Gene editing: a new legal frontier (2023)

Gene editing: a new legal frontier

professora Imogen Goold

April 17, 2023

Prohibited

Today is the third and final talk in my series for this year.

I'm going to talk about a new gene editing technology that gives us the ability to alter our DNA - remove, add and replace parts of our genetic code.

I will focus onmangene editing, but there are many other uses beyond that.

Let me start with a brief explanation ofcompanywe mean by "gene editing", although I'll avoid making it too scientific!

Next, I want to describe the range of applications to which we can apply this technology:

• what are we doing now
• What can we do in the future.

From there, I want to explore some of the benefits of technology and some of the potential impacts that could hold us back.

As usual, I will try to guide you through the issues and get you thinking, rather than trying to convince you to take a specific position.

I will also intervene in explaining the response of regulatory systems, both national and international.

What is Gene Editing?

Gene editing has developed rapidly over the last 10 to 15 years. When people talk about "new gene editing" technology, they mean newly developed technologies that are much more accurate (and therefore have much more potential).

Gene or genome editing technology means a method that allows you to make changes to someone's DNA.

Altering someone's DNA can:

• Change their characteristics where caused by genes (which is pretty much everything, combined with things that happen to us, like what we eat, what we're exposed to, what we do with our bodies, etc.)
• This can include:
  • Eye color
• But our DNA also affects things like how likely we are to get sick, so editing our DNA can
  • reducerisk of developing the disease
    • For example, a disease in which our geneticspredisposeus for it, but that doesn't necessarily mean we're going to get it
  • Removerour disease risk
    • For example, if we could remove all genetic factors in the disease
      • It's easier with diseases caused by just one gene mutation

We've had the ability to edit the genome for decades, but it's not very accurate.

New gene editing tools

Over the past twenty years, new tools have been developed that allow scientists to "cut" DNA sequences at a specific location and then remove the DNA, add or replace some.

They cut the DNA sequence using an enzyme known as "modified nuclease".

A nuclease is a type of enzyme that can break the bonds that connect DNA.

Then when they are designed, we can target them to cut specific loops. These nucleases act like "molecular scissors" and cut the two strands of DNA.

There are many types of nucleases used for gene editing, and the number is increasing:

• meganucleases
• ZFN
  • Means "zinc finger nucleases"
• TALEN
  • Stands for "transcriptional activator-type effector nucleases"

For decades, we managed to introduce new genetic material into organisms, but with little precision.

These new technologies are exciting and important because of them.precision.

• It can focus on very specific sequences
• Don't risk losing the sequence we want to achieve

The big breakthrough that you might have heard about, which is one of those technologies, is CRISPR-Cas9

What is CRISPR-Cas9?

• CRISPR stands for "Clustered Regularly Spaced Short Palindromic Repeats"
• This was groundbreaking and important because it made DNA editing much easier.
  • It's faster
  • It is cheaper
  • It is more accurate.[1]

What is very important is that it allows genome editingLive– that is, inside the body – cheaply and accurately.

This is a huge improvement over previous genome editing tools because it is highly selective and efficient.

The CRISPR system is based on a natural bacterial genome editing system.

CRISPR elements can be found in many bacteria. Bacteria use them to find and destroy pathogens. Specifically, it destroysnucleic acidsof these pathogens (that is, fragments of genetic material) when the pathogens attack a bacterium.

For example, the bacterium Streptococcus uses its CRISPR system to identify and cut the DNA of viruses, destroying them.

For this, the CRISPR system identifies a specific part of the pathogen's DNA, which will then be targeted. It does this using gRNA or "driver RNA" - small pieces of RNA that match and bind to the part of the pathogen's DNA that will be attacked.

Once the gRNA binds to the DNA, it binds to CRISPR-related nuclease (Cas), which cuts the DNA at the site essentially marked by the gRNA.

So the nuclease (Cas9) cuts the DNA where the gRNA tells it to. It's like a genetic template with molecular scissors.

The most important thing is what we can implementsyntheticgRNA – thanks to this we canto choosethe part of the DNA to which the nuclease will bind and thus determine where the cuts will be made.

Scientists had known about CRISPR for some time, but the big leap forward was the discovery of Cas9 nuclease. Unlike TALEN and ZFN, Cas9 nucleases can be assigned different targets by changing the guide RNA (instead of editing the protein itself).

We can use the CRISPR system to:

• Knock out sections of DNA
  • cut to part
• Hit sections of DNA
  • Cut the DNA and insert more
• Activation and inhibition
  • CRISPR can also be used todeliverother proteins to a specific location on the DNA and, instead of removing a section,activelubricantinhibit activationthis sequence
• Screening
  • It can also be used as a screening tool for many potential candidate genes (for research purposes)

It's very simple - I'm not a scientist!

The CRISPR-Cas9 system was discovered decades ago, but it wasn't until the early 2010s that it was developed into a tool that could be used for gene editing. Two of the main scientists involved - Emmanuelle Charpentier and Jennfer Doudna - were awarded the 2020 Nobel Prize in Chemistry.

What can be edited?

WhichDNA editing is also important, and the ethical issues that arise vary from one to another.companywe edit,WhereEUW Kim.

To break it down:

Is there a difference between editing DNA insomaticcells (i.e. most cells in the body) andgermlinecells (i.e. DNA that is passed on during reproduction - eggs, sperm, fertilized eggs).

There are two important differences here:

1. Any change in a germ cell that is fertilized (or that develops into an embryo) will affectallcell of this organism
   • All will bear the changes
   • While somatic cell changes only affect edited cells
     • No other cells are affected
2. These changes will be passed on to any children that person has.
   • However, somatic cell changes are not passed on to future generations.

So another important distinction is when editing cells in a fileembryothat has not yet become a full legal entity, and editing them into aperson

• Maybe we're just editing cellsin vitrowithout intending to enter a person or become a person
  • pure research
  • Something we would do in disease modeling in research
• If the person is an adult, consent is required
• If the person is a child, we would have to decide if it is in their best interest.
• This also applies to embryos, but the issues are more complex, as we will see.
  • But if they are not yet legal entities, the legal approach may differ.
  • There are complicated questions about whether we should treat an embryo like a person.
    • It matters because or we aremoney exchangeperson or we aredoinganother person

And it's for the latter type of change that gene editing made headlines in 2019, when He Jiankui announced that he had edited the genes of two embryos.

Jiankui edited the genomes of two embryos in an attempt to make them genetically immune to HIV using CRISPER-Cas9.

Jiankui's work received approval from the scientific community and philosophers when it was made public. He was fired from his position and ended up arrested by Chinese authorities.

These developments provoked a national and international response, notably the establishment of the World Health Organization Expert Advisory Committee for the Development of Global Standards for the Governance and Oversight of Human Genome Editing, which undertook the task of examining the "scientific, ethical, social, and legal challenges related to human genome editing (somatic and germline)” in December 2018.

There have also been a number of legal responses, which we'll get to, but as an example, the Chinese government has criminalized gene editing practices.

Before delving into this complex set of topics, let's stop and examine the wide range of applications for human gene editing.

I will try to explain what we can doNowwhich ishookbe possible in the future.

The range of applications includes basic research, applied biotechnology and biomedical research, treatment and enhancement.

What can he do now?

Research app to understand gene function

Scientists can modify genes in a highly targeted manner using genome-editing tools (such as ZFN, TALEN, and CRISPR/Cas9).

• It gives them a very powerful method of analyzing gene function.
• For example, they might change a single gene in an animal and then study it to see what that gene does (see what happens when it's "knocked out").
  • Example: The Burgess Lab in the United States is researching deafness, focusing on zebrafish genes that are involved in hearing. Knocks out different genes and then studies function[2]

disease modeling

Because gene editing allows scientists to precisely manipulate the behavior and function of cells.

• This allows them to create very accurate genetically modified animals, and by studying them they can understand how different diseases work.
  • One example is the development of models to study cardiovascular diseases.
    • CVD is usually associated with a single genetic mutation, so it is a good target for this type of research.
    • Researchers are creating models that make it possible to analyze the pathogenic genes involved in the cause of CVD
    • They can then use these to test how well gene therapy can affect gene expression and function, which could allow them to develop a treatment [3].
• This type of research can then be used to develop much more effective treatments and treatments.
  • One example is the development of tumor-targeted T cells [4] that could be used to treat cancer.

Test therapies and medications

As such, gene editing could allow scientists to create models for drug testing or even test animals that have been genetically modified to create an animal model for drug testing or treatment.

• One example is the creation of mice designed to test gene therapy for diabetes.

create treatments

The goal of this research is to develop gene therapies that can be used to remove disease-causing gene sequences and replace them with non-disease-causing sequences.

• One example is therapies that attempt to alter the sequences of the genes that cause Alzheimer's disease.

A successful example is the treatment of leukemia in children

• Layla Richards - was successfully treated with genetically engineered immune cells that eliminated her leukemia - the cells were engineered to be able to destroy cancer cells
  • Great Ormond Street Treaty
• Other children treated since then

A clinical trial uses CRISPR to correct a genetic mutation in a patient's blood stem cells, which, when infused back into the body, produce healthy blood cells.

This would include treatment of:

• Raki
• genetic disorders
  • neurodegenerative disorders
• viral diseases
  • A recent success in relation to viral diseases is the treatment of HIV.
  • Researchers created a genome-editing therapy for HIV that modified infection-related genes to create HIV-resistant CD4+ T cells, which were then injected into patients to help them fight HIV.[5]

What might be able to do?

cure of cancer

It could eventually allow doctors to remove malignant mutations and replace them with normal DNA sequences. [6]

It can produce immunotherapeutics that use genetically modified immune cells to fight cancer.

What ethical issues does this raise?

disease treatment

Reinforcement

controversies

• Embryo editing
  • open future
  • Agreement
    • By parents?
  • The limits of what can be changed
    • Non-disease-related features?
  • Impact on Future Generations - Germinal Editions
  • Health inequalities
  • Impact on parent/child relationship?

Health inequalities

human empowerment

Now that we have the ability to edit our genome, it means that we can not only cure diseases, but also make corrections thatincreasenas.

What does it mean to improve?

• Back to normal operation?
• Bring everyone to a certain level?
• Increase everyone's performance at the same rate?
• Give capacity above the norm?

What would we improve?

• Just a few features?
• All features?
• Would there be any restrictions?
• Physicist
  • body changes
  • Ability to stay awake?
• Cognitive
  • brain capacity
  • Battling with fatigue
• Emotional
  • Empathy

Arguments against the improvement

• problematic consequences
• unknown damage
  • Germinal change?
  • I give life to the status quo
  • Example: increase average IQ
• Signaling damage to people with disabilities
• Reduction of human variability
• Expecting a raise  pressure to do so
• Stratification

Let's look at some of them.

Impact on parent/child relationships

One concern with editing children (and that would be embryos) to improve them is that it would negatively affect the parent-child relationship.

Michael Sandel (again) argues there's value in thisNOto design our children.

“In a social world that values ​​dominance and control, parenting is humbling. The fact that we care a lot about our children, but we can't choose the one we want, teaches parents to be open to what is not asked. This openness is an attitude worthy of affirmation, not only in families, but also in the rest of the world. It invites us to endure the unexpected, to live in dissonance, to resist the urge to control."

He argued that we should appreciate children "as they come" - accepting love - implications for parental relationships

• It enriches this relationship by being one that is not designed

Arguments for reinforcement

Having gone over the cons, let's look at some of the reasons whyI couldwe want to improve our genetics

• Improve the life quality
• Give people experiences they might not have
• Reduce the risk of getting hurt
  • E.g. at work
• increase the capacity
  • in the workplace
  • In social life (e.g. empathy)

Some philosophers have pointed out some important points that we should consider when considering whether it is appropriate to improve.

Guy Kahane and Julian Savulescu point out that:

• Some objections to updates are based on bugs - usually due to focus on extreme updating (which is unlikely)
  • improvements generally modulate naturally existing substances and processes  impact does not lead to radical changes and distortions
  • Upgrades mostly work on natural processes/substances (which are probably not at optimal levels (due to blind processes)
  • Human variability within the normal range means that many people are not at their optimal level.

Therefore, when we want to think about improvements, we need to think carefully about whether the benefits are worth the risks or the disadvantages.

In doing so, we must also consider what we can and cannot control.

This is noticed by Kahane and Savulesu.

• A common objection is that biomedical interventions have both positive and negative effects.
  •  This is not an argument against improvements, but rather an argument for more accurate improvementsFine tune- dostrojoniareinforcement

They're right - we shouldn't see this as a simplistic "maybe right, might be wrong" problem.

• We need to take a closer look at what we can control and the implications of the changes we are making.
• Consider your costs carefully and carefully
• Don't make hasty changes

However, Michael Sandel expresses concern about the very idea of ​​improvement and its impact on our sense of self:

“The deeper danger is that they represent a kind of overexcitement – ​​a Promethean drive to transform nature, including human nature, to serve our purposes and satisfy our desires. The problem is not the engine search, but the domain search."

But as Savulescu and Kahane point out, the natural level is unnatural at all.

• • That's why we've already moved it - it's open to new moves (or the move isn't inherently problematic)

Also, just because something is natural doesn't mean it's necessarily good.

• Apparently we don't think so, otherwise we wouldn't be curing diseases.
  • We would always accept our fate and be okay with it
  • In fact, we do the exact opposite.

Sandel may be right, but is it so powerful that we should reject a way to genuinely improve our lives? And those others?

Mike Parker reflects some of Sandel's thoughts as he speaks

“The two aspects of our lives are intertwined and, indeed, it is this interweaving and our struggle with it that makes us who we are and constitutes, in the play of light and dark, much of what is valuable and meaningful in human existence. "

Savulescu and Kahane respondem:

“Some people have a lot of light and no darkness; others are dark. The problem is whether we should accept what nature gives us or make a choice.”

The important thing is the considerationcompanywe want to improve EUBecauseEUwhat might be the costs.

Germline genome editing

Following the release of He Jiankui's work, there were public calls for a moratorium on the implantation of gene-edited embryos.

For example, Feng Zhang of the Broad Institute of Harvard and MIT made such a connection during a public event on "Changing the Human Genome" at the Harvard Kennedy School.

He explained the need for this as follows:

“A moratorium is a break. Society needs to figure out if we all want to do this, if it's good for society, and that takes time. If we do that, we first need to have guidelines in place so that the people doing the work can act responsibly, with proper oversight and quality control."[7]

Germline genome editing posesspecificproblems, because any changes we make in this way will remain in the population

• they will be transferred

They basically become a permanent part of our collective gene pool.

They will influence the type of people that will be born in the future.

And once that happens, it can be very difficult to reverse.

Therefore, unlike changes made in somatic cells, germline changes are likely to affect all of us as a community (national and global).

Therefore, Zhang rightly asks that we reflect and think about this together.

So how should we think about this particular question?

We might think "it's better not to risk it, as unexpected malfunctions may arise that we won't be able to fix".

Or we may think that "the potential benefits are worth the risk!"

How can we determine what to do, especially when the question is necessarily so speculative:

• We see some benefits, but not all
• We can imagine some failures, but there can be many unpredictable and unpredictable
• But it can also be about benefits.

There are also considerations such as:

• Will the benefits be shared by all?
  • This can take a long time and therefore lead to irregularities initially
    • If technology is expensive, it is likely to increase existing inequalities
• What do we do with very serious defects?
  • Who should shoulder the burden?
  • If the government decides to allow it, shouldn't it facilitate redress?
• How are we going to control it?
  • What if one country does it and another doesn't?

There are a very large number of questions.

Removal of mutations associated with disease or disability

One of the things that can be achieved by altering the germline isremovergenetic mutations that cause disease or disability

• If enough is done, they will be eliminated from the population.
• or at least reduced
• Families will no longer pass them on to their children
• Carriers would not bear the burden of worrying about reproduction

For conditions that are life limiting or too difficult to manage or deal with, editing them from the population might be welcome.

• And why don't we do it formiscarriagelubricantembryo selectionwe avoid many of the moral problems these methods pose
  • We really choose againstillnessnot a person with a disease

This approach assumes that illness and disability aredamage

It focuses on the disadvantages of illness and disability. We can easily imagine what it is about

• painful conditions
• Limiting life conditions
• Conditions Related to Behavior Restrictions

For things we classify as illnesses, it can be reasonable and simple.

• Predisposition to cardiovascular disease
• Huntington's disease
• early dementia

We could list hundreds, thousands. And if gene editing can prevent suffering from these diseases, it seems like a good thing to achieve.

But it gets more confusing when we start to consider things we normally think of as disabilities rather than illnesses.

We often understand disability as damage.

Here is Janet Radcliffe Richards who has this view (referring to embryo selection)

“It is hard to doubt that most people must see disability as a negative value. No matter how strong their total commitment to any or all people with disabilities in existence, however, they are willing to do everything in their power to give them the best life possible, and even if it doesn't change their current child or spouse or partner with a disability. -worker for every able-bodied person in the world, the fact remains that most people would believe that they would be better off if their disabled friends, relatives and employees were not disabled.

But not everyone shares this view, and it's not easy to say that anyone who has something called a "disability" wouldn't necessarily prefer not to have it (and in the case of germline editing, never have it and others don't have it).

Eliminating disability as discrimination

Nor is it easy to say that we should simply eliminate it from the gene pool.

• Is it correct to eliminate this condition?
  • Where the condition is "incapacity" or "difference", it would be lost to the world
    • Down syndrome
    • Autism
  • Perhaps our world is less rich and diverse?
  • What message are we sending to people living with this disease?
    • For some, we can say that the condition is one that should not be valued, but rather avoided.
    • For many people with disabilities, especially those with Down syndrome, the law's position on the elimination of disability has caused significant harm and suffering.
    • A similar reaction was met with the announcement of more research into the genetic basis of autism.

This slide is from the "Don't Screen Us Out" campaign againsttestingfor Down syndrome during pregnancy (to terminate the pregnancy), but the topic is the same

• Heidi Crowther, as seen there, argued in her court filing that the approach to disability screening under the Abortion Act was discriminatory.
  • Disability as a reason for termination
• We could make the same argument about gene editing

Social Model of Disability

And before we consider removing differences and deficiencies, we would at least note whether they are deficiencies simply because we have not considered their differences.

as Mike Oliver argues here, it's not really a disability, but rather society's failure to adjust to a variety of different people.

"It is not individual limitations of any kind that are causing the problem, but society's inability to provide adequate services and adequately ensure [that] the needs of people with disabilities are fully considered in its social organization."

• ADHD
• Autism
• This is based on the social model of disability

Disability as an asset

And more importantly, before we start thinking that we should eliminate certain things, we might consider whether some of these things we call "disability" or "disease" are really conditions that people can suffer from.valor.

• They can value them individually
• We, as a society, can value the presence of people with these genetic characteristics

Greta Thunberg describes her autism as her superpower because of the clarity and focus it gives her.

• Her black and white thinking made her not ignore the truth she saw around her and act accordingly.

Here's Charles Foster on his son's dyslexia:

“I can't say that his dyslexia is pathological. In the ancient and deeply inaccurate language of brain lateralization, he is a right-brain person. He sees holistically; he is a person with an overview; he intuitively; combines extremely distant and different concepts. …

When I see a tree, it is dressed in other people's written descriptions of trees. The tree itself is more or less invisible. But not for Tom. There is nothing substitute in her world. He sees and seems to see a lot more real wood than I do. It is not for him the clear and normative relationship between word and reality that defines and suffocates me.”[8]

This doesn't mean that we shouldn't choose to remove some things, but simply that we need to think carefully about what we're editing and why we're doing it if we're going to permanently alter our collective gene pool.

Application

Gene-editing technology holds great promise for helping to eradicate disease. But navigating the ethical issues that come with it will be tricky. We must tread carefully into the future and consider all aspects of technology's impact rather than acting rashly at our own expense.

© Professor Goold 2023 See More

[1] https://www.genome.gov/about-genomics/policy-issues/what-is-Genome-Editing

[2] https://www.genome.gov/about-genomics/policy-issues/what-is- Genome-Editing; https://www.genome.gov/staff/Shawn-Burgess-PhD

[3] OPEN REVIEW ARTICLE Applications of genome-editing technology in targeted therapy of human diseases: mechanisms, advances and perspectives Hongyi Li1, Yang Yang1, Weiqi Hong2, Mengyuan Huang2, Min Wu3 and Xia Zhao1

[4] OPEN REVIEW ARTICLE Applications of genome-editing technology in targeted therapy of human diseases: mechanisms, advances and perspectives Hongyi Li1, Yang Yang1, Weiqi Hong2, Mengyuan Huang2, Min Wu3 and Xia Zhao1

[5] OPEN REVIEW ARTICLE Applications of genome editing technologies in targeted therapy of human diseases: mechanisms, advances and perspectives Hongyi Li1, Yang Yang1, Weiqi Hong2, Mengyuan Huang2, Min Wu3 and Xia Zhao1

[6] OPEN REVIEW ARTICLE Applications of genome-editing technology in targeted therapy of human diseases: mechanisms, advances and perspectives Hongyi Li1, Yang Yang1, Weiqi Hong2, Mengyuan Huang2, Min Wu3 and Xia Zhao1

[7] https://news.harvard.edu/gazette/story/2019/01/perspectives-on-gene-editing/

[8] https://www.charlesfoster.co.uk/?p=590; https://www.charlesfoster.co.uk/?p=690