“This possibly represents the greatest discovery of the century. With this technology, we could end suffering and disease for billions of people.” Stephen Heitner, M.D., a cardiologist at OHSU in Portland, Oregon, was a member of the research team who showed it is possible to correct genetic defects in embryos. As he explains, this breakthrough could ultimately lead to humankind’s ability to end genetic diseases.
The study involved DNA, which is your hereditary material, inherited from each of your parents. Small pieces of the DNA are called genes. Researchers recruited a patient with a gene defect which caused his heart to develop hypertrophic cardiomyopathy, or HCM, or overly thick heart muscle. HCM can cause heart failure, cardiac arrest and sudden death. Each child of a patient with HCM has a 50 percent risk to inherit the genetic predisposition to develop HCM themselves.
The study team used a technology called CRISPR-Cas9, which works like scissors to DNA. The research participant donated sperm, which researchers combined with eggs from healthy female research participants. This process created embryos. They injected CRISPR-Cas9 into the embryos to scissor out the portion of the patient’s gene that was defective. The embryo then used the healthy egg’s DNA as a template to build healthy DNA, thereby fixing the genetic defect. For a more detailed explanation I’d recommend reading this article https://www.vox.com/science-and-health/2017/8/2/16083300/crispr-heart-disease.
Theoretically, if the embryo had been allowed to develop into a baby, the baby would not be at increased risk for HCM because the genetic defect causing that risk had been fixed. The big-picture concept is this: families with genetic disease due to a single genetic defect could use this technology to prevent the genetic defect from being passed on to future generations. Long-term, this means we could eradicate genetic disease, including sudden death syndromes such as Long QT or HCM, conditions for which there are known genetic causes.
There are obvious benefits to this technology. Parents affected by genetic disorders could be comforted in knowing that their child will not inherit the genetic disease and its associated health problems and risks. Since the child would not have the genetic disorder, the child could not pass it on to the next generation, either. As Amy Koski, clinical research coordinator for the study and manager of the OHSU Center for Embryonic Cell and Gene Therapy, notes, “We’re literally giving children an opportunity to not have to go to the doctor, to be able to run if they want to run, to be able to do what they want to do.” However, despite these benefits, there are significant scientific, legislative and ethical issues to consider before this technology is brought into mainstream health care.
From a scientific standpoint, this study is only the first step in a long series of research studies needed to prove the safety and effectiveness of the technology. This study was able to fix the genetic problem in about 72 percent of the embryos created; we would need to get the accuracy of the technology to nearly 100 percent before using it for patient care.
Additionally, current laws and regulations restrict use of CRISPR-Cas9 only to research, not mainstream clinical use. In fact, the research embryos were destroyed because it is illegal for them to be allowed to develop into babies. The National Institutes of Health will not fund any research involving human embryos, and the Food and Drug Administration is prohibited by Congress from even acknowledging this technology exists. This means that research studies need to be paid for outside of the NIH, and laws would have to be changed in order for the FDA to be able to regulate use of CRISPR-Cas9 technology for humans.
Last but certainly not least, CRISPR-Cas9 has brought to light significant ethical concerns. Many argue that use of this technology amounts to playing God and feel that humans should not have any role in genetic modification. Others worry about the ‘slippery slope’ this creates. In the wrong hands, theoretically this technology could lead to ‘designer babies’ with selected genetic advantages. Heitner, Koski, and many of those on the study team have stated that regulations must be developed and enforced to ensure this technology is used for the greater good. Heitner said, “The ethics of this technology need to be ironed out by a panel of experts, including scientists, physicians, leaders from a variety of religions as well as public health experts and members of the community.”
The study team believes that patients themselves should play a large role in how this technology is applied. Koski said, “What’s really important is hearing from the people who live with genetic diseases. We need them to speak out and tell their story, the positive and the negative. Regulators need to hear this side. Right now the discussion lies with scientists, ethicists and Congress; we all have opinions and facts, but most of us do not fully grasp what hurdles in life come with genetic diseases. They need to show the decision makers why gene correction really matters.”
Despite these and other obstacles to success, it appears for the time being that this research will proceed forward, because researchers worldwide are already working to advance this technology. Heitner stated, “As stewards of science and medicine, we need to be sure this is done correctly, and the only way that that can happen is if we do it. There are people all over the world that are racing to get this technology done and I feel that it’s our obligation to ensure it is done the right way.”
Author Meghan Mannello, M.S., C.G.C., is a cardiovascular genetic counselor at OHSU in Portland, Oregon. She is not a member of the study team.