Andreas Hougaard Laustsen-Kiel
Bitten by snake venom
As a world first, Professor Andreas Hougaard Laustsen-Kiel , biotech entrepreneur and academic center leader , has prototyped a human snake bite antivenom. His expertise in toxins has paved the way to new projects, and today he heads up a large research team at DTU – Technical University of Denmark.
Meeting two children in Tanzania in 2011, one an elbow amputee, the other a knee amputee, made a lasting impression on Laustsen-Kiel, who at the time was 24 and an undergraduate in bioengineering. The children had been bitten by cobras, but had no access to antivenom. The amputations most likely saved their lives. This is not uncommon. Antivenom is costly, hard to come-by in some countries, and of varying quality. The antivenom is made from extracts of blood serum from immunised horses by means of techniques more than a century old. That encounter set his engineering mindcogs whirring.
Cut to a few years later: Laustsen-Kiel succeeds in developing the first-ever experimental antivenoms based on human antibodies. Antibodies are the proteins released into the body by the immune system to detect and combat foreign substances (antigens) like microbes and toxins.
The new types of antivenom are easier to manufacture and distribute and are more effective and cause fewer side effects than existing antidotes. And not only that, Professor Laustsen-Kiel used state-of-the-art biotechnology to develop antivenoms covering multiple types of toxins from snakes, spiders and scorpions.
This innovation catapulted the Danish academic into the top of international researchers in toxinology which is the study of toxins from animals, plants and microorganisms. For this and other outstanding achievements, Laustsen-Kiel has been awarded the Young Investigator Prize 2024 by the Lundbeck Foundation.
“The prize recognises the research conducted by my colleagues, students, collaborating researchers and myself,” the professor explains.
A black widow on the wall
The prize recipient holds a PhD from the University of Copenhagen and an MScEng. from DTU, where he is now professor in antibody technology. He also leads the DTU Center for Antibody Technologies, which he set up in 2018 with substantial grants from the European Research Council (ERC), the Danish foundation Villum Fonden and Wellcome.
At the centre, some fifty researchers and students juggle state-of-the-art biotechnologies to develop antibodies for research, diagnostics and therapeutics. Ongoing projects include an allergy vaccine and immunotherapy to treat cancer.
In East Africa, the black mamba is known as the “seven-steps snake”. Because, it is claimed, seven steps is what the victim can take before succumbing to the venom from the fangs of one of the most poisonous snakes in the world. In reality, the victim has more time, but this snake bite is lethal; the venom from a single bite is enough to kill 40 people. Laustsen-Kiel says that he was “bitten” by research in the black mamba, on which he wrote his PhD. In his native Denmark, poisonous snakes are less of a problem, but worldwide, one person dies every four minutes from snake bite. And snake bite envenoming is on the WHO list of 25 neglected tropical medical conditions.
Inside the professor’s office at DTU, a photo on one wall features a huge close-up of a black widow spider, which he and his team are developing an antivenom for. Hanging on the other wall is an African mask.
The photo and the mask are tell-tale signs that his wife does not share his taste in wall decor, but also reflect his special expertise in analysing toxins, and his interest in the tropical diseases listed by WHO as ‘neglected’. Many of these diseases occur in Africa.
But why did he choose to focus his research on toxins from some of the most terrifying creatures on the planet?
“Probably because this field has real-world applications and holds solvable challenges that require a creative, analytical and engineering mindset,” he explains.
“I like to joke that I’m a born engineer, but didn’t have the papers to prove it until I was 25 and gained my degree here at DTU. I’ve always been into creative, innovative processes.”
A keen interest in the natural world is also a factor. The professor is surrounded by a family of nature lovers and keen travellers.
On his holidays, and as a student and researcher he travelled widely, including trips to find venomous creatures in jungles and deserts on multiple continents.
In one location, Costa Rica, he learned advanced techniques for analysing proteins, studying the toxicity of various substances and conducting experiments to neutralise them. This is where he investigated the venom of the black mamba, which he described in his first scientific article in 2015, before he had even completed his PhD.
Co-founded eight companies
Laustsen-Kiel is not only an academic, but also an entrepreneur, like his father before him, who was also in biotech. In 2012, before even completing his master’s at DTU, he started up his first biotech company. Since then, he has co-launched eight companies that translate research into real-world products.
One such product is a mobile diagnostic tool for the benefit of snake bite victims on the Savannah or in the jungle. This tool determines which type of snake the casualty was attacked by. Another product is an agent that boosts the microbiome in the gastrointestinal tract by neutralising harmful substances, such as toxins from harmful bacteria, and protecting gut-friendly microbes. A third product is an agent that enables food crops to thrive in soil impacted by climate-change salinisation and desertification.
Only one of the eight companies had to be closed down; the commercialisation of the one that was to finalise development of the broad-spectrum human antivenom and put it into production, simply proved too limited. But this enterprise has become what he terms a “spin-in” at DTU and has now made good progress towards a clinical trial. Because the demand is real enough: Every year, more than 5 million people worldwide fall victim to snake bite. 150,000 cases are fatal, and 3 times as many result in amputation.
As an entrepreneur-academic, being involved in creating between 100 and 120 jobs is a source of pride to Laustsen-Kiel.
“I see it as meaningful to create jobs and ultimately also products to help snake bite victims, reduce our climate footprint or tackle infectious diseases.”
The prize nomination statement duly emphasises that Laustsen-Kiel has been instrumental in developing interventions for infectious diseases. He has developed so-called nanobodies to combat pathogens such as E. coli and the bacteria that cause cholera. Nanobodies are tiny targeted proteins that are easier to produce and modify than large proteins.
Develops antibodies with special properties
The prize nomination statement also emphasises that Laustsen-Kiel’s research has led to new insights into how antibodies can be developed and engineered with dynamic binding properties.
This is important because antibodies, which bind to a protein, for example, as in the case of cancer cells, also bind to healthy cells expressing the same protein. But by adapting the antibody’s binding properties to the microenvironment of the cancer cells, it is possible to better ensure selective targeting of diseased cells without causing as much harm to healthy cells. One example of this is to develop an antibody that binds better in an acidic environment. Cancer cells require high oxygenation, making their microenvironment acidic.
Although Laustsen-Kiel’s research is focused on toxins and antibodies, he is convinced that he could just as well have found the same enthusiasm for other fields.
“I’m not driven solely by academic curiosity and personal interest. I think it’s important to think about where the money is going to benefit society the most. So what I do is far more driven by real-world value.”
The next step is to secure funding for a new idea: a platform combining techniques and technologies capable of positioning the research centre internationally.
“Computing capabilities are becoming so powerful, and the algorithms so well-trained that we’re now able to design things on a computer that actually work. If we ally that capability with existing techniques, we will be able to solve problems far more quickly and with greater precision.”
Andreas has not yet decided what the DKK 1 million prize will be invested in, but it should be something that raises awareness of the field.
“My hope is that the prize will help to draw attention to the fact that research in snake bites, tropical diseases and other neglected conditions can be conducted at the highest scientific level. The prize will hopefully also help to open doors to new research areas and collaborations.”
Antibodies are generally known as the proteins the immune system releases into the body to detect and eliminate harmful substances. However, more specifically, they are highly targeted and can bind to specific molecules, making them ideal for disease research, diagnostics and therapeutic drugs.
Several of the so-called ‘biological therapeutics’ launched in recent years are based on antibodies.
Antibody technologies are techniques and procedures used by researchers to develop and produce antibodies. Two examples of antibody technologies are recombinant antibody technology and phage display.
In recombinant antibody technology, the researchers insert genes that code for antibodies into cells that then produce those antibodies. This technology makes it possible to design and modify the structure and properties of the antibodies so that they can be used to treat cancer, autoimmune diseases and infections.
In phage display, researchers use bacteriophages, which are viruses that infect bacteria, to create a form of library of proteins, including antibodies. Genes that code for different proteins are inserted into each their own bacteriophage. Once the bacteriophage has infected a bacterium, the bacterium then starts producing the protein. This is then attached to the surface of the bacteriophage, and in that way ‘displays’ the protein so that the researchers can see which genes code for the individual proteins. This technology is mainly used for developing antibodies. Antibody technologies revolutionised drug discovery, and the two researchers who developed them received the Nobel Prize in Chemistry in 2018.
