Case Studies
Case Study 1: Severely Combined Immunodeficiency
SCID – also known as severe combined immunodeficiency – is a very rare genetic disorder which only affects between 1 in 50,000 and 1 in 100,000 births. Children born with SCID do not have an effective immune system, so they are extremely vulnerable to any form of infection. In the past, the only way of keeping these children alive was to bring them up in a completely sterile environment, with all their food, water, and air sterilised and with no direct contact with other people. Even then, affected children rarely lived into their teens as the slightest contamination could kill them. Patients can also be regularly injected with the enzyme they need, but this involves a lifetime of carefully managed therapy. So, gene therapy, inserting a healthy gene into the DNA using a vector such as a specially modified virus, offers the exciting possibility of a normal life for children who otherwise have a limited life expectancy and relatively inadequate quality of life.
The first ever tries at gene therapy were carried out on children with SCID. Different variations of the technique were tried on children in several countries, including Britain. The trials had considerable success – the children treated all developed functioning immune systems which enabled them to fight off infections and to make antibodies when they were given vaccines. They could leave the hospital, and their sterile environments, and live normal lives.Then came the news that, about 3 years after their treatment, first one and then two of the nine children with SCID treated successfully using gene therapy in France developed leukaemia -like symptoms. They responded well to chemotherapy, but both the French and the American governments halted trials of gene therapy for SCID until more was known about why these boys fell ill and whether it was linked to the gene therapy.
The UK government decided differently, feeling that the potential benefits outweighed the possible risks. This view was backed up both by doctors carrying out the therapy at Great Ormond Street Hospital and by the mother of Rhys Evans, the first British boy to be given gene therapy. He received the treatment in 2001, when he was an infant, and he is now a healthy young man, enjoying normal life with a functioning immune system. Great Ormond Street has had many success stories treating this extremely rare condition with gene therapy. They are now considering ways to use the same techniques to tackle other genetic diseases. Professor Nevin, who chaired the UK committee which made the decision that work should continue commented: "As with all innovative treatments, there will always be the potential for side-effects." Dr Bobby Gaspar of Great Ormond Street Hospital said: "If we stop these studies now, we will be denying extremely effective therapy to children, and they may suffer as a result of not receiving this therapy. Ethically we believe it is the right thing to go on."Marie Evans, the mother of Rhys who has undergone the treatment, also had an opinion. "If they stop something just because one child has an adverse effect at the end of the day medicine and the world just doesn't go on," she said.
Gene therapy is not suitable for all patients, but at Great Ormond Street several children have now been successfully treated, without developing leukaemia, and trials into other uses of the technology are underway.
Case Study 2: Next-Gen Mosquito Zapper
Mosquito-borne diseases are a major concern in many parts of the globe. Diseases that spread to people via mosquitos, including Zika virus, West Nile virus, dengue, and malaria, have serious negative impacts on human health. A company we'll call Kill-M, has utilised CRISPR technology to create a mosquito that will prevent the spread of mosquito-borne diseases by reducing the number of breeding mosquitoes--fewer mosquitos, fewer bites; fewer bites, less disease. Using CRISPR, male mosquitos are genetically modified so that their offspring die before reaching sexual maturity, thus decreasing the mosquito population.
This technique to reduce the insect population is called the "sterile insect technique," which ordinarily involves sterilising insects such as the screw worm and the Mediterranean fruit fly using radiation, not genetic engineering. Radiation is generally quite successful, especially at eliminating invasive insect species. But, radiation kills mosquitoes, so CRISPR technology, rather than radiation, is used to edit mosquito genes. Ecologists have expressed concern at the use of the sterile insect technique to eradicate local insect populations. Eliminating a species of insect like mosquitoes reduces local biodiversity, which is concerning because it accompanies wider trends in decreasing global biodiversity. The elimination of an insect species can also influence other areas of the environment, such as predators who eat the insects or plant species that need to be pollinated.
Now, consider this: In Brazil, there is an urgent outbreak of Zika, a serious illness with no vaccine for prevention or cure once contracted. The symptoms of Zika are usually fairly mild, and may include fever, muscle soreness, headache and rash. Zika is not deadly, and symptoms will usually clear up in about a week without medical intervention. However, Zika is a concern for pregnant women, because the infection can be passed to her feotus causing severe birth defects including severe brain development issues, notably, microcephaly. Kill-M has been asked by the Brazilian Department of Public Health, SUS, to bring their CRISPR sterile insect technology to Brazil in order to eliminate the mosquito population and stop the spread of Zika.
It is unknown what degree of reduction in the mosquito population is required in order to make a positive impact on human health in Brazil (or elsewhere). In order to ensure success of the project and eliminate the spread of disease to pregnant women, Kill-M plans to release enough genetically modified mosquitoes to wipe out the entire native population of mosquitoes within six months.
There is significant uncertainty about the long-term outcomes of releasing a population of genetically modified mosquitoes into the environment in response to Zika in Brazil. Predator species like bats, which are critical to the ecosystem, may be negatively affected by losing a food source. Additionally, mosquitoes are pollinators, so their elimination from the environment may negatively affect native flora and farming in Brazil.
There is a significant amount of uncertainty about the moral status of mosquitoes. Moral status is a concept that determines whether something has intrinsic value, and should be treated with special regard. Humans have very high moral status, while pebbles have much lower moral status.
Now consider another potential application of the CRISPR technology. A wealthy neighbourhood in Florida has decided that they want to hire Kill-M to wipe out the mosquito population in their community. The mosquitoes in this region are not disease vectors, rather, they are simply annoying pests. The residents argue that insect repellants are unpleasant and ineffective. The promise of a mosquito-free vacation will increase the number of visitors to the community, and increase revenue from tourism in addition to increasing the comfort of year-round residents.
There are several reasons why some people are at greater risk of being bitten by mosquitoes than others. These can include: the bacterial population on the skin, how much someone is sweating, a person's blood type, and the presence of certain genetic markers. Suppose the FDA has recently approved a pill that makes people completely repellent to mosquitoes. By taking the inexpensive pill once a day, residents and tourists can completely avoid mosquito bites. However, there are some mild, but unpleasant, side effects including a risk of unusual bleeding and a drop in blood sugar associated with taking the pill. People on blood thinners or who are taking insulin for diabetes should use extreme caution in taking this medication for more than a day or two. Environmental activists argue that despite the risks, the town in Florida should take this drug instead of eliminating the mosquito population.