The genetic lottery: self-destruction or survival?

Illustrated strand of DNA

As one of the many scientists who contributed to our Settlers exhibition, geneticist Dr Calliope Dendrou from the Wellcome Centre for Human Genetics ran a Spotlight talk as part of the exhibition’s event programme, where she explained more about her research into genetics and autoimmune diseases…

Our genes make us who we are – they are what unite us a single species, Homo sapiens – but they are also what make us unique individuals, with a particular set of characteristics. Genes are made up of DNA inherited from one individual to the next, transmitting the code for life through time.

The DNA ‘alphabet’ comprises four letters, A, C, G and T, and three billion of these letters make up the complete human genome. Comparing two unrelated individuals, on average around one in 1,000 of the three billion letters will differ. Genetically speaking, each of us is 99.9 percent the same as every other unrelated person.

Studying our genetic composition and the similarities and differences between individuals is of interest from a historical, geographic and sociological perspective, as the Settlers exhibition at the Museum shows. But it can also have medical implications for our understanding of the types of diseases we are susceptible to.

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Immune cell (yellow) engulfing anthrax bacteria (orange). Image: Volker Brinkmann [CC BY 2.5], via Wikimedia Commons
My lab works on the genetics of autoimmune diseases, which affect some ten percent of people worldwide and include relatively common conditions such as rheumatoid arthritis, multiple sclerosis, and type 1 diabetes.

Autoimmune diseases arise when the cells of the immune system function inappropriately. The immune system is made up of millions of immune cells patrolling the body, sensing their environment and sending signals to each other.

If the body has been injured due to physical trauma or an infection, then upon receiving the right signals immune cells help to clear damaged cells or fight off pathogens. But sometimes immune cells can begin to respond to the wrong signals, triggering a self-destruction. When this happens they can destroy the body’s own tissues and organs and then autoimmune start to diseases develop.

Auto immune illustration
Autoimmune disorders in a nutshell –  illustration by Beatrice the Biologist

The common autoimmune diseases are very complex and are thought to result from a combination of genetic and environmental influences. Hundreds of genetic factors can influence someone’s risk of autoimmune disease development, so having a low or high risk is a genetic lottery – it depends on how many different genetic factors happened to have come together for that person.

We are investigating the biological consequences of these genetic factors to find better ways to target the immune cells that are attacking the body. The trick is to do this without suppressing the immune system’s ability to fight off infection, a problem associated with drugs used treat autoimmune disease patients today.

The ancient mariner

Helen J. Bullard is a PhD candidate at the University of Wisconsin–Madison whose research aims to tell the historical and cultural stories of the horseshoe crab. After visiting the museum, and reading the story of our Natural History After-School Club member’s horseshoe crab fossil find, Helen offered to write a guest post for the blog about these amazing, ancient mariners…

You’re reading this, so I’m guessing you like museums. But have you ever heard of living fossils? Animals such as sharks and crocodiles are often referred to as ‘living fossils’ because they appear pretty unchanged from their ancient fossilized relatives. Of course, by definition, you can’t be both alive and a fossil. But fossils allow us to become primary eyewitnesses to ancient life; we can literally see what life used to look like, how cool is that? They can also dole out some pretty valuable advice, if we just choose to listen.

This summer during a visit to England, I spent some time at the Museum studying another so-called living fossil, the horseshoe ‘crab’. The horseshoe crab is not actually a crab, but is instead more closely related to spiders, scorpions and ticks. In fact, they are the closest living relatives of the extinct trilobites. But unlike their famous trilobite cousins, horseshoe crabs have survived all five of Earth’s major mass extinction events. Today, as a direct result of their ability to survive, the four remaining species of horseshoe crab play a vital role in global medical safety.

The Museum’s fossil specimen of Mesolimulus walchi, from the Upper Jurassic (163-145 million years ago), Solnhofen Germany, shows how little the form of the horseshoe crab has changed since

Not only do living horseshoe crabs look very similar to their early relations, they are also able to survive surprisingly severe injuries that often leave them missing body parts. Being able to see, through fossil evidence, how little their form has changed over time has helped to uncover the answer to this secret superpower. It lies in a very special life-saving trick that the crabs have kept for millions of years: a coagulating blood protein.

Horseshoe crabs on display in the Museum may provide food for thought for visitors

The blood of the horseshoe crab is able to clot quickly if bacteria are introduced, preventing infection, and saving the crab’s life. Since this discovery in the 1970s, this life-saving protein has been extracted from horseshoe crab blood and used in human medicine to test the safety of vaccines, medical laboratories, intravenous drugs, implants, and much, much more. The chances are that you owe a great deal of gratitude to the horseshoe crab.

But after all that surviving, horseshoe crabs, like many species, are now struggling for survival. They are losing their spawning grounds because of coastal development, industry, housing, marinas and coastal defense structures; they are collected and killed by the millions for bait, and bloodlet in their hundreds of thousands for medical use every year. It is likely that horseshoe crabs will not survive much longer.

But don’t despair. Museums are critical because they hold collections that can unlock knowledge about environmental change, and we can use that knowledge to protect life. Of course, horseshoe crabs are not alone in telling their stories through the fossils they leave – natural history museums are full of stories in stone, bones, pollen, and other traces. If you want to learn about and protect biodiversity, visit your local museum, or support organisations like Oxford’s Environmental Change Institute.

And to help the ancient horseshoe crab itself, join in with the efforts of the Ecological Research and Development Group – the crabs have saved us, so let’s return the favour.