This Germ Could Save Your Life

Or at least keep your teeth cavity-free. A growing chorus of medical researchers say our bacteria-killing zealotry is misguided. Instead of fighting bugs, they argue, we should train them to do our bidding and then set them loose in our bodies. The trouble is keeping them there

By Jessica Snyder Sachs Posted 01.31.2008 at 1:24 pm 10 Comments

Health Food: Researchers have created a method to fight Crohn’s disease by modifying the cheese-making Lactococcus lactis bacteria. Dr. Gary D. Gaugler/Phototake

ATTACKING CROHN’S

On day three of the study at the Academic Medical Centre in Amsterdam, the 43-year-old Dutch farmer felt so good that he was packing his bags to leave the hospital. The nurses caught him just as he was headed out the door of the center’s new biocontainment ward for gene therapy. Its rooms are kept under negative pressure so that even if a window breaks, bacteria-laden air will flow in, not out. The man had been spending his days confined to little more than a glorified hospital room, with doctors and nurses coming and going in head-to-toe surgical garb. The bug that was healing his body had to remain isolated, by government order. “We had to explain to him that he was not free to leave, no matter how wonderful he felt,” recalls study leader Maikel Peppelenbosch.

Over the previous eight months, Peppelenbosch had managed to win government approval for a clinical trial that deployed a genetically modified cheese-making bacterium, Lactococcus lactis-Thy12, to relieve Crohn’s disease [launch the gallery
here, to see how it works]. This excruciating bowel disorder is caused by the immune system mistakenly attacking the intestines’ normal complement of digestive microbes. The result is a vicious cycle of painful inflammation and gaping ulcers that can progress to life-threatening perforations of the colon.

Dutch approval of the trial—and the willingness of patients to cycle through 11 days of biological isolation—was a testament to both the seriousness of the disease and the lack of reliable cures, Peppelenbosch says. “These were patients for whom taking out the bowels was their last remaining option.” Funding for the study came from the U.S., by way of a private research grant from billionaires Eli and Edythe Broad, whose son suffers from Crohn’s.

The way to treat the disease is to turn off the immune system’s attack on the intestines’ native bacteria. Researchers have long known that lab animals whose bodies fail to produce the immune-calming molecule interleukin-10 develop severe inflammatory bowel disorders similar to Crohn’s. But efforts to administer IL-10 are fraught with problems. Stomach acid destroys the protein, so it can’t be taken by mouth. And introducing it into the bloodstream risks paralyzing a patient’s immune system.

Any solution must deliver the immune-calming molecule exactly where it’s needed—inside the intestinal tract—but nowhere else. That’s where Lothar Steidler’s creation comes in. In 1999 Steidler was pursuing postdoctoral studies into Crohn’s-disease treatments at Ghent University in Belgium. In an impressive molecular sleight of hand, Steidler took the gene for IL-10 and slipped it into L. lactis.

But he didn’t stick it just anywhere in the cheese bug’s genome. Steidler understood how important it was to prevent his bug from escaping into, say, the sewer system, where any number of nasty, disease-causing bacteria might pick up the IL-10 gene. The result could be pandemic disaster: a pathogen out in the wild with the ability to cripple the body’s disease-fighting response.

“I knew I had to build in some sort of suicidal mechanism,” he explains. He also had to prevent gene swapping between his “good bug” and a potential bad guy. So Steidler made sure that the incoming IL-10 gene always replaces another gene needed to produce the nutrient thymidine. That way, his new bugs can’t make thymidine, and so they die of nutrient starvation within a few days. That fleeting life span is enough to complete their mission but not long enough to survive in the waste that flushes down the toilet.

Even better, if the inserted gene jumps into another organism, it replaces that microbe’s thymidine gene. So any bug that receives the gene likewise becomes a doomed nutritional cripple. “Fortunately, Lothar designed this bacterium very well,” says Peppelenbosch, who collaborated with Steidler to usher the transgenic through regulatory approval in the Netherlands. Their proposal received no objections from either regulators or the public—an unexpected feat in rabidly anti-GMO Europe, he notes.

The team faced no lack of volunteers for the trial. The doctors at the Academic Medical Centre saw scores of patients with severe Crohn’s that failed to respond to standard anti-inflammatory drugs. The researchers ushered 10 patients into their containment ward, one by one, for their seven-day treatment and 11-day isolation.

Eight of the 10 Crohn’s patients experienced relief from pain and diarrhea, five dramatically so. One withdrew early for unrelated reasons, and none experienced any worsening of symptoms or problematic side effects. Most important for the prospect of larger studies, Steidler demonstrated that his transgenic microbe completely disappeared from the volunteers’ stool within a day of swallowing their last capsules of live bacteria.

As expected, the patients’ symptoms reappeared a few weeks after they returned home, and several came back to plead for continued treatment. “We couldn’t, of course,” Peppelenbosch says, because the trial was over. Steidler and Peppelenbosch are seeking Dutch approval for a larger, placebo-controlled trial, this time without the onerous restrictions of isolating patients on a biohazard ward.

Built-in suicide mechanisms such as Steidler’s may prove key to the widespread use of GMO biotherapeutics. “Now that the biocontainment issues are being fully recognized and achieved, I think it’s all going to move very quickly,” predicts North Carolina State University micro-biologist Todd Klaenhammer.

Previous Article: The Breakdown: Head Spins

Next Article: Why Do Itches Itch?

Want to learn more about breakthroughs in electronics, medicine, nanotech, and more?
Subscribe to Popular Science and enter to win $5,000!

10 Comments

link to this comment

ForrestGump

02/05/08 at 8:10 pm

“I honestly think people are more comfortable with the idea of nano-robots scurrying through their bodies than they are of deploying bacteria,” Thaler muses. “But when you think about it, you cultivate your lawn. You’d probably like to cultivate your internal landscape.”

Well said. After we can overcome the hurdles of human timidness toward the implementation of modified bacteria in our bodies, there seems to be an entirely open and new scope of research in terms of productive bacteria. Instead of trying to create new cures and treatments for age old problems, why not manipulate something already in existence and change harmful bacteria into helpful bacteria?

link to this comment

txt

02/10/08 at 10:01 pm

i think people are more willing to adapt than you think i my self think this is a very posible option for the future.

link to this comment

Czar

02/13/08 at 9:16 pm

Once we understand the bacteria or virus genome, we could even reprogram them to hunt down other bacteria or viruses such as Flesh eating bacteria and HIV viruses. they can have a set lifetime of only a few days and have their reproductive genes removed or replaced.

link to this comment

AliveUD

03/06/08 at 1:33 pm

The solution to all of humankind's problems is undoubtedly a natural one. Sunlight, modified bacteria, and algae are our friends. I know it sounds utopian, but seriously, we just need to make nature work for us in a symbiotic way. True, it may mean altering nature through genetic manipulation; but the point is that it can be done.

link to this comment

berne04

from Aviston, IL

03/08/08 at 12:44 am

We have been talking in my Microbiology class about using viruses to carry the (gene manipulated) cure for diabetes; make the body produce it's own insulin again. This is the wave of the future for treatments. There is a huge potential benefit to gene therapy.

link to this comment

svseigel

from APO, AE

03/12/08 at 3:47 pm

I was an AP biology teacher In 1993. Back then I asked a friend who was a doctor if some gut microbe couldn't be engineered to deliver insulin. He laughed. He said the naturally occuring bacteria are too well adapted to share space with a suboptimal organism. I countered that we could start with a patient's own flora, but he said simply adding or deleting anything would render it suboptimal.

In 1997 we attended a lecture on genetic medicine at the Exploratorium in San Francisco, the doctor was very sharp and forward-thinking. He said these avenues are "interesting but beyond our reach at present."

In 1999 my wife graduated with a B.A. in microbiology and almost every honor her university confers. Her signature position was that we view microorganisms the wrong way--a very small percentage are pathogens, while a large number are symbiotes--that we need to learn to work with them. Anyway, I asked her to mention my idea to her faculty. When she did, she was ridiculed by the full professors, tolerated by the more recent Ph.D.s, and taken quite seriously by the M.S. level instructors and graduate students. I'm gratified that she stuck with it long enough for us to learn that tenure often seems to impair the mind!

Fast forward to 2008. People are actually talking about my idea; while her idea is far more important. This plethora of Antimicrobial products not only threatens our personal micro-biomes, but it also accelerates resistance. These products should be tightly controlled lest we really do produce superbugs: PATHOGENS!

It's great if we can get friendly bacteria to do good things for us; it's terrible if we end up killing them off every time we use soap, toothpaste, lotion or even drink water!

link to this comment

Vamphyri

04/06/08 at 9:29 pm

Well, we do have one that eats oil spills then dies of hunger when the source is depleted... Sometimes there are some pretty cool successes.

Naturally our own bodies have bacteria that were not part of our makeup before that do all kinds of things symbiotically - not the least of which is digestion.

The concern is more like the problem in nature when a bacteria or virus gets in a mutated state that causes it to breed fast in a crowded environment and start causing disabilities and death. Don't think for an instant that a genetic 'bug' for good or ill will be the same for everyone, just like some people have large reactions to things like chicken pox and some people get killed by simple diseases on a wide scale.

Just some thoughts :)

link to this comment

kardelen133 (not verified)

05/26/08 at 8:43 am

Hi all
in the words of homer simpson.... holy crap! or maybe just, crap. you work for popsci, folks... what in the *#@* was that? to begin with, how long did it take you to make the two custom length leather straps? more than five minutes, to be sure. how long did you have to look for a belt with a buckle that size? i have never seen a belt like that in my life. wait, i'm sorry, let's start with who in the *&^% would want to do this in the first place? let's assume that you are actually trying to come up with 5 minute projects that someone might want to attempt, and using that assumption lets assume that even one of you has a little pride in what they do. if either of those statements are true, the video i jsut whatched is either the result of complete indifference, or complete ignorance. if this is where my subscription dollars are going, please do a five minute project teaching me how to unsubscribe.
forum plastik cerrahi saç ekimi lazer epilasyon tüp bebek burun estetigi
thanks.

link to this comment

godnews

05/27/08 at 3:02 pm

The concept of using what should kill to relieve sickining people by minor modification to the basics of such is very interresting. although it is very hard to understand by many people, but it is the basic truth.
العاب-العاب بنات-العاب تلبيس-العاب طبخ-صور-صور بنات-صور مضحكة
Thanks

link to this comment

John.k

03/08/09 at 6:04 pm

I think we have a natural, existing, means to to fight tooth decay. I am 73 years old and I have no cavities. I am curious has anyone thought to find out why some people donot have cavities? I eat far too much sugar. I am not being treated with any anticavity agents, including flourides, which I think will be banned someday.