Consolidated Appropriations Act, 2016 (Public Law 114-113)

The Policy

What it does

Disqualifies research involving genetically modified human embryos from applying for investigational new drug exemptions.

Synopsis

Public Law 114-113, more commonly known as the federal budget, is the 2015 law that determines the amount of money allocated to each government agency for the fiscal year of 2016 (October 2015 – September 2016). This funding can come with restrictions; a notable example is Section 749, which prevents public dollars from being used to review drugs or biological products related to the genetic modification of human embryos.

Normally, all new drugs are required to be reviewed by the Food and Drug Administration (FDA) before they are eligible for clinical use. Occasionally, the FDA will receive requests to allow researchers to administer investigational new drugs (those which have yet been approved) to humans for the purposes of testing the drugs’ safety and effectiveness. 21 U.S.C. 355(i) and 42 U.S.C. 262(a)(3) provide the FDA with authority to grant exemptions from review in these situations.

However, Section 749 prohibits the FDA from reviewing such requests if the new drug involves “research in which in which a human embryo is intentionally created or modified to include a heritable genetic modification”. Applications for investigational new drug exemptions involving such technologies now face automatic rejection because Section 749 withholds the federal funding needed by the FDA to process the request.

Context

<p>Research using human embryos is legal in the U.S. but has been <a href="https://embryo.asu.edu/pages/dickey-wicker-amendment-1996">ineligible for federal funding</a> since the <a href="https://www.gpo.gov/fdsys/pkg/PLAW-104publ99/pdf/PLAW-104publ99.pdf#page... Dickey-Wicker Amendment</a>. However, genetic modification of human embryos has occurred internationally in both <a href="http://www.nature.com/news/chinese-scientists-genetically-modify-human-e... science research</a> and in <a href="https://www.theguardian.com/science/2016/sep/27/worlds-first-baby-born-u... settings</a>. The restrictions imposed by Section 749 are distinct from the Dickey-Wicker Amendment. Section 749 prohibits technologies concerning heritable genetic modifications from being considered for regulatory review and market approval in the U.S. In contrast, Dickey-Wicker allows for research on embryo modification, but renders such research ineligible for government grants.</p>

The Science

Science Synopsis

Cells are classified as human embryos during the earliest stages of development following fertilization of an egg (from the mother) by sperm (from the father). Many genetically heritable diseases – which are illnesses such as cystic fibrosis and hemophilia that are caused by harmful mutations passed on from parents to their children – can be identified at the embryo stage. However, many embryos that carry mutations for these diseases are still viable and can survive to become a baby. Yet the genetic diseases carried by these newborns often have no cure, placing limits on the child’s long-term life expectancy. As a result, scientists are working to develop strategies that can help prospective parents overcome the risk of genetic disease transmission. 

A recently developed technology known as CRISPR/Cas9 raises exciting new possibilities about curing heritable mutations. This platform allows scientists to edit the genome of any organism easily and affordably. CRISPR refers to sequences within the DNA that scientists use to mark the spot of their genetic target, which can then be eliminated using Cas9, an enzyme that acts like molecular scissors.

While CRISPR/Cas9 is still early in development, the technology’s ability to create permanent modifications in an embryo (a process referred to as “germline editing”) has raised serious ethical questions. For instance, experts from the National Academies deemed the use of CRISPR/Cas9 to edit human embryos as “irresponsible” during an international summit in December 2015. Nonetheless, CRISPR/Cas9’s ability to create “heritable genetic modifications” renders it ineligible for FDA review under Section 749.

Another technology that can eliminate mutations in embryos is mitochondrial DNA replacement. Mitochondria are known as the powerhouse of the cell, and are vital for many biological processes. However, mutations in the mitochondrial DNA can have severe health consequences.

Mitochondrial DNA (mtDNA) is distinct from nuclear DNA (nDNA). A child’s mtDNA originates solely from the mother, but their nDNA is the combination of both parents’ genetic information. Additionally, the genes in nDNA are responsible for the vast majority of human traits (e.g. height, hair color); mtDNA only contains genes for the mitochondria.

In response, scientists have developed a technique that would replace only the mutated mitochondrial genes in the mother’s egg with DNA from a donor mother; the new cell can now be fertilized with the father’s sperm to produce an embryo free of mitochondrial DNA disease. The National Academies issued a report distinguishing mtDNA replacement from other technologies such as CRISPR/Cas9, concluding that “MRT to produce male offspring would not constitute heritable genetic modification (germline modification)” as “mtDNA is solely maternally inherited.” Nevertheless, the FDA has deemed this technology to be ineligible for review based on Section 749’s prohibition of genetic modification of embryos.


The Debate

Endorsements & Opposition

As Section 749 is a rider attached to Public Law 114-113, broad commentary regarding the legislation focused on broader appropriation questions rather than specific clauses. However, some key congressional documents and academic commentary have focused on this specific financial restriction. These include:

Endorsements:

  • Representative Lamar Smith (R-TX-21), Chair of the House Committee on Science, Space, and Technology: “The new discoveries in genetically engineering human DNA offer potential cures for devastating genetic disorders. But the speed at which these new, simpler and cheaper technologies are being used in the lab also presents ethical and health concerns.”
  • House Committee on Appropriations report: “The Committee understands the potential benefits to society in the genetic modification of living organisms. However, researchers do not yet fully understand all the possible side effects of editing the genes of a human embryo. Editing of the human germ line may involve serious and unquantifiable safety and ethical issues.”

Opposition:

  • Editorial authored by Glenn Cohen and Eli Adashi: “Viewed in this light, this latest congressional intervention appears premature, if not unhelpful, in that the germline modification debate is barely getting under way.” The piece also commented that with the ratification of Section 749, “the United States is ceding its leadership in this arena to other nations.”
  • Comments by bioethicist Arthur Caplan: bans are “just going to shift [funding] into private hands and let the market regulate it.” Considering that “gene editing technologies like CRISPR are still in their infancy,” the FDA’s stance is “basically the most fearful response possible.”