• Question: Why don't they genetically modify people instead of using medicines to combat many diseases?

    Asked by Polpiferrergil on 15 May 2020.
    • Photo: Giulia Paci

      Giulia Paci answered on 15 May 2020:

      Hi that’s a great question! There are both practical and ethical challenges to potentially changing a person’s DNA but some therapies based on this idea (gene therapy) have already been developed and tested in few clinical trials, especially for conditions that have a genetic cause

    • Photo: Jamie McGinn

      Jamie McGinn answered on 15 May 2020:

      This is a very important question, thanks so much!

      There have been lots of experiments looking at how we can fix illness and disease using genetic modifications. You can find examples to try and stop cancer, fix problems at birth amongst so many others. Currently, a lot of this is tested either in animals in the safest ways possible, or on cell lines. The problem with introducing these to humans is that we just can’t be sure what might happen. Over time, things in your body change, it is very hard to know by testing a modification on a cell line, if there may be problems later in life for a human that was treated. Another huge problem is ‘off target effects’ – things that are very hard to predict but could cause problems for use in other parts of the body.

      Use of genetic modification in humans is considered ethically very seriously, and we need to be very careful if this ever becomes common that we do not cause even bigger problems.

      Sometimes, where there is really no other choice (called palliative treatment), things like this can be tested – and sometimes, amazingly they can be seen to work. One example of a small boy with a genetic defect in his skin that caused horrible wounds and blisters (called epidermolysis bullosa) – this was fixed by correcting the mutation that caused the problem. You can read more about it here – https://www.nature.com/articles/nature24487.

      I hope this helps answer your question – let me know if you would like to talk more about this!

    • Photo: Kim Liu

      Kim Liu answered on 15 May 2020:

      This is indeed a great question, with already very good answers 🙂 I’ll just add our genetic code is unbelievably complicated, so it is really, really hard to know what effects changing some of the letters will have on the rest of our health over the course of our life. Also, genetic modifications can be transferred from parents to their children – these children may not need the genetic modifications if they don’t have the disease, in which case it may be better to not have them in case they go wrong later on.

      Practically however – gene editing of an animal or human is also very challenging and expensive! If you compare a relatively simple chemical molecule such as paracetamol to the very complex protein machinery that is required to edit cells accurately (have you heard of CRISPR?) – it is much cheaper to make the chemical than to make very complicated proteins. Also, it’s much easier to eat a drug molecule to absorb it into your body. Gene editing techniques at the moment would require injection of complicated delivery systems. These are some really cool opportunities to discovery new things in drug discovery and new therapeutics, but at the moment there’s a lot of work to be done to make these more reliable.

    • Photo: James Loan

      James Loan answered on 15 May 2020: last edited 15 May 2020 5:56 pm

      A really profound question!

      One other aspect to answering this is that your chance of catching a disease is only partly down to your genes. For example, it doesn’t matter what your genetic background is too much if you step out in front of a car (unless your genetic background gives you superpowers). Rather, good education about road safety is probably more important. This might also be the case for say heart disease or stroke – having a good diet and not smoking may be just as important as your genes.

      Arguably, you could try and modify all humans to be able to deal with getting hit by a car – give them blood that clots really fast – or improve their genes to have a lower chance of getting hit by a car in the first instance – spider senses. Similarly you could ask for a supercharged immune system to fight off infections. However, a balance is needed, and millions of years of evolution seems to have gotten the balance pretty good in most circumstances: if peoples blood clotted too easily then they could get all sorts of problems, such as heart attacks, stroke, blood clots in the lungs or legs. Likewise if people’s immune systems are too aggressive they can develop diseases where the body’s immune system attacks things it shouldn’t – such as in asthma, or certain types of arthritis.

      So meddling with genes to prevent disease is likely to be very difficult to do safely, and might not be the most effective way of doing it. As to treating a disease that has already started – that could be even more challenging – you would have to tailor your genetic modification to both the person who has the disease’s background and also the particular details of the condition that they have. Not to say it will never happen, but it will be very hard!

    • Photo: Nina Rzechorzek

      Nina Rzechorzek answered on 16 May 2020: last edited 16 May 2020 12:40 am

      Hi Polpiferrergil – excellent question, and I can certainly see the attraction – wouldn’t it be amazing if we could stop all the diseases in the world without people having to take drugs or undergo invasive procedures (and suffer potentially nasty side effects)? Problem is, gene therapy and genetic engineering are not without risks either (as others have mentioned), and many diseases are not caused by just one faulty gene or a variation in one gene. Several important diseases have many environmental as well as multiple genetic risk factors – so it would be very difficult to predict exactly what combination of genetic modifications might be useful. Potentially ‘useful’ modifications will also likely vary from person to person, and also within an individual as they age and are exposed to various other risk factors during their lifetime. This means that such complex genetic therapies might also need to be reversible or at least have a way of ‘fine tuning’ their effects depending on context – we certainly do not have any such refined gene therapies like this yet. There is also much overlap and contrast in how different genes modify disease risk – variants in some genes may increase your risk of getting one disease, but at the same reduce your risk of getting another (and perhaps more concerning) disease! A related question is – do we really want to cure all diseases? For example, sickle cell anaemia reduces the severity of malaria; there is also some evidence that parasitic infection may reduce the chance of developing autoimmune diseases. Just the abstract of this paper provides several other examples, and as you will see, some of the greatest medical discoveries have arisen from understanding how one disease might protect you from another
      I think it’s fair to say that being able to sequence the human genome has led to a much greater understanding of genetically-driven disease, but at the same time it has helped us to realise that genes are not the answer to everything. They can certainly be part of the solution however, especially as we move more towards ‘precision medicine’ – using a person’s genetic information and clinical history to work out exactly which kind of drug may be most effective and well-tolerated, and even figure out (as I’m slightly biased by an interest in body clocks), exactly what is the best time of day for that patient to take that drug. ‘Chronotherapy’ is another whole discussion in itself….!

    • Photo: Bilal Ahsan

      Bilal Ahsan answered on 16 May 2020:

      Genetic/congenital diseases, in particular, are already under consideration to be ultimately treated using this approach. However, current approaches aren’t impeccable enough for routine practise and entail risks of missing the target and thereby resulting in an undesirable outcome.
      For non-congenital disorders, conventional drug therapy is easier to administer, and the side effects/risks are also known and acceptable than genetic modification approach.

    • Photo: Melanie Krause

      Melanie Krause answered on 16 May 2020:

      Great question! 🙂

      There are lots of great answers below already but I just wanted to add two things. About a year ago a lab in China has actually announced that they have changed the genetic information of two children so they can never get HIV. We know that HIV enters cells through a specific receptor on the cell surface and if people do not have that one they are ‘immune’ to ever getting HIV. That change in the genetic code was done at the embryonic stage with a method called CRISPR. They did it in a petri dish and then implanted the embryo into the uterus and later the children were born.
      The large majority of scientists heavily criticised this though for all he reasons that my colleague already mentioned below. The journals where the Chinese scientists wanted to publish rejected the manuscript because it was too controversial, also because the children were not cured from anything.. they were genetically changed so they would never get HIV that they might not have been infected with ever in their life to begin with. Since then there has been a big debate about what science should and should not do in ‘changing’ people.

      The other thing is to not change embryos but to only change the genetic code in specific tissues with something called ‘gene therapy’ which is less controversial because it happens when someone is already born and a disease exists and the change would not be passed on to potential children. An example for that is cystic fibrosis where a protein in the lung is formed wrong and that destroys the lung over a period of time and people who have the disease need a transplant or die. The idea is to change the genetic code only in lung tissue so that this one protein can be produced correctly and the lung stays healthy. There have been attempts to try to change the lung tissue by bringing in the right genetic information of the protein using a virus but the most promising one is a new medication that changes the way the cells produce the ‘wrong’ protein into the ‘right’ version which is based on changing the transcript from the DNA. So in a way you change the genetic information but one step later than at DNA stage (at what we call messenger RNA stage).. this also means its not permanent and patients rely on the medication for their whole life though.

    • Photo: Shaline Fazal

      Shaline Fazal answered on 16 May 2020:

      This is a really interesting question and as others above have already explained there are many things to take into consideration. I would say that although we now have very good techniques available (yet still expensive) for doing gene editing, one must not forget that the body has evolved over time in such a way that it needs some of these genes to make proteins for normal functioning at a cellular level. It is also important to note that sometimes although we know the cause of a disease is due to a “fault” in a gene, like with Huntington’s disease for example, it is not as simple as just editing the faulty gene as diseases are a lot more complex than this.
      I like to go by the reasoning that with any disease, it is a population of cells that are dynamically interacting with one another and all the processes that are going on amongst this network forms a very complex circuitry that cannot be treated as separate entities, and it is really important to consider how any therapeutic approach may be affecting all populations.

    • Photo: Ailith Ewing

      Ailith Ewing answered on 18 May 2020:

      Hi! Great question with great answers. Most people have talked mostly about the practical considerations so I’m going to focus on the ethical ones. Firstly, as a lot of people have said already, we usually can’t be sure what the effects of gene editing in a person will be. So there’s a risk of doing more harm than good. There’s also a valid argument that your genes contribute a lot to what makes you you so should you artificially change that? Also the differences in our DNA are what make people different from one another and diversity is important. Ok, it’s easy to justify making changes to cure diseases but where do you begin to draw the line? Is it right to change a baby’s DNA for example for other reasons? Most people would argue justifiably that it isn’t. Also these changes could be passed on to future generations which could have long term implications.

      However, it’s important to make a distinction between ‘germline’ gene editing so making changes to the DNA that you inherit and pass on that is in all your cells and ‘somatic’ gene editing where changes are only made to particular sets of cells ie. stem cells and then putting just those cells back into the body as a treatment. This has been shown as an effective gene therapy for a number of diseases and the ethical issues are understandably much fewer.