SHOTS IN THE DARK

By Pam Eastlick

Welcome to The Deep science and technology column where we cover topics from the deep sea to deep space and beyond.

Greetings everyone and welcome to yet another excursion through the headlines of science. You don’t see this stuff much of anywhere else but here, which is sad. It implies that there isn’t much interest in science but of course, Americans are notorious about their news preferences. The Australian government is currently undergoing a crisis and we get news about bedbugs in the Empire State Building. Although that’s something I would write about, I’m not sure it’s worthy of major headline news.

Today we’re going to take a little excursion into what ails us, and the news for the most part is good. The most dangerous animal on the face of the planet, the one that kills the most humans every single year is sitting somewhere in your back yard right now. Strangely enough, you’re not afraid of it like you are the shark and the grizzly bear and the crocodile. What is this dreadful killer? The mosquito! But there’s good news on the malaria front.

VACCINATION FOR A KILLER

The real problem about malaria which sickens almost a quarter of a billion people each year and kills a child every 30 seconds is that there is no vaccine to prevent the mosquito from infecting you with it. That may soon change. Researchers at Rockefeller University have genetically transformed the yellow fever vaccine to prime the immune system to fend off the mosquito borne parasites that cause the disease. They’ve discovered that the modified vaccine, along with a booster, provided mice with immunity to the deadly disease.

Malaria is one of the most pressing health crises of developing countries: in communities stricken by infection, attendance at work and school drops, and poverty deepens. It’s been known since the ‘60’s that one form of the malaria parasite — called the sporozoite; — can trigger the human immune system and help to protect against future infection. The only way to gather sporozoites, however, is to pluck them one-by-one from the salivary glands of irradiated, malaria-ridden mosquitoes. Then the parasites must be injected into people and you have to use a lot of them. This takes lots of time, lots of lab space and lots of people and it isn’t economically feasible for large-scale use.

Researchers from Rockefeller University and colleagues at New York University decided that fighting infection with infection might be the key. They began experimenting with the attenuated yellow fever strain used in the yellow fever vaccine, known as YF17D, which has been used to successfully vaccinate more than 400 million people since 1937. Previous work in the Rice laboratory and by others had shown that this vaccine strain could be modified to include short sequences from other pathogens, including malaria.

The researchers inserted the nearly complete sequence of a malaria gene into the YF17D vaccine and found that the malaria gene could produce its protein in cultured cells. The protein they chose, called CSP, covers the surface of the malaria sporozoite and is thought to be the main reason that this form of the parasite stimulates the immune system so effectively.

Immunization of mice with the YF17D-CSP vaccine led to a measurable jump in immune activity against the malaria protein, but the single shot was not enough to protect the animals from infection with the mouse form of the malaria parasite.

The group therefore added a booster shot to the vaccination regimen. Animals that had been immunized with YF17D-CSP, or with a saline solution control, were given a low dose of irradiated sporozoites. While the saline-sporozoite group was only partially protected from challenge with viable parasites, vaccination with YF17D-CSP plus the sporozoites protected 100 percent of the animals against infection.

"These results are exciting because they show the YF17D-CSP vaccine can prime the immune response against a malaria parasite," says lead author Cristina Stoyanov. Although the utility of this approach for human immunization is not yet clear, the team hopes that further studies in other animal models might eventually lead to an effective vaccine.

By inserting a gene for the malaria parasite into a vaccine that originally targeted yellow fever, scientists have shown they can boost the immune system’s response to infection in mice. (Credit: James Gathany/CDC)

Guam has the mosquito that carries malaria. All it takes is someone with malaria who comes here from somewhere else. Here’s hoping that this vaccine proves to be cheap and effective!

There’s also some news about a different vaccine that isn’t quite as positive. It highlights the point that sometimes humans meddle with things that they don’t quite understand and perhaps can’t control.

We all breathed a sigh of relief when one of the most dreadful scourges known to man was finally declared eliminated after a massive worldwide vaccination campaign. I’m referring, of course, to smallpox and I am one of the last U.S. citizens to receive a smallpox vaccination. They were no longer routinely given to Americans, but I was traveling to Southeast Asia where it had not been declared eradicated. Shortly after I made my trip, smallpox was declared officially eradicated worldwide and routine vaccinations for smallpox stopped. It turns out that may not have been such a good idea.

TWO BIRDS WITH ONE STONE?

Of course, they say that you stamp out one problem and another arises. That certainly was the case with smallpox because shortly after it was eradicated, the world witnessed another explosive killer disease: HIV or AIDS. Now, researchers have discovered that the two things just could be linked.

According to researchers who published their work in the open access journal BMC Immunology, the smallpox vaccination produces a five-fold reduction in HIV replication in the laboratory. They raise the possibility that the end of smallpox vaccination in the mid-20th century may have caused a loss of protection that contributed to the rapid contemporary spread of HIV.

There have been several proposed explanations for the rapid spread of HIV in Africa, including wars, the reuse of unsterilized needles and the contamination of early batches of polio vaccine. However, all of these have been either disproved or do not sufficiently explain the behavior of the HIV pandemic.

Smallpox immunization was gradually withdrawn from the 1950s to the 1970s following the worldwide eradication of the disease, and HIV has been spreading exponentially since approximately the same time period. The scientists propose that smallpox vaccination may confer protection against HIV by producing long-term alterations in the immune system, possibly including the expression of a certain receptor, CCR5, on the surface of a person’s white blood cells, which is exploited by both viruses.

Although the results are interesting, the researchers say they are very preliminary and it is far too soon to recommend the general use of smallpox vaccinations for fighting HIV.

So now we have two instances of using a bullet for one problem to kill a completely different. Here’s hoping they both work!

Photograph of a Nigerian child being immunized during the Smallpox Eradication and Measles Control Program of West Africa in 1960. (Credit: CDC/Dr. J.D. Millar)

Although we have the malaria mosquito here and most of us know at least one person living with HIV, the place that is the mother lode for both diseases is Africa and the poor countries there have no money to make even the most basic inroads into solving their medical crises. Another disease that is more of a problem here and also a big problem world-wide is diabetes. German researchers are trying to make an economic impact on another of the world’s great killers.

A CHEAP SHOT

There are 25 MILLION people in the U.S. with diabetes and you don’t need to be told that it’s the biggest killer on Guam. But India is the country with the most diabetics with over 50 million people. No one on Guam goes without insulin if they seek help, but that isn’t the case in developing countries. Now German scientists have developed a new method to cheaply produce insulin for the treatment of diabetes.

The researchers wanted to develop a new procedure to increase the yield of an insulin precursor from which the actual insulin can be obtained, and in this way reduce costs. They used a type of yeast to produce the building blocks to make insulin.

In the early 1980s, insulin was the first recombinant product approved by the FDA for human application. Today, human insulin is produced as a recombinant protein, using two major routes. One route involves the production of the insulin precursor using the bacterium Escherichia coli. The other route involves baker’s yeast Saccharomyces cerevisiae. The yeast product is easier to use because the yeast secretes a soluble insulin precursor into the culture medium. This makes it easier to collect.

The newly described method from Ursula Rinas and her group also uses this route but the yeast they used produces much more of the insulin precursor. Insulin produced with this new method is identical to human insulin. The researchers are also working on a method to produce a vaccine against dengue fever using the same system.

For most people in developing countries medicine is too expensive and insulin is often difficult to obtain and very expensive. The researchers hope that this new method of producing insulin will be used in developing countries to produce insulin that everybody can afford.

Taking new shots at old killers. Cruise on over to the Deep Website at www.thedeepradioshow.com to learn more about the frontiers of medicine and many other topics. Enjoy!

PESTS OF ALL SIZES

By Pam Eastlick

Welcome to The Deep science and technology column where we cover topics from the deep sea to deep space and beyond.

Greetings everyone and welcome to the last column of the year. I thought today we’d take a little trip through the animal file and see what we can find about the critters that share our world with us.

One critter I can definitely do without is the mosquito. Besides the fact that the mosquito is annoying and painful, it’s also a notorious spreader of disease. Quite frankly, I personally think we’d be better off without them. Here’s a sad little tale of economics and pests.

TAKING OUT THE STING

After searching for more than 50 years, scientists finally have discovered a number of new mosquito repellents that beat DEET, the gold standard for warding off the pesky insects. They sound like a dream come true. They repel mosquitoes for up to three times longer than DEET, the active ingredient in many of today’s insect repellents. They don’t have the unpleasant odor of DEET. And they don’t cause DEET’s sticky-skin sensation. But there’s a mosquito in the ointment: The odds appear to be stacked against any of the new repellents ever finding a place on store shelves.

Ulrich Bernier, Ph.D., the lead researcher for the repellent study, said that costly, time-consuming pre-market testing and approval is a hurdle that will delay the availability of the repellents, which were discovered last year.

Making the repellents commercially available takes significant investment in both money and time. The cost may be several hundred thousand dollars. Once it’s determined that the repellent works then there’s also a toxicological hazard evaluation involving numerous toxicological tests."

If the repellents continue to work well when tested in the laboratory on human skin, and if they pass the battery of toxicological tests, they still face a series of tests to prove their effectiveness against mosquitoes.

Bernier and his team discovered the repellents with what they say is the first successful application of a computer model using the molecular structures of more than 30,000 chemical compounds tested as repellents over the last 60 years. Using 11 known compounds, they synthesized 23 new ones. Of those, 10 gave about 40 days protection, compared to 17.5 days for DEET, when a soaked cloth was worn by a human volunteer. When applied to the skin, however, DEET lasts about five hours.

Bernier routinely participates in repellency studies, which involve about 500 mosquitoes trying to land on his arm and bite through a repellent-soaked cloth. If the mosquitoes don’t land, the researchers know the repellent is working. If they walk around on the cloth-covered-arm, they’re on the verge of being repelled. If they bite…then it’s on to the next repellent.

To search for the best repellents, the team devised software that recognized structural features of a chemical that would make it effective in keeping the bugs away. They trained it by feeding it the molecular structures of 150 known repellents. Based on this information, the program learned to identify the chemical traits of a good repellent without the chemists even having to know what those traits were. For example, the team checked out 2,000 variants of a compound found in black pepper that repels insects.

I hope that they get some funding to market these new repellants soon. I’d sure buy them!

Mosquitoes stay away from repellent-soaked cloth on the arm of researcher Ulrich Bernier. (Credit: Greg Allen, U.S. Department of Agriculture, Agricultural Research Service)

And now we move on to a tale of another of the least-loved animals on the planet.

YOU THINK WE’VE GOT PROBLEMS??

I’m having a little mini-invasion at my house. I’m surrounded by forest and a large family of brown tree snakes seems to have decided to call my house and my dog food theirs. We whip them around a mop handle and dump them in the freezer. No more blood, no more machete nicks on my stuff. It’s a humane way to die, not that I really care because brown tree snakes are aggressive and I’ve been bitten several times.

Brown tree snakes can get quite large, but they don’t hold a candle to the subjects of this story. The southern United States is being invaded by some of the biggest snakes on the planet.

A new report by the U.S. Geological Survey (USGS) tells all about the risks of nine non-native snake species including boa constrictors, anacondas and pythons. Two of the species have been documented as reproducing in the wild in South Florida where the Burmese python population is already reported to be in the tens of thousands.

Although the giant snakes don’t pose a great threat to humans, adults of the largest pythons have been known to attack and kill people in their native habitats. The snake most often associated with attacks on humans is the reticulated python, a native of Southeast Asia.

Although many of the giant snakes snake species may be confined to the deep South, others like Burmese pythons, northern and southern African pythons, boa constrictors and yellow anacondas put larger portions of the U.S. mainland at risk.

The USGS scientists who authored the report point out that native U.S. birds, mammals, and reptiles have never had to deal with huge predatory snakes before. Individuals of the largest three species reach lengths of more than 20 feet and upwards of 200 pounds. The reticulated python is the world’s longest snake, and the green anaconda is the heaviest snake. Both species have been found in the wild in South Florida, although breeding populations are not yet confirmed for either.

Breeding populations have been confirmed in South Florida for Burmese pythons and the boa constrictor, and there is strong evidence that the northern African python may have a breeding population in the wild as well.

Unfortunately these snakes mature early, produce large numbers of offspring, travel long distances, and have broad diets that allow them to eat most native birds and mammals. In addition, most of these snakes can inhabit a variety of habitats and are quite tolerant of urban or suburban areas. Boa constrictors and northern African pythons, for example, already live wild in the Miami metropolitan area.

The report notes that there are no controls adequate for eradicating an established population of giant snakes once they have spread over a large area. Making the task of eradication more difficult is that in the wild these snakes are extremely difficult to find since their camouflaged coloration enables them to blend in well with their surroundings.

Dr. Gordon Rodda, a herpetologist who lived on Guam, mentions us in the report. “We have a cautionary tale with the American island of Guam and the brown tree snake,” he says. “Within 40 years of its arrival, this invasive snake has decimated the island’s native wildlife: 10 of Guam’s 12 native forest birds, one of its two bat species, and about half of its native lizards are gone. The python introduction to Florida is so recent that the tally of ecological damage cannot yet be made.”

USGS researchers used the best available science to predict areas of the country most at risk of invasion by these giant snakes. Based on climate alone, many of the species would be limited to the warmest areas of the United States, including parts of Florida, extreme south Texas, Hawai
i, and America’s tropical islands, such as Puerto Rico, Guam, and other Pacific islands. For a few species, however, larger areas of the continental United States appear to exhibit suitable climatic conditions. For example, much of the southern U.S. climatic conditions are similar to those experienced by the Burmese python in its native range.

The Fish and Wildlife Service and the National Park Service will use the report to help them figure out what to do about the problem and how to prevent further colonization.

Researchers implant a radio transmitter in a 16-foot, 155-pound female Burmese python at the South Florida Research Center, Everglades National Park. Radio-tracking builds understanding of where pythons spend their time and therefore where they can be controlled in practice. Photo courtesy of Lori Oberhofer, National Park Service. (Credit: U.S. Geological Survey)

I once had a very good friend in Pete, the reticulated python. Despite her name, she was a female and she was a mascot for one of the units at U-tapao Air Base in Thailand. She had been captured on the flightline about five years before I got there and at that time, she was three feet long and weighed 30 pounds.

To keep Pete fed, the Thais who ran the café where she was housed ran a lottery. They put a chicken in the cage with Pete once a week and for a quarter, you could put in your guess of the day and time that Pete ate the chicken. The person who came the closest got the money, less the amount to buy the next week’s chicken.

Reticulated pythons don’t eat that often in the wild and when I left Thailand, Pete was 33 feet long and weighed 300 pounds. Most times, when I came to call, she would rear up her head until it was on the level of mine and we would chat. I never decided if she was just curious about the white lady, or viewed me as lunch. She was an impressive animal, but not one I’d want to meet in my back yard!