GRAIL, Inc and the (Not So) Subtle Sexism in Science & Medicine

There’s a joke among science aficionados that goes like this: “What did Watson and Crick discover? Rosalind Franklin’s notes.”

Well, I have a joke for you. What did the cutting-edge $8 billion revolutionary cancer-diagnostics company GRAIL discover?

Answer: My mom’s proof of concept.

Recently Fast Company published an article titled “How a surprising discovery turned into a promising new early detection test for for cancer” (they have since taken down the article, so I’m linking to the screenshot version). In it they wrote:

I found this interesting because the unnamed pathologist they mention in the article who made this surprising discovery is a woman and is in fact my mom, Dr. Meredith Halks Miller. It was she (and not her male colleague who seems to get all of the credit here), who discovered that the DNA signals on pregnant women’s tests were coming from undetected cancer rather than from chromosomal abnormalities of the fetus.

The article goes on to say:

Let me take a step back and tell you the actual origin story of the company GRAIL.

In 2013, my mom was Laboratory Director for Ilumina, the biotech company from which GRAIL was later spun. At that time, Illumina was offering a then very cutting-edge prenatal blood test (called Non-Invasive Prenatal Testing, or NIPT) in its clinical laboratory.

The test used cell-free DNA (essentially little bits of broken DNA released into the bloodstream) to test pregnant women for chromosomal abnormalities in the fetus. The idea was that instead of needing to subject the women to a potentially risky and invasive amniocentesis, a simple blood test could do the job even better.

At first, Illumina’s NIPT test only spit out a number — a “yes” or “no” of whether a chromosomal abnormality was present. In October 2013, though, Dr. Darya Chudova, the then Associate Director of Bioinformatics at Illumina, created an algorithm that allowed the reviewing pathologist (my mom) to visualize the counts of each specific chromosome.

With this new data, my mom immediately started to notice very strange DNA signals on some of the women’s tests that almost certainly couldn’t be from fetal DNA. She and Dr. Chudova observed cases with not just one abnormality, but multiple chromosomal amplifications and deletions. It was a staggering pattern that, to my mom’s knowledge, could only be explained by cancer.

Despite my mom’s very high level of suspicion, she couldn’t make such a statement without clinical evidence, and so she started the process of having the laboratory’s clinical consultants contact the women’s primary physicians and Ob/Gyn’s to encourage them to have oncology follow up for their patients. It turned out a few of these women did turn out to be diagnosed with cancer on follow up.

It’s what happened next, though, that really cements the whole story in my memory. The article says this discovery was made in 2014, but I’m quite sure it was 2013. The reason I’m quite sure is because it was on December 17, 2013, only two months after Dr. Chudova created her algorithm, that I was unexpectedly diagnosed with Stage IV T-Cell Acute Lymphoblastic Lymphoma at 31 years old.

Despite hearing that her only daughter might imminently die from cancer, my mom had the wherewithal and insight to bring one of Illumina’s NIPT testing kits to my hospital bed, where she asked the wonderful staff at UCLA to draw my blood at bedside into the specially prepared tube. Later, she ran this as a research sample to see if any DNA signals from my cancer cells could be detected on the test and potentially used as a marker later to see if my treatments worked.

I guess you could say I like to consider myself “Patient Zero” of what would later become GRAIL’s test.

In the months after my diagnosis, while flying back and forth between San Francisco and Los Angeles to take care of me, my mom continued to plug along with her work at Illumina, collaborating with Dr. Diana Bianchi (a then professor at Tufts and executive director of the Mother Infant Research Institute of their Medical Center) and the genetic counselors at Illumina to follow up with the physicians of the women, and the women themselves, whose test results demonstrated the strange findings. Of the 10 women whose tests had these findings, all 10 were later diagnosed with cancer.

My mom wanted to get Illumina executives involved in pursuing and developing a cancer detection assay, but no one seemed interested — until she showed the data to Dr. Rick Klausner. I’ll let him tell you what happened next:

Run he did.

Over the next three years, I underwent a grueling regimen of chemotherapy (the details of which I’ve described elsewhere in my blog). I finished treatment in 2016. Unfortunately, it wasn’t too long after that I relapsed. Fortunately, I had a successful Stem Cell Transplant in October 2019 from an anonymous donor in Germany and have been in remission since.

Now, I hope that hearing the real backstory of GRAIL and my mom’s involvement you can understand why, upon reading this GRAIL press release (ahem, I mean “fastidiously-researched example of journalism from Fast Company”) I found myself becoming just a little perturbed. Take this line (emphasis mine):

“A pathologist working on the tests noticed something odd in 10 of the blood samples. They didn’t show evidence of the chromosomal disorders the test was designed to find, but they indicated DNA abnormalities that she couldn’t make sense of.”

Or this one:

“She saved those tests and shared them with Illumina’s chief medical officer at the time, Rick Klausner… “So, I looked at them,” Klausner recalls. “And I said, ‘These women have cancer. I don’t know of anything else that changes the genome the way you’re showing me here.” The research team followed up with the women, and sure enough, one had already been diagnosed with cancer subsequent to her blood test, and the others turned out to have cancer, just as Klausner predicted, even though they hadn’t yet shown any symptoms and appeared to be healthy.”

Hmm… is that how it happened?

Despite my mom having a feeble brain that has trouble making sense of things, she went on to author (along with Dr. Darya Chudova and Dr. Diana Bianchi) the journal article that describes her findings titled “Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies.”

It was published on July 14, 2015 in the Journal of the American Medical Association, or JAMA. If you’re in medicine or science, you’ve probably heard of it since it’s one of the most prestigious medical journals in the world. There was so much publicity around the article that in the days following its publication, Illumina shares spiked almost 10%, adding nearly $3 billion in valuation to the company.

My mom put the finishing touches on the article while also picking up my medications from the pharmacy and driving me to doctor’s appointments and cleaning my vomit off the floor when I couldn’t quite make it to the bathroom because I was so sick from chemotherapy.

Another fact check while we’re at it. The Fast Company article goes on to say:

First, one need only to read the JAMA article to see it was not 150,000 women, but 125,000 (125,426 to be exact). Second, the article is pretty clear that not all 125,000 women were followed up with to see if they were later diagnosed with cancer, so it’s only known that cancer signals weren’t detected in their blood rather than that they didn’t have cancer. Thus, the false negative rate could not be determined.

Following up with 125,000 women is a lot of work, and my mom may be extraordinary but she’s not a god. How much work do you expect one woman to do when you’re not going to give her any of the credit?

Now I know I’m giving GRAIL a hard time, but my story really isn’t about them. If the issue were just one press release from one multi-billion dollar company, I might not have bothered wasting my entire Saturday afternoon writing a blog post about it (I was supposed to go for a hike with my husband today, for your information). The problem is much, much greater; this is by far not the first time a woman’s achievements in science or medicine have been written out of history. I can only imagine that to erase my mom’s contribution from GRAIL’s founding story, many people must have given their explicit (or tacit) consent along the way.

***

I remember one summer in college when a friend of mine who lived in Michigan drove out to California on a road trip and stayed with my family for a few days. When he came to the door my mom answered, and he wrapped his arms around her and said, “Hi Mrs. Miller, it’s so nice to meet you!”

My mom smiled back. “Please, call me Meredith!” she said. Then she lowered her voice. “And it would be Dr. Miller.”

My friend didn’t forget this moment (we still joke about it now), and it perfectly exemplifies my mom and the many roles she so deftly fills in her life — as many women do — and especially those in demanding fields like science and medicine. We’ve all figured out how to find the perfect balance of being confident but not arrogant, pleasing and nice but not weak, attractive but not threateningly so, smart but not too smart, smart but not smarter than any of the men in the room.

Not has much has changed in the last few decades as we’d like to think. Let’s play a little game. Which of the following happened to which Dr. Miller, Dr. Meredith Halks Miller (my mom) who graduated from medical school over 40 years ago, or Dr. Elana Miller (me), who graduated a mere 10 years ago?

Dr. Miller travels with her husband to Europe to celebrate graduating from residency. They arrive in London on their final stop for a two nights stay at ritzy hotel before returning home. When Dr. Miller attempts to check in, however, the hotel staff insist there is no reservation under her name and explain the hotel is completely booked. At first she is indignant, showing them her reservation confirmation, and then she becomes perplexed, and then she becomes desperate. “Please,” she says. “There are no rooms left anywhere in the city.” The manager of the hotel feels bad for her and lets her sleep in the janitorial closet. The following morning the staff realizes a room earmarked for “Dr. Miller” had gone unused the night before because it had not occurred to the staff that Dr. Miller could be a woman. The second night, fortunately, they upgrade her from the closet and give her her reserved room. They also give her a fruit basket.

ANSWER: Dr. Meredith Halks Miller, circa 1979

Dr. Miller arrives at her very expensive office building that she pays quite a bit of money for and realizes she’s forgotten her key. Her first patient appointment starts in only a few minutes. She goes to the security guard to ask to be let in, showing him her ID and explaining that it’s her office and her name is etched on the door. He looks her up and down and types into the computer and sees two (male) physicians’ names listed on the office lease and says, “I need to call your boss.” Dr. Miller tries to explain that she owns the business, and that she sublets the office from her suite mates, two other physicians. She tries to show him her Google business listing with the office as her verified address. He then proceeds to leave humiliating messages on both of her male colleagues’ voicemails that their “employee” is “Googling herself” and wants to be let into “their” office.

ANSWER: Dr. Elana Miller, circa 2018

Dr. Miller returns a voicemail from a potential new patient who wants to see her in her practice. They have a nice conversation where the patient describes what she’s struggling with, and Dr. Miller explains what her treatment approach would be. But then Dr. Miller starts to notice somethings strange, which is that the patient seems to be referring to her in the third person. She says, “This Dr. Miller, does he know how to treat depression? Is he any good?” Dr. Miller is taken aback and says, “I’m Dr. Miller.” The patient, clearly embarrassed, apologizes and says she thought Dr. Miller was the secretary. Dr. Miller then hires a secretary so she doesn’t have to deal with phone calls like this in the future. She realizes that women, too, can internalize sexist messages without realizing it.

ANSWER: Dr. Elana Miller, circa 2017

Dr. Miller, while working at an academic position at UCSF, decides with her husband to adopt a baby. When she informs her boss, she is immediately and unceremoniously fired. Her boss tells her, “You’ll be a great mother, and therefore you will be useless to my department.”

ANSWER: Dr. Meredith Halks Miller, circa 1982 (Spoiler alert: I was the baby!)

Dr. Miller has a supervisor in medical school who, in the middle of a group session with five other medical students, comments on her breasts and hair, saying she is too attractive to ever be taken seriously in medicine (despite the fact that she is wearing pants, loafers, and a button-up shirt clasped to the very top button). When she complains to the school, she’s asked to consider the supervisor’s point of view. The supervisor receives no consequences and continues to supervise her. Thankfully, even the medical school recognizes that the supervisor’s description of her as “charming” in her final evaluation isn’t appropriate, and they remove that sentence.

ANSWER: Dr. Elana Miller, circa 2007

So listen up, leadership team at GRAIL. I’ve gone through a lot (cancer twice) and not much scares me and unfortunately for you I’m not as nice as my mom. Perhaps it’s because when she became a physician, sexism in medicine was overt and rampant, rather than now, when it’s merely implicit and tolerated. I only found out about the Fast Company article because my mom mentioned it offhand, saying she thought it was funny. Well, I’m not laughing.

Please keep in mind I’m a physician and not a journalist, so feel free to correct me if I have any of the facts wrong. I also want to emphasize that I’m speaking for myself and not on behalf of my mom (just ask her and my dad — they gave up on trying to contain me long ago). In talking about GRAIL, both in public and in private, she has always focused on how proud she is of the team there and everything they’ve accomplished. Everything I’ve ever heard her say indicates she very much wants to see GRAIL succeed.

To have a company like GRAIL properly address the issue of sexism in their organization wouldn’t solve the larger problem — but it would set a good example and be an encouraging start. GRAIL is both an entity and a collection of individual people, and I hope the majority of those individual people will want to correct this wrong now that their attention has been called to it.

And look, if you work in leadership at GRAIL and my blog post is stressing you out, I know a great psychiatrist. Her name is Dr. Elana Miller, and after years of having to overcompensate for being a woman by becoming extremely competent, she is very, very good. She is also very, very pricey — but with all of those billions my mom helped you earn, I think you can afford it.

Do you have your own story of experiencing sexism in science or medicine? Leave a comment or Tweet about it with the hashtag #WomensWorkMatters.