Potential Sickle Cell Cure Necessitates Celebration and Reflection

A $17 million grant was announced on Dec. 1, 2021, that will fund a clinical trial aimed at developing a cure for Sick Cell Disease (SCD).

The funding is provided by the National Institute of Health’s Cure Sickle Cell Initiative and the California Institute of Regenerative Medicine.

This could be a game changer for over 100,000 Americans, and the study is ground-breaking for two reasons.

First, it is serious funding for an often-overlooked disease and demographic. While not a racially specific disease, rates of SCD are highest among African Americans, affecting 1 in 365 births.

SCD is an inherited blood disorder that is characterized by abnormal hemoglobin. This often leads to ridged, sickle shaped cells. The abnormal shape can cause restriction of capillary blood flow that causes organ damage.

SCD patients experience anemia, pain, infections and even stroke. Unfortunately, only around 50% of SCD patients live to be 50 years of age.

Historically, SCD has received less funding per patient than genetic diseases associated with white patients, specifically cystic fibrosis (CF). While neither disease is racially specific, CF affects 1 in 2,600 whites versus 1 in 6,000 Blacks.

On average, the National Institute of Health (NIH) spends $84 million a year on CF versus $75 million on SCD. The shocker comes when one realizes that there are 30,000 CF patients nationwide compared to 100,000 SCD patients, according to the JAMA Network.

As a result, there has been less research and few treatments developed for SCD.

Second, the grants fund a four-year trial aimed at using CRISPR-Cas9 technology to treat SCD.

The University of California, San Francisco – in conjunction with the University of California, Los Angeles and the University of California, Berkeley – will be among the first to conduct a trial using CRISPR-Cas9 technology to treat SCD, building on the work of Vertex Pharmaceuticals and CRISPR Therapeutics.

So far there are 45 patients who have received treatment, most notably Victoria Gray who has received treatment for over a year.

Researchers plan to begin with six adults and then later expand to three adolescents. This trial is a big step toward what we hope will be the development of a cure.

But what is CRISPR and how does it work?

CRISPR is a DNA chain of repetitive base sequences that functions as a viral defense mechanism for prokaryotic organisms. The Cas9 enzyme acts like scissors and can cut out defective strands of DNA.

In 2012, Jennifer Doudna and Emmanuelle Carpenter discovered and isolated the sequences. In subsequent years, researchers have figured out how to program these enzymes. Since its discovery, CRISPR technology has been cited in over 450,000 scientific articles and used to treat over 1,000 patents.

In short, CRISPR technology can easily be thought of as a word processor for editing DNA. Technicians can program the Cas9 enzyme to cut defective DNA chains.  Subsequently, DNA can be added, removed or altered so that the genome then can repair itself.

This does not mean scientists can write whatever DNA sequences they want, but DNA can now be edited.

The technology has huge implications for health care. Potential for advancement does not stop with medicine but extends to agriculture and even environmental implications.

While all of this is exciting, it does raise several questions.

First and foremost, is this safe? The benefits are unimaginable but what are the risks?

The National Academies of Sciences Engineering and Medicine have already begun great work on this by hosting two international summits on human gene editing, but more needs to be done.

Experts need to do a better job of explaining CRISPR and related technologies to the general public, and we need to be very careful what DNA sequences are decided to be undesirable.

As the technology progresses, researchers are going to develop procedures that go beyond cancer, SCD and CF. What other genetic abnormalities will be added to the list?

For example, it is possible that researchers could develop procedures for altering the Trisomy 21 sequence which causes Down Syndrome. Should this be allowed?

Similar thought experiments can be applied to other traits. Since our DNA controls hair, eye and skin color, one can envision a scenario where a whole demographic could, in theory, be edited out of the human species.

Considering hypotheticals, even if they seem far-fetched, forces us to ask important questions about the appropriate limits of human gene editing.

It also reminds us that a value judgment will be made every time DNA is edited. These are not decisions that can or should be made without tremendous reflection and public transparency.

The last area of concern takes us back to the beginning.

While it is significant that attention is finally being paid to SCD, we need to reflect upon why SCD is the first genetic disease focused upon for this research.

While SCD is one of the more common genetic diseases, it also dominates minority communities.

There is no indication of racial bias in this trail, but our long national history of improper and appalling research on minorities demands that we pay close attention to what is going on.

If nothing else, the rapid rise of CRISPR technology should remind us that all new technology requires us to evaluate possible moral pitfalls and to consider the assumptions being made about what it means to be human and whole.

Only then can we ensure technology is used appropriately.