to a large degree will penetrate clothing,” he points to the lack of features in images of humans like the one shown at right, far less detail than is obtained from the airport scans. “From a privacy standpoint, I’m hard-pressed to see what the concern or objection could be,” he says.

But EPIC’s Rotenberg says that the scans, like those in the airport, potentially violate the fourth amendment. “Without a warrant, the government doesn’t have a right to peer beneath your clothes without probable cause,” he says. Even airport scans are typically used only as a secondary security measure, he points out. “If the scans can only be used in exceptional cases in airports, the idea that they can be used routinely on city streets is a very hard argument to make.”

The TSA’s official policy dictates that full-body scans must be viewed in a separate room from any guards dealing directly with subjects of the scans, and that the scanners won’t save any images. Just what sort of safeguards might be in place for AS&E’s scanning vans isn’t clear, given that the company won’t reveal just which law enforcement agencies, organizations within the DHS, or foreign governments have purchased the equipment. Reiss says AS&E has customers on “all continents except Antarctica.”

Reiss adds that the vans do have the capability of storing images. “Sometimes customers need to save images for evidentiary reasons,” he says. “We do what our customers need.”

FORBES.com, August 23, 2010  —  LONDON — The fear of falling may be enough to make elderly people more likely to fall, regardless of their actual risk, a new study says.

Australian and Belgian researchers followed 500 men and women, aged 70 to 90, for one year. They split the participants into various groups depending on their perceived and actual risks for falling. While most people had a fairly accurate sense of their chances of falling, about one-third either underestimated or overestimated their risk.

Among the people who were most afraid of falling, nearly 40 percent fell at least once within a year, even though they were rated to have a low actual risk of falling based on their physical health. The study was published online Friday in the medical journal, BMJ.

The authors said doctors should take patients’ fears of falling into consideration when recommending what might help in preventing future injuries. “The inclusion of psychological and cognitive factors should improve the accuracy of prediction of falls,” they wrote, suggesting therapies to ease anxiety about falling could help some people.

Falls in the elderly can be particularly serious since they are more prone to breaking bones or hips, which can leave them unable to walk.

Michelle Mitchell, a director at the British charity Age UK, said fear of falling can reduce people’s quality of life as well as lead to isolation and loneliness. The charity called for Britain to invest more in services specifically to prevent falls in the elderly.

The fungus Cladosporium fulvum in action on a tomato leaf. (Credit: Image courtesy of Wageningen University and Research Centre)

ScienceDaily.com (Aug. 23, 2010) — Fungal and bacterial pathogens are quite capable of infecting plants, animals and humans despite their immune systems. Fungi penetrate leafs, stalks and roots, or skin, intestines and lungs, to infect their hosts. Researchers from Wageningen UR (University & Research centre) discovered, together with Japanese colleagues, how this is possible. They found that the fungus secretes a protein that makes stray building blocks of the fungal cell wall invisible for the immune system of the plant, such that infection remains unnoticed.

They report their findings in the Aug. 20 issue of the journal Science.

Fungi prepare their attack, for instance on a tomato plant, rather well. Take for example the fungus Cladosporium fulvum that causes leaf mould on tomato plants. Once the fungus starts to infect, the tomato plant would recognize the fungus based on the presence of chitin fragments that are derived from the fungal cell wall. Chitin does not naturally occur in plants, but chitin fragments can always be found near fungi, just like cat hairs betray a cat’s presence. The tomato immune system recognizes the chitin fragments as “non-self and unwanted” and alarms the immune system to combat the infection. So far so good.

However, Cladosporium fulvum as well as nearly all other fungi carry a secret weapon. A team of researchers under the supervision of plant pathologist Bart Thomma discovered that the fungus secretes the protein Ecp6 during host attack. Ecp6 is the code name for ‘extracellular protein 6’. Ecp6 finds the chitin fragments that surround the fungus and binds them. This binding makes the chitin fragments invisible for the tomato plant, like a stealth-jet is invisible for radar, such that the immune system is not alarmed. As a result the plant gets diseased. Animal and human fungal pathogens also produce the protein, and are likely to disarm the immune system of their hosts in a similar way.

From experiments that the researchers performed to investigate the role of Ecp6, it appears that a fungus that does not produce Ecp6 is much less aggressive and less capable of causing disease in tomato plants.

Since not only Cladosporium but nearly all fungi, including pathogens of humans and animals, have Ecp6, the binding of chitin fragments appears a general strategy of fungi to evade the immune system of their hosts.

This knowledge may enable scientists to design novel methods to combat fungal diseases in agriculture (leaf mould, root and stalk rot, smut, wilt disease, apple scab, rust, tree cancer) and in health care (dandruff, athlete’s foot, candida-infections, aspergillosis, etc.).


Source:  Wageningen University and Research Centre,.


Journal Reference:

  1. Ronnie de Jonge, Peter van Esse, Anja Kombrink, Tomonori Shinya, Yoshitake Desaki, Ralph Bours, Sander van der Krol, Naoto Shibuya, Matthieu Joosten, and Bart Thomma. Conserved fungal LysM effector Ecp6 prevents chitin-triggered immunity in plants. Science, 2010; 329 (5994): 953-955 DOI: 10.1126/science.1190859

University of York, August 23, 2010  —  The nitrogen cycle is the natural process that makes nitrogen available to all organisms on earth. Scientists at the University of York have discovered that one of the world’s most common and ecologically important groups of fungi plays an unsuspected role in this key natural cycle.

Almost all plants form symbiosis with fungi in their roots, know as mycorrhizas. The commonest type of mycorrhiza is called the arbuscular mycorrhiza (AM) and involves two-thirds of plant species. Unlike most fungi, the AM fungi get their supply of sugars for energy and growth from their plant partner and not from the decomposition of organic matter. . Surprisingly, the researchers found that AM fungi thrive on decomposing organic matter and obtain large amounts of nitrogen from it. The fungus itself is much richer in N than plant roots, and calculations suggest that there is as much nitrogen in AM fungi globally as in roots. Since fungal hyphae (the threads of which the fungus is composed) are much shorter-lived than roots, this finding has implications for the speed with which nitrogen cycles in ecosystems,

The research, by Dr Angela Hodge and Professor Alastair Fitter in the Department of Biology at York was funded by the Biotechnology and Biological Sciences Research Council, is published in the latest issue of Proceedings of the National Academy of Sciences (PNAS).

Because these fungi cannot be grown in pure culture, the researchers created microcosms to isolate the fungi from plant roots and to allow them access to a patch of organic matter, and used stable isotopes to track the movement of nitrogen and carbon. Fungi that exploited decomposing organic matter were also better able to colonize a new plant. In addition, reducing the carbon supply to the fungus by shading the host plant did not diminish he fungal growth in the organic matter. Dr Hodge said: “We have known for a long time that these fungi play a central role in the phosphorus cycle; now it seems that they are equally important in the nitrogen cycle, opening the possibility of exploiting them in the development of more sustainable forms of agriculture. ”


Source:  University of York.


Journal Reference:

  1. 1.                     Hodge et al. Substantial nitrogen acquisition by arbuscular mycorrhizal fungi from organic material has implications for N cycling. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.1005874107

ScienceDaily.com, July/August 2010  —  By tinkering with a type of fungus that lives in association with plant roots, researchers have found a way to increase the growth of rice by an impressive margin. The so-called mycorrhizal fungi are found in association with nearly all plants in nature, where they deliver essential nutrients — specifically phosphate — to plants in return for sugar. The findings are nevertheless a surprise, according to researchers reporting online on June 10th in Current Biology because there has been little evidence thus far to suggest that crop plants actually respond to the fungi.

“Global reserves of phosphate are critically low, and because the demand for phosphate goes hand in hand with human population expansion, it is predicted that there will be major shortages in the next few decades,” said Ian Sanders of the University of Lausanne in Switzerland. “Unfortunately, most of our important crop plants do not respond strongly, if at all, to inoculation with these fungi. This is especially so for rice, the most globally important food plant. There are no clear reports that rice benefits from inoculation with mycorrhizal fungi.”

That is, until now. In fact, the researchers started with a strain of mycorrhizal fungus of the species Glomus intraradices that clearly didn’t benefit rice. They then took advantage of the fungus’s unusual genetics. A single fungal filament can contain genetically distinct nuclei. Those distinct nuclei can fuse together, mixing genes up in different combinations, and fungal spores can also end up with different complements of genes, the new research shows. As such, the supposedly clonal fungi maintain a degree of genetic variation that had been overlooked.

“It turns out we can very simply manipulate their genetics to produce fungi that induce up to a five-fold growth increase in this globally important food plant,” Sanders said.

The genetic changes that the researchers produced in the fungi led to changes in the activity of important genes in the rice, they report. Those affected genes are known to be involved in establishing the mutually beneficial relationship between plant and fungus and in the transport of phosphate at the interface between fungus and plant.

Sanders emphasized that the genetic manipulation the researchers undertook didn’t involve any insertion of new genes into the fungal genome. It rather relied on the same biological processes of genetic exchange and segregation that normally take place in the fungus. “What we have done with these fungi is not much different from what plant breeders, and farmers before them, have done to improve crops,” he said. “The only difference is that the genetics of these fungi is a little bit more unusual, and no one thought it worth doing.”

On a cautionary note, Sanders did emphasize that the plants they studied were grown in a greenhouse in Switzerland under conditions that only mimicked those found in the tropics. “This is clearly not at all the same environment as a rice plant growing in a real paddy field,” he said. It remains to be seen whether the same growth benefits will apply in practice.

“However,” Sanders said, “our study clearly shows that the potential is there to manipulate the genetics of the fungus to achieve greater crop yields.”


Source:  Cell Press


Journal Reference:

  1. 1.                     Caroline Angelard, Alexandre Colard, Hélène Niculita-Hirzel, Daniel Croll, and Ian R. Sanders. Segregation in a Mycorrhizal Fungus Alters Rice Growth and Symbiosis-Specific Gene Transcription. Current Biology, June 10, 2010 DOI: 10.1016/j.cub.2010.05.031

New Publication – How Electronic Data Capture (EDC) Can Be Integrated Into The Data Monitoring Plan (DMP)

Target Health is pleased to announce that an article entitled “How Electronic Data Capture (EDC) Can Be Integrated Into The Data Monitoring Plan (DMP)“ has been accepted for publication by the Society for Clinical Data Management. If you would like a copy, please contact  Dr. Jules T. Mitchel. For other publications by Target Health, please visit our website.

For more information about Target Health contact Warren Pearlson (212-681-2100 ext 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website. 

Salmonella Outbreaks Spur Nationwide Egg Recall

Salmonella

 

1) ___ are behind a nationwide salmonella outbreak that caused hundreds of illnesses each week in June and July, with more outbreaks in August. The nationwide egg recall involves more than a dozen major brands that got eggs from Wright County Egg in Galt, Iowa. CDC and state investigators in California, Colorado, and Minnesota found clusters of 2) ___ food poisoning among people who ate eggs at the same restaurants. Those restaurants got eggs that came from Wright County Egg.

Investigations continue in Arizona, Connecticut, Massachusetts, Maryland, North Carolina, Nevada, Oregon, Pennsylvania, Tennessee, and Texas. Meanwhile, the FDA is conducting a thorough investigation of the Iowa firm to which the contaminated eggs were traced. The company says it already has sent all its remaining eggs to a breaker, where they will be 3) ___ to kill any salmonella.

Shell eggs included in the recall were shipped since May to food wholesalers, distribution centers, and food service companies in eight states, from which they were distributed nationwide. The brand names included in the recall are Lucerne, Albertson, Mountain Dairy, Ralph’s, Boomsma’s, Sunshine, Hillandale, Trafficanda, Farm Fresh, Shoreland, Lund, Dutch Farms, and Kemps. Recalled eggs are in six, dozen, and 18-egg cartons.

Stamped on the end of the recalled egg cartons are Julian dates ranging from 136 to 225 and plant numbers 1026, 1413, and 1946. The plant number begins with the letter P and then the number. The Julian date follows the plant number, for example: P-1946 223. Recalled eggs may be returned to the store for a full 4) ___.

The salmonella strain causing the outbreak is Salmonella Enteritidis, the most common salmonella strain. Usually the 5) ___ gets about 50 reports a week of Salmonella Enteritidis food poisoning; beginning in May there was a fourfold increase in salmonella reports. Each week in late June and early July the CDC received some 200 salmonella samples isolated from patients, all with the same DNA fingerprint.

Symptoms of infection begin 12 to 72 hours after consuming contaminated foods or beverages and include fever, abdominal cramps, and diarrhea. Symptoms usually last four to seven days. Most people recover without 6) ___ treatment, but severe cases can be fatal. People prone to severe illness — particularly severe diarrhea – include the elderly, infants, and those with impaired immune systems, including people on immune suppressive therapy such as cancer chemotherapy.

 

ANSWERS: 1) eggs; 2) salmonella; 3) pasteurized; 4) refund; 5) CDC; 6) antibiotic

Avoid Salmonella: Protect Yourself With Knowledge

 

How to Avoid Food Poisoning From Eggs

If you like your eggs prepared over easy, you may want to change your egg-eating habits. Here’s the CDC’s advice on how to avoid food poisoning from eggs:

  • Don’t eat recalled eggs or products containing recalled eggs. Recalled eggs might still be in grocery stores, restaurants, and homes. Consumers who have recalled eggs should discard them or return them to their retailer for a refund.
  • People who think they might have become ill from eating recalled eggs should consult their health care providers.
  • Keep eggs refrigerated at least to 45 degrees F at all times.
  • Discard cracked or dirty eggs.
  • Wash hands, cooking utensils, and food preparation surfaces with soap and water after contact with raw eggs.
  • Eggs should be cooked until both the white and the yolk are firm and eaten promptly after cooking.
  • Do not keep eggs warm or at room temperature for more than two hours.
  • Refrigerate unused or leftover egg-containing foods promptly.
  • Avoid eating raw eggs.
  • Avoid restaurant dishes made with raw or undercooked, unpasteurized eggs. Restaurants should use pasteurized eggs in any recipe (such as Hollandaise sauce or Caesar salad dressing) that calls for raw eggs.
  • Consumption of raw or undercooked eggs should be avoided, especially by young children, elderly people, and people with weakened immune systems or debilitating illness.

Daniel Elmer Salmon (1850-1914) – Discover of Salmonella

Daniel Elmer Salmon, D.V.M.

 

Daniel Elmer Salmon was the son of Daniel Landon and Eleanor (Flock) Salmon. His early education was at the Mount Olive District School, Chester Institute, and Eastman Business College. In 1868 Salmon was enrolled in the first class at Cornell University, which had been established three years earlier in New York. He graduated from Cornell as bachelor of veterinary science in 1872.

After graduation, Salmon married Mary Thompson Corning from Ithaca, New York, and settled as a veterinary in Newark, New Jersey. For reasons of health he moved to Asheville, North Carolina, situated in the Blue Ridge Mountains at an altitude of 600 meters and known for its mild climate. Two years later he gave a series of lectures on veterinary medicine at the University of Georgia, and the same time commenced a special study of diseases of hogs. Daniel Salmon was granted a doctoral degree in veterinary medicine from Cornell University in 1876. This was the first DVM degree to be awarded in the United States of America.

In 1879 Salmon distinguished himself as a key participant in the New York State campaign to wipe out pleuro-pneumonia in cattle. After this effort he was selected by the Department of Agriculture to study the widespread problem of livestock disease in the south, particularly Texas fever. In 1883 Salmon was asked to organize a veterinary department, thus becoming founding director of the Bureau of Agriculture under the Department of Agriculture. Already the next year this institution was made into the Bureau of Animal Industry, headed by Salmon. He held this position until 1905, when a dispute with the head of the Department of Agriculture in Washington forced him to resign. During his tenure as bureau chief Salmon made epoch-making contributions to veterinary medicine, also becoming a leader in the field of public health administration.

Early in his career Salmon had been a skilled laboratory technician, but administrative duties gradually removed him from the daily details of research work. As head of the bureau he governed its policy, planned the assistants’ work and found time to write close to one hundred articles, alone or in collaboration with others. Together they cover almost the entire field of research in veterinary medicine in this period. One reason for the successful research being done despite Salmon’s administrative duties was the fact that he was probably quite a genius when it came to choosing assistants. Among them was Theobald Smith (1859-1934), one of the greatest names in American medical science who is today best remembered for his research on anaphylaxis (acquired hypersensitivity against proteins that are normally tolerated without problems). Anaphylaxis was long referred to as Theobald Smith’s phenomenon.

The relationship between Salmon and Smith, however, was less than heartily, because Salmon insisted on standing as the sole senior author of several research reports, including the one on the hog cholera bacillus – Salmonella cholerae-suis, which was first discovered by Theobald Smith. Nevertheless, together Salmon and Smith made a major discovery which, today, is still saving children from death or crippling disease. During the study of hog cholera they demonstrated that dead (heat killed) organisms could immunize animals against living organisms. This was the foundation for the development of a vaccine against typhus and Jonas Salk’s (1914-1995) production of polio vaccine.

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