Move Over, Penicillin: Researchers Mold Clay Into Potential Therapy

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Move Over, Penicillin: Researchers Mold Clay Into Potential Therapy

Science Daily

http://www.sciencedaily.com/releases/2006/11/061101150630.htm

Clay is most commonly associated with the sublime experience of the

European spa where visitors have been masked, soaked and basted with

this touted curative since the Romans ruled. If ASU geochemist Lynda

and microbiologist Haydel's research on the

antibacterial properties of clays realizes its full potential,

smectite clay could one day rise above cosmetic use to take its

place comfortably with antibacterial behemoths like penicillin.

" We use maggots and leeches in hospitals, so why not clay? " Haydel

poses. " I had a professor in graduate school say, `Maybe perhaps

once in your life, in your scientific career, you'll come across

something that can change the world.' Sometimes I think: Is this it?

Will this help some people? "

Theirs is an unusual research pairing. They are female scientists,

each in the College of Liberal Arts and Sciences, yet pursuing

different lines of scientific discovery. is an associate

research professor in the School of Earth and Science Exploration

and studies clay mineralogy. Haydel is an assistant professor and

expert in tuberculosis in the School of Life Sciences and with the

Center for Infectious Disease and Vaccinology in the Biodesign

Institute at Arizona State University.

" People are interested in natural cures and I think that there is a

lot of nature that we don't understand yet, " says. " What if

we discover a mechanism for controlling microbes that had never been

discovered before? It is these avenues, at the boundaries of

scientific discovery, at the edges of my field and knowledge (and

's), where such discoveries are made. "

National Institutes of Health (NIH) program directors agreed. They

awarded a $438,970 grant over two years to and Haydel for

the study of clay mineral alternative treatment for Buruli ulcer.

What makes this award even more interesting is the rarity for a

geochemist to net a NIH grant.

National Center encourages alternative studies

The National Center for Complementary and Alternative Medicine at

NIH was established in 1998 for just this kind of study. One of the

27 Institutes making up NIH, the Center funds scientific research

and technologies that examine herbal remedies, such as dandelion,

green tea, valerian, and horse chestnut, and practices like

acupuncture, Tai Chi, and Reiki that fall outside conventional

medicines.

The ASU duo will examine the mechanisms that allow two clays mined

in France to heal Buruli ulcer, a flesh-eating bacterial disease

found primarily in central and western Africa. Buruli ulcer has been

declared to be " an emerging public health threat " by the World

Health Organization (WHO). Related to leprosy and tuberculosis, the

Mycobacterium ulcerans produces a toxin, lesions, and destroys the

fatty tissues under the skin.

" The toxin is immunosuppressant; the patients feel no pain and the

body mounts no response to infection. It leads to disfigurement,

isolation, not unlike that seen in leprosy, " Haydel

explains. " Traditional antibiotics can only make a difference at the

very earliest stages of the disease, so treatments have, in the

past, been largely confined to amputations or surgical excision of

the infected sites. "

This means if the clays are antibacterial in nature and the locus

for that activity can be isolated, they may represent a new form of

treatment, one that goes beyond the capacity of existing

antibiotics. " And they could be produced and distributed cheaply, "

notes.

Humanitarians answer Internet challenge

So how did a clay mineralogist whose background is in low

temperature geochemistry become involved with a health care project

centered in the Ivory Coast? The scientific equivalent of an online

dating or matchmaking service: " I answered a posting on the Clay

Mineral Society's list serve placed by Thierry Brunet de Courssou.

He was asking to have someone take high resolution scanning electron

micrographs of the clays, " explains. " I confess that we all

ignored him initially. "

According to the Brunet de Courssou Web site, the family has been

operating health clinics on the Ivory Coast and in New Guinea. For a

decade, Madame Line Brunet de Courssou, Thierry's mother, had been

importing two French clays to treat people with Buruli ulcer and was

getting startling results, while her use of native clays had no

effect. reviewed the mother's work and notes that " Line

Brunet de Courssou was a careful observer. " However, Madame Brunet

de Courssou was not a scientist. The mother, who is now deceased,

approached the WHO in 2002 at its fifth advisory group meeting on

Buruli ulcer, having documented more than 50 cases of successful

healing with the clay treatments. WHO documents indicate that the

organization was receptive, calling her results " impressive, " yet,

notes, funding was denied for lack of scientific study.

, from a family of physicians, says that it was really the

second message that finally drew her to the project. " He said, `I

guess that no American scientists are interested in helping poor

people in Africa.' "

He guessed wrong. Armed with 100 grams of green powder (clay high in

reduced iron), not only took the micrographs of the

minerals, she went a step further and examined their crystal

structure and chemical compositions. She recruited Haydel to the

project before the microbiologist arrived at ASU in 2005. Haydel

brought more than 13 years of experience with pathogenic bacteria,

in particular tuberculosis, to the project. Within two months of

Haydel's arrival, they submitted the grant proposal to the NIH.

" I approached this work from the viewpoint of a clinical

microbiologist, " Haydel says. " I ordered bacterial strains that

pharmaceutical companies use to test their antimicrobials. "

Haydel and tested both of the French clays that Brunet de

Courssou had been importing. One completely inhibited pathogenic

Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa

(often a problem as an opportunistic infection in burn wards) and

Mycobacterium marinum (related to Mycobacterium ulcerans, which

causes Buruli ulcer disease). The clay was also found to partially

inhibit the growth of pathogenic Staphylococcus aureus, including a

multi-drug resistant variety. " The other clay actually helps the

bacteria to grow, " Haydel adds.

What makes one clay kill bacteria, and the other promote growth? And

why do most clays tested have no effect? Research like that being

done by and Haydel can answer such questions. " Clay can be

as variable as the bacteria we are studying. There is a lot to be

learned yet, " notes.

Clay's properties fuel interest

' career fascination with clay started when she was a

mineral exploration geologist looking for ore deposits. She worked

with `the father of clay mineralogy,' Bob Reynolds, at Dartmouth

College. Later, as a research associate at Louisiana State

University, a colleague was studying geophasia – eating clay, a

behavior seen in animals and people, since the time of the

aborigines.

" In the South Appalachian Mountains, poor women would eat the local

clay to help soothe nausea and stomach ailments, particularly during

pregnancy. The clay was rich in kaolinite. (Kaolinite is the major

ingredient in the over the counter remedy Kaopectate). But one day,

they ran out of clay and moved over to another mountain and people

began dying. We wanted to know why. "

The key to clay's variable nature seems to be its structure. " Clay

is a mineral; it has a crystalline structure that is both flexible

and fluid, " says. She likens them to very thin, two-

nanometer-thick slices of bread in a " peanut butter and jelly

sandwich. " The " bread " is composed of three regions, two silicate

layers with tetrahedral rings bounding an octahedral core.

The " peanut butter " is the charged cations, for example, potassium,

that stick to the negatively charged tetrahedral ring surface. And

the jelly? Organic compounds or other species of any or no charge

are possible. This interlayer, as the peanut butter and jelly are

termed, can vary in width and composition depending on the kinds of

waters and elements present when it was formed. It is this

interlayer where much of the elemental variability between clays can

be found. And the interlayer surface area is huge (greater than 100

square meters per gram of clay – bigger than a football field). As a

result, surface chemical reactions from these sites have an enormous

impact on the geochemistry of the local environment.

is passionate about her subject: " Clays are as individual

in character as people are in personality. They can be as old as

Precambrian time (probably older, since meteorites contain clay

minerals from other celestial bodies) or as young as I can make them

in my lab in a few hours. They form when the chemistry, temperature

and pressure conditions are right. In the case of the two French

clays we are testing, their chemical structures are almost

identical, but the different trace element chemistry of the

interlayer records an older geologic condition, from a time when the

antimicrobial property was likely inherited. "

Crystal structure, the interlayer, the way other materials, metals,

ions bind to clays, the absorptive characteristics of clays, all

could potentially play a role in the antibacterial activity they

find in the one French clay. And, while preliminary results suggest

that the antibacterial activity is associated with the interlayer,

crystal size and structure also seem to play a role.

It is a mystery that engages both research partners: " It's

fascinating, " Haydel says. " Here we are bridging geology,

microbiology, cell biology – transdisciplinary sciences, exactly

what (ASU President) Crow has been promoting. A year ago,

I'd look at the clay and say, `well that's dirt.' Now I know a

little something about clay structure; Lynda knows a little bit

about microbiology. Alone, we each would have had to study for

years; together we are partnering these disciplines with synergy

that really works. "