University of Arizona’s “malaria-proof” mosquito

July 15, 2010

This could be good news:  A genetically-altered mosquito that doesn’t harbor the malaria parasite, and so cannot pass it along to humans it bites in its later life.

One more way to end the use and production of DDT.

Press release from the University of Arizona (one of my alma mater schools):

The first malaria-proof mosquito

Scientists at the University of Arizona have achieved a breakthrough in the fight against malaria: a mosquito that can no longer give the disease to humans

IMAGE: Michael Riehle, holding genetically altered mosquitoes, and his team work in a highly secure lab environment to prevent genetically altered mosquitoes from escaping.

Click here for more information.

For years, researchers worldwide have attempted to create genetically altered mosquitoes that cannot infect humans with malaria. Those efforts fell short because the mosquitoes still were capable of transmitting the disease-causing pathogen, only in lower numbers.

Now for the first time, University of Arizona entomologists have succeeded in genetically altering mosquitoes in a way that renders them completely immune to the parasite, a single-celled organism called Plasmodium. Someday researchers hope to replace wild mosquitoes with lab-bred populations unable to act as vectors, i.e. transmit the malaria-causing parasite.

“If you want to effectively stop the spreading of the malaria parasite, you need mosquitoes that are no less than 100 percent resistant to it. If a single parasite slips through and infects a human, the whole approach will be doomed to fail,” said Michael Riehle, who led the research effort, the results of which will be published July 15 in the journal Public Library of Science Pathogens. Riehle is a professor of entomology in the UA’s College of Agriculture and Life Sciences and is a member of the BIO5 Institute.

Riehle’s team used molecular biology techniques to design a piece of genetic information capable of inserting itself into a mosquito’s genome. This construct was then injected into the eggs of the mosquitoes. The emerging generation carries the altered genetic information and passes it on to future generations. For their experiments, the scientists used Anopheles stephensi, a mosquito species that is an important malaria vector throughout the Indian subcontinent.

The researchers targeted one of the many biochemical pathways inside the mosquito’s cells. Specifically, they engineered a piece of genetic code acting as a molecular switch in the complex control of metabolic functions inside the cell. The genetic construct acts like a switch that is always set to “on,” leading to the permanent activity of a signaling enzyme called Akt. Akt functions as a messenger molecule in several metabolic functions, including larval development, immune response and lifespan.

When Riehle and his co-workers studied the genetically modified mosquitoes after feeding them malaria-infested blood, they noticed that the Plasmodium parasites did not infect a single study animal.

IMAGE: Under UV light, this mosquito larva reveals a red fluorescent marker in its nervous system, causing eyes and nerves to glow. The marker’s presence tells the researchers in Riehle’s…

Click here for more information.

“We were surprised how well this works,” said Riehle. “We were just hoping to see some effect on the mosquitoes’ growth rate, lifespan or their susceptibility to the parasite, but it was great to see that our construct blocked the infection process completely.”

Of the estimated 250 million people who contract malaria each year, 1 million – mostly children – do not survive. Ninety percent of the number of fatalities, which Riehle suspects to be underreported, occur in Sub-Saharan Africa.

Each new malaria case starts with a bite from a vector – a mosquito belonging to the genus Anopheles. About 25 species of Anopheles are significant vectors of the disease.

Only the female Anopheles mosquitoes feed on blood, which they need to produce eggs. When they bite an infected human or animal, they ingest the malaria parasite.

Once the Plasmodium cells find themselves in the insect’s midgut, they spring into action. They leave the insect’s digestive tract by squeezing through the midgut lining. The vast majority of Plasmodium cells do not survive this journey and are eliminated by the mosquito’s immune cells. A tiny fraction of parasite cells, usually not more than a handful, make it and attach themselves on the outside of the midgut wall where they develop into brooding cells called oocysts.

Within 10-12 days, thousands of new Plasmodium cells, so-called sporozoites, sprout inside the oocyst. After hatching from the oocyst, the sporozoites make their way into the insect’s salivary glands where they lie in wait until the mosquito finds a victim for a blood meal. When the mosquito bites, some sporozoites are flushed into the victim’s bloodstream.

“The average mosquito transmits about 40 sporozoites when it bites,” said Riehle, “but it takes only one to infect a human and make a new malaria victim.”

Several species of Plasmodium exist in different parts of the world, all of which are microscopically small single-celled organisms that live in their hosts’ red blood cells. Each time the parasites undergo a round of multiplication, their host cells burst and release the progeny into the bloodstream, causing the painful bouts of fever that malaria is known and feared for.

Malaria killed more soldiers in the Civil War than the fighting, according to Riehle. In fact, malaria was prevalent in most parts of the U.S. until the late 1940s and early 1950, when DDT spraying campaigns wiped the vectors off the map. Today, a new case of malaria occurs in the U.S. only on rare occasions.

The severity of the disease depends very largely on the species of the Plasmodium parasite the patient happens to contract.

“Only two species of Plasmodium cause the dreaded relapses of the disease,” said Riehle. “One of them, Plasmodium vivax, can lie dormant in the liver for 10 to 15 years, but now drugs have become available that target the parasites in the liver as well as those in the blood cells.”

That said, there are no effective or approved malaria vaccines. A few vaccine candidates have gone to clinical trials but they were shown to either be ineffective or provide only short-term protection. If an effective vaccine were to be developed, distribution would be a major problem, Riehle said.

Researchers and health officials put higher hopes into eradication programs, which aim at the disease-transmitting mosquitoes rather than the pathogens that cause it.

“The question is ‘What can we do to turn a good vector into a bad vector?'” Riehle said.

“The eradication scenario requires three things: A gene that disrupts the development of the parasite inside the mosquito, a genetic technique to bring that gene into the mosquito genome and a mechanism that gives the modified mosquito an edge over the natural populations so they can displace them over time.”

“The third requirement is going to be the most difficult of the three to realize,” he added, which is why his team decided to tackle the other two first.

“It was known that the Akt enzyme is involved in the mosquito’s growth rate and immune response, among other things,” Riehle said. “So we went ahead with this genetic construct to see if we can ramp up Akt function and help the insects’ immune system fight off the malaria parasite.”

The second rationale behind this approach was to use Akt signaling to stunt the mosquitoes’ growth and cut down on its lifespan.

“In the wild, a mosquito lives for an average of two weeks,” Riehle explained. “Only the oldest mosquitoes are able to transmit the parasite. If we can reduce the lifespan of the mosquitoes, we can reduce the number of infections.”

His research team discovered that mosquitoes carrying two copies of the altered gene had lost their ability to act as malaria vectors altogether.

“In that group of mosquitoes, not a single Plasmodium oocyst managed to form.”

At this point, the modified mosquitoes exist in a highly secured lab environment with no chance of escape. Once researchers find a way to replace wild mosquito populations with lab-bred ones, breakthroughs like the one achieved by Riehle’s group could pave the way toward a world in which malaria is all but history.

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This study was funded by the National Institutes of Health.

Reference: Corby-Harris et al. Activation of Akt Signaling Reduces the Prevalence and Intensity of Malaria Parasite Infection and Lifespan in Anopheles stephensi Mosquitoes. Public Library of Science (PLoS) Pathogens, July 2010 issue: www.plospathogens.org

How do you like them genetic engineering guys now?


Stealth creationists aim to mess up biology students

July 15, 2010

So, God is a platypus?

Appearing to be aware they are losing the battle of the classroom to real science, creationists have taken a sneakier way to undermine science education.  P. Z. Myers explains:

A lot of people have been writing to me about this free webgame, CellCraft. In it, you control a cell and build up all these complex organelles in order to gather resources and fight off viruses; it’s cute, it does throw in a lot of useful jargon, but the few minutes I spent trying it were also a bit odd — there was something off about it all.

Where do you get these organelles? A species of intelligent platypus just poofs them into existence for you when you need them. What is the goal? The cells have a lot of room in their genomes, so the platypuses are going to put platypus DNA in there, so they can launch them off to planet E4R1H to colonize it with more platypuses. Uh-oh. These are Intelligent Design creationist superstitions: that organelles didn’t evolve, but were created for a purpose; that ancient cells were ‘front-loaded’ with the information to produced more complex species; and that there must be a purpose to all that excess DNA other than that it is junk.

Suspicions confirmed. Look in the credits.

Also thanks to Dr. Jed Macosko at Wake Forest University and Dr. David Dewitt at Liberty University for providing lots of support and biological guidance.

Those two are notorious creationists and advocates for intelligent design creationism. Yep. It’s a creationist game. It was intelligently designed, and it’s not bad as a game, but as a tool for teaching anyone about biology, it sucks. It is not an educational game, it is a miseducational game. I hope no one is planning on using it in their classroom. (Dang. Too late. I see in their forums that some teachers are enthusiastic about it — they shouldn’t be).

No such thing as a free lunch.  If it sounds too good to be true, it probably is.  Free software for use in educating kids about biology, sounds too good to be true.

_____________

In comments, Lars Doucet disavows creationist intent.  So the creationist/intelligent design factors were added just to make the game more playable, and not as an attempt to introduce or endorse creationism or intelligent design.

Lots of discussion, much of it rude (some of it delightfully so), at Myers’ joint.

Maybe, if the makers didn’t intend to make a creationist stealth game, they could jigger the thing to make it more accurate?


Typewriter of the moment: Ayn Rand

July 15, 2010

Ayn Rand at her typewriter

Ayn Rand at her typewriter

Ayn Rand at her typewriter, in an undated photo (do you know the date?).

Contrary to a popular myth, Rand did not take her name from the typewriter.  From the website of the Ayn Rand Institute:

What is the origin of “Rand”?

[From ARI’s monthly newsletter Impact, 06/2000]
“Ayn Rand, born Alisa Rosenbaum, based her professional first name on a Finnish one [see above]. The source of her last name, however, has been a mystery.

“Although its origin is still uncertain, recent biographical research by Drs. Allan Gotthelf and Michael Berliner has eliminated one possible source. An oft-repeated story claims that Ayn Rand took her last name from her Remington Rand typewriter while she was living in Chicago in 1926. This is false and we would like to put the error to rest.

“While still in Russia, c. 1925, and long before Remington-Rand typewriters were produced, Alisa Rosenbaum had adopted the name ‘Rand.’ Letters written in 1926 from Ayn Rand’s family in Russia already refer to the name ‘Rand.’ These were sent from Russia before Ayn Rand had communicated from America. The Remington and Rand companies did not merge until 1927; ‘Rand’ did not appear on their (or any) typewriters until the early 1930s.

“One lead to the actual source of the name comes from Ayn Rand herself. In 1936, she told the New York Evening Post that ‘Rand is an abbreviation of my Russian surname.’ Originally, we thought that this was a red herring in order to protect her family from the Soviet authorities.

“In 1997 Dr. Berliner noted an interesting coincidence when looking at a copy of Miss Rand’s 1924 university diploma. On the diploma was the name Rosenbaum in the Cyrillic alphabet:

The last three letters clearly look like the Roman letters ‘ayn.’ Richard Ralston then noticed that by covering those letters—and dropping out the second and fourth letters—what remains bears a strong resemblance to the Roman letters ‘Rand.’

“Although far from certain, it appears that the quote in the New York Evening Post may not have been a decoy.”

Her most often used typewriter was a Remington, I’ve read (but can’t find a reference now that I need it).  So far as I have found, however, typewriters were always manufactured under the “Remington” marque, and never as “Remington-Rand.”  Contrary to the implications from the ARI, Remington typewriters were produced from Reconstruction times (circa 1870), originally by the Remington Arms company.  Typewriter manufacturing was spun off from the arms producer in 1886; that company merged with Rand, forming Remington-Rand in 1927.


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