Tag Archives: Qiang Chen

Nanotechnology, tobacco plants, and the Ebola virus

Before presenting information about the current Ebola crisis and issues with vaccines and curatives, here’s a description of the disease from its Wikipedia entry,

Ebola virus disease (EVD) or Ebola hemorrhagic fever (EHF) is a disease of humans and other primates caused by an ebola virus. Symptoms start two days to three weeks after contracting the virus, with a fever, sore throat, muscle pain, and headaches. Typically nausea, vomiting, and diarrhea follow, along with decreased functioning of the liver and kidneys. Around this time, affected people may begin to bleed both within the body and externally. [1]

As for the current crisis in countries situated on the west coast of the African continent, there’s this from an Aug. 14, 2014 news item on ScienceDaily,

The outbreak of Ebola virus disease that has claimed more than 1,000 lives in West Africa this year poses a serious, ongoing threat to that region: the spread to capital cities and Nigeria — Africa’s most populous nation — presents new challenges for healthcare professionals. The situation has garnered significant attention and fear around the world, but proven public health measures and sharpened clinical vigilance will contain the epidemic and thwart a global spread, according to a new commentary by Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Dr. Fauci’s Aug. 13, 2014 commentary (open access) in the New England Journal of Medicine provides more detail (Note: A link has been removed),

An outbreak of Ebola virus disease (EVD) has jolted West Africa, claiming more than 1000 lives since the virus emerged in Guinea in early 2014 (see figure) Ebola Virus Cases and Deaths in West Africa (Guinea, Liberia, Nigeria, and Sierra Leone), as of August 11, 2014 (Panel A), and Over Time (Panel B).). The rapidly increasing numbers of cases in the African countries of Guinea, Liberia, and Sierra Leone have had public health authorities on high alert throughout the spring and summer. More recent events including the spread of EVD to Nigeria (Africa’s most populous country) and the recent evacuation to the United States of two American health care workers with EVD have captivated the world’s attention and concern. Health professionals and the general public are struggling to comprehend these unfolding dynamics and to separate misinformation and speculation from truth.

In early 2014, EVD emerged in a remote region of Guinea near its borders with Sierra Leone and Liberia. Since then, the epidemic has grown dramatically, fueled by several factors. First, Guinea, Sierra Leone, and Liberia are resource-poor countries already coping with major health challenges, such as malaria and other endemic diseases, some of which may be confused with EVD. Next, their borders are porous, and movement between countries is constant. Health care infrastructure is inadequate, and health workers and essential supplies including personal protective equipment are scarce. Traditional practices, such as bathing of corpses before burial, have facilitated transmission. The epidemic has spread to cities, which complicates tracing of contacts. Finally, decades of conflict have left the populations distrustful of governing officials and authority figures such as health professionals. Add to these problems a rapidly spreading virus with a high mortality rate, and the scope of the challenge becomes clear.

Although the regional threat of Ebola in West Africa looms large, the chance that the virus will establish a foothold in the United States or another high-resource country remains extremely small. Although global air transit could, and most likely will, allow an infected, asymptomatic person to board a plane and unknowingly carry Ebola virus to a higher-income country, containment should be readily achievable. Hospitals in such countries generally have excellent capacity to isolate persons with suspected cases and to care for them safely should they become ill. Public health authorities have the resources and training necessary to trace and monitor contacts. Protocols exist for the appropriate handling of corpses and disposal of biohazardous materials. In addition, characteristics of the virus itself limit its spread. Numerous studies indicate that direct contact with infected bodily fluids — usually feces, vomit, or blood — is necessary for transmission and that the virus is not transmitted from person to person through the air or by casual contact. Isolation procedures have been clearly outlined by the Centers for Disease Control and Prevention (CDC). A high index of suspicion, proper infection-control practices, and epidemiologic investigations should quickly limit the spread of the virus.

Fauci’s article makes it clear that public concerns are rising in the US and I imagine that’s true of Canada too and many other parts of the world, not to mention the countries currently experiencing the EVD outbreak. In the midst of all this comes a US Food and Drug Administration (FDA) warning as per an Aug. 15, 2014 news item (originated by Reuters reporter Toni Clarke) on Nanowerk,

The U.S. Food and Drug Administration said on Thursday [Aug. 14, 2014] it has become aware of products being sold online that fraudulently claim to prevent or treat Ebola.

The FDA’s warning comes on the heels of comments by Nigeria’s top health official, Onyebuchi Chukwu, who reportedly said earlier Thursday [Aug. 14, 2014] that eight Ebola patients in Lagos, the country’s capital, will receive an experimental treatment containing nano-silver.

Erica Jefferson, a spokeswoman for the FDA, said she could not provide any information about the product referenced by the Nigerians.

The Aug. 14,  2014 FDA warning reads in part,

The U.S. Food and Drug Administration is advising consumers to be aware of products sold online claiming to prevent or treat the Ebola virus. Since the outbreak of the Ebola virus in West Africa, the FDA has seen and received consumer complaints about a variety of products claiming to either prevent the Ebola virus or treat the infection.

There are currently no FDA-approved vaccines or drugs to prevent or treat Ebola. Although there are experimental Ebola vaccines and treatments under development, these investigational products are in the early stages of product development, have not yet been fully tested for safety or effectiveness, and the supply is very limited. There are no approved vaccines, drugs, or investigational products specifically for Ebola available for purchase on the Internet. By law, dietary supplements cannot claim to prevent or cure disease.

As per the FDA’s reference to experimental vaccines, an Aug. 6, 2014 article by Caroline Chen, Mark Niquette, Mark Langreth, and Marie French for Bloomberg describes the ZMapp vaccine/treatment (Note: Links have been removed),

On a small plot of land incongruously tucked amid a Kentucky industrial park sit five weather-beaten greenhouses. At the site, tobacco plants contain one of the most promising hopes for developing an effective treatment for the deadly Ebola virus.

The plants contain designer antibodies developed by San Diego-based Mapp Biopharmaceutical Inc. and are grown in Kentucky by a unit of Reynolds American Inc. Two stricken U.S. health workers received an experimental treatment containing the antibodies in Liberia last week. Since receiving doses of the drug, both patients’ conditions have improved.

Tobacco plant-derived medicines, which are also being developed by a company whose investors include Philip Morris International Inc., are part of a handful of cutting edge plant-based treatments that are in the works for everything from pandemic flu to rabies using plants such as lettuce, carrots and even duckweed. While the technique has existed for years, the treatments have only recently begun to reach the marketplace.

Researchers try to identify the best antibodies in the lab, before testing them on mice, then eventually on monkeys. Mapp’s experimental drug, dubbed ZMapp, has three antibodies, which work together to alert the immune system and neutralize the Ebola virus, she [Erica Ollman Saphire, a molecular biologist at the Scripps Research Institute,] said.

This is where the tobacco comes in: the plants are used as hosts to grow large amounts of the antibodies. Genes for the desired antibodies are fused to genes for a natural tobacco virus, Charles Arntzen, a plant biotechnology expert at Arizona State University, said in an Aug. 4 [2014] telephone interview.

The tobacco plants are then infected with this new artificial virus, and antibodies are grown inside the plant. Eventually, the tobacco is ground up and the antibody is extracted, Arntzen said.

The process of growing antibodies in mammals risks transferring viruses that could infect humans, whereas “plants are so far removed, so if they had some sort of plant virus we wouldn’t get sick because viruses are host-specific,” said Qiang Chen, a plant biologist at Arizona State University in Tempe, Arizona, in a telephone interview.

There is a Canadian (?) company working on a tobacco-based vaccines including one for EVD but as the Bloomberg writers note the project is highly secret,

Another tobacco giant-backed company working on biotech drugs grown in tobacco plants is Medicago Inc. in Quebec City, which is owned by Mitsubishi Tanabe Pharma Corp. and Philip Morris. [emphasis mine]

Medicago is working on testing a vaccine for pandemic influenza and has a production greenhouse facility in North Carolina, said Jean-Luc Martre, senior director for government affairs at Medicago. Medicago is planning a final stage trial of the pandemic flu vaccine for next year, he said in a telephone interview.

The plant method is flexible and capable of making antibodies and vaccines for numerous types of viruses, said Martre. In addition to influenza, the company’s website says it is in early stages of testing products for rabies and rotavirus.

Medicago ‘‘is currently closely working with partners for the production of an Ebola antibody as well as other antibodies that are of interest for bio-defense,” he said in an e-mail. He would not disclose who the partners were. [emphasis mine]

I have checked both the English and French language versions of Medicago’s website and cannot find any information about their work on ebola. (The Bloomberg article provides a good overview of the ebola situation and more. I recommend reading it and/or the Aug. 15, 2014 posting on CTV [Canadian Television Network] which originated from an Associated Press article by Malcolm Ritter).

Moving on to more research and ebola, Dexter Johnson in an Aug. 14, 2014 posting (on his Nanoclast blog on the IEEE [Institute of Electrical and Electronics Engineers] website,) describes some work from Northeastern University (US), Note: Links have been removed,

With the Ebola virus death toll now topping 1000 and even the much publicized experimental treatment ZMapp failing to save the life of a Spanish missionary priest who was treated with it, it is clear that scientists need to explore new ways of fighting the deadly disease. For researchers at Northeastern University in Boston, one possibility may be using nanotechnology.

“It has been very hard to develop a vaccine or treatment for Ebola or similar viruses because they mutate so quickly,” said Thomas Webster, the chair of Northeastern’s chemical engineering department, in a press release. “In nanotechnology we turned our attention to developing nanoparticles that could be attached chemically to the viruses and stop them from spreading.”

Webster, along with many researchers in the nanotechnology community, have been trying to use gold nanoparticles, in combination with near-infrared light, to kill cancer cells with heat. The hope is that the same approach could be used to kill the Ebola virus.

There is also an Aug. 6, 2014 Northeastern University news release by Joe O’Connell describing the technique being used by Webster’s team,

… According to Web­ster, gold nanopar­ti­cles are cur­rently being used to treat cancer. Infrared waves, he explained, heat up the gold nanopar­ti­cles, which, in turn, attack and destroy every­thing from viruses to cancer cells, but not healthy cells.

Rec­og­nizing that a larger sur­face area would lead to a quicker heat-​​up time, Webster’s team cre­ated gold nanos­tars. “The star has a lot more sur­face area, so it can heat up much faster than a sphere can,” Web­ster said. “And that greater sur­face area allows it to attack more viruses once they absorb to the par­ti­cles.” The problem the researchers face, how­ever, is making sure the hot gold nanopar­ti­cles attack the virus or cancer cells rather than the healthy cells.

At this point, there don’t seem to be any curative measures generally available although some are available experimentally in very small quantities.

Boron as a ‘buckyball’ or borospherene

First there was the borophene (like graphene but using boron rather than carbon) announcement from Brown University in my Jan. 28, 214 posting and now US (Brown University again) and Chinese researchers have developed a boron ‘buckyball’. Coincidentally, this announcement comes just after the 2014 World Cup final (July 13, 2014). Representations of buckyballs always resemble soccer balls. (Note: Germany won.)

From a July 14, 2014 news item on Azonano,

The discovery 30 years ago of soccer-ball-shaped carbon molecules called buckyballs helped to spur an explosion of nanotechnology research. Now, there appears to be a new ball on the pitch.

Researchers from Brown University, Shanxi University and Tsinghua University in China have shown that a cluster of 40 boron atoms forms a hollow molecular cage similar to a carbon buckyball. It’s the first experimental evidence that a boron cage structure—previously only a matter of speculation—does indeed exist.

“This is the first time that a boron cage has been observed experimentally,” said Lai-Sheng Wang, a professor of chemistry at Brown who led the team that made the discovery. “As a chemist, finding new molecules and structures is always exciting. The fact that boron has the capacity to form this kind of structure is very interesting.”

The researchers have provided an illustration of their borospherene,

The carbon buckyball has a boron cousin. A cluster for 40 boron atoms forms a hollow cage-like molecule. Courtesy Brown University

The carbon buckyball has a boron cousin. A cluster for 40 boron atoms forms a hollow cage-like molecule. Courtesy Brown University

A July 9, 2104 Brown University news release (also on EurekAlert), which originated the news item, describes the borosphene’s predecessor, the carbon buckyball, and provides more details about this new molecule,

Carbon buckyballs are made of 60 carbon atoms arranged in pentagons and hexagons to form a sphere — like a soccer ball. Their discovery in 1985 was soon followed by discoveries of other hollow carbon structures including carbon nanotubes. Another famous carbon nanomaterial — a one-atom-thick sheet called graphene — followed shortly after.

After buckyballs, scientists wondered if other elements might form these odd hollow structures. One candidate was boron, carbon’s neighbor on the periodic table. But because boron has one less electron than carbon, it can’t form the same 60-atom structure found in the buckyball. The missing electrons would cause the cluster to collapse on itself. If a boron cage existed, it would have to have a different number of atoms.

Wang and his research group have been studying boron chemistry for years. In a paper published earlier this year, Wang and his colleagues showed that clusters of 36 boron atoms form one-atom-thick disks, which might be stitched together to form an analog to graphene, dubbed borophene. Wang’s preliminary work suggested that there was also something special about boron clusters with 40 atoms. They seemed to be abnormally stable compared to other boron clusters.

Figuring out what that 40-atom cluster actually looks like required a combination of experimental work and modeling using high-powered supercomputers.

On the computer, Wang’s colleagues modeled over 10,000 possible arrangements of 40 boron atoms bonded to each other. The computer simulations estimate not only the shapes of the structures, but also estimate the electron binding energy for each structure — a measure of how tightly a molecule holds its electrons. The spectrum of binding energies serves as a unique fingerprint of each potential structure.

The next step is to test the actual binding energies of boron clusters in the lab to see if they match any of the theoretical structures generated by the computer. To do that, Wang and his colleagues used a technique called photoelectron spectroscopy.

Chunks of bulk boron are zapped with a laser to create vapor of boron atoms. A jet of helium then freezes the vapor into tiny clusters of atoms. The clusters of 40 atoms were isolated by weight then zapped with a second laser, which knocks an electron out of the cluster. The ejected electron flies down a long tube Wang calls his “electron racetrack.” The speed at which the electrons fly down the racetrack is used to determine the cluster’s electron binding energy spectrum — its structural fingerprint.

The experiments showed that 40-atom-clusters form two structures with distinct binding spectra. Those spectra turned out to be a dead-on match with the spectra for two structures generated by the computer models. One was a semi-flat molecule and the other was the buckyball-like spherical cage.

“The experimental sighting of a binding spectrum that matched our models was of paramount importance,” Wang said. “The experiment gives us these very specific signatures, and those signatures fit our models.”

The borospherene molecule isn’t quite as spherical as its carbon cousin. Rather than a series of five- and six-membered rings formed by carbon, borospherene consists of 48 triangles, four seven-sided rings and two six-membered rings. Several atoms stick out a bit from the others, making the surface of borospherene somewhat less smooth than a buckyball.

As for possible uses for borospherene, it’s a little too early to tell, Wang says. One possibility, he points out, could be hydrogen storage. Because of the electron deficiency of boron, borospherene would likely bond well with hydrogen. So tiny boron cages could serve as safe houses for hydrogen molecules.

But for now, Wang is enjoying the discovery.

“For us, just to be the first to have observed this, that’s a pretty big deal,” Wang said. “Of course if it turns out to be useful that would be great, but we don’t know yet. Hopefully this initial finding will stimulate further interest in boron clusters and new ideas to synthesize them in bulk quantities.”

The theoretical modeling was done with a group led by Prof. Si-Dian Li from Shanxi University and a group led by Prof. Jun Li from Tsinghua University. The work was supported by the U.S. National Science Foundation (CHE-1263745) and the National Natural Science Foundation of China.

Here’s a link to and a citation for the paper,

Observation of an all-boron fullerene by Hua-Jin Zhai, Ya-Fan Zhao, Wei-Li Li, Qiang Chen, Hui Bai, Han-Shi Hu, Zachary A. Piazza, Wen-Juan Tian, Hai-Gang Lu, Yan-Bo Wu, Yue-Wen Mu, Guang-Feng Wei, Zhi-Pan Liu, Jun Li, Si-Dian Li, & Lai-Sheng Wang. Nature Chemistry (2014) doi:10.1038/nchem.1999 Published online 13 July 2014

This paper is behind a paywall.