Tom patterson was sick. He was in coma for months. In the intensive care unit in the hospital of the university of california in san diego, he could not help him in the spring of 2016 – in any case no antibiotic. His organs began to fail. Because both his blood and his abdominal room were infested by the multi-resistant pathogen acinetobacter baumannii. Also as "iraqibacter" known keim received this nickname because he provided the iraq war in many soldiers for poorly healing wounds. Patterson had recently captured a variant of a variant of a holiday in egypt at the end of 2015. After his return to the california home, it turned out that they were resistant to all antibiotics, including the so-called reserve antibiotics,.
But patterson had enormous gluck. His wife steffanie strathdee is the director of the global health institute of the university in san diego, and she had belonged to a therapy, which can work wonders in such traps: viruses, namely a variant that infested bacteria – so-called bacteriophages. Already discovered a good hundred years ago, they mounted a tremendous potential for the fight against bacterial infections. Because the phages that do not consist of much more than their inheritance material and a hulle drum are specialized in certain bacteria. Your so-called lytic variant (see chart) penetrates into the cells and brings the host to produce as many new phages until it ends up and comes in the end.
For patterson, a phage therapy seemed to be the last chance of rescue. The problem was only: she is almost unsusely untouched in the united states and western europe, there is no general tenant. Strathdee put together with the attending physician robert schooley, a specialist for infectious diseases, all levers in motion to receive permission exceptionally. For gluck, the american researcher community reacted quickly.
While the US zollangwordordorde FDA hurried to grant a special permit, scientists from all over the country already provided appropriate phages.
The first ration reached the abdomen on the clefe, the next was administered to him intravenos. "The risk of septic shock was roughly", says strathdee, "but after three days he hit his eyes." meanwhile, the 71-year psychologist, who has dedicated himself as a scientist of exploring the AIDS virus, is almost completely recovered. Patterson’s case fugulates the largely broke research into the medical use of phages in the USA. "Viruses become our best composites against bacteria", prophesent he.
In the US alone, around 23,000 people die every year due to non-treatable bacterial infections. Responsible is often one of the two multi-resistant bacterial families, which are gathered on the blacklist of world health organization WHO. Nevertheless, the physicians from san diego have been able to treat healing from san diego since patterson’s cure more than a handful of deadly patients with FDA special permit. Strathdee now wants to worry about it that it does not remain. Since the summer, the epidemiologist for infectious diseases together with robert schooley leads the newly grounded center for innovative phage applications and therapeutics (ipath) at the university of california in san diego. There strathdee finally wants to start those clinical trials, which at the end of all patients allows a phage therapy. Bricklt kurten "time magazines" strathdee even for the year 2018 to one of the 50 most influential americans on the health sector.
Also for carl merril, patterson’s story was a turning point: since the 1960s, he had worked for the national institutes of health with phagen. When it came to the therapy of the dark pressor, he had been retired, but headed his expertise. After the holder, he founded with his son adaptive phage therapeutics (APT). With the start-up he wants to develop individualized therapies à la patterson: after a fastest possible analysis of the bacterial infection of the patient, a specially compiled combination is to be moved on the way.
Therefore, APT does not want any individual phages or mixes, but equal to the whole collection, the so-called phage bank, be approved by the FDA. The company can access extensive material of navy. The US militar had created the phage library for its own purposes, but in 2016, however, decided to put them in the service of the public – including the reaction to patterson’s healing.
A competitor, the company amplipi biosciences from san diego, wants to even dare to get to the first studies. The FDA allowed him to test two phagenthereapeutics. The first is supposed to arrange infections with staphylococcus aureus, especially when the blood or joint prostheses are affected. The second is directed against pseudomonas aeruginosa, which excludes about pneumonia. In 2019, the randomized controlled studies should begin. "This will be the first known studies with an intravenos administered phage therapy", says business drivers paul grint.
No question, in the west is a breakthrough of phage therapies. Above all, an aspect electrified the physicians: in the case of patterson, the phages had brought multi-resistant bacteria to develop a certain sensitivity to antibiotics against. The germs had responded to the new selection prere, adapted to gene changes – but apparently drop protection against antibacterial drugs. "We have now observed this in several cases", reported strathdee. For the IPAH co-director, these phages therefore have the potential for game changer. "With these therapies we can resurrect antibiotics", says strathdee.
In this direction, paul turner is also researching the department of ecology and evolutionary biology at yale university and his colleague benjamin chan. Both were first demonstrated in the laboratory in 2016 that a phage called onko1 makes the multi-resistant bacterium pseudomonas aeruginosa recoverable again for antibiotics. When ali khodadoust, an ophthalmologist from connecticut, diseased lifelike to the pathogen, the possibility to test the therapy in a patient. In fact: she was a success. Also, the treatment of a 22 year old mucovic socket patient in autumn 2017 lucked.
Although the phage mix eliminated with her not all infection herd completely. However, this is due to the nature of this difficult-to-therapy hereditary disease. But why do the detour over antibiotics? Why bacteria do not get alone with phages? With this idea, the story took their beginning. In 1915, the english frederick togged discovered the phages, but did not explore it. So it was felix d’herelle, who deserved the scientific laurels from 1917. He was also developing first therapies for cholera and pest in the following years. Father the birth parisian became a father of the eastern european phage tradition. On stalin’s initiative, in the georgian tbilisi, in the georgian tbilisis, together with his friend georgi eliava, the eliava institute known worldwide worldwide georgi eliava. Since then, the viruses are used in georgia or poland. Treatment overlaps – in contrast to the west, even the invention of the antibiotic. Martin witzenrath, internist at the berlin charite, believes that the success of the phage therapies had been founded there in the lack of other antibacterial drugs.
Now german researchers want their project "phage4cure" bring this tradition to the latest medical stand. Because the cocktails traded in eastern europe were not fairly fair. "The phages are hardly characterized and not sequenced. Therefore, you do not know if you can transfer resistance genes", reported witzenrath, who is involved in phage4cure. Above all, however, the solutions administered are not clean, but could contain ingredients of those bacteria in which the phages were contaminated.
Relevant side effects hold witzenrath neverthe for unlikely. The FDA also decided ten years ago, phage principle as "for sure" classify. Finally, they are biologically seen the most common organisms on the planet, and man houses even more of this species when he walks with bacteria. If phages were dangerous for humans, they were known to be known.
Nevertheless, the researchers are careful. "For a dedicated to germany, we do not help but to check the toxicology", meant witzenrath. Just as unassailable is an evidence of action for the phage therapy, which has never been done so far. Although there are a lot of case studies, "but case-reports alone are not enough in this country", so witzenrath.
Phage4cure is supposed to overcome these obstacles. Four institutions have joined forces, in addition to the berlin charite, the charite research organization, the german collection of microorganisms and cell cultures (DSMZ) as well as the fraunhofer institute for toxicology and experimental medicine (item). The goal is comparable to the project of the US start-ups adaptive phage therapeutics: A kind of platform for the production of phage medicines should be created. The process should be standardized so that he will be transferable to other phages with only small changes to other phages. In the end, admitted therapies are to be. For years, this was unthinkable in this country, varies witzenrath. Meanwhile, the political prere is very rough, something against the resistant bacteria to enter: "I am aubert optimistic about the phage therapies."
The patient should always receive a combination of several phages specializing in the same bacterium. Thus, the physicians prevent the bacterium developing resistance to a single phage variant and thereby preventing healing. "These are always individual therapies", christine rohde says from the plasmids working group and phage of the DSMZ over the applications. Each time you have to be discreetly discreet, which bacteria is exactly involved in order to administer according to suitable phages.
Prerequisite is a comprehensive phage collection on which DSMZ has been working for 30 years. To find the bacterial killers, the researchers prefer to search clear plants and any kind of wasses. "The nature plays us in the hand", says rohde. In the meantime, the existence of 800 bacteriophages – including those against the folded zwolf multiresistent germs of the WHO list.
"Now we stand before the first german clinical trial with phage application", the expert is happy. 2020 witzenrath at the charite wants to recruit the first patients to test whether the therapy is suitable for pneumonia caused by pseudomonas aeruginosa. In a few years, it was finally so far that the first phage therapies are allowed in this country.