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Microbiome Update

Microbiome update

20210318

Credit: https://www.nytimes.com/2021/03/18/well/eat/microbiome-aging.html?action=click&algo=bandit-all-surfaces-decay-decay-02&block=trending_recirc&fellback=false&imp_id=986584686&impression_id=0cc53dd8-8b11-11eb-87e0-b362713e87cd&index=8&pgtype=Article&region=footer&req_id=227739339&surface=most-popular-story&variant=2_bandit-all-surfaces-decay-decay-02

By Anahad O’Connor

The secret to successful aging may lie in part in your gut, according to a new report. The study found that it may be possible to predict your likelihood of living a long and healthy life by analyzing the trillions of bacteria, viruses and fungi that inhabit your intestinal tract.

The new research, published in the journal Nature Metabolism, found that as people get older, the composition of this complex community of microbes, collectively known as the gut microbiome, tends to change. And the greater the change, the better, it appears.

In healthy people, the kinds of microbes that dominate the gut in early adulthood make up a smaller and smaller proportion of the microbiome over the ensuing decades, while the percentage of other, less prevalent species rises. But in people who are less healthy, the study found, the opposite occurs: The composition of their microbiomes remains relatively static and they tend to die earlier.

The new findings suggest that a gut microbiome that continually transforms as you get older is a sign of healthy aging, said a co-author of the study, Sean Gibbons, a microbiome specialist and assistant professor at the Institute for Systems Biology in Seattle, a nonprofit biomedical research.

“A lot of aging research is obsessed with returning people to a younger state or turning back the clock,” he said. “But here the conclusion is very different. Maybe a microbiome that’s healthy for a 20-year-old is not at all healthy for an 80-year-old. It seems that it’s good to have a changing microbiome when you’re old. It means that the bugs that are in your system are adjusting appropriately to an aging body.”

The researchers could not be certain whether changes in the gut microbiome helped to drive healthy aging or vice versa. But they did see signs that what happens in people’s guts may directly improve their health. They found, for example, that people whose microbiomes shifted toward a unique profile as they aged also had higher levels of health-promoting compounds in their blood, including compounds produced by gut microbes that fight chronic disease.

Scientists have suspected for some time that the microbiome plays a role in aging. Studies have found, for example, that people 65 and older who are relatively lean and physically active have a higher abundance of certain microbes in their guts compared to seniors who are less fit and healthy. People who develop early signs of frailty also have less microbial diversity in their guts. By studying the microbiomes of people of all ages, scientists have found patterns that extend across the entire life span. The microbiome undergoes rapid changes as it develops in the first three years of life. Then it remains relatively stable for decades, before gradually undergoing changes in its makeup as people reach midlife, which accelerates into old age in those who are healthy but slows or remains static in people who are less healthy.

Although no two microbiomes are identical, people on average share about 30 percent of their gut bacterial species. A few species that are particularly common and abundant make up a “core” set of gut microbes in all of us, along with smaller amounts of a wide variety of other species that are found in different combinations in every person.

To get a better understanding of what happens in the gut as people age, Dr. Gibbons and his colleagues, including Dr. Tomasz Wilmanski, the lead author of the new study, looked at data on over 9,000 adults who had their microbiomes sequenced. They ranged in age from 18 to 101.

About 900 of these people were seniors who underwent regular checkups at medical clinics to assess their health. Dr. Gibbons and his colleagues found that in midlife, starting at around age 40, people started to show distinct changes in their microbiomes. The strains that were most dominant in their guts tended to decline, while other, less common strains became more prevalent, causing their microbiomes to diverge and look more and more different from others in the population.

“What we found is that over the different decades of life, individuals drift apart — their microbiomes become more and more unique from one another,” said Dr. Gibbons.

People who had the most changes in their microbial compositions tended to have better health and longer life spans. They had higher vitamin D levels and lower levels of LDL cholesterol and triglycerides, a type of fat in the blood. They needed fewer medications, and they had better physical health, with faster walking speeds and greater mobility.

The researchers found that these “unique” individuals also had higher levels of several metabolites in their blood that are produced by gut microbes, including indoles, which have been shown to reduce inflammation and maintain the integrity of the barrier that lines and protects the gut. In some studies, scientists have found that giving indoles to mice and other animals helps them stay youthful, allowing them to be more physically active, mobile and resistant to sickness, injuries and other stresses in old age. Another one of the metabolites identified in the new study was phenylacetylglutamine. It is not clear exactly what this compound does. But some experts believe it promotes longevity because research has shown that centenarians in northern Italy tend to have very high levels of it.

Dr. Wilmanski found that people whose gut microbiomes did not undergo much change as they got older were in poorer health. They had higher cholesterol and triglycerides and lower levels of vitamin D. They were less active and could not walk as fast. They used more medications, and they were nearly twice as likely to die during the study period.

The researchers speculated that some gut bugs that might be innocuous or perhaps even beneficial in early adulthood could turn harmful in old age. The study found, for example, that in healthy people who saw the most dramatic shifts in their microbiome compositions there was a steep decline in the prevalence of bacteria called Bacteroides, which are more common in developed countries where people eat a lot of processed foods full of fat, sugar and salt, and less prevalent in developing countries where people tend to eat a higher-fiber diet. When fiber is not available, Dr. Gibbons said, Bacteroides like to “munch on mucus,” including the protective mucus layer that lines the gut.

“Maybe that’s good when you’re 20 or 30 and producing a lot of mucus in your gut,” he said. “But as we get older, our mucus layer thins, and maybe we may need to suppress these bugs.”

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If those microbes chew through the barrier that keeps them safely in the gut, it is possible they could trigger an immune system response.

“When that happens, the immune system goes nuts,” Dr. Gibbons said. “Having that mucus layer is like having a barrier that maintains a détente that allows us to live happily with our gut microbes, and if that goes away it starts a war” and could set off chronic inflammation. Increasingly, chronic inflammation is thought to underlie a wide range of age-related ailments, from heart disease and diabetes to cancer and arthritis.

One way to prevent these microbes from destroying the lining of the gut is to give them something else to snack on, such as fiber from nutritious whole foods like beans, nuts and seeds and fruits and vegetables.

Other studies have shown that diet can have a substantial impact on the composition of the microbiome. While the new research did not look closely at the impact of different foods on changes in the microbiome as we age, Dr. Gibbons said he hopes to examine that in a future study.

“It may be possible to preserve the aging mucus layer in the gut by increasing the amount of fiber in the diet,” Dr. Gibbons said. “Or we might identify other ways to reduce Bacteroides abundance or increase indole production through diet. These are not-too-distant future interventions that we hope to test.”

In the meantime, he said, his advice for people is to try to stay physically active, which can have a beneficial effect on the gut microbiome, and eat more fiber and fish and fewer highly processed foods.

“I have started eating a lot more fiber since I began studying the microbiome,” he said. “Whole foods like fresh fruits and veggies have all the complex carbohydrates that our microbes like to eat. So, when you’re feeding yourself, think about your microbes too.”

Anahad O’Connor is a staff reporter covering health, science, nutrition and other topics. He is also a bestselling author of consumer health books such as “Never Shower in a Thunderstorm” and “The 10 Things You Need to Eat.” 

Arivale busts: a scientific wellness darling

Arivale – the end of a promising “scientific wellness” company

Anyone who cares about well-being, particularly that subset of well-being that many labeled as the “scientific wellness” movement, should note a decade-ender: the failure of Arivale. 

They burned through $50 million. They sold 5,000 customers over their lifetime. The customers were paying $99 per month on LABS tracking and health coaching that was tailored to the person’s genomes and other critical lab work. 

Their conclusion: customers would not pay for what it cost to serve them. In the future? Maybe. But not now. 

=======ARTICLE ON ARIVALE FOLLOWS=======

CREDIT: https://www.geekwire.com/2019/scientific-wellness-startup-arivale-closes-abruptly-tragic-end-vision-transform-personal-health/

Scientific wellness startup Arivale closes abruptly in ‘tragic’ end to vision to transform personal health

BY TODD BISHOP & TAYLOR SOPER on April 24, 2019

Arivale, the genetic testing and personal health coaching startup co-founded by genomics pioneer Leroy “Lee” Hood, shut down unexpectedly Wednesday — bringing an abrupt end to its ambitions to transform the lives of Americans through a new field that Hood dubbed “scientific wellness.”

All of the Seattle-based company’s approximately 120 employees were let go as of noon today, Arivale CEO Clayton Lewis confirmed in an interview. Arivale raised more than $50 million over its lifetime. The company offered ongoing wellness and nutritional coaching tailored to the results of each person’s genetic, blood and microbiome tests.

FOLLOW-UP: Why Arivale failed: Inside the surprise closure of an ambitious ‘scientific wellness’ startup

The decision was a surprise to many Arivale employees and customers. In a message to Arivale customers this afternoon, the company attributed the decision to “the simple fact that the cost of providing the service exceeds what our customers can pay for it.”

The message added, “We believe the costs of collecting the genetic, blood and microbiome assays that form the foundation of the program will eventually decline to a point where the program can be delivered to consumers cost-effectively. However, we are unable to continue to operate at a loss until that time arrives.”

Lewis told GeekWire that the high cost of acquiring customers also played a role in the decision.

“What is tragic on so many levels is that we were not successful in going out and convincing consumers that you could optimize your wellness and avoid disease with a little bit data and some changes in your lifestyle — that there’s not a market for that product that I believe in passionately,” Lewis said. “And that’s what we were trying to do.”

About 5,000 people took part in the Arivale program over the lifetime of the company, and Lewis said he is “incredibly proud” of the results. The program launched at a cost of $3,500 per year, but the price had dropped to the point where most customers were paying $99 per month for the flagship Arivale program, Lewis said.

The larger personal wellness industry includes heavyweights such as 23andMe, a genetic testing startup valued at more than $1 billion, and smaller players including EverlyWell, which raised a $50 million round last week, and Viome, the Seattle-area microbiome company led by Naveen Jain that just announced a new $25 million funding round from investors including Salesforce CEO Marc Benioff.

Global Wellness Institute estimates that the preventative and personalized medicine and public health industry is worth $575 billion.

Some of Arivale’s underlying work will continue at the Institute for Systems Biology (ISB), the not-for-profit biomedical research organization co-founded by Hood, where the ideas that led to Arivale were originally developed. ISB is now part of Providence St. Joseph Health, where Hood is chief science officer. Clayton said ISB is expected to hire some of the employees let go by Arivale as part of its closure. He declined to disclose details of the severance offered to employees, but said the same package was provided to all executives and employees.

Investors in Arivale included Arch Venture Partners, Polaris, and Maveron, where Lewis worked full-time before joining Arivale as co-founder and CEO.

Its scientific advisory board included George Church, a professor at Harvard and MIT; James Heath, president of Institute of Systems Biology; and Ed Lazowska, computer science professor at the University of Washington.

“Lee Hood sees the future with unmatched clarity,” said Lazowska, an early participant in the Arivale program. “A clear view, however, does not always imply a short path. Scientific wellness, as pioneered by Arivale, will be a foundation of 21st century medicine. But not right now. Right now, the cost of providing the service (the tests, the coaching) exceeds what people are willing to pay. Those costs will fall in time, and Arivale’s model and Arivale’s discoveries will see another day.”

Lewis said he has come to believe that Arivale was about a decade too early.

Arivale’s executive team included Sean Bell, chief operating officer; Jennifer Lovejoy, chief translational science officer; Mia Nease, head of healthcare and life sciences partnerships; Andrew Magis, director of research; Ashley Wells, chief product officer; and others.

Hood, who led the Caltech team that pioneered the automated DNA sequencer, said in a 2015 interview with GeekWire that Arivale was “the opening shot in a whole new industry called scientific wellness, and it really stands a chance of being the Google or Microsoft of this whole arena.”

GeekWire chief business officer Daniel Rossi was a longtime paying customer of the program, and we chronicled his early experience with Arivale in series of articles in 2017. “Arivale was crucial to my health journey,” Rossi said. “From them I learned not only the genetic hand I was dealt but also the best ways to maximize my health and well-being. I am most thankful for the weekly calls with my coaches who encouraged me every step of the way. I’ll miss this program. It was terrific.”

Here’s the text of the message sent to Arivale customers earlier today, a version of which was also posted to the Arivale website.

To Our Customers,

We are very sorry to inform you that, effective immediately, Arivale can no longer provide our program to you and our other customers. This letter explains why we are ending the consumer program and answers the questions you are likely to have about the process.

Our decision to terminate the program today comes despite the fact that customer engagement and satisfaction with the program is high and the clinical health markers of many customers have improved significantly. Our decision to cease operations is attributable to the simple fact that the cost of providing the program exceeds what our customers can pay for it. We believe the costs of collecting the genetic, blood and microbiome assays that form the foundation of the program will eventually decline to a point where the program can be delivered to consumers cost-effectively. Regrettably, we are unable to continue to operate at a loss until that time arrives; in other words, we have concluded that it is simply too early for a direct-to-consumer scientific wellness offering to be viable.

We founded Arivale with the vision of making personalized, data-driven, preventive coaching a new wellness paradigm in the United States. Since its launch in 2015, the results of the Arivale program have been remarkable. To cite but one example, our scientific paper describing the improvements seen in multiple health markers in ~2500 participants was recently accepted for publication in the journal Scientific Reports.

While our direct-to-consumer model isn’t yet sustainable, we know that the Arivale program improved the lives of our customers and showed great scientific merit. We are proud of everyone at Arivale for their dedication and devotion to our mission and grateful to you and all of our other customers for joining us on this journey. Together, our efforts have launched a new paradigm—scientific or quantitative wellness—which, we are confident will become a major component of 21st century medicine.

================== END ARTICLE==============

Written by: Todd Bishop is GeekWire’s co-founder and editor, a longtime technology journalist who covers subjects including cloud tech, e-commerce, virtual reality, devices, apps and tech giants such as Amazon.com, Apple, Microsoft and Google. Follow him @toddbishop, email todd@geekwire.com, or call (206) 294-6255.

Digital Immortality

In this week’s Sunday NYT Magazine, a discussion was recorded about the future of technology. One of my favorite writers, Sid Mukerjee, discussed chronic disease. In that discussion, he touched on a notion of immortality that I have been pondering for some time.

Here is what he said, and after is what I say in response.

MUKHERJEE: “In terms of longevity, the diseases that are most likely to kill us are neurological diseases and heart disease and cancer. In some other countries, there is tuberculosis and malaria and other infectious diseases, but here it’s the chronic diseases that dominate. There are three ways to think about these chronic diseases. One is the disease-specific way. So, you attack Alzheimer’s as Alzheimer’s; you attack cancer as cancer. The second one is that you forget about the disease-specific manners of attacking diseases and you attack longevity or aging reversal in general. You change diet, change genes, change whatever else — we might call them “trans factors,” which would simply override the “cis factors” that existed for individual diseases. And the third option is some combination of that and some digital form of immortality, which is that you record yourself forever, that you clone yourself and somehow pass along that recording. Which is to say that the body is just a repository of memories, images, times. And as a repository, there’s nothing special about it. The body per se, the mortal coil, is just a coil.

This is the first time I have heard a major thinker put immortality into this context. And yet – its so obvious to do so!

For example:

– wouldn’t it be fair to say that every autobiography ever written would be a sincere attempt by the writer to achieve some form of immortality?

– in like manner, isn’t the task of the biographer, in part, to immortalize their subject?

– more broadly, how do societies around the world remember their ancestors? Their memories are their attempts to allow ancestors to live forever!

This point is nicely illustrated by the Irish culture. In my work on the History of Ireland, the centrality of “oral tradition” was crystal clear. I came continually across how the Irish told stories to revere their ancestors. The Irish would distill their ancestors into a wide variety of stories that helped the present generation understand the past.

So, by extrapolation from this point (which is obvious), can this be asked: “Can I be immortalized digitally?

Digital storage costs have plummeted. Methods of organizing and tagging video and audio recordings are now commonplace. Search engines are commonplace. Pattern recognition combined with search is exploding.

So what will prevent me in the future from immortalizing myself digitally? What prevents me from storing who I am, what I did, what I learned, where I have been, what I have experienced, who I knew, who my ancestors were, who my children and grandchildren were, etc etc?

Perhaps the answer is: nothing. Nothing prevents me from being digitally immortal.

Well-Being – Real Time Revisited

NOTE: This post revisits a post titled “Well-Being Real Time”. The original post was May, 2014, and can be found at: http://johncreid.com/2014/05/well-being-real-time/.

Well-Being – Real Time Revisited

Well-being is arguably the central mega-trend of the 21st century. As we look to the future, we have an obligation to “unpack” this dense concept, and find its essential component parts.

We describe these components here as “ACE” – ACT, CARE, and EAT. The wish we have for ourselves and for others is to be well. “Be Well” is our salutation and our call to actions.

How far out are we looking?

The future is now. ACE is here – together with real time measuring and monitoring. ACE is our pathway to greater and greater levels of personal well-being.

ACE measuring and monitoring will be supported by all elements of the quantified self movement. FitBit, Apple Watch, and so many other new monitoring devices will allow us to to bring personal well-being into a real-time modality.

ACE represents three pillars, each deceptively simple:

A – ACT: ACT is short for activity. The call to action is “stay active”. Well-being activity has physical activity at its center, but the pillar also embraces social activity, and activities of the mind. Staying active is a critical element of being well.
C – CARE: CARE is short for well-being care. The call to action is “care for yourself” and “care for others.”Well-being care of course has health care at its center, but there is so much more. e.g. genomics, massage, essential oils, acupuncture, etc. “Caring for myself” and “Caring for others” are elements of this pillar. “Preventive care” regular check-ups, colonoscopies after age 50, mammograms, pre-natal care for expecting mothers, etc.
E – EAT: EAT is short for eating and drinking. The call to action is “Eat well.” Well-being eating is the exploration of how what we eat and drink contributes to our well-being.

As simple as these pillars appear, each is complex: deep enough for a life-time of focus. Each represents bodies of research, skills, capabilities, and areas of professional endeavor. All together, these pillars represent pathway that each of us will follow as we attain greater and greater levels of personal well-being.

Discussion:

ACT

A – ACT (walking, running, calories burned etc)

Staying active is a critical element of being well. Well-being activity has physical activity at its center: sports, walking, lifting, climbing, yoga, and all of the other activities that light up a FitBit. The pillar also embraces activity of other kinds, e.g. social activity, and activities of the mind.

CARE

Well-being care is all about promoting health. Of course, it has health care at its center, but there is so much more. e.g. mental health, addictive behaviors, massage, genomics, essential oils, acupuncture, etc.

“Caring for myself” and “Caring for others” are elements of this pillar. “Preventive care”, eldercare and aging, palliative care are included, but so are regular check-ups, colonoscopies after age 50, mammograms, pre-natal care for expecting mothers, etc.

The ability to routinely monitor vital signs at home or at the office will be a part of this pillar. Lab work – including saliva, blood, and stool samples, will be more real time, more regular and less expensive. These trends will be one of the keys to progress in the care pillar. On the innovation side of this pillar will be many technologies, but breakthroughs in genomics will certainly be high on the list. Telemedicine is another innovation that will alter access to well-being care.

Predictive modeling will be more relevant than never. Am I headed for pre-diabetes? If so, what evidence shows me a path to avoid that condition?

CARE-MMEDS (what MEDS I take, what compliance I have, etc)

CARE-RResting Metabolic Rate (calories burned at rest)

CARE-VVITALS (pulse, BP, etc)

CARE-LLABS (blood testing, etc)

CARE-SSleep (duration, deep sleep, etc)

EAT

EAT is short for eating and drinking. The call to action is “Eat well.”

Well-being eating is the exploration of how what we eat and drink contributes to our well-being. Naturally, there is a social element, where eating and drinking together makes the experience more fulfilling. There is a physiological element, having to do with ingestion, osmosis, calories, glucose and glycogen, enzymes, etc. There is a psychological element, related to the feelings of satiety, or hunger, or thirst, and their related cravings. There is a sensory element, where sweet and sour contrasts, aromas, and their related metaphorical associations, play a part.

Eating delicious food and drink with friends is certainly a component. But achieving a balanced diet, with moderation as a central tenant,

On the one hand, this pillar is ancient. For thousands of years, elders have taught daughters and sons how to cook well. and cooking techniques have evolved

On the other hand, this pillar is ripe for innovation. The new breakthrough science related to the micro-biome is a part.

EATS (what I eat and drink, especially calories)

Implications

Monitoring all components of ACE (MEDS, Activity, Resting Metabolism,VITALS, EATS, LABS, Sleep) is now going to accelerate at an exponential rate.

There will be three settings where ACE monitoring will accelerate:

Employees in Workplaces: Employers will offer employees routine monitoring as part of employee benefits and/or health insurance.
Residents in Communities: Communities will offer residents routine monitoring as one of their amenities. Wellbeing facilities and programs will become as important as golf courses and swimming pools. Look for HOA’s,Condo and Coop associations, and subdivision developers to increasingly view MARVELS as critical to “place-making”.
Clients of service-providers: Hotels, spas, assisted-living centers, nursing homes, and many others will increasingly offer MARVELS monitoring as one of their base services.

The Privacy Imperative will be the critical success factor for all of these pushes into the future. It is foundational.

Without it, there will be no progress.

With it, personalized, real-time care will flourish. Each individual will be able to opt-in to his care-coaching community (and to opt-out whenever they choose), and get the extraordinary benefits that such a community can provide.

Want to talk to your well-being coach? FaceTime them, and they – with your permission – will help you sort out what’s going on with you.

Feel like you might need a check-in with a doctor? Send them an email – with your ACE history embedded in it, or get them on the phone or FaceTime, and see if they need you to come in.

The future is now.

BEWELL Centers will be everywhere. Look for:

DWELL CENTERS (part of BEWELL Centers) – for community ACE measuring and monitoring support. Target population is neighbors in the community.

Employee BEWELL CENTERS (part of BEWELL Centers) – for employees in workplaces ACE measuring and monitoring support. Target population is employees in the workplace.

CLIENT BEWELL CENTERS (Part of BEWELL Centers – for service-providers ACE measuring and monitoring support.Target population is clients of the service provider.
(Walgreens and CVS are already moving aggressively in this direction>

References:
The Privacy Imperative
LABS revolution
LABS By Disease
Quantified Self Movement

The Dying Algorithm

CREDIT: NYT Article on the Dying Algorithm

This Cat Sensed Death. What if Computers Could, Too
By Siddhartha Mukherjee
Jan. 3, 2018

Of the many small humiliations heaped on a young oncologist in his final year of fellowship, perhaps this one carried the oddest bite: A 2-year-old black-and-white cat named Oscar was apparently better than most doctors at predicting when a terminally ill patient was about to die. The story appeared, astonishingly, in The New England Journal of Medicine in the summer of 2007. Adopted as a kitten by the medical staff, Oscar reigned over one floor of the Steere House nursing home in Rhode Island. When the cat would sniff the air, crane his neck and curl up next to a man or woman, it was a sure sign of impending demise. The doctors would call the families to come in for their last visit. Over the course of several years, the cat had curled up next to 50 patients. Every one of them died shortly thereafter.
No one knows how the cat acquired his formidable death-sniffing skills. Perhaps Oscar’s nose learned to detect some unique whiff of death — chemicals released by dying cells, say. Perhaps there were other inscrutable signs. I didn’t quite believe it at first, but Oscar’s acumen was corroborated by other physicians who witnessed the prophetic cat in action. As the author of the article wrote: “No one dies on the third floor unless Oscar pays a visit and stays awhile.”
The story carried a particular resonance for me that summer, for I had been treating S., a 32-year-old plumber with esophageal cancer. He had responded well to chemotherapy and radiation, and we had surgically resected his esophagus, leaving no detectable trace of malignancy in his body. One afternoon, a few weeks after his treatment had been completed, I cautiously broached the topic of end-of-life care. We were going for a cure, of course, I told S., but there was always the small possibility of a relapse. He had a young wife and two children, and a mother who had brought him weekly to the chemo suite. Perhaps, I suggested, he might have a frank conversation with his family about his goals?

But S. demurred. He was regaining strength week by week. The conversation was bound to be “a bummah,” as he put it in his distinct Boston accent. His spirits were up. The cancer was out. Why rain on his celebration? I agreed reluctantly; it was unlikely that the cancer would return.

When the relapse appeared, it was a full-on deluge. Two months after he left the hospital, S. returned to see me with sprays of metastasis in his liver, his lungs and, unusually, in his bones. The pain from these lesions was so terrifying that only the highest doses of painkilling drugs would treat it, and S. spent the last weeks of his life in a state bordering on coma, unable to register the presence of his family around his bed. His mother pleaded with me at first to give him more chemo, then accused me of misleading the family about S.’s prognosis. I held my tongue in shame: Doctors, I knew, have an abysmal track record of predicting which of our patients are going to die. Death is our ultimate black box.

In a survey led by researchers at University College London of over 12,000 prognoses of the life span of terminally ill patients, the hits and misses were wide-ranging. Some doctors predicted deaths accurately. Others underestimated death by nearly three months; yet others overestimated it by an equal magnitude. Even within oncology, there were subcultures of the worst offenders: In one story, likely apocryphal, a leukemia doctor was found instilling chemotherapy into the veins of a man whose I.C.U. monitor said that his heart had long since stopped.

But what if an algorithm could predict death? In late 2016 a graduate student named Anand Avati at Stanford’s computer-science department, along with a small team from the medical school, tried to “teach” an algorithm to identify patients who were very likely to die within a defined time window. “The palliative-care team at the hospital had a challenge,” Avati told me. “How could we find patients who are within three to 12 months of dying?” This window was “the sweet spot of palliative care.” A lead time longer than 12 months can strain limited resources unnecessarily, providing too much, too soon; in contrast, if death came less than three months after the prediction, there would be no real preparatory time for dying — too little, too late. Identifying patients in the narrow, optimal time period, Avati knew, would allow doctors to use medical interventions more appropriately and more humanely. And if the algorithm worked, palliative-care teams would be relieved from having to manually scour charts, hunting for those most likely to benefit.

Avati and his team identified about 200,000 patients who could be studied. The patients had all sorts of illnesses — cancer, neurological diseases, heart and kidney failure. The team’s key insight was to use the hospital’s medical records as a proxy time machine. Say a man died in January 2017. What if you scrolled time back to the “sweet spot of palliative care” — the window between January and October 2016 when care would have been most effective? But to find that spot for a given patient, Avati knew, you’d presumably need to collect and analyze medical information before that window. Could you gather information about this man during this prewindow period that would enable a doctor to predict a demise in that three-to-12-month section of time? And what kinds of inputs might teach such an algorithm to make predictions?
Avati drew on medical information that had already been coded by doctors in the hospital: a patient’s diagnosis, the number of scans ordered, the number of days spent in the hospital, the kinds of procedures done, the medical prescriptions written. The information was admittedly limited — no questionnaires, no conversations, no sniffing of chemicals — but it was objective, and standardized across patients.

These inputs were fed into a so-called deep neural network — a kind of software architecture thus named because it’s thought to loosely mimic the way the brain’s neurons are organized. The task of the algorithm was to adjust the weights and strengths of each piece of information in order to generate a probability score that a given patient would die within three to 12 months.

The “dying algorithm,” as we might call it, digested and absorbed information from nearly 160,000 patients to train itself. Once it had ingested all the data, Avati’s team tested it on the remaining 40,000 patients. The algorithm performed surprisingly well. The false-alarm rate was low: Nine out of 10 patients predicted to die within three to 12 months did die within that window. And 95 percent of patients assigned low probabilities by the program survived longer than 12 months. (The data used by this algorithm can be vastly refined in the future. Lab values, scan results, a doctor’s note or a patient’s own assessment can be added to the mix, enhancing the predictive power.)

So what, exactly, did the algorithm “learn” about the process of dying? And what, in turn, can it teach oncologists? Here is the strange rub of such a deep learning system: It learns, but it cannot tell us why it has learned; it assigns probabilities, but it cannot easily express the reasoning behind the assignment. Like a child who learns to ride a bicycle by trial and error and, asked to articulate the rules that enable bicycle riding, simply shrugs her shoulders and sails away, the algorithm looks vacantly at us when we ask, “Why?” It is, like death, another black box.

Still, when you pry the box open to look at individual cases, you see expected and unexpected patterns. One man assigned a score of 0.946 died within a few months, as predicted. He had had bladder and prostate cancer, had undergone 21 scans, had been hospitalized for 60 days — all of which had been picked up by the algorithm as signs of impending death. But a surprising amount of weight was seemingly put on the fact that scans were made of his spine and that a catheter had been used in his spinal cord — features that I and my colleagues might not have recognized as predictors of dying (an M.R.I. of the spinal cord, I later realized, was most likely signaling cancer in the nervous system — a deadly site for metastasis).
It’s hard for me to read about the “dying algorithm” without thinking about my patient S. If a more sophisticated version of such an algorithm had been available, would I have used it in his case? Absolutely. Might that have enabled the end-of-life conversation S. never had with his family? Yes. But I cannot shake some inherent discomfort with the thought that an algorithm might understand patterns of mortality better than most humans. And why, I kept asking myself, would such a program seem so much more acceptable if it had come wrapped in a black-and-white fur box that, rather than emitting probabilistic outputs, curled up next to us with retracted claws?

Siddhartha Mukherjee is the author of “The Emperor of All Maladies: A Biography of Cancer” and, more recently, “The Gene: An Intimate History.”

Microbiome Apps Personalize EAT recommendations

Richard Sprague provides a useful update about the microbiome landscape below. Microbiome is exploding. Your gut can be measured, and your gut can influence your health and well-being. But now …. these gut measurements can offer people a first: personalized nutrition information.

Among the more relevant points:

– Israel’s Weitzman Institute is the global leader academically. Eran Elinav, a physician and immunologist at the Weizmann Institute and one of their lead investigators (see prior post).
– The older technology for measuring the gut is called “16S” sequencing. It tell you at a high level which kinds of microbes are present. It’s cheap and easy, but 16S can see only broad categories,
– The companies competing to measure your microbiome are uBiome, American Gut, Thryve, DayTwo and Viome. DayTwo and Viome offer more advanced technology (see below).
– The latest technology seems to be “metagenomic sequencing”. It is better because it is more specific and detailed.
– By combining “metagenomic sequencing” information with extensive research about how certain species interact with particular foods, machine-learning algorithms can recommend what you should eat.
– DayTwo offers a metagenomic sequencing for $299, and then combines that with all available research to offer personalized nutrition information.
– DayTwo recently completed a $12 million financing round from, among others, Mayo Clinic, which announced it would be validating the research in the U.S.
– DayTwo draws its academic understandings from Israel’s Weitzman Institute. The app is based on more than five years of highly cited research showing, for example, that while people on average respond similarly to white bread versus whole grain sourdough bread, the differences between individuals can be huge: what’s good for one specific person may be bad for another.

CREDIT: Article on Microbiome Advances

When a Double-Chocolate Brownie is Better for You Than Quinoa

A $299 microbiome test from DayTwo turns up some counterintuitive dietary advice.

Why do certain diets work well for some people but not others? Although several genetic tests try to answer that question and might help you craft ideal nutrition plans, your DNA reveals only part of the picture. A new generation of tests from DayTwo and Viome offer diet advice based on a more complete view: they look at your microbiome, the invisible world of bacteria that help you metabolize food, and, unlike your DNA, change constantly throughout your life.
These bugs are involved in the synthesis of vitamins and other compounds in food, and they even play a role in the digestion of gluten. Artificial sweeteners may not contain calories, but they do modify the bacteria in your gut, which may explain why some people continue to gain weight on diet soda. Everyone’s microbiome is different.

So how well do these new tests work?
Basic microbiome tests, long available from uBiome, American Gut, Thryve, and others, based on older “16S” sequencing, can tell you at a high level which kinds of microbes are present. It’s cheap and easy, but 16S can see only broad categories, the bacterial equivalent of, say, canines versus felines. But just as your life might depend on knowing the difference between a wolf and a Chihuahua, your body’s reaction to food often depends on distinctions that can be known only at the species level. The difference between a “good” microbe and a pathogen can be a single DNA base pair.

New tests use more precise “metagenomic” sequencing that can make those distinctions. And by combining that information with extensive research about how those species interact with particular foods, machine-learning algorithms can recommend what you should eat. (Disclosure: I am a former “citizen scientist in residence” at uBiome. But I have no current relationship with any of these companies; I’m just an enthusiast about the microbiome.)

I recently tested myself with DayTwo ($299) to see what it would recommend for me, and I was pleased that the advice was not always the standard “eat more vegetables” that you’ll get from other products claiming to help you eat healthily. DayTwo’s advice is much more specific and often refreshingly counterintuitive. It’s based on more than five years of highly cited research at Israel’s Weizmann Institute, showing, for example, that while people on average respond similarly to white bread versus whole grain sourdough bread, the differences between individuals can be huge: what’s good for one specific person may be bad for another.

In my case, whole grain breads all rate C-. French toast with challah bread: A.

The DayTwo test was pretty straightforward: you collect what comes out of your, ahem, gut, which involves mailing a sample from your time on the toilet. Unlike the other tests, which can analyze the DNA found in just a tiny swab from a stain on a piece of toilet paper, DayTwo requires more like a tablespoon. The extra amount is needed for DayTwo’s more comprehensive metagenomics sequencing.

Since you can get a microbiome test from other companies for under $100, does the additional metagenomic information from DayTwo justify its much higher price? Generally, I found the answer is yes.

About two months after I sent my sample, my iPhone lit up with my results in a handy app that gave me a personalized rating for most common foods, graded from A+ to C-. In my case, whole grain breads all rate C-. Slightly better are pasta and oatmeal, each ranked C+. Even “healthy” quinoa — a favorite of gluten-free diets — was a mere B-. Why? DayTwo’s algorithm can’t say precisely, but among the hundreds of thousands of gut microbe and meal combinations it was trained on, it finds that my microbiome doesn’t work well with these grains. They make my blood sugar rise too high.

So what kinds of bread are good for me? How about a butter croissant (B+) or cheese ravioli (A-)? The ultimate bread winner for me: French toast with challah bread (A). These recommendations are very different from the one-size-fits-all advice from the U.S. Department of Agriculture or the American Diabetes Association.

I was also pleased to learn that a Starbucks double chocolate brownie is an A- for me, while a 100-calorie pack of Snyder’s of Hanover pretzels gets a C-. That might go against general diet advice, but an algorithm determined that the thousands of bacterial species inside me tend to metabolize fatty foods in a way that results in healthier blood sugar levels than what I get from high-carb foods. Of course, that’s advice just for me; your mileage may vary.

Although the research behind DayTwo has been well-reviewed for more than five years, the app is new to the U.S., so the built-in food suggestions often seem skewed toward Middle Eastern eaters, perhaps the Israeli subjects who formed the original research cohort. That might explain why the app’s suggestions for me include lamb souvlaki with yogurt garlic dip for dinner (A+) and lamb kabob and a side of lentils (A) for lunch. They sound delicious, but to many American ears they might not have the ring of “pork ribs” or “ribeye steak,” which have the same A+ rating. Incidentally, DayTwo recently completed a $12 million financing round from, among others, Mayo Clinic, which announced it would be validating the research in the U.S., so I expect the menu to expand with more familiar fare.

Fortunately you’re not limited to the built-in menu choices. The app includes a “build a meal” function that lets you enter combinations of foods from a large database that includes packaged items from Trader Joe’s and Whole Foods.

There is much more to the product, such as a graphical rendering of where my microbiome fits on the spectrum of the rest of the population that eats a particular food. Since the microbiome changes constantly, this will help me see what is different when I do a retest and when I try Viome and other tests.

I’ve had my DayTwo results for only a few weeks, so it’s too soon to know what happens if I take the app’s advice over the long term. Thankfully I’m in good health and reasonably fit, but for now I’ll be eating more strawberries (A+) and blackberries (A-), and fewer apples (B-) and bananas (C+). And overall I’m looking forward to a future where each of us will insist on personalized nutritional information. We all have unique microbiomes, and an app like DayTwo lets us finally eat that way too.

Richard Sprague is a technology executive and quantified-self enthusiast who has worked at Apple, Microsoft, and other tech companies. He is now the U.S. CEO of an AI healthcare startup, Airdoc.

====================APPENDIX: Older Posts about the microbiome =========

Microbiome Update
CREDIT: https://www.wsj.com/articles/how-disrupting-your-guts-rhythm-affects-your-health-1488164400?mod=e2tw A healthy community of microbes in the gut maintains regular daily cycles of activities. A healthy community of microbes in the gut maintains regular daily cycles of activities.PHOTO: WEIZMANN INSTITUTE By LARRY M. GREENBERG Updated Feb. 27, 2017 3:33 p.m. ET 4 COMMENTS New research is helping to unravel the mystery of how […]

Vibrant Health measures microbiome

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Microbiome Update
My last research on this subject was in August, 2014. I looked at both microbiomes and proteomics. Today, the New York Times published a very comprehensive update on microbiome research: Link to New York Time Microbiome Article Here is the article itself: = = = = = = = ARTICLE BEGINS HERE = = = […]

Microbiomes
Science is advancing on microbiomes in the gut. The key to food is fiber, and the key to best fiber is long fibers, like cellulose, uncooked or slightly sauteed (cooking shortens fiber length). The best vegetable, in the view of Jeff Leach, is a leek. Eating Well Article on Microbiome = = = = = […]

Arivale Launches LABS company
“Arivale” Launched and Moving Fast. They launched last month. They have 19 people in the Company and a 107 person pilot – but their plans are way more ambitious than that. Moreover: “The founders said they couldn’t envision Arivale launching even two or three years ago.” Read on …. This is an important development: the […]

Precision Wellness at Mt Sinai
My Sinai announcement Mount Sinai to Establish Precision Wellness Center to Advance Personalized Healthcare Mount Sinai Health System Launches Telehealth Initiatives Joshua Harris, co-Founder of Apollo Global Management, and his wife, Marjorie has made a $5 million gift to the Icahn School of Medicine at Mount Sinai to establish the Harris Center for Precision Wellness. […]

Proteomics
“Systems biology…is about putting together rather than taking apart, integration rather than reduction. It requires that we develop ways of thinking about integration that are as rigorous as our reductionist programmes, but different….It means changing our philosophy, in the full sense of the term” (Denis Noble).[5] Proteomics From Wikipedia, the free encyclopedia For the journal […]

Marketing Automation Software

Pardot believes they are perfecting lead generation through supplemental technologies.

See Pardot Website

Salesforce.com believes in the idea enough to buy them.

At a high level, this is about accepting that most leads are not “hot”, Pardot offers a way to nurture all warm leads and monitor whether they are moving toward cold or hot. If hot, the Pardot nurtures tha relationship in a way most relevant to the lead. They call this Smarter lead generation and effortless email marketing.

My friend Andrew M is a Salesforce expert and swears by them.

Alzheimer’s Genetic Risk Assessment

CREDIT: NPR article

CREDIT: Bill Gates 11.13.17 Blog Post on Alzheimer’s

FDA Approves Marketing Of Consumer Genetic Tests For Some Conditions

April 7, 20171:40 PM ET
JESSICA BODDY

23andMe is now allowed to market tests that assess genetic risks for 10 health conditions, including Parkinson’s and late-onset Alzheimer’s diseases.
Meredith Rizzo/NPR
The U.S. Food and Drug Administration approved 23andMe’s personal genetic test for some diseases on Thursday, including Alzheimer’s, Parkinson’s and celiac diseases.
The tests assess genetic risk for the conditions but don’t diagnose them, the FDA says. The agency urges consumers to use their results to “help to make decisions about lifestyle choices or to inform discussions with a health care professional,” according to a press release about the decision.
Jeffrey Shuren, the director of the FDA’s Center for Devices and Radiological Health, wrote, “it is important that people understand that genetic risk is just one piece of the bigger puzzle, it does not mean they will or won’t ultimately develop a disease.” Other known factors that can play into the development of disease include diet, environment and tobacco use.

SHOTS – HEALTH NEWS
23andMe Bows To FDA’s Demands, Drops Health Claims
The FDA has previously scolded the company for marketing the personal genetic testing kits without the agency’s consent. In 2013, the agency told 23andMe to stop selling its personal genome kits in the United States until they gained FDA approval by proving they were accurate.
The company agreed to work with the FDA, as we reported, and a recent FDA review of peer-reviewed studies found more consistent links between certain gene variants and 10 diseases, the FDA says.
As a result, the FDA is now allowing 23andMe to market tests that assess genetic risks for the following 10 diseases or conditions:
▪ Parkinson’s disease, a nervous system disorder impacting movement 

▪ Late-onset Alzheimer’s disease, a progressive brain disorder that destroys memory and thinking skills 

▪ Celiac disease, a disorder resulting in the inability to digest gluten 

▪ Alpha-1 antitrypsin deficiency, a disorder that raises the risk of lung and liver disease 

▪ Early-onset primary dystonia, a movement disorder involving involuntary muscle contractions and other uncontrolled movements 

▪ Factor XI deficiency, a blood clotting disorder 

▪ Gaucher disease type 1, an organ and tissue disorder 

▪ Glucose-6-phosphate dehydrogenase deficiency, also known as G6PD, a red blood cell condition 

▪ Hereditary hemochromatosis, an iron overload disorder 

▪ Hereditary thrombophilia, a blood clot disorder 


The company’s $199 Health and Ancestry test is available directly to consumers, without seeing a physician or genetic counselor. Consumers’ DNA is extracted from a saliva sample. After mailing in their sample, people can see their results online.
“This is an important moment for people who want to know their genetic health risks and be more proactive about their health,” said Anne Wojcicki, the CEO and co-founder of 23andMe, in a company press release.
Sharon Terry, the CEO of the Genetic Alliance, a nonprofit organization that advocates for health care for people with genetic disorders, likens it to another consumer test. “Women learn they are pregnant using a test directly marketed to them and buy it off the shelf in a drugstore,” she told NPR. “In 10 years we will marvel that this is an ‘advance’ at all. Imagine pregnancy tests being only available through a doctor!”
Robert Green, a professor of medicine at Harvard Medical School, says people should be able to access genetic information in whatever way is best for them. “Some people really want this [genetic] information on their own, and others want it through their physician,” he said. “Both those channels are legitimate. People should just be aware that this information is complicated.”
But some are still concerned about whether the genes in question actually correspond to a higher risk of disease reliably enough to warrant direct-to-consumer marketing and testing, as opposed to genetic testing with the guidance of a professional.

SHOTS – HEALTH NEWS
Don’t Get Your Kids’ Genes Sequenced Just To Keep Up

SHOTS – HEALTH NEWS
Personalizing Cancer Treatment With Genetic Tests Can Be Tricky
Some health professionals worry that consumers will “take the results and run,” as Mary Freivogel put it. Freivogel, a certified genetic counselor and the president of the National Society of Genetic Counselors, added that genetics are just “one piece to the story when it comes to developing a disease.”
Freivogel said speaking with a genetic counselor before getting tested for disease is important. “Direct-to-consumer testing takes away a pre-test conversation,” she said, where counselors can help patients think about questions like: “What do you want to know? What are you going to do with this information? Is it something you’re prepared to know, or is it going to just make you anxious?”
And it isn’t clear what consumers should do with their newly calculated disease risk, especially for conditions like Alzheimer’s for which there isn’t a cure or even a course of action to prevent the disease.
What’s more, having the genes is not the same as having the diseases the genes are associated with. A person may have genes that are associated with Alzheimer’s, for example, but that doesn’t mean he or she will ever get the disease. Conversely, some people develop Alzheimer’s without the identified risk genes.
The Alzheimer’s Association does not recommend routine genetic testing for the disease in the general population because it can’t “productively guide medical treatment.”
A genetic test result for Alzheimer’s is “not going to provide useful information even if you’re at an increased risk,” said Keith Fargo, director of scientific programs at the Alzheimer’s Association. “It’s not like there’s a drug you can take right now [to prevent the disease] or a lifestyle change you can make that you shouldn’t make anyway,” such as exercising and eating right to keep your brain healthy.
John Lehr, the CEO of the Parkinson’s Foundation, says personal genetic tests can help identify risk for Parkinson’s disease. But, he wrote in a statement following the FDA’s announcement, the foundation recommends “that people who are interested in testing first seek guidance from their doctors and from genetic counselors to understand what the process may mean for them and their families.”