A Single Blood Test May Soon Replace Your Annual Physical
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
The measurement of proteins in one blood test could provide a comprehensive snapshot of a person's health in the near future.
For all the excitement over "personalized medicine" in the last two decades, its promise has not fully come to pass. Consider your standard annual physical.
Scientists have measured thousands of proteins from a single blood test to assess many individualized health conditions at once.
Your doctor still does a blood test to check your cholesterol and gauge your risk for heart disease by considering traditional risk factors (like smoking, diabetes, blood pressure) — an evaluation that has not changed in decades.
But a high-risk number alone is not enough to tell accurately whether you will suffer from heart disease. It just reflects your risk compared to population-level averages. In other words, not every person with elevated "bad" cholesterol will have a heart attack, so how can doctors determine who truly needs to give up the cheeseburgers and who doesn't?
Now, an emerging area of research may unlock some real-time answers. For the first time, as reported in the journal Nature Medicine last week, scientists have measured thousands of proteins from a single blood test to assess many individualized health conditions at once, including liver and kidney function, diabetes risk, body fat, cardiopulmonary fitness, and even smoking and alcohol consumption. Proteins can give a clear snapshot of how your body is faring at any given moment, as well as a sneak preview at what diseases may be lurking under the surface.
"Years from now," says study co-author Peter Ganz of UCSF, "we will probably be looking back on this paper as a milestone in personalized medicine."
We spoke to Ganz about the significance of this milestone. Our interview has been edited and condensed.
Is this the first study of its kind?
Yes, it is. This is a study where we measured 5,000 proteins at once to look for patterns that could either predict the risk of future diseases or inform the current state of health. Previous to this, people have measured typically one protein at a time, and some of these individual proteins have made it into clinical practice.
An example would be a protein called C-reactive protein, which is a measure of inflammation and is used sometimes in cardiology to predict the risk of future heart attacks. But what's really new is this scale. We wanted to get away from just focusing on one problem that the patient may have at a time, whether it's heart disease or kidney disease, and by measuring a much greater number of proteins, the hope is that we could inform the health of ultimately just about every organ in the body or every tissue. It's a step forward for what I would call "a one-stop shop."
"I'm very excited about personalized medicine through proteins as opposed to genes because you get both the nature and nurture."
Three things get me excited about this. One is the convenience for the patient of a single test to determine many different diseases. The second thing is the healthcare cost savings. We estimated what the cost would be to get these 11 healthcare measures that we reported on using traditional testing and the cost was upwards of 3,000 British pounds. And even though I don't know for sure what the cost of the protein tests would ultimately be, [it could come down to about $50 to $100].
The last thing is that the measurement of proteins is part of what people have called personalized medicine or precision medicine. If you look at risk factors across the population, it may not apply to individuals. In contrast, proteins are downstream of risk factors. So proteins actually tell us whether the traditional risk factors have set in motion the necessary machinery to cause disease. Proteins are the worker bees that regulate what the human body does, and so if you can find some anomalies in the proteins, that may inform us if a disease is likely to be ongoing even in its earliest stages.
Does protein testing have advantages over genetic testing for predicting future health risks?
The problem with genomics is that genes usually don't take care of the environment. It's a blueprint, but your blueprint has no idea what you will be exposed to during your lifetime in terms of the environment and lifestyle that you may choose and medications that you may be on. These are things that proteins can account for. I'm very excited about personalized medicine through proteins as opposed to genes because you get both the nature and nurture as opposed to genomics, which only gives you nature but doesn't account for anything else.
Proteins can also be tracked over time and that's not something you can do with genes. So if your behavior improves, your genes won't change, but your proteins will.
Could this new test become a regular feature of your annual physical?
That's the idea. This would be basically almost a standalone test that you could have done every year. And hopefully you wouldn't need other tests to complement this. This could be your yearly physical.
How much more does it need to be validated before it can enter the clinic and patients can trust the results?
This was a proof-of concept study. To really make this useful, we need to expand from 11 measures of health to a hundred or more health insights, to cover the whole body. And we need to expand this to all racial groups. Three of the five centers in the study were European – all Caucasian – so it's one of our high priorities to find groups of patients with better representation of minorities.
When do you expect doctors to be routinely giving this test to patients?
Much closer to five years than 20 years. We're scaling up from 11 disease states to 100, and many of those studies are underway. Results should be done within three to five years.
Do you think insurance will cover it?
Good question. I have been approached by an insurance company that wanted to understand the product better – a major insurer, with the possibility that this could actually be cost saving.
I have to ask you a curveball -- do you think that the downfall of Theranos will make consumers hesitant to trust a new technology that relies on using a single blood sample to screen for multiple health risks?
[Laughs] You're not the first person to ask me that today. I actually got a call from Elizabeth Holmes [in 2008 when I was at Harvard]. I met with her for an afternoon and met her team two more times. I gave them advice that they completely disregarded.
In many ways, what we do is diametrically opposite to Theranos. They had a culture of secrecy, and what we do is about openness. We publish, like this paper in Nature Medicine, to show the scientific details. Our supplement is much longer than the typical academic paper. We reveal everything we know. A lot of the research we do is funded by [the National Institutes of Health], and they have strict expectations about data sharing. So we agree to make the data available on a public website. If there is something we haven't done with the data, others can do it.
So you're saying that this is not another Theranos.
No, God forbid. We hope to be the opposite.
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Gene Transfer Leads to Longer Life and Healthspan
In August, a study provided the first proof-of-principle that genetic material transferred from one species to another can increase both longevity and healthspan in the recipient animal.
The naked mole rat won’t win any beauty contests, but it could possibly win in the talent category. Its superpower: fighting the aging process to live several times longer than other animals its size, in a state of youthful vigor.
It’s believed that naked mole rats experience all the normal processes of wear and tear over their lifespan, but that they’re exceptionally good at repairing the damage from oxygen free radicals and the DNA errors that accumulate over time. Even though they possess genes that make them vulnerable to cancer, they rarely develop the disease, or any other age-related disease, for that matter. Naked mole rats are known to live for over 40 years without any signs of aging, whereas mice live on average about two years and are highly prone to cancer.
Now, these remarkable animals may be able to share their superpower with other species. In August, a study provided what may be the first proof-of-principle that genetic material transferred from one species can increase both longevity and healthspan in a recipient animal.
There are several theories to explain the naked mole rat’s longevity, but the one explored in the study, published in Nature, is based on the abundance of large-molecule high-molecular mass hyaluronic acid (HMM-HA).
A small molecule version of hyaluronic acid is commonly added to skin moisturizers and cosmetics that are marketed as ways to keep skin youthful, but this version, just applied to the skin, won’t have a dramatic anti-aging effect. The naked mole rat has an abundance of the much-larger molecule, HMM-HA, in the chemical-rich solution between cells throughout its body. But does the HMM-HA actually govern the extraordinary longevity and healthspan of the naked mole rat?
To answer this question, Dr. Vera Gorbunova, a professor of biology and oncology at the University of Rochester, and her team created a mouse model containing the naked mole rat gene hyaluronic acid synthase 2, or nmrHas2. It turned out that the mice receiving this gene during their early developmental stage also expressed HMM-HA.
The researchers found that the effects of the HMM-HA molecule in the mice were marked and diverse, exceeding the expectations of the study’s co-authors. High-molecular mass hyaluronic acid was more abundant in kidneys, muscles and other organs of the Has2 mice compared to control mice.
In addition, the altered mice had a much lower incidence of cancer. Seventy percent of the control mice eventually developed cancer, compared to only 57 percent of the altered mice, even after several techniques were used to induce the disease. The biggest difference occurred in the oldest mice, where the cancer incidence for the Has2 mice and the controls was 47 percent and 83 percent, respectively.
With regard to longevity, Has2 males increased their lifespan by more than 16 percent and the females added 9 percent. “Somehow the effect is much more pronounced in male mice, and we don’t have a perfect answer as to why,” says Dr. Gorbunova. Another improvement was in the healthspan of the altered mice: the number of years they spent in a state of relative youth. There’s a frailty index for mice, which includes body weight, mobility, grip strength, vision and hearing, in addition to overall conditions such as the health of the coat and body temperature. The Has2 mice scored lower in frailty than the controls by all measures. They also performed better in tests of locomotion and coordination, and in bone density.
Gorbunova’s results show that a gene artificially transferred from one species can have a beneficial effect on another species for longevity, something that had never been demonstrated before. This finding is “quite spectacular,” said Steven Austad, a biologist at the University of Alabama at Birmingham, who was not involved in the study.
Just as in lifespan, the effects in various organs and systems varied between the sexes, a common occurrence in longevity research, according to Austad, who authored the book Methuselah’s Zoo and specializes in the biological differences between species. “We have ten drugs that we can give to mice to make them live longer,” he says, “and all of them work better in one sex than in the other.” This suggests that more attention needs to be paid to the different effects of anti-aging strategies between the sexes, as well as gender differences in healthspan.
According to the study authors, the HMM-HA molecule delivered these benefits by reducing inflammation and senescence (cell dysfunction and death). The molecule also caused a variety of other benefits, including an upregulation of genes involved in the function of mitochondria, the powerhouses of the cells. These mechanisms are implicated in the aging process, and in human disease. In humans, virtually all noncommunicable diseases entail an acceleration of the aging process.
So, would the gene that creates HMM-HA have similar benefits for longevity in humans? “We think about these questions a lot,” Gorbunova says. “It’s been done by injections in certain patients, but it has a local effect in the treatment of organs affected by disease,” which could offer some benefits, she added.
“Mice are very short-lived and cancer-prone, and the effects are small,” says Steven Austad, a biologist at the University of Alabama at Birmingham. “But they did live longer and stay healthy longer, which is remarkable.”
As for a gene therapy to introduce the nmrHas2 gene into humans to obtain a global result, she’s skeptical because of the complexity involved. Gorbunova notes that there are potential dangers in introducing an animal gene into humans, such as immune responses or allergic reactions.
Austad is equally cautious about a gene therapy. “What this study says is that you can take something a species does well and transfer at least some of that into a new species. It opens up the way, but you may need to transfer six or eight or ten genes into a human” to get the large effect desired. Humans are much more complex and contain many more genes than mice, and all systems in a biological organism are intricately connected. One naked mole rat gene may not make a big difference when it interacts with human genes, metabolism and physiology.
Still, Austad thinks the possibilities are tantalizing. “Mice are very short-lived and cancer-prone, and the effects are small,” he says. “But they did live longer and stay healthy longer, which is remarkable.”
As for further research, says Austad, “The first place to look is the skin” to see if the nmrHas2 gene and the HMM-HA it produces can reduce the chance of cancer. Austad added that it would be straightforward to use the gene to try to prevent cancer in skin cells in a dish to see if it prevents cancer. It would not be hard to do. “We don’t know of any downsides to hyaluronic acid in skin, because it’s already used in skin products, and you could look at this fairly quickly.”
“Aging mechanisms evolved over a long time,” says Gorbunova, “so in aging there are multiple mechanisms working together that affect each other.” All of these processes could play a part and almost certainly differ from one species to the next.
“HMM-HA molecules are large, but we’re now looking for a small-molecule drug that would slow it’s breakdown,” she says. “And we’re looking for inhibitors, now being tested in mice, that would hinder the breakdown of hyaluronic acid.” Gorbunova has found a natural, plant-based product that acts as an inhibitor and could potentially be taken as a supplement. Ultimately, though, she thinks that drug development will be the safest and most effective approach to delivering HMM-HA for anti-aging.
A new study provides key insights in what causes Alzheimer's: a breakdown in the brain’s system for clearing waste.
In recent years, researchers of Alzheimer’s have made progress in figuring out the complex factors that lead to the disease. Yet, the root cause, or causes, of Alzheimer’s are still pretty much a mystery.
In fact, many people get Alzheimer’s even though they lack the gene variant we know can play a role in the disease. This is a critical knowledge gap for research to address because the vast majority of Alzheimer’s patients don’t have this variant.
A new study provides key insights into what’s causing the disease. The research, published in Nature Communications, points to a breakdown over time in the brain’s system for clearing waste, an issue that seems to happen in some people as they get older.
Michael Glickman, a biologist at Technion – Israel Institute of Technology, helped lead this research. I asked him to tell me about his approach to studying how this breakdown occurs in the brain, and how he tested a treatment that has potential to fix the problem at its earliest stages.
Dr. Michael Glickman is internationally renowned for his research on the ubiquitin-proteasome system (UPS), the brain's system for clearing the waste that is involved in diseases such as Huntington's, Alzheimer's, and Parkinson's. He is the head of the Lab for Protein Characterization in the Faculty of Biology at the Technion – Israel Institute of Technology. In the lab, Michael and his team focus on protein recycling and the ubiquitin-proteasome system, which protects against serious diseases like Alzheimer’s, Parkinson’s, cystic fibrosis, and diabetes. After earning his PhD at the University of California at Berkeley in 1994, Michael joined the Technion as a Senior Lecturer in 1998 and has served as a full professor since 2009.
Dr. Michael Glickman