Scientists are fascinated with finding compounds in animals to make humans healthier.
Picture: The horseshoe crab, a sea arthropod mainly found on the east coast of North America, contains a coagulating agent called amoebocyte lysate. Pharmaceutical companies use it to detect the presence of endotoxins in certain injectable drugs and implantable medical devices. Horseshoe crabs are collected, and up to 30% of their blood is harvested before they are released back into the environment. Studies estimate mortality rates varying between 15% and as high as 30%.
What if we could find remedies directly in animals and apply them to humans? The concept sounds innovative, but has actually been around for centuries. Back in 1667 in Paris, a young 15-year old man received a transfusion of lamb’s blood to cure him of his fever. Luckily, and probably because only a small amount was injected, the patient survived, and his health even improved. Satisfied with this initial success, the physician Jean-Baptiste Denis attempted the experiment two more times, but with calf’s blood. His patients died during the transfusion.
A few centuries later, transplants were becoming popular. In the early 20th century in Lyon, a surgeon transplanted a goat kidney into a woman. The operation rapidly ended in rejection of the organ. Between 1920 and 1940, a Russian-born French surgeon, Serge Voronoff, became famous for grafting monkey testicle tissue on to men to delay ageing. But he wound up completely discredited.
The lugworm’s haemoglobin could also help wound healing in diabetics, as the natural process can be impaired due to low tissue oxygenation. Special bandages are being studied.
Scientists have always pushed on through setbacks like these, convinced that biological compounds in animals can be useful in developing treatments or drugs to cure humans.
Some applications have been widely accepted for so long that no one even realises that they came from an animal. For example, horseshoe crab blood has been used to guarantee the safety of injectable drugs and vaccines for more than 40 years (see image opposite).
The field of research is expanding as previously unknown or unexplored organisms come under the microscope. “Places with high biodiversity and where access has until recently been limited, such as the ocean floor or tropical forests, hold huge potential,” says Jean-Christophe Vié, Deputy Director, IUCN Species Programme and Director, Save Our Species Initiative at the International Union for Conservation of Nature (IUCN). He sees it as one more argument to encourage the protection of biodiversity, as long as animals are not over-exploited once their medicinal virtues have been established.
But you don’t have to travel to the other side of the world to find new remedies. Animals considered much less exotic, such as worms from the Brittany coast, or even domestic animals, like pigs, are undergoing extensive research and
have already yielded some encouraging results.
1 / A sea worm with superhuman haemoglobin
The “Arenicola marina”, or lugworm, lives on beaches stretching from the North Sea to Biarritz, France. This invertebrate may hold the secret to the universal blood type. In the early 2000s, the French biologist Dr Franck Zal discovered that its haemoglobin could transport 50 times more oxygen than human haemoglobin. The specialist has since patented the molecule and is working on potential applications.
One of these is to develop a substitute for the universal blood type. The lugworm’s haemoglobin, unlike human haemoglobin, is not contained in a red blood cell and circulates freely in its veins. This means blood type compatibility becomes a non-issue. The molecule can even be freeze-dried and therefore potentially used in combat or catastrophe zones.
This research also holds great potential for organ donations. “Today, it’s a race against the clock. The organ is immersed in a water and salt solution but with no oxygen carrier. If we add our solution, the oxygen supply extends the life of the organ,” says Franck Zal. The time that a heart can be preserved goes from 4 to 8 hours and a kidney from 12 to 48 hours. Clinical trials are scheduled to begin this year. Lastly, the lugworm’s haemoglobin could also help wound healing in diabetics, as the natural process can be impaired due to low tissue oxygenation. Special bandages are being studied.
“The idea could potentially revolutionise blood transfusion and tissue oxygenation,” says Raffaele Renella, associate physician and head of the research unit in paediatric haematology-oncology at Lausanne University Hospital (CHUV). But he remains cautious. “There are several major problems with cell-free artificial haemoglobin from other species,” he says. “In humans, some forms can bring about immune reactions or major cardiovascular and renal dysfunction or collect in tissue and cause damage. Much more research is needed before any routine clinical use,” he says, reminding people to donate blood in the meantime.
2 / Pig cell transplants to treat diabetes
These transplants could soon provide a lasting solution for 40% of sufferers of Type 1 diabetes for whom daily injections of insulin are not adequate for keeping the disease under control. “We need to restore endogenous insulin regulation in these patients,” says Philippe Morel, professor of surgery and chief physician of the Visceral and Transplantation Surgery Service at Geneva University Hospitals.
They have two options: a transplant of the pancreas or the islets of Langerhans, the cells directly responsible for producing insulin. But either way, donors are rare.
For 20 years, Dr Morel and his team have been working on a project to transplant the islets of Langerhans from pigs into humans. “As it is a xeno-transplantation [between species], the risk of rejection is extremely high,” he adds. They have teamed up with the Swiss Federal Institute of Technology in Lausanne to develop a capsule surrounding the islets to protect them from being rejected, while secreting insulin into the blood.
The pigs used are certified as having “no pathogenic agents”. They are born by C-section and raised in a completely sterile environment. “Sacrificing young pigs for medical reasons raises a number of ethical issues, but no more than a pig that will be eaten,” the specialist points out. Clinical trials are expected to begin within the next two years.
3 / A protein found in bears could act against Alzheimer’s
What if bear hibernation could help repair Alzheimer’s disease? The link is not obvious. But it prompted a group of researchers from the University of Cambridge led by Dr Giovanna Mallucci, professor of neurobiology, to delve further.
Her team is studying the protein RBM3 produced by bears when hibernating. When the bear wakes up, its neural connections (synapses) are intact due to the action of this compound. “RBM3 is also present in humans, but we don’t yet understand exactly how it interacts with the protection of synapses,” the scientist says.
Tests on mice induced into hibernation showed that healthy mice began secreting RBM3 and recovered their neural connections when they emerged. However, mice with brain disorders did not secrete the protein. Researchers administered RBM3 to them, which prevented neurodegeneration.
Clinical tests are expected to take place in 2016. Researchers eventually hope to develop a drug that can act like this protein to protect against neurodegenerative diseases.
4 / Anti-cancer drugs from sharks
Squalamine, found in the tissues of the dogfish shark (Squalus acanthias), could serve as an ally for humans in fighting cancer or age-related macular degeneration. The compound was discovered in 1993 by a team led by Dr Michael Zasloff from Georgetown University in Washington DC, then was synthesised in 1995.
Its anti-angiogenic activity prevents blood vessels from proliferating abnormally, which can contribute to the growth
of cancerous tumours or cause age-related macular degeneration. That is what interests researchers and the pharmaceutical industry so much. Clinical studies on lung cancer patients are underway and the US group Ohr Pharmaceuticals is conducting clinical research on developing squalamine eye drops.
But that’s not all. “The dogfish shark is surprisingly immune to viral infections,” says Michael Zasloff, who attributes that to squalamine. The broad spectrum of anti-viral properties of the compound is also being studied. In vitro tests on dengue fever and hepatitis B viruses have produced promising results. ⁄
Switzerland has no general ban preventing the use of animal compounds in medicine. However, different laws govern their use.
For transplants of animal organs, tissues or cells into humans, the Swiss Federal Office of Public Health grants the authorisations. Article 43 of the Swiss Transplantation Act stipulates that clinical trials for xeno-transplantation may be authorised if the risk of infection for the population can be ruled out with high probability and if therapeutic benefit is expected.
When products manufactured using animal organs, tissues or cells are standardised, they are considered medicine and are subject to the authorisation procedure of Swissmedic, the Swiss agency that authorises and supervises therapeutic products.
If animal compounds come from protected or genetically modified species, the Animal Protection Act and the Environmental Protection Act apply.