How gene editing and immunotherapy are changing lives

How gene editing and immunotherapy are changing lives

When I started medical school thirty years ago, and learned about the discovery of streptomycin, I wondered what it must have been like for the doctors who first used it to cure the “white death.” How satisfying it must have been to tell a previously hopeless patient, “We can cure you.”

What brought this to mind was my rotation at an old part of the hospital where I was training. I had noticed that some of the windows had bars on them, not decorative, serious bars, and had been told that this wing had been used in the past for tuberculosis patients. It was hard to imagine, at least before the recent pandemic, that thousands of Americans were literally incarcerated in what were called sanitariums to protect the general public from the terrible scourge of consumption. Wealthy Americans were able to flee to European treatment centers with fresh air and mountain trails, but the poorer ones went behind locked doors in their home country.

These had been started in 1884 with a small cottage when Dr. Edward Trudeau opened a little cottage on Saranac Lake in New York. A consumptive himself, it allowed isolation in sunlight and fresh air. By 1900, giant compounds were constructed for this purpose, like the one outside of Booneville, Arkansas. Like a small city, it had its own chapel, dairy farm, fire department, and even a children’s hospital with a school. The fee was ten dollars a week when it opened. Then, in the 1920s and 30s, states began passing public safety laws. This was the era of Buck v. Bell. When the state of Virginia was forcefully sterilizing American citizens, it had deemed unworthy of reproduction. The Supreme Court agreed with the states, and Ms. Bell was sterilized for the crime of having dated outside of her race. Clear evidence of a feeble mind in their eyes. With that attitude and the law on their side, people with tuberculosis were forcefully placed in these facilities, which quickly became overcrowded, causing living conditions to deteriorate.

Then streptomycin was discovered in 1943, and it was possible to treat and even cure the disease. The sanitariums started emptying out, and by 1960, the Arkansas Tuberculosis Sanatorium was at half capacity. It was finally closed in 1972 but has been very well preserved, and I’ve recently seen it myself. Today, tuberculosis still kills around the world, but public health measures, treatments, and vaccines have dramatically reduced its toll on society.

And that brings me to recently approved therapies that I believe will bring about a sea change in medical treatment even larger than antibiotics.

Before antibiotics, you could die from strep throat. My great-grandfather did, in fact. Coughing up large pieces of his throat, I’m told. While some of us long for the “good old days” or think they do, It wasn’t long ago when almost half of all children born in the U.S. did not live to see their fifth birthday. Then vaccines came, and everything changed. The smallpox vaccine alone has saved the lives of an estimated 200 million people. These were great advances. But there were still diseases and medical conditions against which we had no good treatment. Novel viruses, cancer, and genetic diseases are most prominent in my mind. Nothing will shake your belief in divine benevolence like a stroll through a pediatric cancer ward. And the suffering I have seen in my career experienced by those with sickle cell anemia has been horrible. Imagine randomly experiencing bone-crushing pain and having to go to an ER and beg for treatment for your entire life. Treatment was oxygen, IV fluids, and morphine or some other opiate, as nothing else would give any relief. I shudder to think about what these people suffer now, with the opioid panic in full swing and “opioid-free ERs” all the rage. If suffering is good for the soul, then those who suffer from this condition should all be sainted.

That being said, we now have a cure. Not just a treatment, a cure. On December 8 of 2023, the U.S. FDA approved two cell-based gene therapies, exagamglogene autotemcel, also called exa-cel or Casgevy, and lovotibeglogene autotemcel, also called lovo-cel or Lyfgenia, for patients aged 12 and over who suffer from recurrent vaso-occlusive crises caused by sickle cell disease. Casgevy uses a one-time, single-dose infusion of hematopoietic stem cell transplant that has undergone CRISPR/Cas9 gene editing technology to modify the erythroid-specific enhancer region of the BCL11A gene on CD34+ hematopoietic stem cells. This alteration reduces BCL11A expression in erythroid lineage cells and thereby stimulates the production of fetal hemoglobin (HbF). The fetus produces this hemoglobin in utero, but we quickly switch to adult-type hemoglobin (HbA) within about six months of birth. The HbF oxygen dissociation curve is left-shifted compared to HbA, meaning HbF has a higher affinity for oxygen. Lack of oxygen in the bones, joints, and organs of sickle cell disease sufferers is what causes defective HbA-containing red cells to change shape, causing damage and pain. The presence of HbF in the blood of a sickle cell patient reduces sickling and maintains blood flow. A single-dose cure for a genetic disease. How long will it be before other diseases, like cystic fibrosis and Type I diabetes, will be curable? And then, we will have prenatal screening for these conditions during amniocentesis and be able to cure them before the patient suffers at all.

And what about other applications? I think every patient over the age of 50 should be able to undergo a treatment to permanently reduce their myostatin levels. Myostatin is the hormone that triggers muscle resorption. Muscle is a very active tissue, burning a lot of calories, and the body carries the minimum necessary to function. Don’t exercise for three days, and your muscles will start to shrink. Get old, and it’s very hard to keep them. One of the most common causes of death in the elderly is the sequelae of a hip fracture. This occurs because we get too weak to stand and don’t have enough cushion when we fall. We have bone-strengthening treatments for osteopenia and porosis, but nothing for the muscles. We could increase mobility and fitness in the elderly with a single treatment, by DNA vaccine or perhaps CRSPR technology.

Finally, we have immunotherapies for cancer. Treated until now with the disfiguring and toxic therapies of surgery, chemotherapy, and radiation. Life-saving, to be sure. But terrible to experience. Now we have CAR T. Spontaneous remission has been well-known to doctors for over a century. A patient suffering from a terrible cancer will suddenly have a dramatic reversal, with malignant and untreatable tumors suddenly disappearing in days. This happens when a cancer cell has expressed a protein that the body identifies as foreign or dangerous, allowing the cancer cells to be targeted for destruction by the body’s immune system. A scalpel far finer than any surgeon’s. These episodes were rare and random until now. Now, we can collect T cells from the patient and re-engineer them in the lab to produce proteins on their surface called chimeric antigen receptors or CARs, then grow them to a sufficient quantity, and transfuse them back into the patient. Once back in the patient’s body, the CARs recognize and bind to specific antigens on the surface of cancer cells and trigger their destruction.

These three technologies will I believe, bring about a revolution in human health and longevity, unparalleled in human history. While political interference in the practice of medicine has made this a dangerous time in America to be a doctor, there has never been better time to be a patient with one of these conditions.

L. Joseph Parker is a distinguished professional with a diverse and accomplished career spanning the fields of science, military service, and medical practice. He currently serves as the chief science officer and operations officer, Advanced Research Concepts LLC, a pioneering company dedicated to propelling humanity into the realms of space exploration. At Advanced Research Concepts LLC, Dr. Parker leads a team of experts committed to developing innovative solutions for the complex challenges of space travel, including space transportation, energy storage, radiation shielding, artificial gravity, and space-related medical issues. 

He can be reached on LinkedIn and YouTube.


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