International Cooperation in Spaceflight and Gravity-Wave Black Hole Astrophysics leads to Purified Water for the Thirsty Poor and promises Better Bone Grafts for Victims of Landmines

While politics at the moment seems increasingly fragmented and divisive, international scientific cooperation on Earth and in space continues to advance and improve the quality of life for people in many surprising ways.

The International Space Station (ISS) is a triumph of peaceful collaboration between nations: embodying the space-side thaw in Cold War international relations that began with the first international docking & handshake in space during the 1975 Apollo–Soyuz Test Project, and then continued through Asian, European and North American nations’ cooperation with Russia aboard ‘Mir’ (the first modular space station in history), before blossoming into the ongoing 19 year long construction of the ISS – which at roughly 420 tonnes in mass and almost 17 years continuously crewed is the largest and longest occupied space vehicle ever built by the human race. It has taken the collaboration of five participating space agencies and 26 nations to establish the ISS: the USA’s NASA, Russia’s ROSCOSMOS, Japan’s JAXA, the 22 European nation state members of ESA, along with Canada’s CSA.

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Public domain photo. Credit: NASA/Crew of STS-132

The ISS functions as the world’s primary microgravity laboratory, which often directly involves bioscience such as: research into the cardiovascular consequences of long-term microgravity on astronauts, or the successful growth of various edible plants and even flowers in space. However, just establishing this outpost of humanity in Low Earth Orbit has had beneficial spin-offs here on Earth, for example – one of the great challenges of long duration spaceflight is the provision of enough fresh air and clean drinking water, both of which require sophisticated and efficient recycling systems. NASA’s regenerative Environmental Control and Life Support System (ECLSS) provides both air recycling and cutting-edge water purification aboard the ISS.

Increasingly, systems derived from the Water Recovery System (WRS) section of the ISS Life Support have been put to work in areas here on Earth where safe, clean drinking water is otherwise inaccessible. This iodinated-resin system controls microbial growth without the use of power by dispensing iodine into the water in a controlled manner; this iodination is also in itself an important secondary nutrient – which helps promote proper brain function and maintain levels of hormone that regulate cell development and growth. (Children born and raised in iodine-deficient areas are at risk of neurological disorders and problems with mental development.)

The Water Security Corporation (WSC) took up a licence to produce the WRS system on Earth, and cooperated with both the non-profit Concern for Kids and the US Army, all working together to bring the system to the little Kurdish village of Kendala, Iraq in 2006 – where the well had failed leaving the people without safe drinking water.

Since this initial successful deployment, the WSC’s commercialisation of this ISS Life Support technology has provided aid and disaster relief for people across the world, including: home water purifiers in India, village processing systems in remote areas of Central & South America and Mexico, as well as water bottle filling stations in Pakistan, and even a survival bag designed for use in natural disasters and refugee camps.

Meanwhile, another very famous international scientific collaboration – designed to test Einstein’s General Theory of Relativity by detecting the collision of enormous black holes far out across the vast deeps of space – now promises an unexpected biomedical benefit to Earthlings.

The Laser Interferometer Gravitational-Wave Observatory (LIGO) consists of two large observatories in the USA, designed to detect a change in their 4 km mirror spacing of less than 1/10,000th the diameter of a proton. The Advanced LIGO Project cost a total of $620 million to build and operate, all funded by the USA’s National Science Foundation (NSF), along with the UK’s Science and Technology Facilities Council (STFC), the Max Planck Society of Germany (MPG), and the Australian Research Council (ARC).
What’s more, LIGO is part of a larger international collaboration: the LIGO Scientific Collaboration, which itself then collaborates with the VIRGO Collaboration – that operates the large VIRGO gravitational wave detecting interferometer in Italy. VIRGO alone involves funding and scientists from Italy, France, the Netherlands, Poland and Hungary. Altogether the ‘LIGO & VIRGO Collaboration’ involves over 1,000 scientists worldwide.

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Image credit: SXS Lensing (via NASA)

It was the ‘LIGO & VIRGO Collaboration’ that successfully made the first direct gravitational wave detection on the 14th of September 2015 – observing two massive black holes merging 1.3 billion light-years away from Earth!

Now, a group of scientists from four Universities in Scotland and Ireland have used sophisticated laser interferometer systems (based on those built for gravitational wave detectors like LIGO) to encourage donated human mesenchymal stem cells to change into bone cells in 3D printed scaffolds – creating living 3D bone grafts, that could be used in the future to repair or replace damaged sections of bone.

This is an exciting breakthrough, because bone is the second most grafted bodily tissue after blood and is used in a wide variety of important surgeries, but right now surgeons can only harvest small amounts of living bone from the patient for use in grafting. Live bone from other donors will likely be rejected by the body’s immune system, so surgeons must use donor sources without any cells capable of regenerating bone, and that limits the size of repairs they can carry out.

Scientists were able to use a technique called ‘nanokicking’ – which targets cells with very precisely measured, very small, nanoscale vibrations while they are suspended inside collagen gels – ‘nanokicking’ stimulates the cells to differentiate into a ‘bone putty’ that may be used in the future to heal bone fractures and fill bone where there is a gap. Patients’ own mesenchymal stem cells can be harvested from their own bone marrow – which means surgeons will be able to avoid tissue rejection by the immune system, and can bridge larger gaps in bone.

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Public domain image. Internal structure of the femur bone. Credit: Popular Science Monthly Volume 42 1892-1893 {{PD-US}}

Matthew Dalby, professor of cell engineering at the University of Glasgow, said: “In partnership with [Sir Bobby Charlton’s landmine charity] Find A Better Way, we have already proven the effectiveness of our scaffolds in veterinary medicine, by helping to grow new bone to save the leg of a dog who would otherwise have had to have it amputated. Combining bone putty and mechanically strong scaffolds will allow us to address large bone deficits in humans in the future.”
Professor of bioengineering Manuel Salmeron-Sanchez recently visited Cambodia to meet local people who have suffered landmine injuries – he added: “For many people who have lost legs in landmine accidents, the difference between being confined to a wheelchair and being able to use a prosthesis could be only a few centimetres of bone”.

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Notes:
– The four Universities involved in the bone graft research are the Universities of: Glasgow, Strathclyde, the West of Scotland and Galway.
– The research was funded by Find a Better Way, the Engineering and Physical Sciences Research Council (EPSRC) and the Biotechnology and Biological Sciences Research Council (BBSRC), with aspects of the laser interferometry and computational techniques having been developed previously through support from the Science and Technology Facilities Council (STFC) and Royal Society of Edinburgh (RSE).
– The team’s paper, titled ‘Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor’, is published in Nature Biomedical Engineering.

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See also:

https://www.nasa.gov/mission_pages/station/research/benefits/water_filtration

http://www.bbsrc.ac.uk/news/health/2017/170912-pr-lab-grown-bone-cell-breakthrough-benefits-for-orthopaedics/

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“Bunker busting” Antibody-antibiotic-conjugates (AACs) successfully used to target MRSA bacteria hiding inside the host’s cells

One of the difficulties in combating MRSA is that (Staphylococcus aureus) bacteria have the ability to live inside the host’s cells where they are effectively sheltered from the action of systemic antibiotics – it is this reservoir of infection that provides the seed for the relapses that are characteristic of MRSA.

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Magnification 20,000

S. aureus bacteria escaping a white blood cell, x20,000 mag.
Credit: NIAID – Creative Commons CCBY2

A large team of researchers from Genentech in the USA and Symphogen in Denmark has developed a method to destroy these intracellular S.aureus bacteria that would otherwise be protected from antibiotics. The team used a novel conjugate of the antibiotic rifalogue together with monoclonal antibodies. These antibody-antibiotic-conjugates (AACs) are specifically immuno-targeted to S.aureus. The AACs remain inactive in the bloodstream, and only become active in the presence of the bacteria inside the host´s cells.

Once the AACs are taken into the host’s cells they are transported deeper – into the phagolysosomes which enclose the bacteria inside the cell. The phagolysosomes contain a proteolytic environment, and the protease enzymes found there cleave a small peptide group from the AACs – activating them. The active AACs are then able to bind to the surface of the bacteria effectively delivering their antibiotic payload to the infection’s hidden “bunker”.

Infected mice were treated with the AACs, and the team found this new treatment was much more effective than a systemic antibiotic (vancomycin). This work confirms the importance of intracellular S.aureus as a reservoir of MRSA infection, and raises the exciting possibility that these AACs might eventually be used to treat humans. The targeted approach of AACs would avoid damaging the patient’s beneficial microflora, and if their use becomes routine it would probably reduce the rate at which bacteria in general evolve resistance to any one particular antibiotic.

(This study was published in Nature:
Sophie M. Lehar et al. Novel antibody–antibiotic conjugate eliminates intracellular S. aureus, Nature (2015). DOI: 10.1038/nature16057 http://www.nature.com/nature/journal/v527/n7578/full/nature16057.html )

Child’s life saved from leukemia in ground-breaking use of gene-edited immune system cells

Doctors at Great Ormond Street Hospital (GOSH) successfully used “off the shelf” genetically engineered white blood cells (T-cells) in a last ditch effort to treat a one-year old girl, called Layla, who was suffering from acute lymphoblastic leukemia (ALL) that had resisted chemotherapy. This is the world’s first instance of this targeted cancer therapy in a human patient.

To achieve this GOSH doctors worked with research scientists at University College London’s (UCL) Institute of Child Health (ICH) and biotech company Cellectis. The gene-edited T-cells were modified using a “molecular toolkit” that scientists have pirated from a few genes found in certain bacteria – especially a biological editing tool called TALEN.
TALEN is a combination of a modular protein (TAL) that can effectively be “programmed” to find and bind very specific DNA sequences, together with an endonuclease (EN) which is a protein that can cut DNA, ready to replace that gene with the version desired.

The modified T-cells are called UCART19 cells, and they are produced to fight leukemia in a two step process:
First, they have a gene that programs for a characteristic cell surface protein deleted – so the UCART19 cells will be “invisible” and remain safe from the anitibodies that are given to leukemia patients to destroy their existing, diseased immune system.
Secondly, the T-cells have the gene for the CAR19 surface protein added – CAR19 will bind the UCART19 cells to a different protein called CD19, which is only found on the surface of immature white cells (called “blasts” – lymphoblasts in ALL) that proliferate in leukemia and “crowd out” other healthy blood cells, thus causing the disease symptoms. Once bound to the leukemia cells (lymphoblasts) the UCART19 cells recognise them as foreign and destroy them.

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(Above: The blood stream of a healthy subject vs. a leukemia patient.
RBCs = Red Blood Cells. WBCs = White Blood Cells.

Public domain image, credit: NCI, Alan Hoofring.
Modified by J.Overton)

Clinical trials taking place at the moment normally begin with white blood cells taken from the patient because these run least risk of causing auto-immune problems, but this “bespoke” method of production is expensive. However, due to the chemotherapy and highly agressive nature of the leukemia she suffered, little Layla did not have enough white blood cells left to work with, so the team gave her “off the shelf” UCART19 cells created from donated T-cells.

Previously, this experimental treatment had only been tested on mice in the lab, in fact it was so new that GOSH had to convene an emergency ethics meeting to decide whether Layla should receive it. As routine chemotherapy and a bone marrow transplant had already failed to help Layla, and her condition was worsening, all the doctors had left to offer was either palliative care to relieve her suffering during terminal illness, or the hope of possible recovery with the UCART19 cells. So, together with Layla’s parents, they decided to opt for treatment.

After about two weeks of receiving the UCART19 cells, Layla got a rash which is characteristic of the expected immune response, and a few weeks later results showed her system was clear of leukemia cells. After two months Layla received a second bone marrow transplant, which was successful, and once her healthy blood cell count was high enough she was able to return home with her family to recuperate further. While it is still too early to declare Layla cured, and she is still being monitored in case the leukemia returns, so far she is doing well.

Hopefully, further trials will show similar success and this targeted treatment may then become more widely available for other leukemia sufferers.

(Clinical information from GOSH Press Release, biotechnology information from New Scientist  and The Tech Museum of Innovation)

Heart Transplant Breakthrough comes to UK: “Dead” Donor Heart Revived and Transplanted Successfully

Last year surgeons in Sydney, Australia pioneered a ground-breaking new technique that should increase the availability of viable donor hearts. In what was described as the biggest heart transplant breakthrough in a decade, two patients received hearts that had been restarted following the terminal cardiac arrest of donor circulatory death (DCD). Previously, hearts had to be taken from donors who had suffered brain death, but whose hearts were still beating, which severely limited the number of donor organs available.

This year, medics at Papworth Hospital in Cambridge, UK successfully carried out a heart transplant using the new procedure. The patient recovered rapidly, only spending 4 days in the hospital’s critical care unit, before being well enough to return home.

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(Public domain image, colourised by J.Overton)

The new technique, which was first developed by researchers from St. Vincent’s Hospital in Sydney and the Victor Chang Cardiac Research Institute, can be applied to hearts that have stopped for as long as 20 minutes. First, the unbeating heart is restarted inside the donor’s body, where it is assessed for any problems using ultrasound over a 50 minute period. The heart is then removed from the donor and is kept beating, warmed and perfused with blood by an organ care system (a “heart-in-a box” machine) for up to 3 hours before transplantation.

As reported in the Guardian: Consultant surgeon at Papworth, Stephen Large, predicted that, “the use of this group of donor hearts could increase heart transplantation by up to 25% in the UK alone.” Notably, five other specialist heart transplant centres around the UK plan to adopt the procedure soon, which may reduce waiting times for heart transplant patients.

This development came just two years after the world’s first successful “warm liver” transplant in King’s College Hospital, London. Using the “OrganOx” organ support system (developed over a 15 year period by scientists at Oxford University), the liver was warmed to body temperature and kept perfused with blood. This system can keep the donated liver alive outside the body for up to 24 hours – twice as long as a liver kept “on ice” – which increases the time window available for donor-patient matching, transport and transplantation.

It seems that the old technique of keeping donor organs chilled prior to transplant will soon be superseded by these new warm “organ-in-a-box” methods, to the great benefit of patients.

Ultrasound Treatment for Dementia Improves Memory in Mice

An Australian research group has used ultrasound to successfully improve memory in mice suffering from dementia. The ultrasound treatment helps the mice break down peptide plaques in their brains that seem to contribute to their Alzheimer’s-like memory loss.

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(Public domain photo, credit: NASA)

Scientists worked with mice who have a genetic predisposition to produce greater than usual amounts of the peptide beta-amyloid. Just like human Alzheimer’s patients these mice have a build up of beta-amyloid brain plaques and suffer memory problems.

The mice received a non-invasive treatment with ultrasound once a week for five to seven weeks. The treated mice showed between a 50% reduction to complete clearance of brain plaques, without any apparent harm to their brain tissue. They also performed much better in memory tests, such as navigating mazes, in contrast to untreated mice.

The researchers showed that treatment had stimulated microglial cells, which are part of the brain’s immune system, these microglial cells then engulfed and broke down the beta-amyloid plaques.

One of the researchers, Juergen Goetz of the University of Queensland (Brisbane), said he was very excited by this result, but he pointed out that research is still at a very early stage, and we are some years away from human tests. The treatment will next be trialled in sheep, and data should be obtained from those experiments late in 2015.

It’s worth noting that although the mice in this study suffered from beta-amyloid plaques they did not have the cell damage and lost neural connections that are the other two main features seen in the brains of human Alzheimer’s patients. Nevertheless, this looks like a promising line of ongoing research into a disease that currently blights the lives of 50 million sufferers worldwide.

(This study was published in the journal Science Translational Medicine.)

Welcome to Once and Future Science

Welcome to Once and Future Science, where I’ll be blogging about scientific & technological advances in general, and advances in space science, medicine and energy in particular.

I’m Dr Jon Overton – you might be familiar with my space science series Ultra Frontier Explorer (that I produce for www.alwaysaround.net ) – you can catch up on UFEx here: https://www.youtube.com/playlist?list=PLtHji6t6ST4TMSidaU3SGEE1NSNI_QrHE

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The background image I’ve used above is “The Day The Earth Smiled” which is an amazing composite photograph of Saturn, its rings and moons, with some planets of the Inner Solar System in the background. The Earth, as seen from 898million miles away (on Sat 19th July 2013) appears as the Pale Blue Dot in the lower right of the image. This image was produced by NASA’s Cassini mission, and is public domain, credit: NASA/JPL. You can see annotated and larger versions of this image here: http://www.nasa.gov/mission_pages/cassini/multimedia/jpl/pia17172.html#.VjVW8qe6tH0