It is extraordinary that doctors were able to do anything for Todd Nelson.
The former US Army master sergeant’s injuries were so bad the medics thought he would not survive.
“I was on my 300th-plus convoy across Kabul, Afghanistan,” he recalls.
“We were headed home for the night when we passed next to a typical yellow and white sedan. When they saw us getting ready to pass, they flipped the switch.
“The blast came in my side of the truck; I was on the passenger side.
“It flipped the truck through a brick wall and put shrapnel through my right eye, into my sinus cavity.
“Both my upper and lower jawbones were crushed, as was my right orbital rim, and it crushed my forehead.
“It burned my right arm over the top of my head, [and] took my right ear off.”
Nelson went through more than 40 operations to reconstruct his face. The scars are evident but what is not so apparent to someone just talking to him is the pain he still feels over large portions of his body.
Col Hale is trying to develop new techniques that will give wounded soldiers better outcomes.
Nelson’s injuries destroyed all three main skin layers – the epidermis, dermis and hypodermis (the top, middle and bottom), in some places right down to the periosteum, the membrane overlying the bone.
“The way we treat Todd’s condition has been around for 30-some-odd years. It hasn’t evolved much,” said Col Hale.
“We basically removed the dead tissue, we conditioned the wound-bed as best we could, and then we covered it with split-thickness skin grafts taken from his thigh or somewhere that wasn’t burned on his body.
“It is a successful way to close the wound, but it leaves lots of fibrosis and scarring that the face simply cannot tolerate. If you have a lot of scarring and fibrosis, the face doesn’t work like it should – the eyelids can’t close, the nose won’t work, and the mouth won’t work.”
One of the great innovations in recent years has been negative pressure wound therapy. This involves sealing a foam deep in an open wound under suction to help condition the base tissues to get them ready to receive a graft. Patients greatly appreciate the therapy because it reduces the number of painful dressing changes.
“It has revolutionised our care of open wounds,” said Col Hale, “but we can’t use it on the face because there are too many areas of the face that will leak around the silicon seal – the eyelids, the nose, the mouth.”
The US Army doctor is therefore trying to develop a special mask that would do the same job.
Instead of using a foam, it would rely on microchannels in the mask to take away wound fluids. He then wants to take moulded sheets of artificial skin to build up the intermediate layer, the dermis, before adding the outer epithelium graft employing new approaches that lift thin, 20-cell-thick slices from elsewhere on the body.
For the deepest layer, the hypodermis, he is looking at taking fat from the abdomen and injecting under the healing wound.
“All the technologies I’m exploiting currently in my lab and what I’m funding in other research labs are things that are close at hand,” said Col Hale.
“In maybe five, six, and seven years, we should have products and strategies that we can apply to soldiers who have been injured in war, and all of this should be translatable to the general public.”
Living organisms may use bioluminescence for a variety of reasons, such as communication and display
Bioluminescence describes the light that some living creatures such as fireflies and jellyfish emit from their cells. Harnessing these reactions has already transformed key areas of clinical diagnosis and medical research.
But scientists are now looking at whether this “living light” could help enhance food crops, detect pollution or even illuminate our journeys home.
On a night in January 1832, off the coast of Tenerife, a young Charles Darwin wandered up on to the deck of the HMS Beagle.
As the young naturalist looked out to sea, he was struck by the unearthly glow emanating from the ocean.
“The sea was luminous in specks and in the wake of the vessel, of a uniform, slightly milky colour,” he wrote.
“When the water was put into a bottle, it gave out sparks for some minutes after having been drawn up.”
Fluorescence: Energy from an external source of light is absorbed and re-emitted. Fluorescence can only occur in the presence of this light source; it cannot happen in complete darkness.
Bioluminescence: The energy for light production comes from a chemical reaction in living cells, as opposed to the absorption of photons as happens in fluorescence.
Darwin was almost certainly describing the light emitted by tiny marine organisms called dinoflagellates. His accounts of this phenomenon, known as bioluminescence, were unearthed by Prof Anthony Campbell in hand-written notebooks stored at Cambridge University.
While Darwin was one of the first modern scientists to document the phenomenon, it would be more than a century before it was put to practical use. Prof Campbell, from Cardiff University, carried out pioneering research throughout the 1970s and 1980s leading to the discovery that living creatures produce this light using special proteins called luciferases. The proteins take part in a chemical reaction in the cells, which is responsible for the light emission.
“When I started researching bioluminescence 40 years ago at the [Cardiff University] medical school, a lot of people raised their eyebrows and said: ‘What the devil is this guy doing working on animals in the sea? He was brought from Cambridge to do medical research’,” Prof Campbell explains.
But he was able to spot the phenomenon’s potential. Having discovered the proteins involved in bioluminescence, he realised that by combining luciferases with other molecules, it was possible to harness this light emission to measure biological processes.
Bioluminescence could shed light on changes in the marine environment
This would pave the way for something of a revolution in medical research and clinical diagnosis.
For example, by attaching a luminescent protein to an antibody – a protective molecule produced by the body’s immune system – it could be used to diagnose disease. This allowed clinicians to dispense with the radioactive markers that had previously been used in such tests.
“This market is now worth about £20bn. If you go into a hospital and have a blood test which measures viral proteins, cancer proteins, hormones, vitamins, bacterial proteins, drugs, it will almost certainly use this technique,” Prof Campbell told BBC News.
Bioluminescent proteins are also tools in drug discovery and have found widespread applications in biomedical research, where they are used to study biological processes in live cells.
“If you’ve got a university department that doesn’t use these techniques, they are not at the cutting edge,” says Campbell.
Other applications are on the horizon. At the University of Lausanne in Switzerland, Prof Jan van der Meer has developed a test for the presence of arsenic in drinking water using genetically modified bacteria.
Arsenic contamination of groundwater is a pernicious problem in some parts of the world, especially in Bangladesh, India, Laos and Vietnam.
Prof van der Meer’s microbes have been engineered to emit light when they come into contact with arsenic-containing compounds. Potentially contaminated water is injected into vials, activating the dormant GM bacteria. The extent to which the microbes emit light is then measured to provide an indication of arsenic concentrations in the water.
Could glowing trees one day replace street lights?
The work is now being commercialised by the German firm Arsolux. Prof van der Meer says the bacterial-based kits cope well with multiple samples, require fewer materials than standard chemical testing field kits, and are easy to prepare.
But regulatory hurdles remain to the take-up of bacteria-based tests in these countries. And, Prof van der Meer adds: “In the end it comes down to market things… things you cannot control as a scientist.”
So called rainbow proteins (a spin-off from work into bioluminescence), which change colour in response to particular compounds, are also an option for detecting environmental toxins, or the potential agents of terrorism.
There are already several consumer applications of bioluminescence: one US firm has made use of it to manufacture luminous drinks for sale in nightclubs.
And researchers have even modified plants so that they emit light. Bioluminescent crops could indicate when they require water and nutrients, or warn of disease and infestation. However, the controversy surrounding GM foods has so far prevented these ideas from taking hold.
A few years ago, a team of undergraduates at Cambridge University researched the idea of luminescent trees that would act as natural “street lamps”.
“What we achieved in that project was to put together some DNA which allowed bioluminescence, to show that it worked in [the bacterium] E. coli, and to submit it to the ‘parts registry’ which holds this DNA so anyone else can use it in future,” team member Theo Sanderson told BBC News.
“We were approached about a year ago and offered funding to continue developing the project, but we have all gone on to other things and so it wasn’t really an option.”
Previous efforts to create light-emitting plants in the lab have made use of a luciferase gene derived from fireflies. But these plants can only glow when supplemented with an expensive chemical called luciferin. The method used by the Cambridge team is attractive because it is based on bacterial systems which produce their own fuels for luminescence and so can be fed normal nutrients.
Glowing plants have used a bioluminescent protein derived from the firefly
In 2010, a separate team published a study in which they were able to demonstrate that such methods could be used to create plants that glowed without the need for chemical supplements. The US-Israeli team of scientists inserted light-emitting genes from bacteria into the plants’ chloroplasts – the structures in their cells which convert light energy from the Sun into chemical fuel.
Mr Sanderson, who now works at the Sanger Institute near Cambridge, said this was a good choice because chloroplasts are essentially bacteria that have become incorporated into plant cells, so they can easily express the microbe-derived gene without the need for other modifications.
But researchers will need to find ways to boost the light emission from such lab organisms if GM trees are ever to light our way through the urban jungle.
Prof Campbell says the potential of luminescent proteins in drug discovery and medical research has not yet been fully exhausted and he is currently collaborating on a project to use luciferases to research Alzheimer’s disease.
Bioluminescent creatures might also provide a convenient means of studying environmental changes in the sea. Some animals obtain the light-emitting chemicals they need from the organisms they eat. So studying the interactions between these species might allow scientists to detect changes in marine food webs.
Despite the impact on clinical diagnosis and research, Prof Campbell points out that he has only ever received one grant to research bioluminescence. Nevertheless, he says it is a “beautiful example of how curiosity – quite unexpectedly – has led to major discoveries in biology and medicine. And it has created several billion dollar markets”.
It may also lead to the development of a contraceptive to control wild populations of elephants in Africa.
Dr Imke Lueders, of the Liebniz Institute of Zoo and Wildlife Research in Berlin, Germany, told BBC News: “It is very important to study the reproduction of elephants.
“The increased knowledge that we gained through this research can help in the future with elephant breeding management because we have an idea of how the pregnancy is maintained.”
Elephants are highly sociable mammals with a high level of intelligence similar to that of great apes and dolphins.
They have the longest-known gestational period of any animal, lasting up to 680 days.
Elephants are born with an advanced level of brain development, which they use to recognise the complex social structure of the herd and to feed themselves with their dextrous trunks.
Elephants need complex neural development to survive from day one of birth
Until now, the biological processes behind the mammal’s marathon pregnancy has not been fully understood.
But the advent of advanced ultrasound methods has given veterinary scientists a new tool to monitor elephant pregnancies in more detail, as they seek to improve breeding programmes in zoos, including elephant IVF.
Seventeen African and Asian elephants at zoos in the UK, Canada, US, Australia and Germany, including ZSL Whipsnade and Twycross Zoo, were examined in the study.
Dr Lueders said the extended pregnancy was “due to a novel hormonal mechanism, which has not been described in any other species of animal”.
Ovulation is triggered by two surges of the reproductive hormone LH (luteinising hormone), while the pregnancy is maintained by hormones secreted by several ovarian bodies known as corpus lutea.
The knowledge will help conservation efforts to help elephants in the wild, as well as in zoos.
Dr Dennis Schmitt is Director of Research and Conservation at the Centre for Elephant Conservation, set up to safe-guard the future of the Asian elephant.
Commenting on the study, he said: “Not only is the long gestation of elephants unusual (22 months), but the long birth interval (4-5 years between calves) along with a long interval between generations of elephants (average approximately 20 plus years), complicates efforts to manage declining populations of free ranging endangered elephants.”
The research may also help scientists develop a contraceptive for elephants. While some species of elephant are endangered, other populations have grown, leading some to advocate controlling numbers by contraception or, more controversially, culling.