Reengineering Life is a series from Future Human about the astonishing ways genetic technology is changing humanity and the world around us.
In sub-Saharan Africa, millions of people suffer from sickle cell disease, and an estimated 50% to 90% of children born with the ailment die before the age of five. Bill Gates says he has a plan to cure it.
The Microsoft co-founder and billionaire is investing millions of dollars into the development of low-cost gene-editing treatments that could be far more accessible than current transplant-based treatments. “We believe that over the next decade, we will be able to make this breakthrough,” Gates said at the annual meeting of the American Association for the Advancement of Science in February.
Recently, the Bill & Melinda Gates Foundation has awarded several grants to biotech companies, academic organizations, and nonprofits to further that goal. It’s all part of an initiative announced last year, in which the Gates Foundation and the U.S. National Institutes of Health each pledged $100 million to develop affordable, gene-based cures for sickle cell and HIV, which disproportionately affect Africans and those of African descent. They plan to launch trials of these treatments in the United States and sub-Saharan Africa within the next seven to 10 years.
Sickle cell arises when a person inherits a genetic mutation that causes their blood cells to become sticky and sickle-shaped. These misshapen cells stick together and block blood vessels, causing severe pain, infection, and stroke. In the United States, about 100,000 people, most of them Black, are affected by the disease.
The side effects of sickle cell can be treated with pain medications and blood transfusions, and in some cases, children and teenagers can even be cured with a bone marrow transplant. But the vast majority of people with sickle cell live in resource-poor countries and can’t access or afford these treatments. Even in the United States, a transplant is only possible for a fraction of people because it requires the candidate to have a healthy sibling with closely matching bone marrow who can serve as a donor. The procedure can cost up to $300,000 and comes with the risk of serious and sometimes life-threatening complications.
In hopes of curing more people with sickle cell, researchers are turning to gene editing. One company, CRISPR Therapeutics, is using CRISPR to genetically alter a person’s blood-forming stem cells outside of the body to counteract the disease-causing mutation. The modified cells are then infused back into the patient, where they travel to the bone marrow and make healthy new blood cells.
So far, at least two people have been treated with the approach, and it appears effective, but there are downsides. It requires an expensive and complicated procedure that involves altering cells outside of the body, which can prove impractical in resource-poor countries. Similar to a bone marrow transplant, people first need to undergo a high dose of chemotherapy to make room for the newly edited cells. This requires several weeks in the hospital and often comes with side effects like nausea, vomiting, and fatigue.
At the February AAAS meeting, Gates called the approach “very promising” but added that the procedure’s complexities mean it can’t be used broadly in low-income countries.
“It works, but it’s just not widely deployable,” Laura Sepp-Lorenzino, PhD, chief scientific officer of Intellia Therapeutics, which received a grant of $2.8 million from the Gates Foundation in November, tells Future Human. The company, based in Cambridge, Massachusetts, was co-founded by CRISPR pioneer and Nobel Prize winner Jennifer Doudna, PhD.
Gates and Intellia envision a simpler gene-editing procedure that doesn’t require chemotherapy, a hospital stay, or modifying cells outside the body.
Intellia plans to use CRISPR directly inside the body to edit a person’s blood stem cells. Doing so is potentially risky because the gene-editing molecules need to find their way to the right cells. In contrast, CRISPR Therapeutics is editing cells outside the body, which allows scientists to make precise edits and to meticulously check their work before returning the cells to a person.
Intellia’s scientists are engineering microscopic vessels called lipid nanoparticles — essentially tiny fat bubbles — to carry CRISPR to the bone marrow. The nanoparticles are biodegradable and are meant to break down after reaching their target in the body. They’re also easy to manufacture and can be scaled up, Sepp-Lorenzino said. The company envisions that the therapy would be given in an outpatient procedure via an IV, which are used widely even in developing countries.
“The goal here is to not have the multidecade lag between when a breakthrough is available in the United States and when it gets out broadly to help anyone,” Gates said in February.
Sepp-Lorenzino couldn’t comment on when Intellia plans to start treating human patients but said the company is conducting experiments in mice right now.
As I wrote in 2017, many sickle cell patients and their doctors are excited about the promise of CRISPR to bring cures to more people with the disease. But in the United States, the shadow of the Tuskegee study, in which African American men with syphilis were deliberately left untreated, and many other instances of experimentation on Black Americans means that some sickle cell patients may be wary of gene-editing trials led by white researchers.
There’s also a long history of medical exploitation in Africa. Over the years, Big Pharma has run clinical trials in African countries, an in some cases, companies failed to seek proper government permission or informed consent from patients.
Researchers working on new gene-editing treatments for sickle cell will not only need to gain the trust of people with sickle cell, but also clearly convey the risks of the procedure to them. Then, if these in-the-body treatments end up working, drug companies and organizations like the Gates Foundation will have to figure out how to deploy them widely to the people who need them most.