Prohibitions related to scientific research and clinical applications

Background

In 1989, the Government of Canada asked the Royal Commission on New Reproductive Technologies to consider the latest medical developments in infertility treatment (e.g., in vitro fertilization). Based on the ethical, social and economic issues linked to infertility treatment, policies and safeguards were suggested and developed.  In addition to considering the recommendations in the Commission's final report^{Footnote 1} the Government worked with health professionals, researchers, ethicists and individuals using or thinking about using assisted human reproduction to build their families to develop its approach to infertility treatment. The result was the Assisted Human Reproduction Act (AHR Act), which became law in March 2004.

The law respects Canadians' values, and sets out broad principles to guide how Health Canada applies and enforces the Act and its regulations. Health Canada also encourages health professionals, researchers and other interested groups to follow the principles (stated below) while carrying out AHR based activities.

Principles

• In the use of AHR technologies, children's health and well-being must come first;
• Using appropriate measures will help protect the health, safety, dignity and rights of people affected by the use of AHR technologies;
• Because women, not men, are more significantly affected by AHR technologies, their health must be protected;
• Free and informed consent must always be given before these technologies can be used;
• People who use AHR technologies must not be discriminated against;
• Commercial trade and abuse of the reproductive capabilities of children, women and men is, for health and ethical reasons, a crime;
• Preservation and protection of human individuality and diversity must be upheld.

Prohibitions related to scientific research and clinical applications

Under section 5(1) and section 9 of the AHR Act, no person shall knowingly:

(a) create a human clone by using any technique, or transplant a human clone into a human being or into any non-human life form or artificial device;

"human clone" means an embryo that, as a result of the manipulation of human reproductive material or an in vitro embryo, contains a diploid set of chromosomes obtained from a single – living or deceased – human being, fetus or embryo. (section 3 of the AHR Act)

Clones are beings that share their exact genetic code with at least one other being. When people think of cloning, they may think of Dolly the sheep, which was the first cloned animal created through medical research.

In order to create a clone, scientists use somatic cell nuclear transfer. With this method, a cell from an already-living being that contains two sets of chromosomes is injected into an egg (ovum) that has had its nucleus removed. After stimulating the egg to begin to divide, an embryo would be created that has the same nuclear DNA as the person being cloned.

Under the AHR Act, it is illegal to knowingly create a human clone, regardless of the purpose, including therapeutic and reproductive cloning. In some countries, laws separate these two types of medical cloning. The differences, described below, depend on how the embryo will be used.

In therapeutic cloning, a cloned embryo is created for the purpose of harvesting stem cells that might be used in treating a disease or disability in the person who was "cloned." This type of cloning has been given attention in recent years due to the potential value of creating "personalized" stem cell lines. However, with the advances made in inducible pluripotent stem (iPS) cell technologies, which make adult cells become more like embryonic stem cells, it is likely that therapeutic cloning will be replaced by iPS technology.

In reproductive cloning, the embryo is not destroyed, but is transferred into a woman's uterus for the purpose of creating a genetically identical individual.

In the United States, United Kingdom, Australia and several other countries, legislation exists banning human reproductive cloning but permitting human therapeutic cloning^{Footnote 2}; additional non-binding agreements on human cloning have been ratified by the United Nations^{Footnote 3}.

(b) create an in vitro embryo for any purpose other than creating a human being or improving or providing instruction in assisted reproduction procedures;

In addition to the ban on cloning, the AHR Act also prohibits knowingly creating an in vitro embryo for any purpose other than those set out in paragraph 5(1)(b):

• "creating a human being:" In this case, the embryo is created with the purpose of trying to establish a pregnancy. This might be during a fresh In Vitro Fertilization (IVF) cycle, or it may be after the embryo is frozen for a period of time.
• "improving or providing instruction in assisted reproduction procedures:" In this case, an embryo can be created, for example, by a trainee embryologist to test out a new technique or product, or to train embryologists on a new piece of equipment. Any embryos created for the purpose of improving or providing instruction would be discarded in the lab. In cases where a novel technology or product is being assessed, the process would likely be performed under a clinical trial protocol that had been approved by an ethics panel.

Because of this prohibition, the AHR Act allows human embryo research only if the embryo to be used in the research is no longer needed for reproductive purposes and both gamete donors and the individual(s) for whom the embryo was created have given their consent for its research use in accordance with the regulations ( Assisted Human Reproduction (Section 8 Consent) Regulations).

(c) for the purpose of creating a human being, create an embryo from a cell or part of a cell taken from an embryo or fetus or transplant an embryo so created into a human being;

The prohibition in paragraph 5(1)(c) is related to the cloning prohibition in paragraph 5(1)(a) explained above. However, in this case, the cell used to make the embryo would be from an embryo or fetus rather than from a living person. This practice is also illegal in Canada and is based on the belief that a child born as a result of AHR should have adult biological parents.

(d) maintain an embryo outside the body of a female person after the fourteenth day of its development following fertilization or creation, excluding any time during which its development has been suspended;

When an embryo is created in a lab, it generally cannot survive more than a week without a uterus wall to implant into. This may change as artificial tissues used in cell culture become more complex, and so several professional organizations and countries have chosen 14 days as the cut-off for keeping an embryo in the lab. [This does not include time in which the embryo is frozen, or cryopreserved. Embryos may be kept frozen in storage tanks indefinitely, though their potential to establish a pregnancy after being thawed may lessen over long periods of time.]

Why 14 days? In human development, a fertilized egg becomes an embryo after its cells begin to divide and this period lasts until 8 weeks of development. At about 14 days after fertilization, there are changes that cause the early embryo's cells to start to have assigned jobs. For example, some cells become part of the nervous system, while others become other organs. Until this change, cells of the embryo are "pluripotent" - that is, they can become nearly any type of cell that makes up a human.

(e) for the purpose of creating a human being, perform any procedure or provide, prescribe or administer any thing that would ensure or increase the probability that an embryo will be of a particular sex, or that would identify the sex of an in vitro embryo, except to prevent, diagnose or treat a sex-linked disorder or disease;

In Canada, as in many other countries, attempting to cause a future child to be of one sex or the other by using AHR technologies is illegal. This paragraph of the AHR Act addresses situations where, for example, potential parents wish to have a child of a particular sex in order to "balance" their family make-up.

In terms of assisted reproduction, the prohibition on sex selection for non-medical purposes affects two main types of technologies. The first, sperm sorting, is a method that generally relies on sperm size in order to separate a semen sample into two parts, with sperm containing an X^{Footnote 4} chromosome separated from sperm containing a Y chromosome. [Y chromosomes are smaller than X chromosomes.] The sperm from the selected layer is then used for insemination. This method increases the chance of creating an embryo of a certain sex. The second method involves taking a cell or fluid from an embryo and performing tests that will determine the sex of an embryo after it is created in a lab. Usually, this is done as part of a larger genetic screening panel such as preimplantation genetic screening (PGS) or preimplantation genetic diagnosis (PGD).

It is not illegal to undergo genetic testing in order to assess viability of an embryo (such as with PGS) or, for example, to determine whether embryos carry a genetic trait that is known to be carried by one or both of the gamete donors (usually with PGD). Under the exception allowed in this prohibition, it is recognized that there are many devastating genetic diseases and disorders that are linked to the sex chromosomes. For instance, Duchenne muscular dystrophy is caused by a mutation on the X chromosome, which makes males more likely to express the disease since they do not have a second X chromosome to "mask" the condition.

(f) alter the genome of a cell of a human being or in vitro embryo such that the alteration is capable of being transmitted to descendants;

"genome" means the totality of the deoxyribonucleic acid sequence of a particular cell. (section 3 of the AHR Act)

This prohibition prevents people from using genetic technologies to alter the DNA of embryos before transferring them to a uterus. In the case of genetic testing, DNA may be removed from an embryo for the tests, but the rest of the embryo's DNA is not changed. It would be against the law if different DNA was knowingly put back into the embryo before transferring the embryo to attempt a pregnancy. This prohibition is in place to prevent, for example, so-called "designer babies" that would be made to have specific genetic traits that the intended parent(s) consider to be desirable. It also prohibits embryo "gene therapy" that is intended to remove a disease-causing gene.

Because the definition of "genome" in the AHR Act includes all the genetic information in a cell, this prohibition also prevents the use of technologies intended to replace defective mitochondrial DNA in a woman's eggs. Mitochondrial DNA is inherited only from the female contributor to an embryo, and is separate from the nuclear DNA that makes up most of our genetic profile. Mitochondrial DNA makes up less than 1% of the total DNA in a cell, but defective mitochondria can cause some serious diseases and disorders. In some countries, mitochondrial replacement technologies are allowed under research and clinical trial programs. However, it is unknown what long-term effects may occur when an embryo has mitochondrial DNA from a person unrelated to the genetic parents (who contributed nuclear DNA). This prohibition makes it illegal in Canada to knowingly create embryos that have nuclear DNA from two people and mitochondrial DNA from a third person.

(g) transplant a sperm, ovum, embryo or fetus of a non-human life form into a human being;

The prohibition on transplanting non-human gametes, embryos or fetuses into a human makes it illegal to attempt to create a pregnancy in a human that is partially or fully non-human. In the animal kingdom, sometimes members of two species can mate and produce offspring, such as the case of female horses and male donkeys producing mules. Usually members of different species are incapable of mating to produce offspring, but this prohibition makes it illegal to try to do so when one member of the pair is a human. It is unlikely that a human would be able to maintain a non-human pregnancy or that human and non-human gametes could create a viable embryo, but this prohibition makes it illegal to transplant non-human gametes, embryos or fetuses into a human being.

(h) for the purpose of creating a human being, make use of any human reproductive material or an in vitro embryo that is or was transplanted into a non-human life form;

This prohibition adds to the previous one, and makes it illegal to use any human reproductive material or embryos that are or have been in a non-human prior to being used to create a human being. In experimental research, scientists have been able to create viable sperm and eggs by grafting human ovarian or testicular tissue into laboratory animals and stimulating the tissue to mature and produce gametes. This has been investigated in order to determine ways to restore fertility or to supply gametes for people who have had to have their ovaries or testes removed. This prohibition makes the use of any human reproductive material or embryos that were created in such experimental models, for example, illegal to use for the purpose of establishing a human pregnancy. 

(i) create a chimera, or transplant a chimera into either a human being or a non-human life form;

"chimera" means

• (a) an embryo into which a cell of any nonhuman life form has been introduced; or
• (b) an embryo that consists of cells of more than one embryo, foetus or human being. (section 3 of the AHR Act)

A chimera is a being that is made up of tissues that came from at least two different zygotes or early embryos. If two separate eggs are fertilized by two separate sperm, and the resulting fertilized eggs fuse before or after beginning to divide into separate embryos, a chimera can result. This occurs naturally in humans and animals, and often a person does not know they have some type of chimerism. Some cases don't have an effect on a person's health, such as a person whose genetic make-up of their eyes came from separate genetic pairings, resulting in two different-coloured eyes. In other cases, an internal organ may be affected, which can cause problems with the immune system trying to reject the organ. This prohibition makes it illegal to knowingly artificially create chimeras using either human or non-human starting materials, or to transfer a known chimeric embryo into a human or non-human.

(j) create a hybrid for the purpose of reproduction, or transplant a hybrid into either a human being or a non-human life form.

"hybrid" means

• (a) a human ovum that has been fertilized by a sperm of a non-human life form;
• (b) an ovum of a non-human life form that has been fertilized by a human sperm;
• (c) a human ovum into which the nucleus of a cell of a non-human life form has been introduced;
• (d) an ovum of a non-human life form into which the nucleus of a human cell has been introduced; or
• (e) a human ovum or an ovum of a non-human life form that otherwise contains haploid sets of chromosomes from both a human being and a non-human life form. (section 3 of the AHR Act)

This prohibition makes it illegal to knowingly create embryos for reproductive purposes where the starting materials are partly non-human. In "hybrid" definitions (a) and (b) (see above), an embryo would be created by fusing a human and non-human egg and sperm. As described in paragraph 5(1)(g) of the AHR Act above, it is unlikely that a fusion of human and non-human gametes would result in a viable embryo that is capable of establishing a pregnancy, but this prohibition makes it illegal to try to make such a pregnancy happen. In paragraph 3, under "hybrid", definitions (c) and (d), the nuclear DNA of an egg would be removed and replaced with the nuclear DNA of a different species. This could mean a human egg that receives non-human DNA or an animal egg that receives human DNA. Paragraph 3, under "hybrid", definition (e) makes it illegal to create an embryo using genetic input from human and non-human sources. In this case, the DNA does not necessarily have to come from eggs or sperm, but could be single copies of DNA from any cell of a human and non-human that are placed together in a human or non-human egg.

Note that none of the above activities are illegal for the purpose of research. Hybrids are sometimes used in experiments to find out how to improve assisted reproduction activities and to develop ways to allow people to have genetic offspring where they might not otherwise be able to. In research use, non-human gametes may be used due to easy access and fewer ethical concerns. However, the hybrids from such research cannot be transferred to a human or animal uterus in order to attempt a pregnancy, since that is illegal under this prohibition.

9. No person shall obtain any sperm or ovum from a donor under 18 years of age, or use any sperm or ovum so obtained, except for the purpose of preserving the sperm or ovum or for the purpose of creating a human being that the person reasonably believes will be raised by the donor.

The prohibition in section 9 of the AHR Act protects people under the age of 18 from being used as sperm and egg donors. The exception to the prohibition allows people under the age of 18 to preserve their sperm and eggs. For example, a person under the age of 18 with cancer may wish to preserve his or her gametes prior to starting cancer treatments that may cause sterility. The person can then use these gametes after overcoming the disease in order to have genetic offspring.

Additional Information

Any person in Canada who breaks the law under the AHR Act is committing a crime. If found guilty, the person could be fined up to $500,000 or jailed for up to ten years, or both.

As with any criminal act, if a person is actively helping or advising another person who has committed an offense under the AHR Act, the person giving the help could be considered an accomplice to the crime. This judgment would be based on the particular facts of the situation and the level of knowledge of the person giving the help.

If you need more information on the application of the Act or its regulations, please contact Health Canada in one of the following ways:

By Mail:

Office of Policy and International Collaboration
Health Products and Food Branch
Health Canada
Address Locator: 0601B
100 Eglantine Driveway
Ottawa, ON
K1A 0K9

Email: hc.bgtd.ahr-pa.dpbtg.sc@canada.ca
Telephone: 613-957-2991
Toll Free: 1-866-225-0709