Are Nanobacteria
Making Us Ill?
By Amit Asaravala
Wired News
Olavi Kajander didn't mean to discover the mysterious particles that have been called the most primitive organisms on Earth and that could be responsible for a series of painful and sometimes fatal illnesses.
He was simply trying to find out why certain cultures of mammalian cells in his lab would die no matter how carefully he prepared them.
So the Finnish biochemist and his colleagues slipped some of their old cultures under an electron microscope one day in 1988 and took a closer look. That's when they saw the particles. Like bacteria but an astonishing 100 times smaller, they seemed to be thriving inside the dying cells.
Believing them to be a possible new form of life, Kajander named the particles "nanobacteria," published a paper outlining his findings and spurred one of the biggest controversies in modern microbiology.
At the heart of the debate is the question of whether nanobacteria could actually be a new form of life. To this day, critics argue that a particle just 20 to 200 nanometers in diameter can't possibly harbor the components necessary to sustain life. The particles are also incredibly resistant to heat and other methods that would normally kill bacteria, which makes some scientists wonder if they might be an unusual form of crystal rather than organisms.
In 1998, Kajander tried to prove the skeptics wrong by turning up what he believed to be an example of nanobacteria's ribosomal RNA, something that only organisms have. But the claim was squashed two years later by a National Institutes of Health study, which found that the RNA was actually a remnant from a bacteria that often contaminates lab equipment.
The debate would have ended there, except for a steadily increasing number of studies linking nanobacteria to serious health problems, including kidney stones, aneurysms and ovarian cancer. The studies show that nanobacteria can infect humans, a find that has helped push nanobacteria back into the limelight. Now the pressure is on to resolve the controversy and expose how nanobacteria works -- no matter what it is.
"It's all pretty exciting stuff," said David McKay, chief scientist for astrobiology at NASA's Johnson Space Center. "Whether these are bacteria or not -- it doesn't matter at this point. What matters is if we can figure out the association between nanobacteria and kidney stones and develop some kind of countermeasure."
The link between nanobacteria and human diseases was first noticed by Kajander and microbiologist Neva &laqno;iftÁioglu in 1998. The researchers had observed, through an electron microscope, nanobacteria particles building shells of calcium phosphate around themselves. They began to investigate whether such particles played a role in causing kidney stones, which are also made of calcium compounds. Sure enough, at the center of several stones was a nanobacteria particle.
Another breakthrough came in 2003 when a team from the University of Vienna Medical Center discovered nanobacteria in the calcified debris found in tissue samples from ovarian cancer patients. Meanwhile, several other studies revealed nanobacteria in samples of calcified arteries.
Sensing a growing need for tools to detect and study nanobacteria, Kajander and &laqno;iftÁioglu formed a company called NanoBac in 1998. The decision was greatly criticized as a conflict of interest and is still brought up whenever either of the two publishes a new paper.
Fortunately for the researchers, a 2004 study by the esteemed Mayo Clinic supported many of their key findings and helped them regain some of their support. The Mayo study found that nanobacteria does indeed self-replicate, as Kajander had noticed, and endorsed the idea that the particles are life forms.
Kajander and &laqno;iftÁioglu were further vindicated this February when patients with chronic pelvic pain -- thought to be linked to urinary stones and prostate calcification -- reported "significant improvement" after using an experimental treatment manufactured by NanoBac. The study was conducted by a team at Cleveland Clinic Florida.
There's a lot riding on studies like these. Roughly 177,500 patients were discharged from U.S. hospitals with kidney stones and related problems in 2001, according to the NIH. More than 25,000 women in the United States are diagnosed with ovarian cancer each year. In the same period, 14,000 Americans die from complications caused by calcified arteries.
"It brings up a lot of questions," said John Lieske, who led the 2004 Mayo Clinic study. "How many kidney stones are caused by this? Are there other calcification-related diseases that are caused by nanobacteria? Is it infectious?"
Surprisingly, few groups are actually working on answering these questions. One would be hard-pressed to find more than a half-dozen research teams around the globe studying nanobacteria full time.
Lieske suggests it's because the field is still relatively young. But it's clear that there's an additional culprit: the often heated controversy over whether nanobacteria particles are, in fact, alive.
"There's a reluctance to get into controversial areas. It's hard to get proposals funded," said McKay. "Most people are waiting until there's a little more meat on the bones."
Even John Cisar, who led the 2000 NIH study that contradicted Kajander's initial findings, agrees that the issue has become muddled. Though he maintains his stance that nanobacteria are not alive, he said in a phone interview that he is not against further research.
"I'm not saying there's nothing there," said Cisar. "It's just that we were looking at it from a microbiologist's perspective. And when we didn't find any signs of life, we moved on."
Kajander stands by his original assertion that nanobacteria are life forms. However, he blames himself for getting researchers hung up on the life question by using the name "nanobacteria."
"Calcifying self-propagating nanoparticles would have been much better," he wrote in an e-mail to Wired News.
But he added that his regrets about the name don't change the fact that nanobacteria have "miraculous" properties. Those include a growth cycle that closely matches typical biological cycles, the ability to form a shell and the "presence of both mammalian and bacterial components."
It's these properties -- and the potential to save lives -- that keep researchers focused on nanobacteria.
In February, NASA's McKay and Nanobac's &laqno;iftÁioglu announced that they had observed nanobacteria growing at five times its normal rate after they placed it in an incubator that simulates the microgravity conditions of space. The findings mean astronauts may be at an elevated risk for kidney stones on long flights -- something NASA is extremely worried about in light of its new plans to send humans to Mars.
The findings could also add fuel to nanobacteria research by giving scientists a way to grow cultures faster.
"The trouble with studying nanobacteria is that trying to get enough material is very hard," said Lieske. "Trying to culture a lot of it takes time."
Indeed, nanobacteria particles double about once every three days. In comparison, typical bacteria doubles about every 20 minutes.
Lieske's group has continued to experiment with nanobacteria since its 2004 paper. Though he said the team is looking for evidence of DNA and RNA, he is cautious about saying whether he thinks the particles are alive or just an unknown form of crystal.
As a possibility, he offered a third option: The particles could be a form of archaea, a relatively new category of tiny organisms whose DNA is vastly different from that found in typical bacteria. Over the past two decades, archaea has surprised scientists by turning up in places where life was least expected, like in sulfurous lakes and hydrothermal sea vents.
Whatever the case, the Mayo Clinic team may publish a paper outlining new findings in about six months, according to Lieske.
The world may not be waiting, but a handful of faithful microbiologists certainly will.
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