Exposing some blood to Ultraviolet light has treated various health problems, then antibiotics came along – April 2016

Ultraviolet blood irradiation: Is it time to remember “the cure that time forgot”? (book chapter)

J Photochem Photobiol B. 2016 Apr; 157: 89–96. 10.1016/j.jphotobiol.2016.02.007
PMCID: PMC4783265, NIHMSID: NIHMS761387
Ximing Wu,a,b,c Xiaoqing Hu,b,c,d and Michael R. Hamblinb,c,e,*
M.R. Hamblin (*) Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA
Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA e-mail: Hamblin at helix.mgh.harvard.edu

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Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma and even poliomyelitis. The early studies were carried out by several physicians in USA and published in the American Journal of Surgery. However with the development of antibiotics, the use of UBI declined and it has now been called “the cure that time forgot”. Later studies were mostly performed by Russian workers and in other Eastern countries, and the modern view in Western countries is that UBI remains highly controversial. This review discusses the potential of UBI as an alternative approach to current methods used to treat infections, as an immune-modulating therapy and as a method for normalizing blood parameters. Low and mild doses of UV kill microorganisms by damaging the DNA, while any DNA damage in host cells can be rapidly repaired by DNA repair enzymes. However the use of UBI to treat septicemia cannot be solely due to UV-mediated killing of bacteria in the bloodstream, as only 5–7% of blood volume needs to be treated with UV to produce the optimum benefit, and higher doses can be damaging. There may be some similarities to extracorporeal photopheresis (ECP) using psoralens and UVA irradiation. However there are differences between UBI and ECP in that UBI tends to stimulate the immune system, while ECP tends to be immunosuppressive. With the recent emergence of bacteria that are resistant to all known antibiotics, UBI should be more investigated as an alternative approach to infections, and as an immune-modulating therapy.

Historical Introduction

Ultraviolet (UV) radiation is part of the electromagnetic spectrum with a wavelength range (100-400 nm) shorter than that of visible light (400-700 nm), but longer than x-rays (<100 nm). UV radiation is divided into four distinct spectral areas including vacuum UV (100-200 nm), UVC (200-280 nm), UVB (280-315 nm) and UVA (315-400 nm). Only part of UVB and UVA can reach on earth, because wavelengths shorter than 280 nm are filtered out by the atmosphere especially by the “ozone layer”.
In 1801 Johann Wilhelm Ritter, a Polish physicist working at the University of Jena in Germany discovered a form of light beyond the violet end of the spectrum that he called “Chemical Rays” and which later became “Ultraviolet” light [1]. In 1845, Bonnet [2] first reported that sunlight could be used to treat tuberculosis arthritis (a bacterial infection of the joints).
In the second half of the nineteenth century, the therapeutic application of sunlight known as heliotherapy gradually became popular. In 1855, Rikli from Switzerland opened a thermal station in Veldes in Slovenia for the provision of heliotherapy [3]. In 1877, Downes and Blunt discovered by chance that sunlight could kill bacteria [4]. They noted that sugar water placed on a window-sill turned cloudy in the shade but remained clear while in the sun. Upon microscopic examination of the two solutions, they realized that bacteria were growing in the shaded solution but not in the one exposed to sunlight.
In 1904, the Danish physician Niels Finsen was awarded the Nobel Prize in Physiology or Medicine for his work on UV treatment of various skin conditions. He had a success rate of 98% in thousands of cases, mostly the form of cutaneous tuberculosis known as lupus vulgaris [5]. Walter H Ude reported a series of 100 cases of erysipelas (a cutaneous infection caused by Streptococcus pyogenes) in the 1920s, with high cure rates using irradiation of the skin with UV light [6].
Emmett K Knott (Fig. 25.1) in Seattle, WA reasoned that the beneficial effects of UV irradiation to the skin obtained by Ude, might (at least partly) be explained by the irradiation of blood circulating in the superficial capillaries of the skin. With his collaborator Edblom, an irradiation chamber was constructed to allow direct exposure of the blood to UV. The irradiation chamber was circular and contained a labyrinthine set of channels that connected the inlet and outlet ports. All these channels were covered with a quartz window that formed the top of the chamber. The irradiation chamber was so designed as to provide maximum turbulence of the blood flowing through (see Fig. 25.2). This was done in order to: (a) prevent the formation of a thin film of blood on the chamber window that would absorb and filter out much of the UV light; (b) insure that all the blood passing through the chamber was equally exposed to UV [7].
Knott and co-workers then carried out a series of experiments using UV irradiation of blood extracted from dogs that had been intravenously infected with Staphylococcus aureus bacteria and hemolytic Streptococcus species, and then the treated blood was reinfused into the dogs. They found that it was unnecessary to deliver a sufficient exposure of UV light to the blood to directory kill all the bacteria in the circulation. It was also found unnecessary to expose the total blood volume in the dogs. The optimum amount of blood to be irradiated was determined to be only 5-7% of the estimated blood volume or approximately 3.5 mL per kg of body weight. Exceeding these limits led to loss of the benefits of the therapy. All the dogs that were treated with the optimized dose of UV to the blood, recovered from an overwhelming infection (while many dogs in the control group died). None of the dogs that were treated and survived, showed any long-term ill effects after 4 months of observation [7].
The first treatment on a human took place in 1928 when a patient was determined to be in a moribund state after a septic abortion complicated by hemolytic streptococcus septicemia. UBI therapy was commenced as a last resort, and the patient responded well to the treatment and made a full recovery [7]. She proceeded to give birth to two children.
Hancock and Knott [8] had similar success in another patient suffering from advanced hemo-lytic streptococcal septicemia. These workers noted that in the majority of cases, a marked cyanosis (blue tinge to the skin caused by a lack of oxygenated blood flow) was present at the time of initiation of UBI. It was noted that during (or immediately following) the treatment a rapid relief of the cyanosis occurred, with improvement in respiration accompanied by a noticeable flushing of the skin, with a distinct loss of pallor.
These observations led to application of UBI in patients suffering from pneumonia. In a series of 75 cases in which the diagnoses of pneumonia were confirmed by X-rays, all patients responded well to UBI showing a rapid decrease in temperature, disappearance of cyanosis (often within 3-5 min), cessation of delirium if present, a marked reduction in pulse rate and a rapid resolution of pulmonary consolidation. A shortening of the time of hospitalizations and accelerated convalescence was regularly observed.
The knowledge gained in these successful studies led to the redesign of the irradiation chamber to allow a more thoroughly uniform exposure of the circulating blood, and led to the development of the “Knott Technic of Ultraviolet Blood Irradiation.” A number of irradiation units were manufactured and placed in the hands of physicians interested in the procedure, so that more extensive clinical data could be accumulated [7]. The Knott technique involved removing approximately 3.5 mL/kg venous blood, titrating it as an anticoagulant, and passing it through the radiation chamber. The exposure time per given unit of blood was approximately 10 s, at a peak wavelength of 253.7 nm (ultraviolet C) provided by a mercury quartz burner, and the blood was immediately re-perfused [7].
George P Miley at the Hahnemann Hospital, Philadelphia, PA published a series of articles on the use of the procedure in the treatment of thrombophlebitis, staphylococcal septicemia, peritonitis, botulism, poliomyelitis, non-healing wounds, and asthma [9-22].
Henry A Barrett at the Willard Parker Hospital in New York City in 1940 reported on 110 cases including a number of different infections. Twenty- nine different conditions were described as being responsive, including the following: infectious arthritis, septic abortion, osteoarthritis, tuberculosis glands, chronic blepharitis, mastoiditis, uveitis, furunculosis, chronic paranasal sinusitis, acne vulgaris, and secondary anemia [23, 24].
EV Rebbeck at the Shadyside Hospital in Pittsburgh, PA, reported the use of UBI in Escherichia coli septicemia, post-abortion sepsis, puerperal sepsis, peritonitis, and typhoid fever [25-29] and Robert C Olney at the Providence Hospital, Lincoln, NE, treated biliary disease, pelvic cellulitis and viral hepatitis [30-32].
In this chapter, we will discuss the mechanisms and the potential of UBI as an alternative approach to infections and as a new method to modulate the immune system. Our goal is to remind people to continue to do more research and explore more clinical uses. The topics include the efficacy of UBI for infections (both bacterial and viral), to cure autoimmune disease, disease, and the similarities and differences between UBI, and intravenous ozone therapy, and extracorporeal psoralen-mediated photochemotherapy (photophoresis).

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Conclusions Regarding Mechanisms

UBI has always caused much confusion, both in the general public and also in some medical professionals, because germicidal UV light (UVC) is used to sterilize water, disinfect surfaces, and as an aid to infection control in operating rooms, and food processing and packaging plants. Many people therefore assume that UBI must act by killing pathogens (bacteria, viruses or other microorganisms) circulating in the bloodstream. However there is no evidence that this is actually the case. Therefore the mechanisms of action must lie in some other action of UV on the various components of blood. Although the entire body of evidence on the mechanisms of action of UBI is very complex, as can be seen from the foregoing material, we can attempt to draw some general conclusions. Firstly UBI is clearly an example of the well-known phenomenon called “hormesis” or “biphasic dose response’. This phenomenon has been well reviewed by Edward Calabrese from U Mass Amherst [73, 74]. The basic concept states that any toxic chemical substance or drug, or any physical insult (such as ionizing radiation, hyperthermia, or oxidative stress) can be beneficial, protective or even therapeutic, provided the dose is low enough. If the dose is increased, the beneficial or protective effects disappear, and if the dose is even further increased, then the detrimental effects of the treatment become very evident. This is clearly shown by Knott’s original experiments on dogs that led to the establishment of only 5-7% of total blood volume as the optimal amount of blood to be irradiated.
UBI appears to have three broadly different classes of effects on different blood components. In the case of neutrophils, monocytes, macrophages, and dendritic cells, UBI can activate phagocytosis, increase the secretion of NO and reactive nitrogen species, and convert the DC phenotype from an immunogenic one into a tolerogenic one, thus perhaps lessening the effects of a “cytokine storm” as is often found in sepsis. In the case of lymphocytes, the effects of UBI are to inhibit (or in fact kill) various classes of lymphocytes. This is not perhaps very surprising, considering the well-established cell-death pathways and apoptotic signaling found in lymphocytes. However it is not impossible, that the killing of circulating lymphocytes could reduce systemic inflammation, which would again be beneficial in cases of sepsis. It is also clear that UBI can oxidize blood lipids and lipoproteins, and therefore increase oxidative stress. However it is also possible that a brief burst of oxidative stress, may be beneficial, whereas continued chronic levels of oxidative stress have been generally considered as detrimental. Many antioxidant defenses are up- regulated by brief exposure to oxidative stress, and this has been postulated to be one of the fundamental mechanisms responsible for may aspects of hormesis. The oxidative nature of UBI has encouraged us to draw parallels with ozone therapy and other forms of ‘oxygen therapy”.

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Modern Devices to Carry Out UBI

Although it is often said that UBI is “the cure that time forgot” [90, 91], it has not actually been completely forgotten. There are several companies, organizations and devices existing at the present time, which are being used or proposed (on a rather small scale) to carry out UBI, or as it often called “Photoluminescence Therapy (PT)”. Several websites provide information on UBI and PT. Perhaps one of the most comprehensive is (http://www.mnwelldir.org/docs/uv_light/uv_ light3.htm) that provides a listing of practitioners located in USA that offer UBI to patients. UBI medical (http://ubimedical.com/about-us.html) also has a lot of information available. The website entitled “Infections cured” (http://infections- cured.com) is also worth checking out. Physicians UBI Awareness Center (http://drsubi.com) even has a video posted online comparing different kinds of UBI machines.

Conclusion

UV irradiation of blood was hailed as a miracle therapy for treating serious infections in the 1940s and 1950s. In an ironic quirk of fate, this historical time period coincided with the widespread introduction of penicillin antibiotics, which were rapidly found to be an even bigger medical miracle therapy. Moreover another major success of UBI, which was becoming increasingly used to treat polio, was also eclipsed by the introduction of the Salk polio vaccine in 1955 [91]. UBI had originally been an American discovery, but then was transitioned to being more studied in Russia and other eastern countries, which had long concentrated on physical therapies for many diseases, which were more usually treated with drugs in the West.
However in the last decade the problem of multi-antibiotic resistant bacteria has grown relentlessly. Multidrug-resistant (MDR) and pandrug resistant (PDR) bacterial strains and their related infections are emerging threats to public health throughout the world [92]. These are associated with approximately two-fold higher mortality rates and considerably prolonged hospital admissions [93]. The infections caused by antibiotic resistant strains are often exceptionally hard to treat due to the limited range of therapeutic options [94]. Recently in Feb 2015, the Review on Antimicrobial Resistance stated “Drug-resistant infections could kill an extra 10 million people across the world every year by 2050 if they are not tackled. By this date they could also cost the world around $100 trillion in lost output: more than the size of the current world economy, and roughly equivalent to the world losing the output of the UK economy every year, for 35 years” [95].
Sepsis is an uncontrolled response to infection involving massive cytokine release, widespread inflammation, which leads to blood clots and leaky vessels. Multi-organ failure can follow. Every year, severe sepsis strikes more than a million Americans. It is estimated that between 28-50% percent of these people die. Patients with sepsis are usually treated in hospital intensive care units with broad-spectrum antibiotics, oxygen and intravenous fluids to maintain normal blood oxygen levels and blood pressure. Despite decades of research, no drugs that specifically target the aggressive immune response that characterizes sepsis have been developed.
We would like to propose that UBI be reconsidered and re-investigated as a treatment for systemic infections caused by multi-drug resistant Gram-positive and Gram-negative bacteria in patients who are running out of (or who have already run out) of options. Patients at risk of death from sepsis could also be considered as candidates for UBI. Further research is required into the mechanisms of action of UBI. The present confusion about exactly what is happening during and after the treatment is playing a large role in the controversy about whether UBI could ever be a mainstream medical therapy, or must remain side-lined in the “alternative and complementary” category where it has been allowed to be forgotten for the last 50 years.

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