As a continuation regarding my experience in a discussion of a single-payer healthcare system in other countries that I visited the CBS 60 minutes story last Sunday discussing the CRISPR discovery struck me. Why do I mention this? Because in speaking with various of my sailing “buddies” from Europe I found out that many don’t have choices of some of the newer more effective treatment therapies including chemotherapy drugs and immunotherapy due to the cost. It is difficult to understand, especially when one listens to the CBS 60 Minute’s episode narrated by commentator Bill Whitaker.

He reviewed a new tool could be the key to treating genetic diseases and may be the most consequential discovery in biomedicine this century

It’s challenging to tell a story about something that’s invisible to the naked eye and tricky to explain. But it’s one we undertook because rarely does a discovery come along that could revolutionize medicine.  It’s called CRISPR and it stands for Clustered Regularly Interspaced Short Palindromic Repeats. CRISPR sounds more like a refrigerator compartment than a gene-editing tool, but it’s giving scientists power they could only imagine before – to easily edit DNA – allowing them to reprogram the genetic code of living things. That’s opening up the possibility of curing genetic diseases. Some researchers are even using it to try to prevent disease entirely by correcting defective genes in human embryos. We wanted to see for ourselves, so we went to meet a scientist at the center of the CRISPR craze.

Bill interviewed Dr. Feng Zhang a young tenured professor at MIT and one of the brains behind CRISPR, he figured out a way to override human genetic instructions using CRISPR.

For the last seven years, Zhang has been working on CRISPR at the Broad Institute in Cambridge, Massachusetts. It’s a research mecca brimming with some of the brightest scientific minds from Harvard and MIT on a mission to fight disease. CRISPR is making medical research faster, cheaper, and easier. Zhang’s colleagues predict it will help them tackle diseases like cancer and Alzheimer’s.  

Bill Whitaker asked how many diseases are we talking about that this could be used to treat?

Feng Zhang stated that there are about 6,000 or more diseases that are caused by faulty genes. The hope is that we will be able to address most if not all of them.

Eric Lander, Director of the Broad Institute, commented that he thought that CRISPR, it’s fair to say, is perhaps the most surprising discovery and maybe most consequential discovery in this century so far.

To understand exactly what CRISPR is, we went to Eric Lander for a quick science lesson. He’s director of the Broad and Zhang’s mentor. He is best known for being a leader of the Human Genome Project that mapped out our entire DNA, which is like a recurring sequence of letters.

Eric Lander stated that during the Human Genome Project, we could read out the entire human DNA, and then, in the years afterward, find the misspellings that caused human diseases. But we had no way to think about how to fix ’em. And then, pretty much on schedule, this mind-blowing discovery that bacteria have a way to fix those misspellings, appears.

Eric Lander went on to clarify that this comes from bacteria.  Bacteria, you know, they have a problem. And they came up with a really clever solution. When they get infected by viruses, they keep a little bit of DNA, and they use it as a reminder. And they have this system called CRISPR that grabs those reminders and searches around and says, “If I ever see that again, I am gonna cut it.”

Zhang used that same bacterial system to edit DNA in human cells. Our DNA is made up of chemical bases abbreviated by the letters A, T, C, and G. As you can see in this animation from Zhang’s lab at MIT, a mutation that causes disease reads like a typo in those genetic instructions. If scientists can identify the typo, they can program CRISPR to find it and try to correct it. Dr. Zhang went on to further describe how the CRISPR will go in, and out of billions and billions of letters on your DNA, find the exact ones that have been programmed and cut it to edit it, snip out the bad part and add something to give the cell a new piece of DNA that carries the sequence you want to be incorporated into the genome.

More was discussed such as the multiple uses and studies and the potential for curing diseases and preventing disease. Mr. Lander states that he didn’t think that we’re close to ready to use it to go edit the human population. He thought that we’ve gotta use it for medicine for a while. I think those are the urgent questions. That’s what people want right now, is they want cures for disease.

Urgent questions are being answered as we speak with small clinical trials, the first in the U.S. using CRISPR to target certain types of cancer, which is now enrolling patients. We all believe that this is gonna have a real effect over the course of the next decade and couple of decades. And for the next generation, others and I believe that it’ll be transformative. Consider these other reports.

Last year, the Food and Drug Administration approved the first cellular immunotherapies to treat cancer and that CRISPR can enhance cancer immunotherapy. These therapies involve collecting a patient’s own immune cells — called T cells — and supercharging them to home in on and attack specific blood cancers, such as hard-to-treat acute lymphoblastic leukemia and non-Hodgkin lymphoma.

But so far, these T cell immunotherapies — called CAR-T cells — can’t be used if the T cells themselves are cancerous. Even though supercharged T cells can kill cancerous T cells, they also can kill each other because they resemble one another so closely.

Scientists at Washington University School of Medicine in St. Louis now have used the gene-editing technology CRISPR to engineer human T cells that can attack human T cell cancers without succumbing to friendly fire.

The study evaluating the approach in mice appears online in the journal Leukemia. The researchers also engineered the T cells so any donor’s T cells could be used. A “matched” donor with similar immunity is not required and neither is the patient’s own T cells, which is important for the obvious reason: Many of the patient’s own T cells are cancerous.

“Cancerous T cells and healthy T cells have exactly the same protein — CD7 — on their surfaces,” said senior author John F. DiPersio, MD, Ph.D., the Virginia E. and Sam J. Golman Professor of Medicine in Oncology.

DiPersio’s team first generated a novel CAR-T strategy targeting CD7, allowing for the targeting and killing of all cells with CD7 on the surface.

“But if we program T cells to target CD7, they would attack the cancerous cells and each other, thus undermining this approach,” DiPersio said. “To prevent this T cell fratricide, we used CRISPR/Cas9 gene editing to remove CD7 from healthy T cells, so they no longer carry the target.”

DiPersio, who treats patients at Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital, and his colleagues also used CRISPR gene editing to simultaneously eliminate the therapeutic T cells’ ability to see healthy tissues as foreign.

To do this, they genetically deleted the T cell receptor alpha (TCRa) subunit. This way, T cells from any normal donor can be used without risk of life-threatening toxicities such as graft-versus-host disease, in which T cells attack the organs of the recipient, sometimes resulting in death. This new approach also may have broad implications for the CAR-T field, allowing for use of therapeutic T cells from any healthy donor. Healthy T cells could be collected in advance and stored for any patient with a relapsed T cell malignancy.

“We have genetically modified these T cells so they are unable to cause graft-versus-host disease but can still kill cancerous cells,” said first author Matthew L. Cooper, Ph.D., an instructor in medicine. “One additional benefit of this approach is that a patient could receive this therapy much more quickly after diagnosis. We wouldn’t need to harvest the patient’s own T cells and then modify them, which takes time. We also wouldn’t have to find a matched donor. We could collect T cells from any healthy donor and have the gene-edited T cells ready in advance, a strategy termed ‘off-the-shelf’ CAR-T cell therapy.”

The researchers demonstrated that this approach is effective in mice with T cell acute lymphoblastic leukemia (T-ALL) taken from patients. Mice treated with the gene-edited T cells targeted to CD7 survived 65 days, compared with 31 days in a comparison group that received engineered T cells targeting a different protein. The researchers also found no evidence of graft-versus-host disease in mice that received T cells lacking the molecular machinery that sees healthy tissues as foreign. They also found that the therapeutic T cells remained in the blood for at least six weeks after the initial injection, suggesting it could ramp up again to kill cancerous T cells if they return.

“T cell malignancies represent a class of devastating blood cancers with high rates of relapse and death in children and adults with the disease,” Cooper said. “In an effort to develop the first clinically viable targeted therapy for this type of cancer, we are scaling up the manufacturing of our gene-edited CAR-T cells for clinical trials, which we hope to complete at Siteman Cancer Center.”

And another announcement about a new application of CRISPR in the report that researchers from the Wellcome Trust Sanger Institute have reported that a new target for the treatment of leukemia has been found. 

A new drug target for acute myeloid leukemia (AML) has been identified that could open new avenues for the development of new treatments against the deadly disease. Researchers from the Wellcome Trust Sanger Institute have published research in Nature that shows the inhibition of the METTL3 gene specifically kills human and mouse leukemia cells. The gene is responsible for the survival of cancer cells but not healthy cells, meaning it could be targeted safely.

AML is an aggressive blood cancer that can affect people of all ages. It develops in the bone marrow, overwhelming the healthy cells that reside there, which impairs the immune system leading to serious infections and bleeding. The disease is rare, with just 3,100 cases per year in the UK, but it develops quickly making it difficult to catch. Current treatments used for AML include chemotherapy and bone marrow transplants, but these save fewer than one in three patients.

The researchers used CRISPR-Cas9 gene-editing technology to screen cancer cells for potential therapeutic targets. They created a leukemia mouse model containing mutations that could be targeted in human AML cells. Each gene was tested to decipher its role in the disease. Forty-six genes were identified that could modify RNA, including METTL3, which had a particularly strong effect.

The group found that the METTL3 protein binds 126 genes, many of which support AML cell survival, and then modifies the RNA that is subsequently produced, increasing their translation. When this modification was blocked, essential proteins for the survival of the leukemia were no longer produced.

George Vassiliou, the joint project leader and consultant hematologist at Cambridge University Hospitals NHS Trust, commented on the implications of the study’s findings: “Our treatments have changed little for decades and outcomes remain poor… We believed that we had to think differently and look in new places for ways to treat the disease… We hope that this discovery will lead to more effective treatments that will improve the survival and the quality of life of patients with AML.”

One way to boost survival could be to improve the treatments that we already have. This is what Italian biotech, MolMed, has done, developing Zalmoxis, which ups the safety of bone marrow transplants. A major area of hype in the blood cancers field is CAR-T, and Novartis’Kymriah was the first to be approved by the FDA after demonstrating efficacy against B cell leukemia, while Celyad has developed a Natural Killer Receptor T cell platform, which cleared a patient of cancer during the early stages of a clinical trial.

Consider the announcement that the F.D.A. Panel Recommended the Approval for a Gene-Altering Leukemia Treatment.

Denise Grady last year reported on a set of cases that started me on my investigation into CRISPR where a Food and Drug Administration panel opened a new era in medicine on Wednesday, unanimously recommending that the agency approve the first-ever treatment that genetically alters a patient’s own cells to fight cancer, transforming them into what scientists call “a living drug” that powerfully bolsters the immune system to shut down the disease.

If the F.D.A. accepts the recommendation, which is likely, the treatment will be the first gene therapy ever to reach the market in the United States. Others are expected: Researchers and drug companies have been engaged in intense competition for decades to reach this milestone. Novartis is now poised to be the first. Its treatment is for a type of leukemia, and it is working on similar types of treatments in hundreds of patients for another form of the disease, as well as multiple myeloma and an aggressive brain tumor.

To use the technique, a separate treatment must be created for each patient — their cells removed at an approved medical center, frozen, shipped to a Novartis plant for thawing and processing, frozen again and shipped back to the treatment center.

A single dose of the resulting product has brought long remissions, and possibly cures, to scores of patients in studies who were facing death because every other treatment had failed. The panel recommended approving the treatment for B-cell acute lymphoblastic leukemia that has resisted treatment or relapsed, in children and young adults aged 3 to 25.

One of those patients, Emily Whitehead, now 12 and the first child is ever given the altered cells, was at the meeting of the panel with her parents to advocate for approval of the drug that saved her life. In 2012, as a 6-year-old, she was treated in a study at the Children’s Hospital of Philadelphia. Severe side effects — raging fever, crashing blood pressure, and lung congestion — nearly killed her. But she emerged cancer free and has remained so.

“We believe that when this treatment is approved it will save thousands of children’s lives around the world,” Emily’s father, Tom Whitehead, told the panel. “I hope that someday all of you on the advisory committee can tell your families for generations that you were part of the process that ended the use of toxic treatments like chemotherapy and radiation as standard treatment, and turned blood cancers into a treatable disease that even after relapse most people survive.”

The main evidence that Novartis presented to the F.D.A. came from a study of 63 patients who received the treatment from April 2015 to August 2016. Fifty-two of them, or 82.5 percent, went into remission — a high rate for such a severe disease. Eleven others died.

“It’s a new world, an exciting therapy,” said Dr. Gwen Nichols, the chief medical officer of the Leukemia and Lymphoma Society, which paid for some of the research that led to the treatment.

The next step, she said, will be to determine “what we can combine it with and is there a way to use it in the future to treat patients with less disease so that the immune system is in better shape and really able to fight.” She added, “This is the beginning of something big.”

At the meeting, the panel of experts did not question the lifesaving potential of the treatment in hopeless cases. But they raised concerns about potentially life-threatening side effects — short-term worries about acute reactions like those Emily experienced, and longer-term worries about whether the infused cells could, years later, cause secondary cancers or other problems.

Oncologists have learned how to treat the acute reactions, and so far, no long-term problems have been detected, but not enough time has passed to rule them out. Patients who receive the treatment will be entered in a registry and tracked for 15 years.

Treatments involving live cells, known as “biologics” are generally far more difficult to manufacture than standard drugs, and the panelists also expressed concerns about whether Novartis would be able to produce consistent treatments and maintain quality control as it scaled up its operation.

Another parent at the meeting, Don McMahon, described his son Connor’s grueling 12 years with severe and relapsing leukemia, which started when he was 3. Mr. McMahon displayed painful photographs of Connor, bald and intubated during treatment. And he added that chemotherapy had left his son infertile.

A year ago, the family was preparing for a bone marrow transplant when they learned about the cell treatment, which Connor then underwent at Duke University. He has since returned to playing hockey. Compared with standard treatment, which required dozens of spinal taps and painful bone marrow tests, the T-cell treatment was far easier to tolerate, Mr. McMahon said, and he urged the panel to vote for approval.

A third parent, Amy Kappen, also recommended approval, even though her daughter, Sophia, 5, had died despite receiving the cell treatment. But it did relieve her symptoms and give her a few extra months. Sophia’s disease was far advanced, and Ms. Kappen thought that if the treatment could have been given sooner, Sophia might have survived.

The treatment was developed by researchers at the University of Pennsylvania Children’s Hospital and licensed to Novartis. The use will not be widespread at first because the disease is not common. It affects only 5,000 people a year, about 60 percent of them children and young adults. Most children are cured with standard treatments, but in 15 percent of cases — like Emily and Connor’s — the disease does not respond, or it relapses.

Although the figure may seem high, people with cancer often endure years of expensive treatment and repeat hospital stays that can ultimately cost even more.

Because the treatment is complex and patients need expert care to manage the side effects, Novartis will initially limit its use to 30 or 35 medical centers where employees will be trained and approved to administer it, the company said.

As to whether the treatment, known as CTL019 or tisagenlecleucel (pronounced tis-a-gen-LEK-loo-sell), will be available in other countries, Ms. Masow said by email: “Should CTL019 receive approval in the U.S., it will be the decision of the centers whether to receive international patients. We are working on bringing CTL019 to other countries around the world.” She added that the company would file for approvals in the European Union later this year.

By late November 2016, 11 of the 52 patients in the study who went into remission relapsed. Twenty-nine were still in remission. Eleven others had further treatments, like bone marrow transplants. One patient was not available for assessment. Three who had relapses died, and one who did not relapse died from a new treatment given during remission. The median duration of remission is not known because it has not been reached: Some patients were still well when last checked.

Researchers are still debating about which patients can safely forgo further treatment, and which might need a bone marrow treatment to give the best chance of a cure.

The treatment requires removing millions of a patient’s T-cells — a type of white blood cell often called soldiers of the immune system — and genetically engineering them to kill cancer cells. The technique employs a disabled form of H.I.V., the virus that causes AIDS, to carry new genetic material into the T-cells to reprogram them. The process turbocharges the T-cells to attack B-cells, a normal part of the immune system that turns malignant in leukemia. The T-cells home in on a protein called CD-19 that is found on the surface of most B-cells.

The altered T-cells are then dripped back into the patient’s veins, where they multiply and start fighting cancer.

Dr. Carl H. June, a leader of the University of Pennsylvania team that developed the treatment, calls the turbocharged cells “serial killers.” A single one can destroy up to 100,000 cancer cells.

Because the treatment destroys not only leukemic B-cells but also healthy ones, which help fight germs, patients need treatment to protect them from infection. So every few months they receive infusions of immune globulins.

In studies, the process of re-engineering T-cells for treatment sometimes took four months, and some patients were so sick that they died before their cells came back. At the meeting, Novartis said the turnaround time was now down to 22 days. The company also described bar-coding and other procedures used to keep from mixing up samples once the treatment is conducted on a bigger scale.

The Food and Drug Administration, ushering in a new era of cancer treatment, has approved the revolutionary cancer therapy that uses genetically engineered immune cells. The FDA calls the treatment, made by Novartis, the “first gene therapy” in the U.S. The therapy is designed to treat an often-lethal type of blood and bone marrow cancer that affects children and young adults. Known as a CAR-T therapy, the approach has shown remarkable results in patients. The one-time treatment will cost $475,000, but Novartis says there will be no charge if a patient doesn’t respond to the therapy within a month.

Michael Werner, a lawyer and expert on gene and cell technologies and regulation, and a partner at Holland and Knight in Washington said that results so far proved that T-cell treatment works. “The fact that it can be done means more people will go into the field and more companies will start developing these products.” He added, “I think we’re in for really exciting times.”

The FDA defines gene therapy as a medicine that “introduces genetic material into a person’s DNA to replace faulty or missing genetic material” to treat a disease or medical condition. This is the first such therapy to be available in the U.S., according to the FDA. Two gene therapies for rare, inherited diseases have already been approved in Europe.

This is the future! But will a new single-payer health care system allow the newer techniques to be used to treat patients? Consider the European experience and wait to see what is on the horizon for the CRISPR technology. I for one am excited!!