Perfecting Imperfections

Yesterday I watched the final day of Crufts, a dog extravaganza and highlight in the British social calendar that dates back 125 years. The competition attracts dog lovers from around the world with over 22,000 taking part. It is unashamedly seeking dog perfection: the characteristics and behaviours the judges believe epitomise the ideal in each breed.

Evidently a lot of time and effort goes into keeping pedigrees untainted from diversity, and for their troubles these top dog breeders gain little more than glory, pomp and ceremony. The dog that deviates least from perfection, in the eyes of the judges, is the celebrated winner of the coveted Best in Show trophy and title. This year it was claimed by, Devon, a fluffy white West Highland Terrier and the runner up prize went to a very sleek Whippet called Hazel.

Whippet CREDIT: TRISHA SHEARS                                                                                        

Although faltering in the breeding ranks, certain Whippets may prove man’s saviour as well as man’s best friend. Some dogs, known as Bully Whippets, are born with a natural genetic mutation that makes them extra muscular and strong. A fault in a gene called myostatin means they don’t produce a muscle inhibiting protein which would normally put the brakes on muscle growth. For this reason scientists in America think this genetic anomaly holds the key to treating patients with the muscle wasting disease Duchenne muscular dystrophy. The inherited disorder usually affects boys whose weakening muscles gradually paralyze them before they die prematurely at around 25 years of age.

Taking the cue from the Bully Whippets, scientists in America are using new gene editing technologies to knock out the myostatin gene in an attempt to treat Duchenne muscular dystrophy. As the whole field of genetic engineering is rapidly gaining ground such a treatment is a most promising.

In dog competing circles like Crufts, a Whippet with such a “fault” (even if not a visible one) would not make the mark. The deviation from the ideal would be picked up in the DNA tests breeders now use to validate dogs’ parentage. DNA is the sequence of letters that forms our genes. This genetic information governs our traits and how our bodies functions. Three billon letters of DNA make up the 25,000 genes inherited from our parents. We receive a copy of each gene from both our mother and father. Therefore, if a genetic mutation is passed on from just one parent, we are usually unaffected as the other parent’s gene steps in.  But there can be profound ramifications if we inherit two mutated genes.

With genetic engineering advancing so swiftly, scientists around the world are debating the consequences of editing the mistakes out of our genes. Therefore, I thought it worth mentioning a few more of these mistakes that are actually beneficial to mankind.

A potential cure for HIV

A select ten percent of the world’s population are born with a gene mutation which makes them resistant the lethal AIDS’s virus. This genetic quirk means that their immune cells lack the receptor HIV needs to enter them. Much like a door handle, without it HIV just can’t get inside and infect them. Scientists have already developed new antiretroviral drugs to try and block this receptor. Furthermore, human trials are underway which use gene editing technologies to cut out this entry gene.

The concept has already been used cure a man of HIV. As the patient also had leukaemia his savvy doctor chose a bone-marrow donor who had this mutation, thus giving him a life-time’s supply of HIV-resistant cells. Therefore, hopes are high that this gene therapy, which mimics this mutation but doesn’t carry the health risk of a transplant, will cure this deadly disease. Inevitably this research has paved the way for other diseases, like Duchenne muscular dystrophy, that could be also treated by editing out a single gene.

Low cholesterol on a high fat diet.

Some lucky people are born with a genetic mutation which means they can eat as much cheese, red meat, and fry-ups as they like. In fact any foods that would have the average person’s cholesterol shooting up make little difference to them. These people lack a gene known as PCSK9: a discovery that has triggered a flurry of research to block the gene and develop a new anti-cholesterol pill. Patients on the first trial achieved a reduction of up to 75% in their cholesterol levels so side effects from statins could become a thing of the past.

Malaria resistance

People blighted with the life-threatening genetic disorder sickle cell disease (SCD) also have unusually high resistance to Malaria. SCD is caused by mutations in the beta-globin gene that distorts red blood cells into a sickle shape. This causes these crucial oxygen-carrying cells to die prematurely leading to anaemia. Because of their awkward shape they get stuck in blood vessels causing extreme pain and life-threatening organ damage. The Malaria parasites also find the awkward shape a sticking point. Usually they infiltrate and destroy red blood cells with ease, but they find the sickle cell hard to latch on to which effectively shuts them out.

People who have inherited this genetic fault from just one of their parents benefit from Malaria protection and are also spared from sickle cell disease. Therefore, it is not surprising that this debilitating disease is prevalent in African communities that are connected to lands where Malaria is endemic.

As we gain the scientific know-how to edit out genetic faults it is worth remembering all of the mistakes that have benefited humanity and enriched our society. Crufts is a fantastic four-day spectacle of dog perfection and long may it last. But long may such pursuit of perfection stay within the canine kingdom.