Medical News

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A diagnostic blood test may provide early detection of lung cancer in asymptomatic patients, according to a new study.

Lung cancer, the leading cause of cancer death, is usually diagnosed at a late stage when the survival rate is extremely low. Early stage lung cancer is mostly asymptomatic, and low-dose spiral CT imaging, the current method for detecting early lung cancer lesions, isn’t feasible as a widespread screening test for the general population due to high cost and the radiation hazard of repeated screenings.

The study, published in Proceedings of the National Academy of Sciences provides proof-of-concept for the ability of a drop of blood to reveal lung cancer in asymptomatic patients. It was co-led by researchers at Harvard-affiliated Massachusetts General Hospital: Leo Cheng, associate biophysicist in pathology and radiology, Athinsula A. Martinos Center for Biomedical Imaging, and David Christiani, pulmonary and critical care physician.

“Our study demonstrates the potential for developing a sensitive screening tool for the early detection of lung cancer,” says Cheng. “The predictive model we constructed can identify which people may be harboring lung cancer. Individuals with suspicious findings would then be referred for further evaluation by imaging tests, such as low-dose CT, for a definitive diagnosis.”

Cheng, Christiani, and their co-investigators built a lung-cancer predictive model based on metabolomics profiles in blood. Metabolomics analyzes cellular metabolite flows to decipher healthy and pathological states by studying the metabolome — the dynamic biochemical suite found in all cells, fluids, and tissues of the body. The presence of lung cancer, with its altered physiology and pathology, can cause changes in the blood metabolites produced or consumed by cancer cells in the lungs. The researchers measured metabolomics profiles in blood using high-resolution magnetic resonance spectroscopy, a tool that can examine an array of compounds within living cells by measuring the collective reactions of metabolites.

The investigators screened tens of thousands of blood specimens stored in MGH’s biobank and others and found 25 patients with non-small cell lung cancer (NSCLC) with stored blood specimens obtained at the time of their diagnosis and at least six months prior to their diagnosis. They matched these patients with 25 healthy controls.

The researchers first trained their statistical model to recognize lung cancer by measuring metabolomic profile values in blood samples obtained from patients at the time of their diagnosis and comparing them to blood samples from the healthy controls. They then validated their model using blood samples from the same patients obtained prior to their lung cancer diagnosis. Here the predictive model yielded values between the healthy controls and the patients at the time of their diagnosis.

“This was very encouraging, because screening for early disease should detect changes in blood metabolomic profiles that are intermediate between healthy and disease states,” says Cheng.

The investigators then tested their model with a different group of 54 patients with NSCLC using blood samples obtained before their cancer diagnosis, which confirmed that the model’s predictions were accurate.

Values from the predictive model measured from prior-to-diagnosis blood samples could also predict five-year survival for patients, which may be useful in guiding clinical strategies and treatment decisions. A previous study by the investigators showed the potential for magnetic resonance spectroscopy-based metabolomics to differentiate cancer types and stages of diseases. Larger studies are needed to validate the use of blood metabolomics models as NSCLC early screening tools in clinical practice.

Next, the researchers will analyze metabolomic profiles of lung cancer’s clinical characteristics to understand the entire metabolic spectrum of the disease, which may be useful in choosing targeted therapies. They have also measured metabolomics profiles of more than 400 patients with prostate cancer to create a model that will distinguish between indolent cancer, which needs to be monitored, and more aggressive cancer that requires immediate treatment. The investigators also plan to use the same technology to screen for Alzheimer disease using blood samples and cerebrospinal fluid.

Cheng is associate professor of radiology at Harvard Medical School. Christiani is professor of medicine at HMS, and professor of environmental genetics at the Harvard T.H. Chan School of Public Health.

The National Cancer Institute funded this study.

Beliefs about which specific maternal behaviors or experiences have lasting effects on gestating offspring have shifted widely over time. In her new book, “The Maternal Imprint: The Contested Science of Maternal-Fetal Effects,” Sarah S. Richardson, professor of the history of science and of studies of women, gender, and sexuality, gives this rich history a clearer context in the discussion of reproductive responsibility. The Gazette spoke to Richardson, director of the Harvard GenderSci Lab, which studies biomedical research on sex and gender, about birth weight, bibliometrics, and her personal connection to histories of maternal stress. This interview was edited for clarity and length.

Q&A

Sarah S. Richardson

GAZETTE: “The Maternal Imprint” seems to intersect your professional and personal lives. Can you talk about why you wrote it?

RICHARDSON: My ear was turned by reading about studies of intergenerational Holocaust trauma at the level of the gene. This was around 2010, when a new field of science called epigenetics was emerging, claiming to solve a longstanding and problematic question in genetics, which is: How does the environment interact with our genes to change the way we grow and develop?

The hope was that these patterns of intergenerational transmission of trauma that had been explained narratively through stories could somehow be verified through empirical, material science. And I am the granddaughter of a Holocaust survivor. I am also the granddaughter of somebody who lived through the famed Dutch famine, which is another major study area in this field. So I couldn’t help but be riveted.

Furthermore, all of these claims were constructed through the matriline. I recognized as a historian of science that this new science was re-energizing a set of claims from the history of biology and genetics regarding the unique contribution of the mother to heredity. I saw it as deeply intertwined with a set of contestations about genetic determinism, and with conceptions of our bodies as both biological and social.

GAZETTE: Your research details a lot of eugenics history. What did this field have to offer you in the context of reproduction?

RICHARDSON: I was writing the chapter on prenatal culture when I was pregnant with my first child, and I actually found comfort in reading some of those funny ideas — for example, that you could do math equations while you’re pregnant to make a child who would be an accountant. It was sort of a beautiful thing. They were encouraging women to take control of their lives as pregnant women and suggesting that you could have some control over your future offspring, which in our current environment, where the risk discourse and the surveillance of pregnant people is incredibly intense, was such a different, almost magical space to step into.

I also think people will be surprised — and this is a well-known fact, though continuously underappreciated — that in the eugenic era, it wasn’t all about genetic determinism. It encompassed a wide range of prescriptions for health that included modes of behavior for before getting pregnant, while you are pregnant, and early development, that were laden with social values about the kinds of lives that were valuable.

GAZETTE: Maybe my favorite phrase in the book is “pop-science catnip,” which is what you call epigenetics. Can you explain?

RICHARDSON: Epigenetics has been cast in public conversation as something that allows you to shape your own potential and overcome hereditary limitations. This possibility of self-help, of plasticity, and of improvement and optimization walks right into our constantly contested ideas about our bodies, how we’re situated in generational time, and the degree to which outcomes are the result of nurture versus nature. And then you add the gender part, with women warned that if you eat a single potato chip you could be destining your child to a life of sloth and ADHD — definitely pop-science catnip.

We’re all very familiar with claims of the risks of fetal alcohol poisoning, or of not having enough folic acid in your diet when pregnant. This all comes from an earlier era of teratological research, which focused on an exposure to or deficit in a specific chemical agent or teratogen, imbibed by the mother, carried across the placenta, and impacting the fetus.

I am, in this book, talking about a different register of claims: this phenomenological thing called “maternal effects.” It’s something mediated by the mother’s body — her constitution, her condition, her environment. An obese mother would be an example of the prototypical exposure environment. The causes are very subtle exposures, and the effect sizes are small. We’re not talking about birth defects that are visible at birth that are extremely disabling. We’re talking about a couple of extra centimeters on the waist at age 59 after some exposure in the womb.

In short, this new field of science studies the coupling of small variations in the fetal environment with small variations in long-term health or development. It’s a different register of claims — and this is something I’m very interested to explore in the book, what I call crypticity, which characterizes the field’s knowledge landscape.

GAZETTE: You devote a chapter to birth weight, which has such an outsized reputation as a birth marker. Talk about your findings.

RICHARDSON: I could have written a whole book on birth weight, and maybe I should. It’s fascinating. Isn’t it incredible that we write on our birth announcements what the weight was?

The fascination with birth weight really developed in the ’60s and ’70s, a precursor to the same set of questions fascinating scientists today in the field of fetal epigenetic programming research. Could it be that the variation in fetal environment is a cryptic, as-yet-unappreciated cause of variation in life outcomes in the world? A whole body of scholarship — tens of thousands of papers — emerged correlating birth weights, which you can easily retrieve from birth certificates, with everything from health conditions and lung disorders to things like IQ, which I talk about in this chapter.

This research was racialized from its inception. It’s well known that there’s quite a racial disparity in birth weight in the United States, and that’s been quite persistent over time. I tell the story of scientists’ attempts to figure out why. The original theory was that it was all genetic, and there was just a different baseline for Black American babies [more of whom have low birth weights] compared to white American babies.

Two African American pediatricians, whose stories I was delighted to tell in this book, turned that theory around in the 1950s and ’60s by showing that birth weight cleanly correlates with income and access to prenatal care. This is the moment that maternal-effects science becomes entangled with a progressive biosocial science that has a vision of understanding how the social gets under our skin.

But as I show, the story turns out to be endlessly complex. Interpreting birth weight requires knowledge of the life history of how an individual became small as well as the context for how they became small. As a result, scientists eventually agree that birth weight is not a measure that is informative across populations for thinking about prenatal exposures. And that’s how we get to epigenetics.

GAZETTE: You said you could have written an entire book on birth weight. Were there other topics on which you found yourself deep in a rabbit hole that could have gone deeper?

RICHARDSON: Well, eugenics has been widely written about, so people think we have told its story. The literature is voluminous, encompassing nearly 50 years of production across the globe. My question was: What did these folks think about prenatal influences? That story had not been told. To get at this, I engaged in some mild empirical bibliometrics, which for me was new. I counted lines of text in dozens of formative eugenic books and made tables! After this work, it’s clear to me that we have so much more to understand about the full scope of eugenic ideas.

GAZETTE: Some pregnant people have access to so much information while others have not enough. What’s the lesson for researchers — or doctors, for that matter — in this book?

RICHARDSON: I would argue that in this moment we are at a high point for a highly medicalized approach to pregnancy combined with an expectation that pregnant people are aware of and following the most recent science, with genetics being our premier, elite paradigm for understanding risk. So, there is a priming of pregnant people to be very aware of every new piece of evidence and, in fact, to adapt their behavior in relation to it, combined with tremendous anxiety about optimizing birth outcomes.

Scientists in this field are incredibly passionate about bringing empirical science and novel tools like epigenetics to bear on questions on improving fetal outcomes. Regardless of their intentions, however, their work is received in a heightened risk discourse frame, where everything is positioned as either you are either hurting or helping your fetus. Under these conditions, parents and practitioners are not well-empowered by new epigenetic claims to make reasonable judgments about which risks to accept or not in the context of their own life.

Scientists estimate that a one-year increase in alcohol consumption during the COVID-19 pandemic will result in 8,000 additional deaths from alcohol-related liver disease, 18,700 cases of liver failure, and 1,000 cases of liver cancer by 2040.

In the short term, alcohol consumption changes due to COVID-19 are expected to cause 100 additional deaths and 2,800 additional cases of liver failure by 2023.

The new research, published in Hepatology, was led by investigators at Harvard-affiliated Massachusetts General Hospital.

Using data from a national survey of U.S. adults on their drinking habits that found that excessive drinking (such as binge drinking) increased by 21 percent during the COVID-19 pandemic, investigators simulated the drinking trajectories and liver disease trends in all U.S. adults. The researchers noted that a sustained increase in alcohol consumption for more than one year could result in 19 to 35 percent additional mortality.

“Our findings highlight the need for individuals and policymakers to make informed decisions to mitigate the impact of high-risk alcohol drinking during the COVID-19 pandemic in the U.S.,” says senior author Jagpreet Chhatwal, associate director of MGH’s Institute for Technology Assessment and an assistant professor of radiology at Harvard Medical School.

“While we have projected the expected impact of societal drinking changes associated with the COVID-19 pandemic without any interventions, we hope that our research can help jumpstart needed conversations at every level of society about how we can respond to the many behavioral changes, coping mechanisms, and choices that have short- and long-term implications for the health of individuals, families and communities in America,” adds lead author Jovan Julien, a data analyst at the MGH Institute for Technology Assessment.

“The COVID-19 pandemic has had many unintended consequences with unknown long-term impact. Our modeling study provides a framework for quantifying the long-term impact of increased alcohol consumption associated with COVID-19 and initiating conversations for potential interventions,” notes co-author Turgay Ayer, the George Family Foundation Early Career Professor of Systems Engineering at Georgia Institute of Technology.

Co-authors include Elliot B. Tapper, Carolina Barbosa, and William Dowd.