The possibilities of correcting defective genes came to light nearly 50 years ago¹. At that time there was great hope for the emerging idea of repairing genes as a way to end cancer and genetic diseases. But here we are, still waiting for the cures. Progress has been steady and we appear to be getting very close to the day when gene therapy will be a commonly used treatment. In this article I will present an overview of the most recent advances toward that goal and how this might affect the current medical world.

Nobel Prize winning discovery may be key to the dream: CRISPR/Cas9

Emmanuelle Charpentier and Jennifer A. Doudna have discovered one of gene technology’s sharpest tools: the CRISPR/Cas9 genetic scissors. Using these, researchers can change the DNA of animals, plants and microorganisms with extremely high precision. This technology has had a revolutionary impact on the life sciences, is contributing to new cancer therapies and may make the dream of curing inherited diseases come true.

https://www.nobelprize.org/prizes/chemistry/2020/press-release/

Since Charpentier and Doudna discovered the CRISPR/Cas9 genetic scissors in 2012 their use has exploded. This tool has contributed to many important discoveries in basic research, and plant researchers have been able to develop crops that withstand mould, pests and drought. In medicine, clinical trials of new cancer therapies are underway, and the dream of being able to cure inherited diseases is about to come true. These genetic scissors have taken the life sciences into a new epoch and, in many ways, are bringing the greatest benefit to humankind.

https://www.nobelprize.org/prizes/chemistry/2020/press-release/

The need for patience and money

Reading the above article and the links below, you might wonder to yourself, “Why haven’t we seen these diseases being cured yet?”. There seem to be several reasons. 1. Researchers are still discovering exactly what works and what doesn’t, and refining processes of getting the gene therapy into the proper place in the body. 2. It takes time to get approval for human trials and time to discover long-term effects and efficacy. 3. Research costs money.

But also, it is my guess that the reason is money and politics ,based on what I read in the website that is embedded below for The Alliance For Regenerative Medicine, a group that promotes the goals and interests of biomedical companies involved in gene therapy.

1. The people with the technology want to get paid. They want to be sure that the government approves and pays for this treatment/cure so they are lobbying for favorable legislation including payment by Medicaid.
2. I would assume that gene therapy is seen as a threat to the established medical industry and they may seek to control it’s explosion onto the scene.

ARM’s Impact

Politics and Profits

Curing cancer and inherited diseases sounds wonderful to the many billions suffering from them or seeing their children or family members suffer. But it doesn’t take much thought to realize that this will be hugely disruptive to the current medical model. Similar to the resistance of big oil to solar, wind, and biofuels, some players in the traditional and lucrative system of treating rather than curing disease are going to resist this innovation even if it means saving lives.

The reason people innovate is to make money, even if their goal is to also help people. I’m sure researchers derive great pride and satisfaction from their work, but if no one paid them, they would have to do something else. As you can see by this list of lobbyists for the business of health issues, there is big money to be made in this field. Healthcare is the fastest growing industry and occupation and gene therapy is the hot investment. Also growing is the belief that governments should play a much larger role in financing health-related research and care. This new technology may lead to the acceptance of that change.

Discrimination against ‘Imperfect’ People?

Utilizing genome manipulation tools and performing genetic selection is tantamount to engaging in what Rosemarie calls “velvet eugenics.” Enforced by laissez-faire commercialism, rather than by the state, velvet eugenics seems like common sense, yet it hides its violence and inequality behind claims of patient autonomy and under a veil of voluntary consent. Ultimately, market-driven velvet eugenics embodies a similar goal of purging unacceptable human variations that campaigns to eliminate the supposedly unfit and inferior have held in the past. Both enact a mandate to exclude people with disabilities from coming into the world.

https://www.scientificamerican.com/article/the-dark-side-of-crispr/

The above is just one voice that is warning that CRISPR could be used to create a divided world of people with perfect genes and those without them. I agree that eliminating disabilities could cause the few people that have them to be at risk of some kind of discrimination. But I think the benefits outweigh the risks. As far as purging the gene pool of ‘unacceptable human variations’, that is going to happen over time anyway as more and more people abort babies with genetic problems. I think it would be better to eliminate the genes, not the pre-born babies. Until then, I believe we should do all that we can to help people who would rather live without disabilities. As for being divided, what’s new?

Designer Babies?

Discovering a cure for cancer and other diseases brings with it complicated questions. You will many find articles like the one below from the UN that mention the ethical dilemmas of gene-editing in cloning and “designer babies. Personally I find the UNESCO statement very hypocritical considering they are perfectly okay with aborting babies and do not see that as jeopardizing “ the inherent and therefore equal dignity of all human beings“.

https://en.unesco.org/news/unesco-panel-experts-calls-ban-editing-human-dna-avoid-unethical-tampering-hereditary-traits

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Recent advances have opened the door to genetic screening and testing for inherited diseases, gene therapy, the use of embryonic stem cells in medical research and the possibility of cloning and genetic “editing” for both medical and non-medical ends.

“Interventions on the human genome should be admitted only for preventive, diagnostic or therapeutic reasons and without enacting modifications for descendants,” says the IBC, arguing that the alternative would “jeopardize the inherent and therefore equal dignity of all human beings and renew eugenics.”

The IBC reports that rapid advances in genetics are making “designer babies” an increasing possibility, prompting calls among scientists and bioethicists for a wider public debate about the power of science to modify genetically human embryos in the laboratory, so as to control inherited traits, such as appearance and intelligence.

A new genome “editing” technique called CRISPR-Cas9 makes it possible for scientists to insert, remove and correct DNA simply and efficiently. It holds out the prospect of treating or even curing certain illnesses, such as sickle cell diseases, cystic fibrosis and some cancers. But germline editing can also make changes to DNA, such as determining a baby’s eye colour, easier for scientists working with human embryos, eggs and sperm.”

Honestly, I feel like this concern about people wanting “designer babies” may be overblown. We already allow many other interventions in human life, including IVF and donated embryos in reproduction, surgical enhancements, abortion, assisted suicide, and even gender change surgery, so I don’t see how this is any different. I doubt most people would choose to design their baby other than eliminating non-disease traits. But only time will tell. Gene therapy may be able to eliminate the need for expensive IVF and other fertility procedures.

Risks and controversies

And the following story of the Chinese scientist who altered the genes of embryos was quite controversial at the time, but will it become an accepted practice one day? https://www.statnews.com/2019/01/31/crispr-babies-michael-deem-rice-he-jiankui/ The reason it was illegal is that altering the genes of germline cells, which are embryos, sperm or eggs, will have the effect of altering the genes of the future children and grandchildren and so on and therefore is seen as too risky. This risk is not present in altering cells that have already divided, which are called somatic cells. He was actually sentenced to 3 years in prison for what he did.² Although his intentions seemed good, he did not follow the law. The children developed normally and have been born, but we will have to wait to see what the long term effects of his experiment will be.

The now infamous Chinese scientist created a sensation when he announced the birth of twin girls, whose genes had been altered using CRISPR technology, before an international conference in Hong Kong last November. He received intense criticism for violating scientific and ethical norms against starting a pregnancy with genetically modified human embryos, and Nature quickly decided not to proceed with peer review of the paper.

https://www.statnews.com/2019/01/31/crispr-babies-michael-deem-rice-he-jiankui/

In November 2018, He announced that he had modified a key gene in a number of human embryos in a way thought to confer resistance to HIV. The modification might be passed on to the descendants of children born with it. He recruited couples in which the father was infected with HIV and the mother was not. In a talk at the International Summit on Human Genome Editing in Hong Kong, China, He said he wanted to spare the babies the possibility of becoming infected with HIV later in life. The technique could be used to reduce the HIV/AIDS disease burden in much of Africa, he argued, where those infected often face severe discrimination.

https://www.sciencemag.org/news/2019/12/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail

Current Gene therapy Research on Humans

Research is currently being conducted with gene-editing therapy on humans and the results have been very encouraging. Correcting genetic errors is no longer a dream of the future. It is being used now such as in this experiment on restoring vision to blind people with a genetic disease. https://www.npr.org/sections/health-shots/2021/05/10/993656603/blind-patients-hope-landmark-gene-editing-experiment-will-restore-their-vision

“Instead, doctors made three small incisions in Kalberer’s right eye and in Knight’s left eye so they could infuse billions of copies of a harmless virus. Each virus had been engineered to carry genetic instructions to manufacture the CRISPR gene-editor inside their retinas.”

And in this experiment with sickle cell disease. https://consumer.healthday.com/12-5-could-gene-therapy-or-crispr-cure-sickle-cell-disease-2649124930.html Treatment for sickle cell with stem cells in one of the studies in the previous article was still difficult due to requiring bone marrow and chemotherapy to eliminate an immune reaction. But in the latest experiment here, https://news.berkeley.edu/2021/03/30/fda-approves-first-test-of-crispr-to-correct-genetic-defect-causing-sickle-cell-disease/ they are doing it an easier way, correcting the genes inside the body instead of in a lab. This article says that the research will take four years.

Investment in Gene Therapy companies is popular

Here is another study . https://graphitebio.com/graphite-bio-receives-ind-clearance-to-initiate-clinical-trial-for-next-generation-gene-editing-therapy-gph101-in-sickle-cell-disease/ From their own website we find this article describing the excitement and investments going into this new therapy. https://graphitebio.com/graphite-bio-secures-150-million-series-b-financing-to-advance-pipeline-of-next-generation-gene-editing-therapies/

And look at this very recent FDA approval for multiple myeloma using gene therapy. The article states that other methods of treatment must be attempted first. https://investor.bluebirdbio.com/news-releases/news-release-details/us-food-and-drug-administration-approves-bristol-myers-squibbs

I could give many more links describing the rush to get this to market. It was only two years ago that this article was written and some of these questions have been largely resolved. https://www.statnews.com/2019/02/01/crispr-cas9-commercialization-delivery-manufacturing/ The currently being used (experimentally) Covid vaccines are using the LNP method of delivery that is mentioned in the quote below.

Lipid nanoparticles are the system of choice for delivering CRISPR-Cas9 therapies to the liver because the liver is designed to filter particles that enter the bloodstream. In practice, the liver takes up lipid nanoparticles and delivers their CRISPR-Cas9 components to the nuclei of liver cells, where the payload does its work. More research is needed to find lipid nanoparticles that can target different tissues in the body while delivering their payloads safely and effectively into cells.

https://www.statnews.com/2019/02/01/crispr-cas9-commercialization-delivery-manufacturing/

The Future of Gene Therapy looks Bright

Based on the success of working out delivery methods, the approval of human trials, the millions being invested in gene therapy companies, and the use of this technology in the COVID vaccines, I think it is safe to say that it is only a matter of time before the current medical industry experiences a major disruption , even if they resist. Lobbyists have their work cut out for them. I’m sure the back door deals for lawmakers will be lucrative.

Switching from needing lifelong prescription drugs, therapy, doctor visits and surgery to being CURED by one treatment of gene therapy is hard to imagine, but seems very possible. (Click that last link to read multiple articles about gene therapy research.) Exciting times we live in!

I believe that we may still be 5 or more years away from widespread commercial use of gene therapy. But as you can see, companies are working feverishly to be the one that gets the gold. There will still be a need for conventional medical treatments for non-genetic diseases and surgery for accidents and prescriptions for pain and other human conditions, at least until some figures out how to cure those with nanites. 😉

I will save my thoughts on the question of curing my daughter’s genetic brain malformation for another post when we have more data on whether that is a possibility. https://penntoday.upenn.edu/news/getting-gene-therapy-brain Until then I am thankful for her seizure medications and gastrostomy and oxygen tanks and antibiotics and respiratory therapies and all the things that help her to stay alive and healthy.

Comments and opinions are welcome! This is a favorite topic of mine and I hope to continue learning and updating my blog as things progress.

References:

1. https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.1997.tb52165.x
2. https://www.sciencemag.org/news/2019/12/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail