Takeaways:

• A strong majority of people favor gene-editing for treatment over enhancement
• In general, the highly religious, politically conservative, women, and less educated support gene-editing less than their counterparts.
• There is some evidence that people begin to support gene-editing more once they learn more about it.

Canned Transparency (see footnotes)1 :

• How trustworthy are you?2
• How/why is this post important?[^why_is_this_important]
• How much external review has this post undergone?4
• What is your epistemic confidence?5
• What types of support does this post’s claims use?6
• What shortcuts did you take?7
• What are this post’s major inadequacies?8
• How did you update your beliefs after writing this?[]
• How should I update my beliefs after reading this?[]
• Did you contribute anything notable by creating post??9

Post Notes (see footnotes)10

Acknowledgements: Thank you Nuño Sempere, Misha Yagudin, and the Long Term Future Fund for funding this essay. Thank you to Metaculus for existing and hosting this essay (thank you Christian for approving this). Thank you Ryan Beck (Metaculus, LW, EAF), alwaysrinse (Metaculus), Nuño Sempere (Metaculus, LW, EAF), Pablo Stafforini (Metaculus, EAF), and Ege Erdil (Metaculus, LW) for reading this and providing feedback. For anyone else who reads this, thank you, and if you believe that something I’ve said is incorrect, poorly disseminated, or otherwise inadequate, please reach out - I will likely edit the essay to include some form of update.

Also Posted Here: Metaculus, LW, EAF

## Overview

Humans generally seek states of contentedness, and want to feel well, to live long and healthily, and to experience fulfillment. The realization of these things often requires many conditions to be met, including, but not limited to, freedom from certain physical and psychological afflictions, supportive social environments, and healthy lifestyle practices.

The frequency and intensity of

With respect to these aspirations, which guide much of human behavior, and to the activities of human civilization more broadly, gene and genome editing is a practice with transformative potential.

There are over 4600 genes in humans with phenotype-causing mutations; these genes account for >6000 single gene disorders11, ~700 instances of increased suseptibility to complex diseases or infections, and ~250 somatic cell genetic diseases12.

Among these maladies are genetic disorders such as Sickle Cell Disease, which results in a person’s blood cells being mishapen, dying early, and clogging blood vessels, and can cause the person “pain and other serious problems such infection, acute chest syndrome and stroke”13. Another genetic disorder is Phenylketonuria (PKU), which affects roughly 1 in 15,000 US children, and can lead to cognitive and behavioral problems and can also stunt development, among other things, if left untreated.14

Gene and genome editing could one day enable people to be free from these and other disorders and diseases by targeting and ameloriating15 the affected gene(s)16. To me and, as we will see, a fair number of other people, a future devoid of the suffering induced from genetic disorders seems like a GOOD thing.

In addition, gene and genome editing, if further developed, could safely permit humans to enhance themselves17 - robuster immune systems18; reduced suspecibility to infections and disease19; reduced aggression20; reduced risk of addiction21; reduced depression22 or anxiety23; higher life satisfaction24; longer lifespans25; greater physical attractiveness26, endurance27, strength28, and dexerity29; increased cognitive capabilities30 or creativity31; increased self-control32; or stronger ethical inclinations33 - among plausibly many other things34.

Given present uncertainties35 with the genetic nature of these traits, it’s difficult to predict how well or much gene or genome editing technology will be able to enhance them. There are also many ethical considerations that need to be taken in account36 in this regard.

This essay examines one factor - people’s attitudes towards human gene-editing - that guides how and, in some instances, whether certain gene or genome editing technologies are applied to humans. I investigate people’s attitudes towards human gene-editing by reviewing research which includes surveys or sentiment analyses on this topic.

Before discussing my findings on people’s attitudes towards human gene-editing, I distill the present landscape of ethical discourse and research in human gene or genome editing. I recommend treating this section as a primer to gene-editing - a fraction of “what’s out there” - and not as an authoritative resource on the topic.

After discussing people’s attitudes towards human gene-editing, I try to unpack what factors might best explain these attitudes. My explanations and considerations for what drives people’s beliefs concerning human gene-editiing should be received with skepticism, as I believe my claims here are especially speculative. Next, I look at how people’s attitudes towards human gene-editing guides the governance, rate of development, and usage of gene and genome editing technologies.

Finally, I consider some questions that interest me and that I think are important to timelines and outcomes involving human gene-editing. From the list of questions I generate, I select those whose outcomes I think are somewhat dependent on changes in or those that are directly about people’s attitudes towards human gene-editing to write up on Metaculus. I then predict on these questions, and outline my rationale for my forecasts.

This is essay was written primarily with the goal of determining what people think about human gene-editing and of generating forecasting questions on this topic. All in all, I think this essay reasonably accomplishes these goals.

I took some shortcuts in writing this essay.

• I haven’t extensively analyzed all or most of my referenced works, which means that I have treated them as though they are likely true, even though I don’t suspect this is the case (i.e., I’m not sure how accurate my references are, how evidenced they are, and what their main issues are). Two examples of this: I haven’t taken into account the problems with twin studies37 when examining which human traits might be able to be enhanced, and I haven’t taken into account the problems that occur with self-reporting38 when looking at surveys of people’s attitudes on human gene-editing.
• I did not write down many of the search terms I used for finding my evidence and the resources I used in this essay. This makes it more difficult for others to find resources to invalidate or validate my evidence and claims. I apologize for this.
• I have not considered the “economics” of human gene-editing, which is something that might be an even more detailed indicator, in certain instances, of how people will respond to human gene-editing. Economic indicators - stocks, bets, funding, etc… - for companies and organizations that investors believe might make widespread human gene-editing possible were not considered in this essay, but I imagine that they might add substantial support to some of this essay’s findings if I had considered them.

## Prospects and Perils

This section tries to offer a fractional look at the questions:

• What is gene-editing, broadly speaking?
• What is the state of research on human gene-editing?
• What benefits might human gene-editing offer to humanity?
• What concerns for humanity are there with human gene-editing?

### Gene-Editing, -Therapy, -Engineering, -Modification,…?

I expect that most people reading this (LW, EAF, Metaculus users) recognize the following terms - genetic engineering, gene-editing, genetic modification, gene therapy, genome editing - but might not know the nuances between them.

Thus far, I have not actually found a resource that adequately differenties these terms, but in reading about them, I’ve come across many instances where they’re used interchangeably39, which seems somewhat intuitve to me.

Nevertheless, gene-editing, genome editing, and gene therapy refer to slightly different things, and are all examples of genetic engineering, alteration, and modification, which are terms I feel more comfortable using interchangeably.

Here I list several definitions I’ve come across for genetic engineering, genetic modification, gene therapy, gene-editing, and genome editing. Note that this essay concerns human gene-editing, which includes both gene therapy and genome editing.

Genetic Engineering

Genetic engineering, also called recombinant DNA technology, involves the group of techniques used to cut up and join together genetic material, especially DNA from different biological species, and to introduce the resulting hybrid DNA into an organism in order to form new combinations of heritable genetic material.

[It’s in Your DNA: From Discovery to Structure, Function and Role in Evolution, Cancer and Aging.40]

Genetic engineering is defined as the direct manipulation of an organism’s genes including heritable and nonheritable recombinant DNA constructs.

Genetic engineering is the use of molecular biology technology to modify DNA sequence(s) in genomes, using a variety of approaches. For example, homologous recombination can be used to target specific sequences in mouse embryonic stem (ES) cell genomes or other cultured cells, but it is cumbersome, poorly efficient, and relies on drug positive/negative selection in cell culture for success. Other routinely applied methods include random integration of DNA after direct transfection (microinjection), transposon-mediated DNA insertion, or DNA insertion mediated by viral vectors for the production of transgenic mice and rats. Random integration of DNA occurs more frequently than homologous recombination, but has numerous drawbacks, despite its efficiency. The most elegant and effective method is technology based on guided endonucleases, because these can target specific DNA sequences. Since the advent of clustered regularly interspaced short palindromic repeats or CRISPR/Cas9 technology, endonuclease-mediated gene targeting has become the most widely applied method to engineer genomes, supplanting the use of zinc finger nucleases, transcription activator-like effector nucleases, and meganucleases.

[Principles of Genetic Engineering41]

Genetic Modification

Genetically modified organisms (GMOs) are those whose genetic material has been altered via genetic engineering such as molecular cloning, recombinant DNA technology, gene delivery in which the three Ts (transformation, transfection, and transduction) are used to introduce foreign DNA, and gene editing.
…the genetic modification or manipulation of an organism today is brought about by using different bioengineering techniques that alter the genome of an organism by introducing or transferring fragments of DNA from other species (transgene) to create a new organism (a GMO) that expresses the desired features.

[Dictionary of Global Bioethics42]

Gene editing

A technique that allows researchers to alter the DNA of cells or organisms to insert, delete, or modify a gene or gene sequences to silence, enhance, or otherwise change the gene’s characteristics (NASEM, 2016a, p. 182).

[Human Genome Editing: Science, Ethics, and Governance43]

Gene Therapy

…a set of technologies aimed at correcting genes that have been injured (mutations) and cause new diseases as a consequence. Gene therapy involves introducing DNA containing a functioning gene (created by genetically modified viruses) into a patient to correct the effects of a disease-causing mutation. There are two basic types of gene therapy depending on the cells targeted or treated: somatic and germline therapy. Most cells of the human body are somatic cells and transferring DNA to such (differentiated, non-reproductive) cells will just produce effects in this patient without being transmitted to the patient’s off- spring. Cells of the germline are gamete cells (undifferentiated, reproductive), eggs, and sperm and any change in them will be transmitted to the patient’s children.

[Dictionary of Global Bioethics42]

Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use 1.

Gene therapy is a technique that modifies a person’s genes to treat or cure disease. Gene therapies can work by several mechanisms:

• Replacing a disease-causing gene with a healthy copy of the gene
• Inactivating a disease-causing gene that is not functioning properly
• Introducing a new or modified gene into the body to help treat a disease

Gene therapy products are being studied to treat diseases including cancer, genetic diseases, and infectious diseases.

There are a variety of types of gene therapy products, including:

• Plasmid DNA: Circular DNA molecules can be genetically engineered to carry therapeutic genes into human cells.
• Viral vectors: Viruses have a natural ability to deliver genetic material into cells, and therefore some gene therapy products are derived from viruses. Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells.
• Bacterial vectors: Bacteria can be modified to prevent them from causing infectious disease and then used as vectors (vehicles) to carry therapeutic genes into human tissues.
• Human gene editing technology: The goals of gene editing are to disrupt harmful genes or to repair mutated genes.
• Patient-derived cellular gene therapy products: Cells are removed from the patient, genetically modified (often using a viral vector) and then returned to the patient.

Genome editing

The process by which the genome sequence is changed through the intervention of a DNA break or other DNA modification.

[Human Genome Editing: Science, Ethics, and Governance43]

Genome editing technologies enable scientists to make changes to DNA, leading to changes in physical traits, like eye color, and disease risk. Scientists use different technologies to do this. These technologies act like scissors, cutting the DNA at a specific spot. Then scientists can remove, add, or replace the DNA where it was cut.

Genome editing is a powerful new tool for making precise additions, deletions, and alterations to the genome an organism’s complete set of genetic material. The development of new approaches—involving the use of meganucleases; zinc finger nucleases (ZFNs); transcription activator-like effector nucleases (TALENs); and, most recently, the CRISPR/Cas9 system—has made editing of the genome much more precise, efficient, flexible, and less expensive relative to previous strategies. With these advances has come an explosion of interest in the possible applications of genome editing, both in conducting fundamental research and potentially in promoting human health through the treatment or prevention of disease and disability. The latter possibilities range from restoring normal function in diseased organs by editing somatic cells to preventing genetic diseases in future children and their descendants by editing the human germline.

[Human Genome Editing: Science, Ethics, and Governance43]

Human genome editing has great potential to improve human health and medicine. Human genome editing technologies can be used on somatic cells (non-heritable); germline cells (not for reproduction) and germline cells (for reproduction). Potential benefits of human genome editing include new strategies for diagnosis, treatment and prevention of genetic disorders; new avenues to treat infertility; new ways to promote disease resistance; contribution to vaccine development and enhanced knowledge of human biology. For example, application of somatic human genome editing has already been undertaken, including in vivo editing, to address HIV, sickle-cell disease and transthyretin amyloidosis1. Germline human genome editing contributes to deepen our understanding of the role of specific genes and processes in early human development, physiology and diseases. However, there are important areas of ongoing uncertainty as to potential benefits and risks, and gaps in scientific understanding in such key domains as off target effects and long-term risks.

At the same time, however, somatic, germline and heritable human genome editing raise important and outstanding ethical and social issues. Challenges associated with somatic human genome editing include, for example, rogue clinics, medical travel, as well as the reporting of illegal, unregistered, unethical or unsafe research and other activities including the offer of unproven so-called therapeutic interventions. Heritable human genome editing also gives rise to great concerns as the edit might be passed to subsequent generations. Additional issues include enhancement to improve certain traits, the lack of diversity in collections of human samples and associated data, the need for equity of access to and benefit from human genome editing. There are important differences in the scale of the current challenges posed by somatic, germline and heritable human genome editing.

People usually partition discussions on human gene-editing along the “treatment/therapy vs. enhancement” and “somatic vs. germline” axes. These axes have existed for a long time.

In the 1970s, certain central distinctions were drawn (Juengst, 1997; Walters and Palmer, 1997). First, the distinction between somatic and germline genome modifications was established: somatic enhancements affect only a single individual, but heritable enhancements can be passed down through the generations. Discussions of heritable enhancements included concerns about possible effects on the gene pool and fears of a return to some form of eugenics. Second, a distinction was drawn between treating or preventing disease (therapy) and enhancement. Discussions of enhancement focused on issues such as safety and (especially in competitive environments such as sports) unfair advantage, with the definition of “unfair” highly dependent on context.

[Human Genome Editing: Science, Ethics, and Governance43]

I’ve found that the scope of discussion in the “treatment/therapy vs. enhancement” debate is more subsuming than the “somatic vs. germline” debate, given that both somatic and germline gene-editing are tools for both treatment and enhancement.

A note should be made that “prenatal vs. postnatal” might also be a useful distinction in human gene-editing. There is much discussion on the ethics of pre-natal gene-editing separate from discussion on the ethics and affordances of gene-therapy, which has historically been done postnatally45, and other postnatal gene-editing interventions.

Coverage of pre-natal gene-editing typically centers on the idea of designer babies46 - that parents may one day be able to select their child’s traits, such as eye color or physical attractiveness, and how strongly these traits are expressed.

### Major Milestones and Developments

What is the state of research on human gene-editing?

Let’s take a step back and look at the history of gene-editing47.

• 1953: Discovery of the Double Helix
• 1958: DNA is Made in a Test Tube for the First Time
• 1962: Jellyfish Protein Turns Into a Tool to Observe Invisible Cellular Processes
• 1967: DNA Ligation Links DNA Fragments Together
• 1968: Discovery of Restriction Enzymes
• 1970: Purification of Type II Restriction Enzymes
• 1971: Gene Splicing Experiment Paves the Way for Recombinant DNA (rDNA)
• 1971: Type II Restriction Enzymes Used for Mapping DNA
• 1972: Recombinant DNA (rDNA) is Created
• 1974: National Academy Moratorium on Genetic Engineering Experiments
• 1975: Hybridoma Technology Revolutionizes Diagnostics
• 1981: The First Transgenic Animal
• 1982: First Genetically Engineered Human Drug - Synthetic Insulin
• 1983: The Development of the Polymerase Chain Reaction (PCR)
• 1985: Discovery of Zinc Finger Nuclease (ZFN)
• 1986: First Recombinant Vaccine for Humans is Approved
• 1988: The First Bt Corn Appears in Fields
• 1993: Discovery of the Principles of CRISPR
• 1994: A Tomato Engineered to Stay Ripe is Brought to Market (and bombs)
• 1996: The Cloning of Dolly the Sheep
• 1999: History of Genetic Engineering in Humans is Made when the First Human Chromosome is Sequenced
• 2001: The First Gene-Targeted Drug Therapy is Approved
• 2003: Sale of the Glo-Fish as a Pet for the Home
• 2006: FDA Approval of the First Preventative Cancer Vaccine
• 2006: First Induced Pluripotent Stem Cells (iPSCs)
• 2010: The World’s First Synthetic Life Form
• 2011: Discovery of TALENs
• 2012: Discovery of CRISPR Genome Engineering Tool
• 2013: Showed CRISPR Utility in Eukaryotic Cells
• 2014: Identifying the Possibility of a Gene Drive

In 2015, scientists successfully used somatic gene therapy when a one-year old in the United Kingdom named Layla received a gene editing treatment to help her fight leukemia, a type of cancer. These scientists did not use CRISPR to treat Layla, and instead used another genome editing technology called TALENs. Doctors tried many treatments before this, but none of them seemed to work, so scientists received special permission to treat Layla using gene therapy. This therapy saved Layla’s life. However, treatments like the one that Layla received are still experimental because the scientific community and policymakers still have to address technical barriers and ethical concerns surrounding genome editing.

• 2015: First GMO Salmon Sold in Canadian Markets
• 2015: A Human Embryo is Edited with CRISPR

The first clinical application of CRISPR/Cas9 gene editing was in 2016, when a clinical trial delivered CRISPR gene-edited immune cells to a patient with advanced lung cancer.

• 2017: First CAR T Therapy for Cancer is Approved
• 2018: First Human Trials for CRISPR are Approved

The world was shocked in Nov. 25, 2018 by the revelation that He Jiankui had used clustered regularly interspaced short palindromic repeats (‘CRISPR’) to edit embryos—two of which had, sometime in October, become living babies.

• 2019: Prime Editing Makes Single Stranded Cuts a Possibility
• 2020: Success of Clinical Trials and More

Think about these accomplishments for a moment. In roughly 43 years humanity went from learning about DNA to cloning a sheep! Then, in roughly half that time, humanity altered the genes of a human embryo. That’s phenomenal, and somewhat concerning. In how many years will prenatal gene-editing in humans become commonplace?

Even without understanding the details of these developments, it’s apparent, in my mind, that the science of gene-editing and its application in humans is transitioning rapidly.

The abstract of Hirakawa et al.’s 2020 paper Gene editing and CRISPR in the clinic: current and future perspectives51 can attest to this (likely as many other papers do).

Genome editing technologies, particularly those based on zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR (clustered regularly interspaced short palindromic repeat DNA sequences)/Cas9 are rapidly progressing into clinical trials.

One proxy for verifying this is to observe changes in the frequency of terms such as “gene-editing” or, more interestingly, “human gene-editing” over time. Searching “gene-editing” (with quotations) on Google Scholar (not including citations), we get the following52 for the years in the closed interval [2000, 2021].

Note that the line indexed with (1) refers to the cumulative number of search results, the line indexed with (2) corresponds to the number of results for each year.

If it is true that search term frequency is closely correlated with research activity, then this above graph implies interest and research in gene-editing is growing tremendously. This is not too surprising given the theoretical benefits gene-editing could afford. I was more surprised to see how abruptly results “human gene-editing” grew.

What’s missing from this search is the proportion of these research results that concern the ethics surrounding, the governance of, the technology of, and people’s attitudes towards human gene-editing (i.e., what is the breakdown for different types of research on human gene-editing).

I do not investigate these things in this essay, but would appreciate if anyone can comment on this; my premonition is that most research is technical in nature, with the next largest group being ethics and governance, which in my experience often coincide with each other.

Other than search term frequency, looking at changes in the number of clinical trials involving gene-editing should also be useful.

Though this is taken from a 2 year-old paper, it provides some sense of the changes in registered trials.

The U.S. clinical trials database (clinicaltrials.gov) contains all studies which meet the definition of an ‘applicable clinical trial’ initiated on or after 27 September 2007 or continuing beyond 26 December 2007. In addition to trials required to register, voluntary registration is also accepted; studies conducted outside U.S.A., and those which may meet one of the conditions in the future, often register voluntarily. We searched the U.S. clinical trials database (01/01/2020) for any trial containing at least one of the following terms: CRISPR, Cas9, Cas12, Cas13, ZFN, zinc finger, gene edit, gene modification, and genome edit. Trials that did not use the genome editor as part of the therapeutic intervention were excluded from the analysis; these included trials to create cell lines from patients using Cas9; use of patient cells to develop therapeutic strategies, but where the cells were not used as a therapeutic themselves; CRISPR use for genome sequencing; and surveys of opinions regarding human gene editing. This search identified 41 trials utilizing genome editing agents including ZFNs, TALENs, and CRISPR/Cas9 for therapeutic interventions, no studies utilizing Cas12 or Cas13 have been registered (Table 1).

Gene editing and CRISPR in the clinic: current and future perspectives51

Here is some more information on the genome-editors that are used for gene-editing53:

The results in this passage, taken from Hirakawa et al.’s Table 1 by year (they mention 41 trial results, but there are 50 entities in their Table; I have not resolved why this is the case, but don’t think it matters too much), is in line with my earlier Google Scholar query results on gene-editing and human gene-editing.

For greater context, I get the following results after going on https://clinicaltrials.gov/, and searching separately “genome editing” and “human gene editing” (searched on 05/24/2022):

Another repository for clinical trials related to human gene-editing is the World Health Organization’s (WHO) Human Genome Editing (HGE) Registry, which was created in 2019 and gets it’s data from the WHO’s International Clinical Trials Registry Platform (ICTRP)54.

At the time of writing this (around May 23 2022), the most recently registered clinical trial Safety and Efficacy of HMI-103, a Gene Editing Development Candidate in Adults With Classical PKU Due to PAH Deficiency (see here) is aimed at aiding those with PKU, which we discussed briefly in the Overview and Shortcuts section.

This is an open-label, sequential ascending dose-escalation, Phase 1 study to evaluate the safety and efficacy of a single intravenous administration of HMI-103, a gene editing development candidate, in adult participants aged 18 to 55 years, inclusive, with classical PKU due to PAH deficiency who have uncontrolled disease despite Phe-restricted dietary management. [See https://clinicaltrials.gov/ct2/show/NCT05222178]

Although I haven’t taken the time to analyze the nature and distribution of these trials, which would be helpful for evaluating timelines for certain technical breakdowns in gene-editing (e.g., a reduction in mosacisims following some therapy), getting a sense of the landscape of clinical trials on gene-editing seems revelant to a discussion on people’s attitudes towards human gene-editing.

Given we’ve now looked at what gene-editing broadly entails, and where the state of research on it stands, let’s look at the potential affordances and risks of human gene-editing.

### Affordances

What benefits might human gene-editing offer to humanity?

### Risks and Concerns

What concerns for humanity are there with human gene-editing?

Recommendations for Germline Genome editing55:

There are a wide range of ethical and technical concerns regarding human gene-editing.

These concerns organically fall into several different categories: enhancement ethics, societal consequences of widespread genome editing (any usage), germline genome editing ethics, the line between enhancement and treatment, and unintended biological consequences stemming from somatic (or germline) genome editing.

Note that I have delimited these myself - these categories could likely be more precise, but likely not tremendously more precise, given the amount of content I’ve been exposed to.

While I don’t consider the scenario in this next passage to be especially plausible (I am open to being updated), I find it interesting nonetheless, and have generally found the author’s other works to be insightful.

Erik Hoel’s Nietzschean future56 in his post How to prevent the coming inhuman future provides a vivid picture of a future involving some undesirable social consequences of human genome editing for enhancement:

The future consists of what the name implies: Übermensch. If we imagine significant genetic editing becoming widespread, we may first simply imagine designer babies, little beings who seem quite unthreatening, just robust and happy creatures with perfect teeth and beautiful eyes. So let’s grow them up and imagine them as designer people, their rich parents having selected their genes specifically for athleticism, competitiveness, IQ, and leadership, with whatever polygenetic profiles those require. They’ll look a lot like the Greek gods. They’ll get into whatever college they want, they’ll never get sick, they’ll run faster, think deeper, and they’ll fuck harder. They will be gorgeous and whip-smart. But, just like the Greek gods, they will be a bunch of petulant, racist, sociopathic superpredators, great in bed but terrible in a relationship. For the sought-after designer traits will likely be things that only give direct selfish benefits, and knowledge of their genetic superiority will likely breed arrogance and contempt.

For imagine being told you’ve been chosen, forged to be objectively better than other people. In the tiniest mechanisms of your cells. Now, look out at the world of normies. What is your level of respect for them? And if your answer isn’t a sneer, that you’re looking at a bunch of Neanderthals who should be replaced, that they are pitiable at best, you don’t understand the darker aspects of psychology. Shakespeare? Why should they care what he wrote? He’s just another Neanderthal.

I imagine that most people, even without having thought extensively about the social and economic forces guiding humanity’s reactions to human gene-editing, or about the different ways in which gene-editing can be used on humans, would agree that the future in Hoel’s vignette is undesirable.

Similar to my presentation of the various definitions adjacent to human gene-editing, I present some selected ethical concerns from papers or descriptions I’ve come across57

For those unaware, a distinction is typically made between risk outlooks on the future of human genome before and after the affair58.

Summary of ethical concerns

Scientists and all of us should carefully consider the many ethical concerns that can emerge with genome editing, including safety. First and foremost, genome editing must be safe before it is used to treat patients. Some other ethical questions that scientists and society must consider are:

• Is it okay to use gene therapy on an embryo when it is impossible to get permission from the embryo for treatment? Is getting permission from the parents enough?
• What if gene therapies are too expensive and only wealthy people can access and afford them? That could worsen existing health inequalities between the rich and poor.
• Will some people use genome editing for traits not important for health, such as athletic ability or height? Is that okay?
• Should scientists ever be able to edit germline cells? Edits in the germline would be passed down through generations.

From59,

Jodie Rothschild’s 2020 paper Ethical considerations of gene editing and genetic selection60 synthesizes, in greater detail than we’ve seen previously, some of the major ethical concerns with human genome editing in response to the He Jiankui affair.

Summarized:

• Off-target effects: Using CRISPR and other gene-editing technologies can result in mutations, deletions, or insertions in DNA that were not originally intended to occur, and that might lead to complications.
• Downstream modification consequences: Given that the full function of many genes is not adequately understood, editing certain genes might help treat a person, but also might lead to complications later in life, such as a weakening of the immune system.
• Not all sequence variations are created equally: The changes engendered by gene alterations should be extensively studied before embryo implantation or use in humans.
• Mosaicism: “There is no way to sequence a cell’s genome without destroying the cell itself; as such, it is currently impossible to rule out mosaicism in a blastocyst”, where a mosaicism is “variation among cells, such that the cells are not all the same— for example, in an embryo when not all the cells are edited.”43 that might lead to such things as disease and tumors, and to defects in the organs.
• Which genes/diseases to target?: Oftentimes, which genes to target for a disease are not known. Also, the line between disease and disability is not clear, and what constitutes an “unfair” advantage from conferred by gene-editing is nebulous.
• Clinical Research Ethics:
• First and foremost, clinical trial participants should be informed of all of the associated risks and benefits.
• [How participants are selected for a study]
• Study participants should be able to voluntarily withdraw from the research at any point
• Ethics reviews boards, committees, and training is important
• Socioeconomic disparities:
• Stigma:
• Insurance:

#### Contra-Concerns and Nuances

Some papers provide counter-arguments to some of the concerns detailed previously.

Vera Lucia Raposo61, in her paper 2019 paper The First Chinese Edited Babies: A Leap of Faith in Science, is one example.

In summary, the four main axes of contention are:

• (1) sanctity of genome
• (2) genetic discrimination and eugenics
• (3) undermining human genetic pool
• (4) loss of human nature

Ethical concerns have long been asserted against genetic interventions. However, most of the objections have been based more on prejudice than substantive arguments. Critics have invoked the sanctity of the human genome, as if changing it would equate to playing God (Habermas, 2003). However, protecting the human genome should not prevent genetic interventions that can improve our lives. What brings real value to our lives is having a genetic code that allows us to live free of severe diseases, not to have an unmodified but unhealthy genetic code. Some have argued the perils of genetic discrimination (Mehlman & Botkin, 1998) and eugenics (Habermas, 2003), but if that were truth no medical treatment would be allowed under the suspicion of discriminating the ones not that are not treated and of aspiring to create a “superior” society of healthy people. The risk of undermining the human genetic pool (Committee on Science, Technology, and Law, 2016) is also a recurrent concern, but “there are more than six billion humans on the planet. Absent some kind of magic wand, it is initially difficult to see how any given genetic intervention could change human nature” (McConnell, 2010). The eventual loss of our human nature (Habermas, 2003) has been also invoked, but changing our genes does not change our human nature. Humanity does not reside in a specific genetic code, but in a certain perception of the world and our role in it. That role adds to the story of how we overcome the surrounding environment and ourselves.

My aim in this paper is to argue that debates about enhancement are of limited value in dealing with questions about foreseeable clinical uses of germline gene editing. This is for two reasons. First, the use of gene editing for biomedical enhancement in any sort of interesting way is not just technically far off, it involves a different kind of use of gene editing than is currently being pursued in research. Any use of gene editing to enhance our physical or psychological characteristics would likely involve affecting the developmental pathways for these traits in completely different ways than researchers are currently exploring. Second, and more importantly, there are significant questions about future clinical use even for very clearly thera- peutic uses of germline gene editing. I will focus on one in depth: determining rationale for germline gene editing in cases where there are competing therapeutic options.

## Mixed Feelings

Let’s now examine the following questions:

• What do people currently think about human gene-editing? Why?
• How has what people have thought about human gene-editing changed? Why?
• How is what people think / will think about human gene-editing important for humanity’s future?

### Today and the Last 7 Years

There are two main mediums through which researcher’s have examined what people think about human gene-editing: surveys63 and semantic text analyses64 of posts and other media on platforms such as Twitter and Reddit.

Within these groupings, there is considerable deviation in methodology, most notably in which groups questions are asked and in which questions are asked.

At the end of this the end of this section you can find my notes on each of the articles I’ve covered.

Notes65: AI and Human Enhancement: Americans’ Openness Is Tempered by a Range of Concerns

United States, N=5107/10260, Nov.1-7 2021

• gene-editing for prevention (GEP)
• There is a roughly equal split between some (47%) and no (44%) experience in gene-editing, with 8% reporting a lot of experience.66
• (*) Most aren’t sure whether widespread use of gene-editing would be good or bad, but the other 60% is evenly split between good and bad.
• There is an even split in people’s beliefs about whether (16-highly likely, 32-likely)% or not (25-unlikely, 24-highly unlikely)% they are likely to use gene-editing if it’s available; however, there are 33% more people that are highly unlikely to use gene-editing than who are highly likely to use it.
• Most people believe that GEP is likely (45%-highly likely, 39%-likely) be used in morally egregrious manner; only 5% believe it’s highly unlikely that gene-editing will be used this way.
• Despite the above beliefs, 65% of people (13%-highly likely, 52%-likely) believe that widespread GEP will help people to live longer and better; 10% of people believe the complete opposite, i.e. widespread GEP will highly likely not improve people’s health, wellbeing, or lifespans. There is a nearly identical distribution for beliefs on whether widespread GEP will engender new medical progress.
• Most people (24%-highly likely, 44%-likely) believe that GEP will likely go too far in decreasing humanity’s genetic diversity. Less than 10% (7%), believe that it’s highly unlikely that GEP goes too far in this regard.
• (**) In general, there are slightly more (52% vs. 46%) people who believe GEP is an example of meddling than those who believe it’s an example of betterment.
• Roughly 3/4ths (73%) of people believe that if GEP is widespread parents would feel pressured to use it.67
• Roughly 4/5ths of people are split evenly between believing that widespread GEP will either increase (39%) or not change (40%) quality of life; the remaining 1/5th (18%) believe it will decrease quality of life.
• Slightly over half of people (55%) believe that income inequality will be increased as a result of gene-editing; those remaining heavily lean towards the belief that there will be no change in income inequality (35%).
• roles in regulating GEP
• There is a slight majority of people (41%) beliefing federal government agencies should have a major role in regulating gene-editing technologies; the rest are split between believing the government should have a minor role (31%) or no role (26%).
• gene-editing companies [44, 35, 19, 2]
• gene-editing users [55, 29, 15, 2]
• medical scientists [67, 21, 10, 2]
• (***) government regulation [47, 51, 2] (too far, not far enough, N/A)
• test standards for gene-editing technology [17, 80, 2] (higher, normal, N/A)
• circumstances of GEP
• choose diseases/conditions [49, 15, 34, 2] (more, less, no difference, N/A)-morally acceptable
• somatic cell [48, 16, 34, 2]
• postnatal [53, 11, 34, 2]
• use cases for GEP
• more attractive [5, 74, 20, 1] (favor, oppose, not sure, N/A)
• treatment [71, 10, 18, 1]
• general question breakdowns
• (*: widespread use (good, bad, not sure)), Men: [36, 29, 35], Women: [24, 32, 44], HS or less: [23, 34, 43], Some college: [33, 28, 39], College graduate: [33, 29, 38], Postgraduate: [38, 28, 34], Much experience: [43, 31, 26], Little experience: [34, 33, 33], No experience: [23, 28, 49], High religiousity: [14, 46, 39], Medium religiousity: [29, 29, 41], Low religiousity: [43, 20, 36]
• (**: betterment vs. meddling?), High religiousity: [26, 72], Medium religiousity: [45, 53], Low religiousity: [64, 36]
• (***: government regulation (too far, not far enough)), Republican/lean Republican: [62, 37], Democrat/lean Democrat: [35, 63]

Translation: In 2022, Americans self-report:

Notes68: Biotechnology Research Viewed With Caution Globally, but Most Support Gene Editing for Babies To Treat Disease

• pre-natal gene-editing (PrGE)
• treat disease at birth
• prevent / reduce risk of disease
• enhance intelligence
• research on gene-editing
• Europe and Russia: [Spain: ]

## Forecasting These Attitudes

Thus far, I cannot recall having come across any research articles on human gene-editing that explicitly outline the social, regulatory, technological, and/or economic pathways to different scenarios across the axes (treatment vs. enhancement, somatic vs. germline) of gene-editing, or that actually attach probabilities to any future scenario involving gene-editing in humans.69

Despite the potential paucity of work in this regard, I believe that generating scenarios for how humanity might employ gene-editing and change as a result of it, and making forecasts on these scenarios, is a useful activity. I imagine one could find other examples of the usefulness of making scenarios and forecasts in the development and adoption histories of various technologies.70

Here is a list of important and/or interesting questions concerning human gene-editing that I’ve generated. Any further questions or operationalizations (for the questions I choose to write on Metaculus) would be welcome in the comments.

I’ve written up some of the questions, which range in clarity and resolvability, from this list on Metaculus71 and Manifold Markets; my criteria for doing this was whether I (and some others) thought the outcome of the question seemed to strongly depend on people’s attitudes towards human gene-editing72.

Gene-Editing Technology

• How many research results will there be for [TALENS, ZFNs, CRISPR, other genome editors] in [2025, 2030, 2035, etc…]?

Gene-Editing Timelines (General)

• When will the [4th, 100th, 1000th, etc…] gene-edited human child be born?
• When [2022 - 2100] will prenatal human gene-editing become widespread (100k births)?
• When [2022 - 2100] will postnatal human gene-editing become widespread (100k usages)?
• When [2022 - 2100] will the first germline genome edited child be born?
• When [2022 - 2100] will any country legalize prenatal germline genome editing in humans?
• When [2022 - 2100] will there be > 100 clinical trials involving somatic cell genome editing? (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146048/pdf/bsr-40-bsr20200127.pdf)
• Will prenatal gene-editing in humans be legalized in the jurisdiction where the 4th gene-edited baby is born?
• In the first year after human genome editing is legalized in any country, how many other countries will legalize it?

Gene-Editing Timelines (Localized)

• When will [China, US, EU nation, etc…] legalize any form of prenatal human genome editing? (multi-question)
• Which of the following countries [China, Israel, USA, Singapore, India, etc…] will be first to legalize prenatal human genome editing? (multi-question)
• Where [China, Israel, USA, Singapore, India, etc…] will prenatal germline genome editing in humans first be legalized?
• Where [China, Israel, USA, Singapore, India, etc…] will the first germline genome edited child be born?

External Factors and Indicators

• How will religiousity change globally by [2025, 2030, 2035, etc…]?
• How will global education levels change in [2025, 2030, 2035, etc…]?
• What percent of citizens in [China, Israel, USA, Singapore, India] will consider human gene-editing a misuse of science [2025, 2030, 2035, etc…]?
• What will be the ratio of support for highly religious to non-religious Americans for human gene-editing in 2027?
• Google Trends Interest on human gene-editing in [2025, 2030, 2035, etc…]?
• In the next PEW Research Survey on Global Attitudes Towards Biotechnology, what percentage of people will classify gene-editing as a misuse or appropriate use of science?

The questions I’ve decided to create on Metaculus are:

## Appendix

### The Landscape

Before writing this report, I had to gauge the landscape of research on people’s attitudes towards human gene-editing. To do this, I came up with a list of search terms that I thought might be useful.

Despite the many terms on this list, I only ended up formally searching for “human gene editing survey” on OpenAlex and for “attitudes towards human gene-editing” on Google.

By “formally searching”, I mean that for these searches, I recorded my search process (see OpenAlex Queries and Google Queries). The rest of my searches were conducted on CrossRef or included terms and chains of links that I cannot recall.

My rationale for “formally” outlining some of my search processes is to allow others to reproduce my search results and to give them a well-defined path to finding research on people’s attitudes towards human gene-editing. I imagine there are likely other benefits from me outlining my search processes that I am missing.

I began by searching for “human gene editing survey” on OpenAlex for years in the interval [2016, 2021].

I did not include results from the search that I thought weren’t especially relevant to people’s attitudes towards human gene-editing73, but made the initial mistake of including many results that only discussed the ethics of human gene-editing, but didn’t include much on people’s attitudes towards human gene-editing.

After my OpenAlex search, I searched for “attitudes towards human gene-editing” on Google and looked at the first 3 pages of results (this means clicking “More Results” 2 times) on FireFox.

It’s worth noting that each search did not include quotation marks; this means that my searches were not for the exact phrases human gene editing survey or attitudes towards human gene-editing (e.g., “attitudes toward human gene-editing” means I searched [attitudes toward human gene-editing] not [“attitudes toward human gene-editing”]).

I conducted my searches during the first 15 days of May 2022. Ideally, I would search for all of the terms in the Search Terms list on all of the following platforms - Google Scholar, CrossRef, OpenAlex, and Google - but this, presently, is not something I want to do and is something that I believe is not necessary, given that the number of reports I’ve covered thus far is in line with the scope of this essay.

There were many duplicates between searches; I tried not to list any search result twice.

Note: In the query-lists below (OpenAlex Queries and Google Queries), the list structure is organized in the following manner: the outermost list is what I searched (a query, phrase, or a remark indicating that I forgot what I originally searched); the next sub-list contains the relevant results returned from that query or phrase; and all subsequent nested lists are the works I found from looking at the references or links of a specific result.

Research that I found outside of this “formal” search is included under “Other Research”.

After collecting all the search results, I then rated them (★), usually after reading the abstract, (★★) after skimming the paper, and (★★★) after evaluating all of the (★★) results.

All PEW Research reports were exceptions in that I automatically gave them (★★★), given the insights and enjoyment I’ve gained from them in the past.

In all search lists,

• (★) indicates a search result that was useful in understanding people’s attitudes on human gene-editing
• (★★) indicates that I selected this result to examine more closely, and found that it very useful for understanding opinions on human gene-editing, but didn’t include it in the final collection due to my limited energies or to its deficits
• (★★★) indicates this result was very useful for understanding opinions on human gene-editing to the point where I decided to include it in my collection.

In some instances, I may still reference studies or results with (★) or (★★) in this essay, though I didn’t spend much time investigating these.

Abbreviations for the quickly-chosen reasons for not including the (★) or (★★) results in the final collection of surveys and studies:

• N: The number of participants was small, especially relative to some of the other studies I looked at
• L: The survey seemed to narrow in scope or was too localized for our interests
• Q: The credibility of the work is questionable, or the quality of the work seems low (an impression that this report and survey were hastily written)
• C: The survey or report is not comprehensive enough, especially relative to the other studies I looked at.

The “Table of Covered Research” collects the research I ended up using to update my beliefs on people’s attitudes towards human gene-editing. Given my limited time, I aimed to look at around 15-20 surveys, and ended up selecting and reading .

#### Search Phrases

• “survey on human gene-editing”
• “survey on human gene editing”
• “survey on human genetic-engineering”
• “survey on human genetic engineering”
• “human genetic-engineering survey”
• “human genetic engineering survey”
• “human genetic-engineering opinions”
• “human genetic engineering opinions”
• “human gene-editing survey”
• “human gene editing survey”
• “human gene-editing opinions”
• “human gene editing opinions”
• “opinions on human gene-editing”
• “opinions on human gene editing”
• “opinions on human genetic-engineering”
• “opinions on human genetic engineering”
• “attitudes on human gene-editing”
• “attitudes on human gene editing”
• “attitudes towards human gene-editing”
• “attitudes towards human gene editing”
• “attitudes on human genetic-engineering”
• “attitudes on human genetic engineering”
• “attitudes towards human genetic-engineering”
• “attitudes towards human genetic engineering”

This only occurred to me later in my writing of this essay, but “human genome editing” and its variations (e.g., “opinions of human genome editing”) should have been included in this list.

#### Other Research

A note should be made that

#### Coverage Extent

Ideally, an explanation for my “Extent” labels would be placed elsewhere on this site, but I haven’t gotten to this, so I’ve included the explanation here. Note that “Extent” applies to searching for something, or to reading and thinking about something.

• (1) My brain (writing it to get it written)
• (2) Internet querying and/or reading/thinking ~5 minutes
• (3) Internet querying and/or reading/thinking 5 - 30 minutes
• (4) Internet querying and/or reading/thinking 30 - 60 minutes
• (5) 2 - 5, 60 minute Internet querying and/or reading/thinking sessions
• (6) 6 - 15, 60 minute Internet querying and/or reading/thinking sessions
• (7) 16 - 35, 60 minute Internet querying and/or reading/thinking sessions
• (8) 36 - 75, 60 minute Internet querying and/or reading/thinking sessions
• (9) > 75, 60 minute Internet querying and/or reading/thinking sessions

#### Table of Covered Research

AI and Human Enhancement: Americans’ Openness Is Tempered by a Range of Concerns (2022) PEW Research Center https://www.pewresearch.org/internet/2022/03/17/ai-and-human-enhancement-americans-openness-is-tempered-by-a-range-of-concerns/ and here 4/9: I looked over the section on human gene-editing, but skimmed their descriptions. I took notes on their methodology and figures for this section.
The Public Perception of the #GeneEditedBabies Event Across Multiple Social Media Platforms: Observational Study (2022) Congning Ni, Zhiyu Wan, Chao Yan, Yongtai Liu, Ellen Wright Clayton. Bradley Malin, and Zhijun Yin https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957000/ and here 3/9: I read the first 3 pages in full and skimmed the rest, only looking for descriptions of support/opposition to gene-editing. I took notes on the figures and the support/opposition metrics.
Citizen views on genome editing: effects of species and purpose (2021) Gesa Busch, Erin Ryan, Marina A. G. von Keyserlingk, and Daniel M. Weary https://www.semanticscholar.org/paper/Citizen-views-on-genome-editing%3A-effects-of-species-Busch-Ryan/1aea990504a69e961d6aaf0bdec7db56b63a6b7b and here 1/9
Examining the relationship between gene editing knowledge, value predispositions, and general science attitudes among U.S. farmers, scientists, policymakers, and the general public (2021) Christopher Calabrese, Jieyu Ding Featherstone, Matthew Robbins, and George A. Barnett https://www.semanticscholar.org/paper/Examining-the-relationship-between-gene-editing-and-Calabrese-Featherstone/04804b6fb2a4a4a872635268bc696d4fa996ae21 and here 1/9
The View from the Benches: Scientists’ Perspectives on the Uses and Governance of Human Gene-Editing Research (2021) Margaret Waltz, Eric T. Juengst, Teresa Edwards, Gail E. Henderson, Kristine J. Kuczynski, John M. Conley, Paige Della-Penna, and R. Jean Cadigan https://pubmed.ncbi.nlm.nih.gov/34406038/ and here 1/9
Gene editing for treatment and prevention of human diseases: a global survey of gene editing-related researchers. (2020) Leonardo Fernandes Moutinho Rocha, Luiza Amara Maciel Braga, and Fabio Batista Mota https://pubmed.ncbi.nlm.nih.gov/32718240/ and here 1/9
Assessing Public Opinion on CRISPR-Cas9: Combining Crowdsourcing and Deep Learning (2020) Martin Müller, Manuel Schneider, Marcel Salathé, and Effy Vayena https://pubmed.ncbi.nlm.nih.gov/32865499/ and here 1/9
Public acceptability of gene therapy and gene editing for human use: A systematic review (2020) Juliette Delhove, Ivana Osenk, Ivanka Prichard, and Martin Donnelley https://www.semanticscholar.org/paper/Public-acceptability-of-gene-therapy-and-gene-for-A-Delhove-Osenk/09a910402fef12158b91fab6ab6286c2191ff87e and here 1/9
Increased awareness and decreased acceptance of genome-editing technology: The impact of the Chinese twin babies (2020) Daiki Watanabe, Yoko Saito, Mai Tsuda, and Ryo Ohsawa https://www.semanticscholar.org/paper/Increased-awareness-and-decreased-acceptance-of-The-Watanabe-Saito/6ccba038e919e6b49468b0fde6084356eb892dd4 and here 1/9
Enhanced threat or therapeutic benefit? Risk and benefit perceptions of human gene editing by purpose and heritability of edits (2020) Emily L. Howell, Patrice Kohl, Dietram A. Scheufele, Sarah Clifford, Anqi Shao, Michael A. Xenos, and Dominique Brossard https://www.semanticscholar.org/paper/Enhanced-threat-or-therapeutic-benefit-Risk-and-of-Howell-Kohl/47aa3f2bfc10485523fce14076030f3b8c4d11b0 and here 1/9
Biotechnology Research Viewed With Caution Globally, but Most Support Gene Editing for Babies To Treat Disease (2020) PEW Research Center https://www.pewresearch.org/science/2020/12/10/biotechnology-research-viewed-with-caution-globally-but-most-support-gene-editing-for-babies-to-treat-disease/ and here 1/9
Genetics experience impacts attitudes towards germline gene editing: a survey of over 1500 members of the public (2020) Abbie Jedwab, Danya F. Vears, Cheryl Tse, and Christopher Gynge https://www.nature.com/articles/s10038-020-0810-2 and here 1/9
Attitudes of Members of Genetics Professional Societies Toward Human Gene Editing (2019) Alyssa J Armsby, Yvonne Bombard, Nanibaa’ A Garrison, Bonnie L Halpern-Felsher, and Kelly E Ormond https://pubmed.ncbi.nlm.nih.gov/31599688/ and here 1/9
Predicting Public Attitudes Toward Gene Editing of Germlines: The Impact of Moral and Hereditary Concern in Human and Animal Applications. (2019) Christine Critchley, Dianne Nicol, Gordana Bruce, Jarrod Walshe, Tamara Treleaven, and Bernard Tuch https://pubmed.ncbi.nlm.nih.gov/30687386/ and here 1/9
D2.5: Public views on genetics, genomics and gene editing in 11 EU and non-EU countries (2019) Tim Hanson, Heidi Carmen Howard, Emilia Niemiec, Javier Prieto, Marie Prudhomme, Oliver Greene, and George Spedding https://www.sienna-project.eu/digitalAssets/801/c_801912-l_1-k_d2.5_societal-acceptance-and-awareness-surveys_with-foreword.pdf and here 1/9
The Uproar Over Gene-Edited Babies: A Semantic Network Analysis of CRISPR on Twitter (2019) Christopher Calabrese, Jieyu Ding, Benjamin Millam & George A. Barnett https://www.semanticscholar.org/paper/The-Uproar-Over-Gene-Edited-Babies%3A-A-Semantic-of-Calabrese-Ding/08522485298d7431f79ee2bcf122058f0a88f49a and here 1/9
Chinese Public Attitudes on Gene Editing (2018) Liang Chen and Zhi’an Zhang https://www.globaltimes.cn/pdf/ChinesePublicAttitudesOnGeneEditing2018.11.12.pdf and here 1/9
Public Views of Gene Editing for Babies Depend on How It Would Be Used (2018) PEW Research Center https://www.pewresearch.org/science/2018/07/26/public-views-of-gene-editing-for-babies-depend-on-how-it-would-be-used/ and here 1/9
A Need for Better Understanding Is the Major Determinant for Public Perceptions of Human Gene Editing (2018) Tristan McCaughey, David M Budden, Paul G Sanfilippo, George EC Gooden, Li Fan, Eva Fenwick, Gwyneth Rees, Casimir MacGregor, Lei Si, Christine Chen, Helena Hai Liang, Alice Pébay, Timothy Baldwin, and Alex W Hewitt https://pubmed.ncbi.nlm.nih.gov/29926763/ and here 1/9
Public views on gene editing and its uses (2017) George Gaskell, Imre Bard, Agnes Allansdottir, Rui Vieira da Cunha, Peter Eduard, Juergen Hampel, Elisabeth Hildt, Christian Hofmaier, Nicole Kronberger, Sheena Laursen, Anna Meijknecht, Salvör Nordal, Alexandre Quintanilha, Gema Revuelta, Núria Saladié, Judit Sándor, Júlio Borlido Santos, Simone Seyringer, Ilina Singh, Han Somsen, Winnie Toonders, Helge Torgersen, Vincent Torre, Márton Varju & Hub Zwart https://philpapers.org/archive/ZWAPVO.pdf and here 1/9
A Global Social Media Survey of Attitudes to Human Genome Editing (2016) Tristan McCaughey, Paul G. Sanfilippo, George E. C. Gooden, David M. Budden, Li Fan, Eva Fenwick, Gwyneth Rees, Casimir MacGregor, Lei Si, Christine Chen, Helena Hai Liang, Timothy Baldwin, Alice Pébay, and Alex W. Hewitt https://www.sciencedirect.com/science/article/pii/S1934590916300546 and here 1/9
U.S. Public Wary of Biomedical Technologies to ‘Enhance’ Human Abilities (2016) PEW Research Center https://www.pewresearch.org/science/2016/07/26/u-s-public-wary-of-biomedical-technologies-to-enhance-human-abilities/ and here 1/9
Chapter 5: Public Views About Biomedical Issues (2015) PEW Research Center https://www.pewresearch.org/science/2015/07/01/chapter-5-public-views-about-biomedical-issues/ and here 1/9

### Expert Questioning

Asking people for help or information is a relatively low-cost enterprise, so I took the time to email most of the authors whose research I included in the “Table of Covered Research”. In total, I sent 24 emails on 05/15/2022 and, as of 05/19/2022, have received 0 responses. I’ve included the template I used, along with the responses I received.

#### Templates

Thank you Ryan Beck and Ege Erdil for providing some feedback on the first of these two templates. The first template was sent to 1 researcher. I revised the first template to only address the corresponding authors of the articles I listed in “Table of Covered Research”. If the another author’s email was present in the research document, I emailed them as well.

Template 1

To reduce space, and since I only used this template once, I’ve copied it over to a text file; see here.

Template 2

Title: Forecasting Gene-Editing - [my actual name]

Dear [Author],

I am writing a short literature review (informal) on attitudes people have towards human gene-editing, for both enhancement and treatment purposes, with the goal of forecasting how people’s attitudes might change in the coming years. My essay will be hosted on Metaculus.com (a crowd forecasting platform that focuses on scientific and technological change). I am not affiliated with Metaculus, but do forecast there.

I recently came across your work [paper I read] in my review, and really find it useful. Given your experience with research directly involved with or adjacent to gene-editing, I am interested in hearing your thoughts on the following questions (*):

Q1: What general attitude do you think people will have towards human gene-editing in 2030, 2050, and 2075?

and

Q2: What will be the cumulative number of genetically edited babies born by 2030, 2050, and 2075?

Any thoughts on these questions from you (and your research colleagues), even brief ones, would be helpful. It would also be helpful if you specified, on a scale of 0-100, what you believe is your current level of familiarity with human gene-editing.

Once I am finished with the review, I will have a set of 5-10 forecasting questions that operationalize this area of study. If you are interested in these more formal questions on people’s attitudes towards gene-editing (I would love to hear your thoughts on these as well) or in the review, I can reach out to you again when they’re ready.

Thank you for taking the time to read this! I really appreciate it.

Kind Regards,
[My actual name]

(*) An example response my look like: My familiarity: 23/100; Q1: Same trend, people are much less supportive of enhancement than treatment, until ~2050. Q2: 95% confidence intervals for 2030, 2050, and 2075, respectively: 1-25000, 100-1.5m, 10k-25m

#### Responses

As of 06/02/2022, there has been 1 response. This response indicated that the author believed they were not qualified to answer any of the forecasting questions provided.

### Glossary and Visuals

Genetic Disorder: “A genetic disorder is a disease caused in whole or in part by a change in the DNA sequence away from the normal sequence. Genetic disorders can be caused by a mutation in one gene (monogenic disorder), by mutations in multiple genes (multifactorial inheritance disorder), by a combination of gene mutations and environmental factors, or by damage to chromosomes (changes in the number or structure of entire chromosomes, the structures that carry genes). [See https://www.genome.gov/For-Patients-and-Families/Genetic-Disorders]74

### Graph Code

I made some graphs in the section on progress in gene-editing. Here is the Python code.

import numpy as np
import matplotlib.pyplot as plt
plt.rcParams['text.usetex'] = True
plt.rcParams['text.latex.preamble'] = r''
plt.rcParams["font.family"] = "Times New Roman"

def graph_timeframes():

fig = plt.figure(figsize=(9.5, 6))

ax.set_title("Interventional Trials with Genome Editors, https://doi.org/10.1042/BSR20200127", color='black', fontsize=17.0)

ax.set_ylabel('Results Count', color='black', fontsize=15.0)
ax.set_xlabel('Year', color='black', fontsize=15.0)
ax.tick_params(axis='x', labelrotation = 45)
ax.set_xticks(ticks=np.arange(2009, 2019+1))

y2 = list(range(2009, 2019+1))

# trials from 2009 to 2019
trial_counts = [1, 2, 0, 1, 0, 1, 2, 10, 10, 13, 10]

ax.plot(
y2,
np.cumsum(trial_counts),
color='black',
linewidth=2.0,
marker='o',
markersize=5.0,
markerfacecolor='green',
label="trials (cumulative)''",
)

ax.plot(
y2,
trial_counts,
color='black',
linewidth=2.0,
marker='o',
markersize=5.0,
markerfacecolor='limegreen',
label="trials''",
)

ax.legend(loc="upper left")
plt.savefig('trials.png', dpi=300)
plt.show()

def main():

years = list(range(2000,2021+1))
gene_editing_results = [
487, 809, 818, 898, 855, 853,
804, 769, 771, 922, 843, 953,
914, 1090, 1780, 3900, 6050,
8720, 11900, 14800, 17700,
19900]
human_gene_editing_results = [
3, 1, 1, 2, 1, 1, 0, 1,
0, 1, 1, 6, 19, 27, 19,
73, 202, 228, 232, 374,
331, 371
]
graph_timeframes()

if __name__ == "__main__":
main()


• CRISPR People: The Science and Ethics of Editing Humans (2021)
• Genome Engineering via CRISPR-Cas9 System (2020)
• Human Flourishing in an Age of Gene Editing (2019)
• Altered Inheritance: CRISPR and the Ethics of Human Genome Editing (2019)
• Gene Editing, Law, and the Environment: Life Beyond the Human (2019)
• Between Moral Hazard and Legal Uncertainty: Ethical, Legal and Societal Challenges of Human Genome Editing (2018)
• Human Genome Editing: Science, Ethics, and Governance43 (2017)

## Notes

### Cover Image

The cover image for this page was likely taken by Martin Woortman. I found the photo on Unsplash. To my knowledge, my use of this photo is permissible under Unsplash’s license:

Unsplash grants you an irrevocable, nonexclusive, worldwide copyright license to download, copy, modify, distribute, perform, and use photos from Unsplash for free, including for commercial purposes, without permission from or attributing the photographer or Unsplash. This license does not include the right to compile photos from Unsplash to replicate a similar or competing service.

### Footnotes

1. One of my favorite articles is Open Philanthropy’s Reasoning Transparency (see https://www.openphilanthropy.org/reasoning-transparency), as it does a good job at capturing what robust epistemics looks like in practice.

2. How trustworthy are you?: This is partially for you to determine after reading this post and perhaps after looking through my other content, if you decide to do this. No, I am not an expert in anything related to genetic engineering. I have no formal training in genetics, and am not able to explain the technicalities or present progress bottlenecks of the various gene-editing technologies currently in use. Moreover, I am not too confident in my remembrance and understanding of the core definitions related to gene-editing, though, Anki has helped in this regard). As for my education, I have a B.A. in Neuroscience and Mathematics and, with regard to gene-editing, have read roughly 25 papers on the topic, but not the content (e.g., I don’t fully understand how CRISPR-Cas9 works on a detailed level - i.e., I am not currently able to use CRISPR-Cas9 in a lab, even if I had the resources to). That I’ve published 1 research paper in applied ML is some further evidence towards my capabilities. As for forecasting expertise, I am currently rank 54 on Metaculus, with an average Brier score of 0.057 (173 questions). My underconfidence is 25%. Subjectively speaking, I believe that I am slightly above average at making and updating forecasts, but am very likely not yet at the level of a superforecaster. More about me as a person with interests and goals can be found here

3. Priors?: Before working on this essay, I want to outline my current thoughts on human gene-editing; doing this might help me better determine how people might update their beliefs after reading this essay. My current understanding of the regulations, technology, and biology of gene-editing comes predominantly from working on my Forecasting Designer Babies essay. However, I still do not feel that I strongly understand gene-editing. Floating around in my mind, not well grounded, are the concepts “assisted reproductive technology”, “IVF”, “CRIPSR-Cas9”, “germline genome editing”, “somatic cell genome editing”, and “treatment vs. enhancement distinction”, among others. Each of these I could explain broadly, but if pressed to go deeper, I would fail. Generally speaking, I believe that most Western liberal-leaning people are cautiously optimistic about human gene-editing, that religious and/or older and/or conservative people are less likely to support gene-editing research, that most people are not familiar with what gene-editing entails, and that most people who support gene-editing favor treatment over enhancement. Note that once the essay is written and submitted, I will post a brief update of my beliefs in the comments.

4. External Review and Feedback?: Here are some notes and comments given by others on this piece, along with my responses to them. I indicate when and how I update the content based on these notes.

5. Epistemic confidence?: This essay includes several sections: [a small coverage of gene-editing, a look at research progress in gene-editing, some affordances of human gene-editing, some risks and concerns regarding human gene-editing], [people’s attitudes towards human gene-editing, the relevance of people’s attitudes towards human gene-editing], and [forecasting questions on human gene-editing relating primarily to people’s attitudes on human gene-editing]. Before going further, my confidence scales are in line with “Kesselman List of Estimative Words”, where ([word] indicates subjective [probability] of “I’ve made accurate statements and/or I’ve not omitted major or many pieces of evidence”): Impossible = 0.0, Small Possibility = 0.10, Small Chance = 0.20, Somewhat Doubtful = 0.30, Possible = 0.40, Toss-up = 0.50, Somewhat Likely = 0.60, Likely = 0.70, Very Likely = 0.80, Quite Certain = 0.90, Certain = 1.00. For the first block, I’m somewhat doubtful that my coverage of gene-editing is adequate (I omitted economic and detailed technical considerations, and might be too narrow in my coverage of the clinical trials and risks and concerns; I think my coverage of the affordances is adequate though). For the second block, I believe it’s very likely that my coverage of people’s attitudes towards human gene-editing is accurate and comprehensive but believe it’s only somewhat likely as to whether my examination of the relevance of people’s attitudes towards gene-editing is correct. I would be very surprised if someone scanned the same research literature and came to a different conclusion on people’s attitudes towards human gene-editing, but not as suprised if someone gave a different assessment of how useful these findings are. Lastly, I think it’s possible that the forecasting questions I’ve generated are impactful

6. Type of support for my claims?: Most of the claims in my review are supported by findings from research articles I surveyed, and for the claims that aren’t directly supported, I try to make it clear whenever I am speculating, such as when I am investigating causal drivers for some of the research findings. I believe that my forecasting claims have less support in the sense that they are speculation about human behavior, which I do not presently know how to use the tools to understand well.

7. Shortcuts taken?: I operate within the results produced by my initial searches, and haven’t considered what fraction of the research landscape I am covering, which means I’m not sure how much I am missing. I did not spend much time learning about gene-editing before writing this, and I did not completely read all the relevant research I came across (I did, however, indicate the extent I engaged with each relevant piece of research). I admit my forecasting analyses are likely missing many considerations. More on my shortcuts can be found in the overview. The articles I looked at could be accused of being cherry picked. I am not sure how much I’ve omitted from my discussion of gene-editing.

8. Major Inadequacies?: I would accuse my report of the following general inadequacies: “Appalling prose”, “Could be”, and “Stating the Obvious”.

9. Actual Contribution?: In this essay, I have surveyed, at different levels, X published research articles that deal with people’s attitudes towards human gene-editing. I have aggregated and distilled the survey data from these articles. I’ve generated 12 forecasting questions related to people’s future attitudes towards human gene-editing. Outside these things, I emailed X corresponding authors and 1 other author of X published articles the following questions: What general attitude do you think people will have towards human gene-editing in 2030, 2050, and 2075? and What will be the cumulative number of genetically edited babies born by 2030, 2050, and 2075?. I have yet to receive any responses, but will include them below once I’ve received some. If you know anyone with genetics training, I would appreciate if you asked them these questions and referred them to me.

11. … single gene disorders…: For other examples of single gene disorders, see https://learn.genetics.utah.edu/content/disorders/singlegeneeg/ and https://www.ncbi.nlm.nih.gov/books/NBK132154/. ex2_single_cell_disorders.html

12. There are over 4600 genes in humans with phenotype-causing mutations; these genes account for >6000 single gene disorders, ~700 instances of increased suseptibility to complex diseases or infections, and ~250 somatic cell genetic diseases.: See https://omim.org/statistics/geneMap. Accessed 05/27/2022. For HTML of page during access, click here: https://rodeoflagellum.github.io/assets/2022/for_attitudes_gene_editing/docs/OMIM_05272022.html.

Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), {05/24/2022}. World Wide Web URL: https://omim.org/

Welcome to OMIM®, Online Mendelian Inheritance in Man®. OMIM is a comprehensive, authoritative compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 16,000 genes. OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries contain copious links to other genetics resources.

This paper https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986124/pdf/AJMG-187-48.pdf also references OMIM (I believe this increases the credibility of OMIM. I am not familiar with how credible OMIM is by default, given that I am not an expert in genetics): “The etiologies for many rare diseases have been discovered. Online Inheritance in Man (OMIM) (https://omim.org/statistics/geneMap, October 31, 2020) lists 4,339 genes with phenotype-causing variants. Orphanet (http://www.orphadata.org/cgi-bin/index.php, 10/09/2020) includes more than 7,800 disease-gene relationships. Each year about 250 rare genetic disease discoveries are added to the lists. These discoveries include pathogenic variants in a gene that had not previously been associated with disease and pathogenic variants in a gene previ- ously associated with a different disease (Boycott et al., 2017)” Extent: (1/9). Support Type:

13. …Sickle Cell Disease, which results in a person’s blood cells being mishapen, dying early, and clogging blood vessels, and can cause the person “pain and other serious problems such infection, acute chest syndrome and stroke”: See https://www.cdc.gov/ncbddd/sicklecell/facts.html: “SCD is a group of inherited red blood cell disorders. Healthy red blood cells are round, and they move through small blood vessels to carry oxygen to all parts of the body. In someone who has SCD, the red blood cells become hard and sticky and look like a C-shaped farm tool called a “sickle”. The sickle cells die early, which causes a constant shortage of red blood cells. Also, when they travel through small blood vessels, they get stuck and clog the blood flow. This can cause pain and other serious problems such infection, acute chest syndrome and stroke.”. To see the saved document (05/01/2022 - 07/01/2022)?, click here: https://rodeoflagellum.github.io/assets/2022/for_attitudes_gene_editing/docs/cdc_sickle_cell_05272022.html

14. For more about PKU see https://learn.genetics.utah.edu/content/disorders/singlegeneeg/: “Babies who have PKU are usually healthy at first, but symptoms appear within a few months. These may include slow growth, eczema (a skin rash), musty body odor (from too much Phe), small head size, and fair skin (because Phe is converted into skin pigment). Without treatment, children with PKU experience developmental delays, behavior problems, intellectual disability, and seizures.”

15. NEED

16. For other examples of therapeutic applications of somatic cell genome editing, please refer to this table.

17. NEED List all books on enhancement I can find. Reference the Wikipedia link.

18. NEED

19. NEED

20. NEED

21. Genetic nature: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1360-0443.2008.02213.x;

22. NEED

23. NEED

25. NEED

26. NEED

27. NEED

28. NEED

29. NEED

30. NEED

32. https://pubmed.ncbi.nlm.nih.gov/30822436/

33. NEED

34. In finding resources and evidence for the genetic components and malleability of the following potential enhancements, I searched one or all of “heretibility of X”, “genetics of X”, “X genetics”, “X enhancement”, “enhancement of X”, “biological basis of X” where X is one the traits that I listed.

36. NEED

37. NEED

38. I believe I should be thinking more about how opinions change over time, and about how people’s self-reported opinions are biased. Here are some considerations (maybe a simple Google search would suffice): (1) how do people’s views change, (2) opinion drift, (3) how attitudes change, (4) how opinions change, (5) how often do opinions change, (6) response bias, (7) measuring response bias, and (8) self-reported data issues.

39. From https://en.wikipedia.org/wiki/Genome_editing#cite_note-75: “Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism.”.

From https://www.genome.gov/genetics-glossary/Genetic-Engineering, “Genetic engineering (also called genetic modification) is a process that uses laboratory-based technologies to alter the DNA makeup of an organism. This may involve changing a single base pair (A-T or C-G), deleting a region of DNA or adding a new segment of DNA.

From https://en.wikipedia.org/wiki/Genetic_engineering, “Genetic engineering, also called genetic modification or genetic manipulation, is the direct manipulation of an organism’s genes using biotechnology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms. New DNA is obtained by either isolating and copying the genetic material of interest using recombinant DNA methods or by artificially synthesising the DNA.

Genome editing, also called gene editing, is an area of research seeking to modify genes of living organisms to improve our understanding of gene function and develop ways to use it to treat genetic or acquired diseases. Genome editing can be used to correct, introduce or delete almost any DNA sequence in many different types of cells and organisms.https://www.nih.gov/news-events/gene-editing-digital-press-kit

From https://allianceforscience.cornell.edu/wp-content/uploads/2022/02/Gene-editing-FAQ_V2.pdf, “Gene editing is also sometimes referred to as genome editing, CRISPR, and GE and included in the broader terms of genetic engineering and biotechnology.” and “…In this case, gene editing is used to generate GMOs.”.

40. Rosenberg, Eugene. It’s in Your DNA: From Discovery to Structure, Function and Role in Evolution, Cancer and Aging. Academic Press, 2017.

Note that I am citing this definition from Chapter 10: Genetic Engineering of this book.

41. Lanigan, Thomas M., Huira C. Kopera, and Thomas L. Saunders. “Principles of genetic engineering.” Genes 11, no. 3 (2020): 291.

See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140808/

42. ten Have, Henk, and Maria do Céu Patrão Neves. “Dictionary of Global Bioethics.” (2021).  2

43. National Academies of Sciences, Engineering, and Medicine. Human genome editing: science, ethics, and governance. National Academies Press, 2017.

Notes: I used this book (Chapters 3 and 4, and the Appendices) to learn about gene-editing science and regulation, and most of the content in this essay’s gene-editing section and glossary section come from my reading of this text.  2 3 4 5 6

44. WHO Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing. Human Genome Editing: recommendations. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO.

45. Prenatal gene-editing is newer than postnatal genetic interventions. In 2018: “For the first time, scientists have performed prenatal gene editing to prevent a lethal metabolic disorder in laboratory animals, offering the potential to treat human congenital diseases before birth. Published today in Nature Medicine, research from Children’s Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania offers proof of concept for prenatal use of a sophisticated, low-toxicity tool that efficiently edits DNA building blocks in disease-causing genes.

Using both CRISPR-Cas9 and base editor 3 (BE3) gene-editing tools, the team reduced cholesterol levels in healthy mice treated in utero by targeting a gene that regulates those levels. They also used prenatal gene editing to improve liver function and prevent neonatal death in a subgroup of mice that had been engineered with a mutation causing the lethal liver disease hereditary tyrosinemia type 1 (HT1).

See https://www.chop.edu/news/prenatal-gene-editing-shows-proof-concept-treating-congenital-disease-birth and https://penntoday.upenn.edu/news/study-prenatal-gene-editing-dna-utero

46. From search “designer babies” (without the quotations) on Google Scholar, the following results come up. This list is not exhaustive. See https://scholar.google.com/scholar?hl=en&as_sdt=0%2C43&q=designer+babies&btnG=#d=gs_cit&t=1653965068073&u=%2Fscholar%3Fq%3Dinfo%3AI9F9JEQZcpgJ%3Ascholar.google.com%2F%26output%3Dcite%26scirp%3D6%26hl%3Den

Pang, Ronald TK, and P. C. Ho. “Designer babies.” Obstetrics, Gynaecology & Reproductive Medicine 26, no. 2 (2016): 59-60. See https://www.sciencedirect.com/science/article/abs/pii/S1751721415300063

Designer babies are either created from an embryo selected by preimplantation genetic diagnosis (PGD) or genetically modified in order to influence the traits of the resulting children. The primary aim of creating designer babies is to avoid their having heritable diseases coded by mutations in DNA.

Suter, Sonia M. “A brave new world of designer babies.” Berkeley Tech. LJ 22 (2007): 897. See https://www.sciencedirect.com/science/article/abs/pii/S1751721415300063

Steinbock, Bonnie. “Designer babies: choosing our children’s genes.” The Lancet 372, no. 9646 (2008): 1294-1295. See https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61538-X/fulltext

Fordham, Brigham A. “Disability and Designer Babies.” Val. UL Rev. 45 (2010): 1473. See https://heinonline.org/HOL/Page?handle=hein.journals/valur45&div=47&g_sent=1&casa_token=

47. I searched “timeline of human gene-editing” in FireFox on 05/17/2022, looked at the first page of results, and found the timeline that looked the most useful (where usefulness = some mental function of credibility and comprehensiveness). I chose the timeline on https://www.synthego.com/learn/genome-engineering-history and added links to Wikipedia pages; Synthego claims of itself:
Synthego is a genome engineering company that enables the acceleration of life science research and development in the pursuit of improved human health.

The company leverages machine learning, automation, and gene editing to build platforms for science at scale. With its foundations in engineering disciplines, the company’s platform technologies vertically integrate proprietary hardware, software, bioinformatics, chemistries, and molecular biology to advance basic research, target validation, and clinical trials.

With its technologies cited in hundreds of peer-reviewed publications and utilized by thousands of commercial and academic researchers and therapeutic drug developers, Synthego is at the forefront of innovation enabling the next generation of medicines by delivering genome editing at an unprecedented scale.
”

48. The first clinical application of CRISPR/Cas9…: Cyranoski D. CRISPR gene-editing tested in a person for the first time. Nature. 2016 Nov 24;539(7630):479. doi: 10.1038/nature.2016.20988. PMID: 27882996.

49. The world was shocked in Nov. 25, 2018…: Greely, Henry T. “CRISPR’d babies: human germline genome editing in the ‘He Jiankui affair’.” Journal of Law and the Biosciences 6, no. 1 (2019): 111-183.

50. Meagher, Karen M., Megan A. Allyse, Zubin Master, and Richard R. Sharp. “Reexamining the ethics of human germline editing in the wake of scandal.” In Mayo Clinic Proceedings, vol. 95, no. 2, pp. 330-338. Elsevier, 2020.

51. Hirakawa, Matthew P., Raga Krishnakumar, Jerilyn A. Timlin, James P. Carney, and Kimberly S. Butler. “Gene editing and CRISPR in the clinic: current and future perspectives.” Bioscience reports 40, no. 4 (2020). See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146048/pdf/bsr-40-bsr20200127.pdf  2

52. Example search for “gene-editing” for the year 2000: https://scholar.google.com/scholar?q=%22gene-editing%22&hl=en&as_sdt=0%2C43&as_vis=1&as_ylo=2000&as_yhi=2000. Exact numbers for the searches:

gene_editing_results = [487, 809, 818, 898, 855, 853, 804, 769, 771, 922, 843, 953, 914, 1090, 1780, 3900, 6050, 8720, 11900, 14800, 17700, 19900]

human_gene_editing = [3, 1, 1, 2, 1, 1, 0, 1, 0, 1, 1, 6, 19, 27, 19, 73, 202, 228, 232, 374, 331, 371]

53. Li, Guanglei, Xiangyang Li, Songkuan Zhuang, Liren Wang, Yifan Zhu, Yangcan Chen, Wen Sun et al. “Gene editing and its applications in biomedicine.” Science China Life Sciences (2022): 1-41.

54. You can find the ICTRP trials that are related to human genome editing here https://trialsearch.who.int/AdvSearch.aspx?SearchTermStat=1&SearchTermFlag=2&ReturnUrl=~/ListBy.aspx?TypeListing=0

55. Ormond, Kelly E., Douglas P. Mortlock, Derek T. Scholes, Yvonne Bombard, Lawrence C. Brody, W. Andrew Faucett, Garrison Nanibaa’A et al. “Human germline genome editing.” The American Journal of Human Genetics 101, no. 2 (2017): 167-176.

56. I am inclined to be somewhat skeptical of this being a plausible future. I imagine that aggression and other emotions important to coordination and relationships could also be modified in the enhancement future Hoel outlines. Across many socio-economic and demographic strata, most people I’ve seen want their children to be kind. I don’t think it’s likely that parents wouldn’t select [kindness, compassion, morality, etc…] if they were available alongside things like IQ, creativity, and competitiveness.

57. NEED

58. A reaction after the He Jiankui affair: “In conclusion, based on currently available information, we believe there is no sound scientific reason to perform this type of gene editing on the human germline, and that the behavior of He and his team represents a gross violation of both the Chinese regulations and the consensus reached by the international science community. We strongly condemn their actions as extremely irresponsible, both scientifically and ethically. We strongly urge the international community of scientists and regulators to initiate a comprehensive discussion as soon as possible to develop the criteria and standards for genome editing in the human germline for reproductive purposes. After reaching a clear consensus, clear and strict laws need to be passed, implemented, and enforced at an international level. We also believe, however, that it is necessary to further develop and improve the technologies for introducing precise genetic modifications into the human germline, including early embryos, sperm, and oocytes, using in vitro experimental setups. These improved technologies may provide solutions for genetic diseases but only when consensus has been met and a regulatory framework has been put in place for treating specific medical implications

Wang, Haoyi, and Hui Yang. “Gene-edited babies: What went wrong and what could go wrong.” PLoS Biology 17, no. 4 (2019): e3000224. See https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000224

59. Coller, Barry S. “Ethics of human genome editing.” Annual Review of Medicine 70 (2019): 289-305.

60. Rothschild, Jodie. “Ethical considerations of gene editing and genetic selection.” Journal of General and Family Medicine 21, no. 3 (2020): 37-47.

61. Raposo, Vera Lucia. “The first Chinese edited babies: a leap of faith in science.” JBRA assisted reproduction 23, no. 3 (2019): 197.

Note that I recycled the list and blockquote relating to Vera’s paper from my other essay Forecasting Designer Babies

62. Cwik, Bryan. “Moving beyond ‘therapy’and ‘enhancement’in the ethics of gene editing.” Cambridge Quarterly of Healthcare Ethics 28, no. 4 (2019): 695-707.

63. List the examples. NEED

64. List the examples. NEED

65. Pew Research Center, March 2022, “AI and Human Enhancement: Americans’ Openness Is Tempered by a Range of Concerns”

Quotes: “Americans strongly support using gene editing techniques for people’s therapeutic needs. But, when it comes to their potential use to enhance human health over the course of a lifetime by reducing a baby’s risk of getting serious diseases or conditions, as many Americans think this would be a bad idea for society as say it would be a good idea. The public is also closely divided over whether they would want this for their own baby. As with previous Pew Research Center surveys on this topic, women and more religious Americans are less accepting of gene editing for this purpose.”

66. …roughly equal split between some (47%) and no (44%) experience in gene-editing, with 8% reporting a lot of experience: See here

67. Roughly 3/4ths of people believe that if GEP is widespread parents would feel pressured to use it: See here

68. Pew Research Center, Dec. 2020, “Biotechnology Research Viewed With Caution Globally, but Most Support Gene Editing for Babies To Treat Disease”

69. It is also possible (and somewhat likely) that I am missing a lot here by not having extensively explored search results such as “human gene-editing scenarios”. NEED

70. NEED

71. …from this list on Metaculus…: A note should be made that there are already some questions on human gene-editing on Metaculus. Searching “gene edit” on Metaculus produces the following: Total Gene-Edited Human Births before 2030 https://www.metaculus.com/questions/3289/how-many-gene-edited-babies-will-have-been-born-worldwide-by-the-end-of-2029/; Date of Birth of First Cloned Human https://www.metaculus.com/questions/1537/when-will-the-first-cloned-human-be-born/; By the year 2100, will any jurisdiction enforce requirements for all births to be genetically engineered? https://www.metaculus.com/questions/7250/ban-on-genetically-unmodified-humans/; Will the first human clone be made in China? https://www.metaculus.com/questions/7660/will-the-first-human-clone-be-made-in-china/; Will an anti-discrimination law be enacted to protect U.S. federal employees who have been genetically-edited or screened as embryos by 2100? https://www.metaculus.com/questions/9752/protection-for-the-gene-editedscreened/; When will a person who was not screened or genetically modified as an embryo file a lawsuit against their parents for not doing so? https://www.metaculus.com/questions/9793/unscreenunmodified-person-sues-parents/

72. This is an aside, but since there is a non-trivial chance that I will be able to lead a tournament on “genetic evolution” on Metaculus in the coming months, I’ve avoided choosing questions from this list that would be better suited for such a tournament.

73. e.g., the OpenAlex query https://api.openalex.org/works?search=Human%20Gene%20Editing%20Survey&filter=publication_year:2021 produces the result “Consumer valuation of and attitudes towards novel foods produced with new plant engineering techniques: A review”, but I did not include this.

74. See https://rodeoflagellum.github.io/assets/2022/for_attitudes_gene_editing/docs/NHFRI_GDisorders_05272022.html for page during access date: 05/27/2022.