By Justin Yamashita. Benchtop, site, CRO. Three levels of basic and clinical research, explained without spin.

Twenty-five years ago this month, a drug was approved that changed what a cancer diagnosis could mean. The discovery that made it possible was published in 1960 and ignored for over a decade. This is how it began.

Last week we mapped the full drug development pipeline: target identification, lead optimization, preclinical testing, the IND application, three phases of human trials, and FDA review. Good Clinical Practice is the support beam that holds it accountable. The rulebook written in blood, from Nuremberg to Tuskegee.

This week the pipeline stops being abstract. We follow one drug through every stage we described, starting at the very beginning, 41 years before it reached a patient. Issue 005 covers the discovery that started it. Issues 006 through 008 cover the decade it almost died, the trials that almost did not happen, and what the survival numbers look like now.

The drug is Gleevec. The disease is chronic myeloid leukemia, or CML. The discovery that made it possible began with something two scientists noticed and nobody believed for 13 years.

The science in this issue runs from 1960 to 2001. But this issue is also about what happens when that science walks into a living room uninvited. The Root Room section is a demonstration of the Skeptic’s Toolkit in action, with a real claim, real resistance, and no easy wins. Debby is trying to respond to her brother-in-law. Sam and Rooty are helping. If you have ever wanted to push back on a health claim at home without starting a fight, that section is where to go first.

NEW HERE? START WITH THESE THREE.

May is National Cancer Research Month. The story below is one reason why.

Gleevec received FDA approval on May 10, 2001 [8]. The agency reviewed it in less than three months. The evidence was so clear that the FDA did not require a full advisory committee meeting. The disease it treated, CML, carried a five-year survival rate of roughly 30 percent in the year before approval [7]. Within a decade, that number had risen above 90 percent [5].

Kareem Abdul-Jabbar was diagnosed with CML in 2008, seven years after Gleevec was approved. He is still alive today. His story is in Issue 008. The survival rate you just read is the reason.

The story of how Gleevec happened does not begin in a pharmaceutical company. It does not begin in 2001. It begins in 1960, in a laboratory at the University of Pennsylvania, with something so small it could only be seen under a microscope.

Peter Nowell was a pathologist at the University of Pennsylvania. David Hungerford was a doctoral student at the Fox Chase Cancer Center across town. Working in separate labs but collaborating, they were examining chromosomes from the leukemia cells of patients with CML.

Chromosomes are the structures inside cell nuclei that carry genetic information. Human cells normally contain 46 chromosomes arranged in 23 pairs. Nowell and Hungerford noticed something in the CML cells they examined: one chromosome was distinctively, consistently shorter than it should be. Patient after patient.

They published in Science in 1960 [1]. They named the anomaly the Philadelphia chromosome, after the city. The scientific community responded with near-total silence. For 13 years, nothing happened.

Janet Rowley was a physician-scientist at the University of Chicago. She had been studying chromosomes in cancer cells, and she had access to something Nowell and Hungerford did not have in 1960: better staining techniques that allowed individual chromosomes to be identified more precisely.

In 1973, Rowley made a discovery that transformed the Philadelphia chromosome from a curiosity into a mechanism. The short chromosome was not simply missing genetic material. A piece of chromosome 22 had broken off and attached to chromosome 9, while a piece of chromosome 9 had broken off and attached to chromosome 22. This type of exchange is called a translocation.

The translocation was not random damage. It was a specific, recurring event in CML cells. And it had a consequence: it fused two genes together to create something that did not exist in normal cells. A gene that produced a protein that did not exist in a healthy body. That protein was permanently switched on, constantly signaling the cell to divide.

Rowley published in Nature in 1973 [2]. The translocation she described, the fusion of the BCR and ABL genes that produces a protein called BCR-ABL, became the molecular explanation for CML. It also became, eventually, the target that made Gleevec possible.

Here is a way to picture it. Your DNA in the nucleus is the master cookbook. Each gene is a recipe. Proteins are what the cell bakes from those recipes. In a healthy cell, every recipe produces something the body actually needs.

A translocation tears two recipe pages out of the cookbook and tapes them together. The recipe for BCR fuses to the recipe for ABL. The cell, dutifully, follows the new combined instructions and bakes the result: a meatloaf with frosting, breadcrumbs in the batter, ground beef where the eggs should be. Nobody ordered it. The cell cannot tell. And worse, the new combined recipe lost the line that says stop when the timer goes off. The cell keeps making it. Forever.

Now the target was the meatloaf cake.

In Issue 004 we described target identification as the first stage of drug development: understanding the biological mechanism of a disease before trying to treat it. The Philadelphia chromosome story is what that stage actually looks like.

From 1960 to the late 1980s, researchers were doing target identification without calling it that. They were building the foundation that would make a drug possible: identifying the chromosome, characterizing the BCR-ABL fusion gene, and showing that BCR-ABL was a constitutively active tyrosine kinase [3]. Always switched on. Always telling the cell to divide.

By the late 1980s, the target was understood. BCR-ABL was the lock. The next question was whether anyone could cut a key. The scientific consensus at the time was that they could not. Selective kinase inhibitors were widely considered chemically impossible [3][4].

One oncologist disagreed. His name was Brian Druker. That is Issue 006.

The Philadelphia chromosome story is the answer to one of the most persistent claims in health misinformation: that a cure for cancer exists and is being suppressed. Apply four toolkit questions:

Q1. What evidence would change my mind? “Big Pharma is hiding a cancer cure” requires every oncologist, researcher, journal editor, regulator, NIH grant reviewer, and government health agency, in every country, to participate in the silence. That is not a conspiracy. That is a coordination problem at a scale no documented institution has ever managed.

Q4. Who funded this, and do they have a stake in the answer? The Philadelphia chromosome was discovered in 1960. The mechanism was characterized in 1973. The BCR-ABL fusion protein was understood by the late 1980s. The drug arrived in 2001. Forty-one years from observation to FDA approval. That is a lot of University based non-pharmaceutical or investor money funding. That is how research works, by building upon layers of research.

Q2. Am I evaluating the evidence, or defending my belief? “Cancer” is not one disease. It is more than 200 distinct diseases driven by hundreds of different molecular events [6]. “A cure for cancer” is like asking for “a key for all locks.” Gleevec did not cure CML. It treated it. The drug transformed a leukemia that killed most patients within five years into a manageable chronic condition for most people who take it. The targeted-therapy field that Gleevec pioneered now includes hundreds of drugs for hundreds of specific cancer subtypes. So is this about the belief that there is a hidden cure, or evidence that cancer is an umbrella term for hundreds of diseases.

Q10. If the claim is wrong, what would that mean? It would mean the suppression narrative provides emotional comfort to people who are scared, in pain, or grieving, while pulling them away from treatments that demonstrably work. The cost is measurable in lives.

The Skeptic’s Toolkit, ten questions we built in Issue 003b, is the framework underneath all of this.

The Philadelphia chromosome was published in 1960. For 13 years, no one knew what to do with it. Janet Rowley figured out the translocation in 1973 using a better staining dye. The molecular characterization took another decade. The drug came in 2001.

Forty-one years.

Nothing in that timeline was suppressed. Every step was published in peer-reviewed journals. Every advance built openly on the one before it. The work was hard. The biology was hard, the chemistry was hard, the clinical trials were hard. And one specific oncologist had to push the company that owned the molecule for six years before they would test it in a patient [3]. That is Issue 006.

When someone tells you a cancer cure is being hidden, the question is not whether it could be. The question is whether the work to find one has been done, and whether it would be visible if it had. For Gleevec, the work has been done, and every step is in the public scientific record. The same is true for hundreds of targeted therapies that followed. The cure was not hidden. The work just was not being watched. Almost nobody was looking. Now you are.

The hidden cure myth has a sibling worth running through the same toolkit: the claim that COVID vaccines never worked, or that the data showing they worked has been rigged. Apply the same questions we just applied to Gleevec.

What is the source? The 2024 to 2025 COVID vaccines were studied across multiple peer-reviewed analyses. The CDC’s VISION and IVY networks reported in MMWR that vaccine effectiveness against emergency department or urgent care visits was 33 percent in adults overall and 76 percent in immunocompetent children aged 9 months to 4 years. Effectiveness against hospitalization was 45 to 46 percent in immunocompetent adults aged 65 and older, and 40 percent in immunocompromised adults aged 65 and older. A separate IVY Network case-control study of 1,888 adults with COVID and 6,605 controls, published in JAMA Network Open in February 2026, estimated 40 percent effectiveness against hospitalization and 79 percent effectiveness against invasive mechanical ventilation or death.

What is the timeline? The 2024 to 2025 interim vaccine effectiveness analysis was published in MMWR in late 2025. As of this writing in May 2026, an analogous interim analysis covering the 2025 to 2026 season has not appeared in the MMWR archive. Whether that is a delay, a deprioritization, or something else is not something the public record can answer on its own. The peer-reviewed analyses we do have are listed below. Read them. Run the toolkit on them.

Who benefits from each version of the story? If the published data is accurate, the vaccines reduced severe outcomes meaningfully and the public benefits from knowing that. If the published data is wrong, whoever is selling alternatives benefits from you doubting it. Examine both directions.

The peer-reviewed record is what it is. Read it for yourself. Run the toolkit on it. References below.

My path through both sides of research started with my Master’s. Benchtop research, running the studies. The test tubes, the petri dishes, the microscopes, and living in the lab. Then years in clinical research across multiple therapeutic areas before finding my home in oncology, where targeted therapy is now the standard.

Within cancer research, the hidden-cure myth and the rigged-record myth share a structure. Both ask you to believe that thousands of researchers, monitors, sponsors, regulators, and journal editors are silent in unison. From inside the work, that picture does not match what I have seen. The record gets built one signature, one query, one database lock at a time. You can walk it backward. The toolkit shows you how.

And there are thousands upon thousands of colleagues and clients I work with now, or shared labs with previously, who are dedicating their lives to finding treatments for many forms of cancer. Part of what keeps us motivated in clinical trials is finding a better way every day. Finding ways to open studies faster, to clean data faster, to get drugs to market faster.

PARTY-TEST MOMENT 1

The Philadelphia chromosome was discovered in 1960. The drug that targeted it was approved in 2001. Forty-one years from observation to treatment. That is how long the work actually takes when nothing is being suppressed.

PARTY-TEST MOMENT 2

Janet Rowley unlocked the molecular mechanism of CML in 1973 using an improvement in staining dye. The key to chronic myeloid leukemia was better dye.

PARTY-TEST MOMENT 3

Before Gleevec, roughly 30 percent of CML patients survived five years. After Gleevec, that number rose above 90 percent. A survival improvement of that scale from a single drug had not been seen before in oncology.

PARTY-TEST MOMENT 4

“Cancer” is not one disease. It is more than 200 distinct diseases. Gleevec treated one of them, the one driven by the BCR-ABL protein, transforming it from a death sentence into a manageable chronic condition. The targeted-therapy field that Gleevec pioneered now includes hundreds of drugs for specific subtypes of specific cancers.

We are building something called the Wall of Sams. Real stories from real people who used to be skeptical of clinical research, pharmaceutical development, or vaccine science, and who have since gotten Rooted. Not converts. Not cheerleaders. People who learned to evaluate evidence rather than just accept or reject conclusions.

If you have a story, we want it. Reply to this email or leave a comment on the newsletter with three sentences: what you used to believe, what changed it, and where you are now. The best ones will appear in a future issue with your permission.

About 80 percent of clinical trials don’t meet their enrollment timelines on time, and when trials are stopped early, the leading reason is poor recruitment [12]. Root to Rx exists to close that gap by building a public that understands the process. One person you forward this to is one more Rooted reader. One more branch.

Branch someone in. One referral earns you the Skeptic’s Toolkit, 10 questions that will change how you evaluate any health claim.

This issue continues with two web-only sections. The Root Room is where Debby brings a viral “newly declassified CIA document” claim about hidden cancer cures, and Sam and Rooty walk through the toolkit. The Informed goes into the molecular biology: what BCR-ABL actually is, how a chromosomal translocation creates a cancer-driving protein, and why the scientific consensus that kinase inhibitors were impossible was wrong.

Read The Root Room and The Informed on the web →

Root to Rx is a clinical research literacy newsletter from Justin Yamashita. Most people see one part of the research pipeline. Justin has worked across all three: benchtop research during his Master’s, clinical site execution, and global CRO oversight. Each Thursday, two tracks. Plain Talk explains how the system actually works. The Informed goes deeper for the curious.

If this is your first issue, the three foundation issues are: 003b (the Skeptic’s Toolkit), 001 (why your distrust is rational), and 004 Plain Talk (how the drug development pipeline works).

Disclosure: Root to Rx is published independently by Open Label Media LLC. Views expressed are personal views of Justin Yamashita and do not represent his employer or any affiliated organization. No employer resources or proprietary information are used. Every claim is sourced from publicly available materials.