King cancer: The top 10 therapeutic areas in biopharma R&D

July 23, 2017

It’s not going to come as a surprise to anyone who’s been paying attention to drug R&D trends that cancer is the number 1 disease in terms of new drug development projects. But it is amazing to see exactly how much oncology dominates the industry as never before.

At a time the first CAR-T looks to be on the threshold of a pioneering approval and the first wave of PD-(L)1 drugs are spurring hundreds of combination studies, cancer accounted for 8,651 of the total number of pipeline projects counted by the Analysis Group, crunching the numbers in a new report commissioned by PhRMA. That’s more than a third of the 24,389 preclinical through Phase III programs tracked by EvaluatePharma, which provided the database for this review.

That’s also more than the next 5 disease fields combined, starting with number 2, neurology — a field that includes Parkinson’s and Alzheimer’s. Psychiatry, once a major focus for pharma R&D, didn’t even make the top 10, with 468 projects.

Moving downstream, cancer studies are overwhelmingly in the lead. Singling out Phase I projects, cancer accounted for 1,757 out of a total of 3,723 initiatives, close to half. In Phase II it’s the focus of 1,920 of 4,424 projects. Only in late-stage studies does cancer start to lose its overwhelming dominance, falling to 329 of 1,257 projects.

PhRMA commissioned this report to underscore just how much the industry is committed to R&D and significant new drug development, a subject that routinely comes into question as analysts evaluate how much money is devoted to developing new drugs instead of, say, marketing or share buybacks.

The report makes a few other points to underscore the nature of the work these days.

— Three out of four projects in the clinic were angling for first-in-class status, spotlighting the emphasis on advancing new medicines that can make a difference for patients. Me-too drugs are completely out of fashion, unlikely to command much weight with payers.

— Of all the projects in clinical development, 822 were for orphan drugs looking to serve a market of 200,000 or less. Orphan drugs have performed well, able to command high prices and benefiting from incentives under federal law.

— There were 731 cell and gene therapy projects in the clinic, with biopharma looking at pioneering approvals in CAR-T, with Novartis and Kite, as well as the first US OK for a gene therapy, with the first application accepted this week for a priority review of a new therapy from Spark Therapeutics.


Distribution of products and projects by therapeutic area and phase


Source: Analysis Group, using EvaluatePharma data


Unique NMEs in development by stage (August 2016)

CRISPR kills HIV and eats Zika ‘like Pac-man’. Its next target? Cancer

June 29, 2017

There’s a biological revolution underway and its name is CRISPR.

Pronounced ‘crisper’, the technique stands for Clustered Regularly Interspaced Short Palindromic Repeat and refers to the way short, repeated DNA sequences in the genomes of bacteria and other microorganisms are organised.

Inspired by how these organisms defend themselves from viral attacks by stealing strips of an invading virus’ DNA, the technique splices in an enzyme called Cas creating newly-formed sequences known as CRISPR. In bacteria, this causes RNA to make copies of these sequences, which help recognise virus DNA and prevent future invasions.This technique was transformed into a gene-editing tool in 2012 and was named Science magazine’s 2015 Breakthrough of the Year. While it’s not the first DNA-editing tool, it has piqued the interest of many scientists, research and health groups because of its accuracy, relative affordability and far-reaching uses. The latest? Eradicating HIV.

At the start of May, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) and the University of Pittsburgh demonstrated how they can remove HIV DNA from genomes of living animals – in this case, mice – to curb the spread of infection. The breakthrough was the first time replication of HIV-1 had been eliminated from infected cells using CRISPR following a 2016 proof-of-concept study.

 

In particular, the team genetically inactivated HIV-1 in transgenic mice, reducing the RNA expression of viral genes by roughly 60 to 95 per cent, before trialling the method on infected mice.

“During acute infection, HIV actively replicates,” Dr. Khalili explained. “With EcoHIV mice, we were able to investigate the ability of the CRISPR/Cas9 strategy to block viral replication and potentially prevent systemic infection.”

Since the HIV research was published, a team of biologists at University of California, Berkeley, described 10 new CRISPR enzymes that, once activated, are said to “behave like Pac-Man” to chew through RNA in a way that could be used as sensitive detectors of infectious viruses.

These new enzymes are variants of a CRISPR protein, Cas13a, which the UC Berkeley researchers reported last September in Nature, and could be used to detect specific sequences of RNA, such as from a virus. The team showed that once CRISPR-Cas13a binds to its target RNA, it begins to indiscriminately cut up all RNA making it “glow” to allow signal detection.

 

Two teams of researchers at the Broad Institute subsequently paired CRISPR-Cas13a with the process of RNA amplification to reveal that the system, dubbed Sherlock, could detect viral RNA at extremely low concentrations, such as the presence of dengue and Zika viral RNA, for example. Such a system could be used to detect any type of RNA, including RNA distinctive of cancer cells.

This piece has been updated to remove copy taken from WIRED US.

http://www.wired.co.uk/article/crispr-disease-rna-hiv

QuintilesIMS Institute Study: U.S. Drug Spending Growth of 4.8 Percent in 2016

June 29, 2017

DANBURY, Conn. & RESEARCH TRIANGLE PARK, N.C.

(Business Wire) Growth in U.S. spending on prescription medicines fell in 2016 as competition intensified among manufacturers, and payers ramped up efforts to limit price increases, according to research released today by the QuintilesIMS Institute. New medicines introduced in the past two years continue to drive at least half of total spending growth as clusters of innovative treatments for cancer, autoimmune diseases, HIV, multiple sclerosis, and diabetes become accessible to patients. The prospects for innovative treatments over the next five years are bright fueled by a robust late-phase pipeline of more than 2,300 novel products that include more than 600 cancer treatments. U.S. net total spending is expected to increase 2-5 percent on average through 2021, reaching $375-405 billion.

Drug spending grew at a 4.8 percent pace in 2016 to $323 billion, less than half the rate of the previous two years, after adjusting for off-invoice discounts and rebates. The surge of innovative medicine introductions paused in 2016, with fewer than half as many new drugs launched than in 2014 and 2015. While the total use of medicines continued to climb—with total prescriptions dispensed reaching 6.1 billion, up 3.3 percent over 2015 levels—the spike in new patients being treated for hepatitis C ebbed, which contributed to the decline in spend. Net price increases—reflecting rebates and other price breaks from manufacturers—averaged 3.5 percent last year, up from 2.5 percent in 2015.

“After a year of heated discussion about the cost and affordability of drugs, the reality is that after adjusting for population and economic growth, total spending on all medicines increased just 1.1 percent annually over the past decade,” said Murray Aitken, senior vice president and executive director of the QuintilesIMS Institute. “Understanding how the dynamics of today’s healthcare landscape impact key stakeholders is more important than ever, as efforts to pass far-reaching healthcare legislative reforms remain on the political agenda.”

In its report, Medicine Use and Spending in the U.S. – A Review of 2016 and Outlook to 2021, the QuintilesIMS Institute highlights the following findings:

  • Patients age 65 years and over have accounted for 41 percent of total prescription growth since 2011. While the population of seniors in the U.S. has increased 19 percent since 2011, their average per capita use of medicines declined slightly—from 50 prescriptions per person in 2011 to 49 prescriptions per person last year. In the age 50-64 year population, total prescriptions filled increased 21 percent over the past five years, primarily due to higher per capita use, which reached 29 prescriptions per person. The largest drivers of prescription growth were in large chronic therapy areas including hypertension and mental health, while the largest decline was in pain management.
  • Average patient out-of-pocket costs continued to decline in 2016, reaching $8.47 compared to $9.66 in 2013. Nearly 30 percent of prescriptions filled in 2016 required no patient payment due in part to preventive treatment provisions under the Affordable Care Act, up from 24 percent in 2013. The use of co-pay assistance coupons by patients covered by commercial plans also contributed to the decline in average out-of-pocket costs, and were used to fill 19 percent of all brand prescriptions last year—compared with 13 percent in 2013. Those patients filling brand prescriptions while in the deductible phase of their commercial health plan accounted for 14 percent of prescriptions and 39 percent of total out-of-pocket costs. Patients in the deductible phases of their health plan abandoned about one in four of their brand prescriptions.
  • The late-phase R&D pipeline remains robust and will yield an average of 40-45 new brand launches per year through 2021. At the end of 2016, the late-phase pipeline included 2,346 novel products, a level similar to the prior year, with specialty medicines making up 37 percent of the total. More than 630 distinct research programs are underway in oncology, which account for one-quarter of the pipeline and where one in four molecules are focused on blood cancers. While the number of new drug approvals and launches fell by more than half in 2016, the size and quality of the late-phase pipeline is expected to drive historically high numbers of new medicines.
  • Moderating price increases for branded products, and the larger impact of patent expiries, will drive net growth in total U.S. spending of 2-5 percent through 2021, reaching $375-405 billion. Net price increases for protected brands are forecast to average 2-5 percent over the next five years, even as invoice price growth is expected to moderate to the 7-10 percent range. This reflects additional pressure and influence by payers on the pricing and prescribing of medicines, as well as changes in the mix of branded products on the market. Lower spending on brands following the loss of patent protection is forecast to total $140 billion, including the impact of biosimilar competition, through 2021.

The full version of the report, including a detailed description of the methodology, is available at www.quintilesimsinstitute.org. The study was produced independently as a public service, without industry or government funding.

In this release, “spending on medicines” is an estimate of the amount received by pharmaceutical manufacturers after rebates, off-invoice discounts and other price concessions have been made by manufacturers to distributors, health plans and intermediaries. It does not relate directly to either the out-of-pocket costs paid by a patient, except where noted, and does not include mark-ups and additional costs associated with dispensing or other services associated with medicines reaching patients. For a fuller explanation of methods to estimate net spending, see the Methodology section of the report.

https://www.quintilesims.com/press-releases/quintilesims-institute-study-us-drug-spending-growth-of-48-percent-in-2016

 

Artificial intelligence could build new drugs faster than any human team

May 7, 2017

Artificial intelligence algorithms are being taught to generate art, human voices, and even fiction stories all on their own—why not give them a shot at building new ways to treat disease?

Atomwise, a San Francisco-based startup and Y Combinator alum, has built a system it calls AtomNet (pdf), which attempts to generate potential drugs for diseases like Ebola and multiple sclerosis. The company has invited academic and non-profit researchers from around the country to detail which diseases they’re trying to generate treatments for, so AtomNet can take a shot. The academic labs will receive 72 different drugs that the neural network has found to have the highest probability of interacting with the disease, based on the molecular data it’s seen.

Atomwise’s system only generates potential drugs—the compounds created by the neural network aren’t guaranteed to be safe, and need to go through the same drug trials and safety checks as anything else on the market. The company believes that the speed at which it can generate trial-ready drugs based on previous safe molecular interactions is what sets it apart.

Atomwise touts two projects that show the potential of AtomNet, drugs for multiple sclerosis and Ebola. The MS drug has been licensed to an undisclosed UK pharmacology firm, according to Atomwise, and the Ebola drug is being prepared for submission to a peer-reviewed publication.

Alexander Levy, the company’s COO and cofounder, said that AtomNet learns the interactions between molecules much like artificial intelligence learns to recognize images. Image recognition finds reduces patterns in images’ pixels to simpler representations, teaching itself the bounds of an idea like a horse or a desk lamp through seeing hundreds or thousands of examples.

“It turns out that the same thing that works in images, also works in chemistry,” Levy says. “You can take an interaction between a drug and huge biological system and you can decompose that to smaller and smaller interactive groups. If you study enough historical examples of molecules … and we’ve studied tens of millions of those, you can then make predictions that are extremely accurate yet also extremely fast.”

Atomwise isn’t the only company working on this technique. Startup BenevolentAI, working with Johnson & Johnson subsidiary Janssen, is also developing new ways to find drugs. TwoXAR is working on an AI-driven glaucoma medication, and Berg is working on algorithmically-built cancer treatments.

One of Atomwise’s advantages, Levy says, is that the network works with 3D models. To generate the drugs, the model starts with a 3D model of a molecule—for example a protein that gives a cancer cell a growth advantage. The neural network then generates a series of synthetic compounds (simulated drugs), and predicts how likely it would be for the two molecules to interact. If a drug is likely to interact with the specific molecule, it can be synthesized and tested.

Levy likens the idea to the automated systems used to model airplane aerodynamics or computer chip design, where millions of scenarios are mapped out within software that accurately represents how the physical world works.

“Imagine if you knew what a biological mechanism looked like, atom by atom. Could you reason your way to a compound that did the thing that you wanted?” Levy says.

Artificial intelligence could build new drugs faster than any human team

10 Tech Trends That Made the World Better in 2016

March 30, 2017

2016 was an incredible year for technology, and for humanity.

Despite all the negative political-related news, there were 10 tech trends this year that positively transformed humanity.

For this “2017 Kick-Off” post, I reviewed 52 weeks of science and technology breakthroughs, and categorized them into the top 10 tech trends changing our world.

I’m blown away by how palpable the feeling of exponential change has become.

I’m also certain that 99.99% of humanity doesn’t understand or appreciate the ramifications of what is coming.

In this post, enjoy the top 10 tech trends of the past 12 months and why they are important to you.

Let’s dive in…

1. We Are Hyper-Connecting the World

In 2010, 1.8 billion people were connected. Today, that number is about 3 billion, and by 2022 – 2025, that number will expand to include every human on the planet, approaching 8 billion humans.

Unlike when I was connected 20 years ago at 9,600 baud via AOL, the world today is coming online at one megabit per second or greater, with access to the world’s information on Google, access to the world’s products on Amazon, access to massive computing power on AWS and artificial intelligence with Watson… not to mention crowdfunding for capital and crowdsourcing for expertise.

Looking back at 2016, you can feel the acceleration. Here are seven stories that highlight the major advances in our race for global connectivity:

a) Google’s 5G Solar Drones Internet Service: Project Skybender is Google’s secretive 5G Internet drone initiative. News broke this year that they have been testing these solar-powered drones at Spaceport America in New Mexico to explore ways to deliver high-speed Internet from the air. Their purported millimeter wave technology could deliver data from drones up to 40 times faster than 4G.

b) Facebook’s Solar Drone Internet Service: Even before Google, Facebook has been experimenting with a solar-powered drone, also for the express purpose of providing Internet to billions. The drone has the wingspan of an airliner and flies with roughly the power of three blowdryers.

c) ViaSat Plans 1 Terabit Internet Service: ViaSat, a U.S.-based satellite company, has teamed up with Boeing to launch three satellites to provide 1 terabit-per-second Internet connections to remote areas, aircraft and maritime vehicles. ViaSat is scheduled to launch its satellite ViaSat2 in early 2017.

d) OneWeb Raises $1.2B for 900 Satellite Constellation: An ambitious low-Earth orbit satellite system proposed by my friends Greg Wyler, Paul Jacobs and Richard Branson just closed $1.2 billion in financing. This 900-satellite system will offer global internet services as soon as 2019.

e) Musk Announces 4,425 Internet Satellite System: Perhaps the most ambitious plan for global internet domination was proposed this year by SpaceX founder Elon Musk, with plans for SpaceX to deploy a 4,425 low-Earth orbit satellite system to blanket the entire planet in broadband.

2. Solar/Renewables Cheaper Than Coal

We’ve just exceeded a historic inflection point. 2016 was the year solar and renewable energy became cheaper than coal.

In December, the World Economic Forum reported that solar and wind energy is now the same price or cheaper than new fossil fuel capacity in more than 30 countries.

“As prices for solar and wind power continue their precipitous fall, two-thirds of all nations will reach the point known as ‘grid parity’ within a few years, even without subsidies,” they added.

This is one of the most important developments in the history of humanity, and this year marked a number of major milestones for renewable energy.

Here’s 10 data points (stories) I’ve hand-picked to hammer home the historic nature of this 2016 achievement.

a) 25 percent of the World’s Power Comes From Renewables: REN21, a global renewable energy policy network, published a report showing that a quarter of the world’s power now comes from renewable energy. International investment in renewable energy reached $286 billion last year (with solar accounting for over $160b of this), and it’s accelerating.

b) In India, Solar Is Now Cheaper Than Coal: An amazing milestone indeed, and India is now on track to deploy >100 gigawatts of solar power by 2022.

c) The UK Is Generating More Energy From Solar Than Coal: For the first time in history, this year the U.K. has produced an estimated 6,964 GWh of electricity from solar cells, 10% higher than the 6,342 GWh generated by coal.

d) Coal Plants Being Replaced by Solar Farms: The Nanticoke Generating Station in Ontario, once North America’s largest coal plant, will be turned into a solar farm.

e) Coal Will Never Recover: The coal industry, once the backbone of U.S. energy, is fading fast on account of renewables like solar and wind. Official and expert reports now state that it will never recover (e.g., coal power generation in Texas is down from 39% in early 2015 to 24.8% in May 2016).

f) Scotland Generated 106% Energy From Wind: This year, high winds boosted renewable energy output to provide 106% of Scotland’s electricity needs for a day.

g) Costa Rica Ran on Renewables for 2+ Months: The country ran on 100% renewable energy for 76 days.

h) Google to Run 100% on Renewable Energy: Google has announced its entire global business will be powered by renewable energy in 2017.

i) Las Vegas’ City Government Meets Goal of 100% Power by Renewables: Las Vegas is now the largest city government in the country to run entirely on renewable energy.

j) Tesla’s Gigafactory: Tesla’s $5 billion structure in Nevada will produce 500,000 lithium ion batteries annually and Tesla’s Model III vehicle. It is now over 30 percent complete… the 10 million square foot structure is set to be done by 2020. Musk projected that a total of 100 Gigafactories could provide enough storage capacity to run the entire planet on renewables.

3. Glimpsing the End of Cancer and Disease

Though it may seem hard to believe, the end of cancer and disease is near.

Scientists and researchers have been working diligently to find novel approaches to combating these diseases, and 2016 saw some extraordinary progress in this regard.

Here’re my top 10 picks that give me great faith about our abilities to cure cancer and most diseases:

a) Cancer Immunotherapy Makes Strides (Extraordinary Results): Immunotherapy involves using a patient’s own immune system (in this case, T cells) to fight cancer. Doctors remove immune cells from patients, tag them with “receptor” molecules that target the specific cancer, and then infuse the cells back in the body. During the study, 94% of patients with acute lymphoblastic leukemia (ALL) saw symptoms vanish completely. Patients with other blood cancers had response rates greater than 80%, and more than half experienced complete remission.

b) In China, CRISPR/Cas9 used in First Human Trial: A team of scientists in China (Sichuan University) became the first to treat a human patient with an aggressive form of lung cancer with the groundbreaking CRISPR-Cas9 gene-editing technique.

c) NIH Approves Human Trials Using CRISPR: A team of physicians at the University of Pennsylvania’s School of Medicine had their project of modifying the immune cells of 18 different cancer patients with the CRISPR-Cas9 system approved by the National Institute of Health. Results are TBD.

d) Giant Leap in Treatment of Diabetes from Harvard: For the first time, Harvard stem cell researchers created “insulin producing” islet cells to cure diabetes in mice. This offers a promising cure in humans as well.

e) HIV Genes Cut Out of Live Animals Using CRISPR: Scientists at the Comprehensive NeuroAIDS Center at Temple University were able to successfully cut out the HIV genes from live animals, and they had over a 50% success rate.

f) New Treatment Causes HIV Infected Cells to Vanish: A team of scientists in the U.K. discovered a new treatment for HIV. The patient was treated with vaccines that helped the body recognize the HIV-infected cells. Then, the drug Vorinostat was administered to activate the dormant cells so they could be spotted by the immune system.

g) CRISPR Cures Mice of Sickle Cell Disease: CRISPR was used to completely cure sickle cell by editing the errant DNA sequence in mice. The treatment may soon be used to cure this disease, which affects about 100,000 Americans.

h) Eradicating Measles (in the U.S.): The World Health Organization (WHO) announced that after 50 years, they have successfully eradicated measles in the U.S. This is one of the most contagious diseases around the world.

i) New Ebola Vaccine Proved to be 100% Effective: None of the nearly 6,000 individuals vaccinated with rVSV-ZEBOV in Guinea, a country with more than 3,000 confirmed cases of Ebola, showed any signs of contracting the disease.

j) Eradicating Polio: The World Health Organization has announced that it expects to fully eradicate polio worldwide by Early 2017.

4. Progress on Extending Human Life

I am personally convinced that we are on the verge of significantly impacting human longevity. At a minimum, making “100 years old the new 60,” as we say at Human Longevity Inc.

This year, hundreds of millions of dollars were poured into research initiatives and companies focused on extending life.

Here are five of the top stories from 2016 in longevity research:

a) 500-Year-Old Shark Discovered: A Greenland shark that could have been over 500 years old was discovered this year, making the species the longest-lived vertebrate in the world.

b) Genetically Reversing Aging: With an experiment that replicated stem cell-like conditions, Salk Institute researchers made human skin cells in a dish look and behave young again, and mice with premature aging disease were rejuvenated with a 30% increase in lifespan. The Salk Institute expects to see this work in human trials in less than 10 years.

c) 25% Life Extension Based on Removal of Senescent Cells: Published in the medical journal Nature, cell biologists Darren Baker and Jan van Deursen have found that systematically removing a category of living, stagnant cells can extend the life of mice by 25 percent.

d) Funding for Anti-Aging Startups: Jeff Bezos and the Mayo Clinic-backed Anti-Aging Startup Unity Biotechnology with $116 million. The company will focus on medicines to slow the effects of age-related diseases by removing senescent cells (as mentioned in the article above).

e) Young Blood Experiments Show Promising Results for Longevity: Sakura Minami and her colleagues at Alkahest, a company specializing in blood-derived therapies for neurodegenerative diseases, have found that simply injecting older mice with the plasma of young humans twice a week improved the mice’s cognitive functions as well as their physical performance. This practice has seen a 30% increase in lifespan, and increase in muscle tissue and cognitive function.

More at: https://singularityhub.com/2017/01/05/10-tech-trends-that-made-the-world-better-in-2016/

Scientists reverse aging in mice by repairing damaged DNA

March 30, 2017

Could lead to an anti-aging drug that counters damage from old age, cancer, and radiation.

A research team led by Harvard Medical School professor of genetics David Sinclair, PhD, has made a discovery that could lead to a revolutionary new drug that allows cells to repair DNA damaged by aging, cancer, and radiation.

In a paper published in the journal Science on Friday (March 24), the scientists identified a critical step in the molecular process related to DNA damage.

The researchers found that a compound known as NAD (nicotinamide adenine dinucleotide), which is naturally present in every cell of our body, has a key role as a regulator in protein-to-protein interactions that control DNA repair. In an experiment, they found that treating mice with a NAD+ precursor called NMN (nicotinamide mononucleotide) improved their cells’ ability to repair DNA damage.

“The cells of the old mice were indistinguishable from the young mice, after just one week of treatment,” said senior author Sinclair.

Disarming a rogue agent: When the NAD molecule (red) binds to the DBC1 protein (beige), it prevents DBC1 from attaching to and incapacitating a protein (PARP1) that is critical for DNA repair. (credit: David Sinclair)

Human trials of NMN therapy will begin within the next few months to “see if these results translate to people,” he said. A safe and effective anti-aging drug is “perhaps only three to five years away from being on the market if the trials go well.”

What it means for astronauts, childhood cancer survivors, and the rest of us

The researchers say that in addition to reversing aging, the DNA-repair research has attracted the attention of NASA. The treatment could help deal with radiation damage to astronauts in its Mars mission, which could cause muscle weakness, memory loss, and other symptoms (see “Mars-bound astronauts face brain damage from galactic cosmic ray exposure, says NASA-funded study“), and more seriously, leukemia cancer and weakened immune function (see “Travelers to Mars risk leukemia cancer, weakend immune function from radiation, NASA-funded study finds“).

The treatment could also help travelers aboard aircraft flying across the poles. A 2011 NASA study showed that passengers on polar flights receive about 12 percent of the annual radiation limit recommended by the International Committee on Radiological Protection.

The other group that could benefit from this work is survivors of childhood cancers, who are likely to suffer a chronic illness by age 45, leading to accelerated aging, including cardiovascular disease, Type 2 diabetes, Alzheimer’s disease, and cancers unrelated to the original cancer, the researchers noted.

For the past four years, Sinclair’s team has been working with spinoff MetroBiotech on developing NMN as a drug. Sinclair previously made a link between the anti-aging enzyme SIRT1 and resveratrol. “While resveratrol activates SIRT1 alone, NAD boosters [like NMN] activate all seven sirtuins, SIRT1-7, and should have an even greater impact on health and longevity,” he says.

Sinclair is also a professor at the University of New South Wales School of Medicine in Sydney, Australia.


Abstract of A conserved NAD+ binding pocket that regulates protein-protein interactions during aging

DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD+ (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD+ to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate–ribose) polymerase], a critical DNA repair protein. As mice age and NAD+ concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD+. Thus, NAD+ directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging.

Exponential Growth Will Transform Humanity in the Next 30 Years

February 25, 2017

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By Peter Diamantis

As we close out 2016, if you’ll allow me, I’d like to take a risk and venture into a topic I’m personally compelled to think about… a topic that will seem far out to most readers.

Today’s extraordinary rate of exponential growth may do much more than just disrupt industries. It may actually give birth to a new species, reinventing humanity over the next 30 years.

I believe we’re rapidly heading towards a human-scale transformation, the next evolutionary step into what I call a “Meta-Intelligence,” a future in which we are all highly connected—brain to brain via the cloud—sharing thoughts, knowledge and actions. In this post, I’m investigating the driving forces behind such an evolutionary step, the historical pattern we are about to repeat, and the implications thereof. Again, I acknowledge that this topic seems far-out, but the forces at play are huge and the implications are vast. Let’s dive in…

A Quick Recap: Evolution of Life on Earth in 4 Steps

About 4.6 billion years ago, our solar system, the sun and the Earth were formed.

Step 1: 3.5 billion years ago, the first simple life forms, called “prokaryotes,” came into existence.These prokaryotes were super-simple, microscopic single-celled organisms, basically a bag of cytoplasm with free-floating DNA. They had neither a distinct nucleus nor specialized organelles.

Step 2: Fast-forwarding one billion years to 2.5 billion years ago, the next step in evolution created what we call “eukaryotes”—life forms that distinguished themselves by incorporating biological ‘technology’ into themselves. Technology that allowed them to manipulate energy (via mitochondria) and information (via chromosomes) far more efficiently. Fast forward another billion years for the next step.

Step 3: 1.5 billion years ago, these early eukaryotes began working collaboratively and formed the first “multi-cellular life,” of which you and I are the ultimate examples (a human is a multicellular creature of 10 trillion cells).

Step 4: The final step I want to highlight happened some 400 million years ago, when lungfish crawled out of the oceans onto the shores, and life evolved from the oceans onto land.

The Next Stages of Human Evolution: 4 Steps

Today, at a massively accelerated rate—some 100 million times faster than the steps I outlined above—life is undergoing a similar evolution. In this next stage of evolution, we are going from evolution by natural selection (Darwinism) to evolution by intelligent direction. Allow me to draw the analogy for you:

Step 1: Simple humans today are analogous to prokaryotes. Simple life, each life form independent of the others, competing and sometimes collaborating.

Step 2: Just as eukaryotes were created by ingesting technology, humans will incorporate technology into our bodies and brains that will allow us to make vastly more efficient use of information (BCI) and energy.

Step 3: Enabled with BCI and AI, humans will become massively connected with each other and billions of AIs (computers) via the cloud, analogous to the first multicellular lifeforms 1.5 billion years ago. Such a massive interconnection will lead to the emergence of a new global consciousness, and a new organism I call the Meta-Intelligence.

Step 4: Finally, humanity is about to crawl out of the gravity well of Earth to become a multiplanetary species. Our journey to the moon, Mars, asteroids and beyond represents the modern-day analogy of the journey made by lungfish climbing out of the oceans some 400 million years ago.

The 4 Forces Driving the Evolution and Transformation of Humanity

Four primary driving forces are leading us towards our transformation of humanity into a meta-intelligence both on and off the Earth:

  1. We’re wiring our planet
  2. Emergence of brain-computer interface
  3. Emergence of AI
  4. Opening of the space frontier

Let’s take a look.

1. Wiring the Planet: Today, there are 2.9 billion people connected online. Within the next six to eight years, that number is expected to increase to nearly 8 billion, with each individual on the planet having access to a megabit-per-second connection or better. The wiring is taking place through the deployment of 5G on the ground, plus networks being deployed by Facebook, Google, Qualcomm, Samsung, Virgin, SpaceX and many others. Within a decade, every single human on the planet will have access to multi-megabit connectivity, the world’s information, and massive computational power on the cloud.

2. Brain-Computer Interface: A multitude of labs and entrepreneurs are working to create lasting, high-bandwidth connections between the digital world and the human neocortex (I wrote about that in detail here). Ray Kurzweil predicts we’ll see human-cloud connection by the mid-2030s, just 18 years from now. In addition, entrepreneurs like Bryan Johnson (and his company Kernel) are committing hundreds of millions of dollars towards this vision. The end results of connecting your neocortex with the cloud are twofold: first, you’ll have the ability to increase your memory capacity and/or cognitive function millions of fold; second, via a global mesh network, you’ll have the ability to connect your brain to anyone else’s brain and to emerging AIs, just like our cell phones, servers, watches, cars and all devices are becoming connected via the Internet of Things.

3. Artificial Intelligence/Human Intelligence: Next, and perhaps most significantly, we are on the cusp of an AI revolution. Artificial intelligence, powered by deep learning and funded by companies such as Google, Facebook, IBM, Samsung and Alibaba, will continue to rapidly accelerate and drive breakthroughs. Cumulative “intelligence” (both artificial and human) is the single greatest predictor of success for both a company or a nation. For this reason, beside the emerging AI “arms race,” we will soon see a race focused on increasing overall human intelligence. Whatever challenges we might have in creating a vibrant brain-computer interface (e.g., designing long-term biocompatible sensors or nanobots that interface with your neocortex), those challenges will fall quickly over the next couple of decades as AI power tools give us ever-increasing problem-solving capability. It is an exponential atop an exponential. More intelligence gives us the tools to solve connectivity and mesh problems and in turn create greater intelligence.

4. Opening the Space Frontier: Finally, it’s important to note that the human race is on the verge of becoming a multiplanetary species. Thousands of years from now, whatever we’ve evolved into, we will look back at these next few decades as the moment in time when the human race moved off Earth irreversibly. Today, billions of dollars are being invested privately into the commercial space industry. Efforts led by SpaceX are targeting humans on Mars, while efforts by Blue Origin are looking at taking humanity back to the moon, and plans by my own company, Planetary Resources, strive to unlock near-infinite resources from the asteroids.

In Conclusion

The rate of human evolution is accelerating as we transition from the slow and random process of “Darwinian natural selection” to a hyper-accelerated and precisely-directed period of “evolution by intelligent direction.” In this post, I chose not to discuss the power being unleashed by such gene-editing techniques as CRISPR-Cas9. Consider this yet another tool able to accelerate evolution by our own hand.

The bottom line is that change is coming, faster than ever considered possible. All of us leaders, entrepreneurs and parents have a huge responsibility to inspire and guide the transformation of humanity on and off the Earth. What we do over the next 30 years—the bridges we build to abundance—will impact the future of the human race for millennia to come. We truly live during the most exciting time ever in human history.

https://singularityhub.com/2016/12/21/exponential-growth-will-transform-humanity-in-the-next-30-years/

Nanoarray sniffs out and distinguishes ‘breathprints’ of multiple diseases

February 25, 2017

breathprint-system

An international team of 63 scientists in 14 clinical departments have identified a unique “breathprint” for 17 diseases with 86% accuracy and have designed a noninvasive, inexpensive, and miniaturized portable device that screens breath samples to classify and diagnose several types of diseases, they report in an open-access paper in the journal ACS Nano.

As far back as around 400 B.C., doctors diagnosed some diseases by smelling a patient’s exhaled breath, which contains nitrogen, carbon dioxide, oxygen, and a small amount of more than 100 other volatile chemical components. Relative amounts of these substances vary depending on the state of a person’s health. For example, diabetes creates a sweet breath smell. More recently, several teams of scientists have developed experimental breath analyzers, but most of these instruments focus on one disease, such as diabetes and melanoma, or a few diseases.

Detecting 17 diseases

The researchers developed an array of nanoscale sensors to detect the individual components in thousands of breath samples collected from 1404 patients who were either healthy or had one of 17 different diseases*, such as kidney cancer or Parkinson’s disease.

The team used mass spectrometry to identify the breath components associated with each disease. By analyzing the results with artificial intelligence techniques (binary classifiers), the team found that each disease produces a unique breathprint, based on differing amounts of 13 volatile organic chemical (VOC) components. They also showed that the presence of one disease would not prevent the detection of others — a prerequisite for developing a practical device to screen and diagnose various diseases.

Based on the research, the team designed an organic layer that functions as a sensing layer (recognition element) for adsorbed VOCs and an electrically conductive nanoarray based on resistive layers of molecularly modified gold nanoparticles and a random network of single-wall carbon nanotubes. The nanoparticles and nanotubes have different electrical conductivity patterns associated with different diseases.**

The authors received funding from the ERC and LCAOS of the European Union’s Seventh Framework Programme for Research and Technological Development, the EuroNanoMed Program under VOLGACORE, and the Latvian Council of Science.

* Lung cancer, colorectal cancer, head and neck cancer, ovarian cancer, bladder cancer, prostate cancer, kidney cancer, gastric cancer, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, idiopathic Parkinson’s, atypical Parkinsonism, multiple sclerosis, pulmonary arterial hypertension, pre-eclampsia, and chronic kidney disease.

** During exposure to breath samples, interaction between the VOC components and the organic sensing layer changes the electrical resistance of the sensors. The relative change of sensor’s resistance at the peak (beginning), middle, and end of the exposure, as well as the area under the curve of the whole measurement were measured. All breath samples identified by the AI nanoarray were also examined using an independent lab-based analytical technique: gas chromatography linked with mass spectrometry.


Abstract of Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules

We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others. Cluster analysis showed a reasonable classification power of diseases from the same categories. The effect of confounding clinical and environmental factors on the performance of the nanoarray did not significantly alter the obtained results. The diagnosis and classification power of the nanoarray was also validated by an independent analytical technique, i.e., gas chromatography linked with mass spectrometry. This analysis found that 13 exhaled chemical species, called volatile organic compounds, are associated with certain diseases, and the composition of this assembly of volatile organic compounds differs from one disease to another. Overall, these findings could contribute to one of the most important criteria for successful health intervention in the modern era, viz. easy-to-use, inexpensive (affordable), and miniaturized tools that could also be used for personalized screening, diagnosis, and follow-up of a number of diseases, which can clearly be extended by further development.

http://www.kurzweilai.net/nanoarray-sniffs-out-and-distinguishes-multiple-diseases?utm_source=KurzweilAI+Weekly+Newsletter&utm_campaign=599cd194cc-UA-946742-1&utm_medium=email&utm_term=0_147a5a48c1-599cd194cc-282129417

14-year-old girl who died of cancer wins right to be cryogenically frozen

December 18, 2016

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A 14-year-old girl who said before dying of cancer that she wanted a chance to live longer has been allowed by the high court to have her body cryogenically frozen in the hope that she can be brought back to life at a later time.

The court ruled that the teenager’s mother, who supported the girl’s wish to be cryogenically preserved, should be the only person allowed to make decisions about the disposal of her body. Her estranged father had initially opposed her wishes.

During the last months of her life, the teenager, who had a rare form of cancer, used the internet to investigate cryonics. Known only as JS, she sent a letter to the court: “I have been asked to explain why I want this unusual thing done. I’m only 14 years old and I don’t want to die, but I know I am going to. I think being cryo‐preserved gives me a chance to be cured and woken up, even in hundreds of years’ time.

“I don’t want to be buried underground. I want to live and live longer and I think that in the future they might find a cure for my cancer and wake me up. I want to have this chance. This is my wish.”

Following the ruling, in a case described by the judge as exceptional, the body of JS has now been preserved and transported from where she lived in London to the US, where it has been frozen “in perpetuity” by a commercial company at a cost of £37,000.

The girl’s parents are divorced. She had lived with her mother for most of her life and had had no face-to-face contact with her father since 2008. She resisted his attempts to get back in touch when he learnt of her illness in 2015.

The judge, Mr Justice Peter Jackson, ruled that nothing about the case should be reported while she was alive because media coverage would distress her. She was too ill to attend the court hearing but the judge visited her in hospital.

Jackson wrote: “I was moved by the valiant way in which she was facing her predicament. It is no surprise that this application is the only one of its kind to have come before the courts in this country, and probably anywhere else. It is an example of the new questions that science poses to the law, perhaps most of all to family law … No other parent has ever been put in [the] position [of JS’s father].”

He added: “A dispute about a parent being able to see his child after death would be momentous enough on its own if the case did not also raise the issue of cryonic preservation.”

Since the first preservation by freezing in the 1960s the process has been performed only a few hundred times. The body has to be prepared shortly after death, ideally within minutes. Arrangements then have to be made for the body to be transported by a registered funeral director.

“The scientific theory underlying cryonics is speculative and controversial, and there is considerable debate about its ethical implications,” Jackson said. “On the other hand, cryopreservation, the preservation of cells and tissues by freezing, is now a well-known process in certain branches of medicine, for example the preservation of sperm and embryos as part of fertility treatment. Cryonics is cryopreservation taken to its extreme.”

The judge said the girl’s family was not well off but that her mother’s parents had raised the money. A voluntary UK group of cryonics enthusiasts, who were not medically trained, had offered to help make arrangements.

Co-operation of a hospital was required. “This situation gives rise to serious legal and ethical issues for the hospital trust,” the judge observed, “which has to act within the law and has duties to its other patients and to its staff.”

The hospital trust in the case was willing to help although it stressed it was not endorsing cryonics. “On the contrary, all the professionals feel deep unease about it,” the judge said.

The Human Tissue Authority (HTA), which regulates organisations which remove, store and use human tissue, had been consulted but said it had no remit to intervene in such a case.

“The HTA would be likely to make representations that activities of the present kind should be brought within the regulatory framework if they showed signs of increasing,” Jackson said.

The HTA said: “We are gathering information about cryopreservation to determine how widespread it is currently, or could become in the future, and any risks it may pose to the individual, or public confidence more broadly. We are in discussion with key stakeholders … and the possible need for regulatory oversight.”

The government may need to intervene in future, Jackson said: “It may be … events in this case suggest the need for proper regulation of cryonic preservation in this country if it is to happen in future.”

Inquiries made of American authorities revealed that there was no prohibition on human remains being shipped to the US for cryonic preservation, providing certain provisions were made.

During the course of the 14-year-old’s case, the father changed his mind and told the court: “I respect the decisions [my daughter] is making. This is the last and only thing she has asked from me.”

A child cannot make a will and the court had to decide where the girl’s best interests lay. The judge concluded that allowing the mother to make a decision about her daughter would be in her best interests. The girl died peacefully knowing that her body would be frozen, the judge recorded.

The Department of Health said: “Cases such as this are rare. Although there are no current plans for legislative change in this area, this is an area we will continue to keep under review with the Human Tissue Authority.

https://www.theguardian.com/science/2016/nov/18/teenage-girls-wish-for-preservation-after-death-agreed-to-by-court

Ark of the immortals: The future-proof plan to freeze out death

December 18, 2016

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Life at the edge of death Murray Ballard, from the book The Prospect of Immortality

“WE’RE taking people to the future!” says architect Stephen Valentine, as we drive through two gigantic gates into a massive plot of land in the middle of the sleepy, unassuming town that is Comfort, Texas. The scene from here is surreal. A lake with a newly restored wooden gazebo sits empty, waiting to be filled. A pregnant zebra strolls across a nearby field. And out in the distance some men in cowboy hats are starting to clear a huge area of shrub land. Soon the first few bricks will be laid here, marking the start of a scientific endeavour like no other.

After years of searching, Valentine chose this site as the unlikely home of the new Mecca of cryogenics. Called Timeship, the monolithic building will become the world’s largest structure devoted to cryopreservation, and will be home to thousands of people who are neither dead nor alive, frozen in time in the hope that one day technology will be able to bring them back to life. And last month, building work began.

computer image
Computer rendering of the Timeship project

Cryonics, the cooling of humans in the hope of reanimating them later, has a reputation as a vanity project for those who have more money than sense, but this “centre for immortality” is designed to be about much more than that. As well as bodies, it will store cells, tissues and organs, in a bid to drive forward the capabilities of cryogenics, the study of extremely low temperatures that has, in the last few years, made remarkable inroads in areas of science that affect us all; fertility therapy, organ transplantation and emergency medicine. What’s more, the cutting-edge facilities being built here should break through the limitations of current cryopreservation, making it more likely that tissues – and whole bodies – can be successfully defrosted in the future.

Timeship is the brainchild of Bill Faloon and Saul Kent, two entrepreneurs and prominent proponents of life extension research. Their vision was to create a building that would house research laboratories, DNA from near-extinct species, the world’s largest human organ biobank, and 50,000 cryogenically frozen bodies. Kent called it “all part of a plan to conquer ageing and death”.

In 1997, Kent asked Valentine, an architect based in New York, whether he could design a building that was stable enough to operate continuously for 100 years with minimal human input. It needed to withstand earthquakes, to be protected from natural disasters and acts of violence, and to survive without the main power supply for months on end. It was a list of demands that no building in the world currently satisfies.

Valentine spent months drawing up proposals for the building, together with advice from engineers who had previously worked for NASA and security experts from around the world. “We had to address everything from pandemics and cyberattacks to snipers and global warming,” says Fred Waterman, a risk mitigation expert on the Timeship team. The designs were approved by Kent but immediately put on ice. He believed the technology that would make the building worthwhile was not yet advanced enough to warrant its construction.

At body temperature, cells need a constant supply of oxygen. Without it they start to die and tissues decay. At low temperatures, cells need less oxygen because the chemical activity of metabolism slows down. At very low temperatures, metabolism stops altogether. The problem faced when trying to preserve human tissue by freezing it is that water in the tissue forms ice and causes damage. The trick is to replace the water with cryoprotectants, essentially antifreeze, which prevent ice from forming. This works well for small, uncomplicated structures like sperm and eggs. But when you try to scale it up to larger organs, damage still occurs.

But in 2000, Greg Fahy, a cryobiologist at 21st Century Medicine in Fontana, California, made a breakthrough with a technique called vitrification. It involves adding cryoprotectants then rapidly cooling an organ to prevent any freezing; instead the tissue turns into a glass-like state. Fahy later showed that you could vitrify a whole rabbit kidney that functioned well after thawing and transplantation. This was the breakthrough Kent and Faloon had been waiting for.

Cold comfort farm

The pair gave Valentine a multimillion-dollar budget and told him to find land on which to build Timeship. Valentine spent five years scouring the US, believing it to be the country most likely to remain politically stable for the next 100 years. He homed in on four states that fitted his exacting criteria. And after evaluating more than 200 sites in Texas alone, Valentine ended up in Comfort. Here he discovered the Bildarth Estate, which came with acres of land, a 1670-square-metre mansion and even a few zebras.

“There’s an urgent need to be able to store whole organs for longer”

Since then, Valentine, together with a team of specialists, has fine-tuned the project. Timeship’s architectural plans make it look like something between a fortress and a spaceship. The central building is a low-lying square with a single entrance. This sits inside a circular wall surrounded by concentric concrete rings. Inside are what Valentine calls “neighbourhoods”, collections of thermos-like dewars that will store the cryopreserved DNA, organs and bodies (see “Cool design”).

Parts of the project are somewhat theatrical – backup liquid nitrogen storage tanks are covered overhead by a glass-floored plaza on which you can walk surrounded by a fine mist of clouds – others are purely functional, like the three wind turbines that will provide year-round back-up energy.

The question is, do we need Timeship? Such an extravagant endeavour might not be vital, but it looks as if something similar will be necessary sooner or later. In fact, the strongest argument for such a facility, and the technological developments it promises, might have nothing to do with the desire to be frozen for the future.

We already have small biobanks for storing bones from human donors, as well as tendons, ligaments and stem cells. But with rapid advances in regenerative medicine, there is a growing need for large-scale facilities in which we can store more cryogenically frozen biological material.

Stem cells, for instance, are increasingly cryopreserved after being extracted and grown outside the body for use in regenerative therapies. “Beyond the age of 50, it’s harder to isolate stem cells for regenerative medicine,” says Mark Lowdell at University College London. “If I were in my 30s, I would certainly be cryopreserving some bone marrow for future tissue to fix my tennis injuries.” Lowdell will soon do the first transplant of a tissue-engineered larynx created from a donor larynx that has been seeded with cryopreserved stem cells to reduce the risk of rejection.

Then there’s the problem of organ shortage. In the US, almost 31,000 transplants were carried out in 2015, but at least six times as many people are on the waiting list – each day 12 people die before they can get a kidney. To make matters worse, many organs go to waste because their shelf life is too short to find a well-matched patient. Nearly 500 kidneys went unused in the US last year because the recipient couldn’t get the organ in time.

So there’s an urgent need to be able to store whole organs for longer. The issue is so important that the US government this month pledged to start funding research into this very area. We can already reversibly cryopreserve small bundles of cells – many thousands of babies have been born from vitrified human embryos. Doing the same with large organs, like kidneys or hearts, is harder, but not impossible. Over the past decade, for instance, several babies have been born from ovarian tissue that was removed before chemotherapy, cryopreserved and later replaced. Similarly, rabbit kidneys and rat limbs have been cryopreserved, thawed and placed in a new body. Fahy says his team is well on its way to the first human trial of a cryogenically frozen organ. “After decades of research, we’re now at a tipping point,” he says. Having improved both the vitrification technique and the cryoprotectant solution, they are moving to trials in pigs, and human trials could follow within five years, he says.

That might help prevent wastage, but we would still have a shortage of organs for transplant. Another solution is to grow them from scratch using our own stem cells, and keep them until we need them. So far, tiny 3D heart-like organs have been made from stem cells alone, as well as mini kidneys and livers, all with the ultimate aim of bioengineering replacement organs for transplantation.

Once organs can be produced like this, we will need a way of storing either the raw material or the organs themselves. “I’m not enthusiastic about the notion of freezing whole heads, but I can certainly imagine people needing to freeze cells, or ‘starter kits’ for the development of tissues, or even whole organs – and in the not-so-distant future,” says Arthur Caplan, a bioethicist at New York University Langone Medical Center.

Like Caplan, most scientists I spoke to said it was becoming more likely that we could bring individual cryopreserved organs back to life, but were less convinced by the idea of freezing whole bodies. So I decided to visit Alcor Life Extension Foundation, the world’s biggest cryonics facility, in Scottsville, Arizona, to find out what happens when a body is put on ice.

Alcor’s lobby has the feel of a doctor’s waiting room, except that lining the walls are portraits of men, women, children and the occasional dog. The people in the pictures are preserved there, some alongside their beloved pets.

Cool design

Aaron Drake, head of Alcor’s medical response team, says the company has more than 1000 clients signed up worldwide – 99 per cent are healthy, but 1 per cent have a terminal disease. Some of them want to freeze their whole body, others – known as “neuros” – opt for just the head.

Drake admits that the techniques his firm uses aren’t perfect, which is why they continue to research the process. Recently, Alcor scientists placed acoustical devices on the brains of neuros as they were lowered into liquid nitrogen, listening as the heads cooled to -196 °C. The colder they got, the more frequently the team heard acoustical anomalies, which they attribute to micro-fracturing of the tissue. “That’s damage happening,” says Drake. It’s difficult to say what effects this might have. “It’s not universal or consistent, but it’s something we know doesn’t happen at around -140 °C.”

The problem is, to store a person at -140 °C, you have to keep them warmer than nitrogen’s boiling point, which is incredibly hard to do – certainly much harder than placing a body in a giant thermos full of liquid nitrogen, letting it boil and occasionally topping it up.

But at Timeship, Valentine thinks he’s cracked the problem. After years of experimentation, he has designed a system called a Temperature Control Vessel (TCV), a dewar that houses cryogenically preserved bodies, heads or tissues. Inside the dewar are moving rods that can be dipped into a pool of liquid nitrogen whenever a sensor notes that the temperature has risen from -140 °C. This would provide a relatively autonomous way of maintaining the contents at an ideal temperature (see “Cool design”).

Each TCV can carry hundreds of samples of tissue and organs, or four bodies and five heads.They are designed to be stacked together in a tessellating pattern that forms the neighbourhoods within the main building.

This should reduce some of the damage to brain tissue that the Alcor team heard. But even with that technology, is there any hope of reanimating a brain?

There is some evidence to suggest that certain properties of the mind – memories, for instance – can survive cryopreservation. In 2015, researchers trained worms to recognise a smell, then froze them. On thawing, the worms retained the smell memories. And this year, Fahy’s team cryopreserved a rabbit brain in a near-perfect state. Although the group used a chemical fixative that is not yet used in human preservation, the thawed rabbit brain appeared “uniformly excellent” when examined using electron microscopy.

“These kinds of experiments show that it’s not such a massive leap of faith to think that we could preserve the human mind,” says Max More, president and CEO of Alcor. But not everyone is convinced. Even if you could preserve the delicate structures of the human brain, the cryoprotectants themselves are toxic. “No matter how smart scientists are in the future, you can’t change mush into a functional brain,” says Caplan, “and I just don’t think that what we’re able to do right now to preserve the brain is good enough to ever bring it back to life.”

There are precedents for the idea that the human brain can be revived after being cooled, however. In 1986, two-and-a-half-year-old Michelle Funk fell into an icy creek where she was submerged for just over an hour. Despite showing no signs of life, doctors spent 2 hours warming her blood through a heart-lung machine. Eventually, she recovered fully. Her doctors figured that the sudden cooling of her brain must have slowed the organ’s need for oxygen, staving off brain damage.

“What we are doing is just an extension of emergency medicine – we are stretching time“

Funk’s recovery was so remarkable it spurred researchers to repeat the scenario experimentally in pigs and dogs – cryopreserving them for hours before bringing them back to life. The same procedure is now being tested in humans in a groundbreaking trial by surgeons at UPMC Presbyterian Hospital in Pittsburgh, Pennsylvania. There they are placing patients in suspended animation for a few hours, to buy time to fix injuries that would otherwise be lethal, such as gunshot wounds. The technique involves replacing the person’s blood with a cold saline solution and cooling the body. They will then try to fix the injuries and bring the patient back to life by slowly warming the body with blood.

That’s not so different from what goes on at Alcor, says More. “What we’re doing is trying to stretch the time in which the person is suspended. It’s just an extension of emergency medicine.” I ask More whether he really believes that his members will be brought back to life. “I don’t know if it will ever happen,” he says, “but we’re breaking no laws of physics here. Who is to say that in 100 years we won’t have the medical tools – some kind of nanotechnology perhaps – that can fix cells at an individual level and repair what’s necessary to revive someone in good health.”

This is the central argument in favour of cryonics – the possibility, no matter how slim, that it offers a chance of survival. “We think of cryonics as a scientific experiment,” says More. “People that are buried or cremated are our control group, and so far, everyone in the control group has died.”

Facing the future

It is an expensive experiment, however. Cryopreserving your body will set you back up to $220,000, payable on death – often via life insurance, with Alcor as the beneficiary.

“People often say that the money would be better spent on family or given to charity,” says Ole Moen, a philosopher and ethicist at the University of Oslo, Norway. “But what’s strange about this is that nobody complains when people spend money on expensive cancer treatments or long-term care – people drain the public healthcare budget trying to stay alive all the time,” he says. “So why complain when people want to spend their own money trying to live longer via cryonics?”

If you’re happy to fork out, there’s the big question of what kind of future you’d wake up to. “Even if you could get this technique up and running by some magical future science I believe you’d be a freak – you’d be so far out of it culturally, so lost, that you’d be at risk of being driven mad,” Caplan says.

With so many big unknowns, I leave Alcor and Timeship undecided on the utility of cryonics. What’s clear, though, is that the underlying research into cryopreservation is worthwhile. Whether it’s to help me have children, fix a future tennis injury or potentially even provide me with a new heart, I’d be first in line to freeze cells and tissues today that might help my future self live longer, and healthier.

On my way out of Alcor, I ask Drake whether he wants to be frozen, given that he has cryopreserved so many others. “Yes,” he says. “Not because I want to be immortal, I don’t think that’s possible. I just want to see if all this work was futile. I was the last person these people saw before they took their last breath. Will they see me again? Will they thank me? I don’t know if that will ever happen. But wouldn’t that be nice?”

What is death?

Death has been redefined several times over the past century. It was once considered the cessation of a heartbeat and breathing. Today it includes other scenarios, such as the cessation of brain activity. But even that’s not good enough for some.

“Death is a process, not a switch,” says Max More, president and CEO of the Alcor Life Extension Foundation in Scottsdale, Arizona. “If you go back 100 years and someone falls over in the street and stops breathing, doctors would say ‘this person is dead’. Today we can do CPR and defibrillation to restart their heart and they can be brought back to life. So when that doctor declared them dead, were they? With today’s standards, no they weren’t.” Instead, says More, what we’re really saying is “given today’s technology and the medicine I have available to me right now, there’s nothing more I can do for you”.

A definition that emerged in the 1990s in response to this problem is the information-theoretic definition of death. It states that a person is dead only when the structures that encode memory and personality are so disrupted that it is no longer possible in principle to restore them.

Therefore a person who is cryogenically frozen, with brain structures preserved in a state close to what they were before the pronouncement of clinical death, is not by this definition, actually dead. So if the people frozen at Alcor aren’t dead, what are they? “There’s no good word for what they are,” says More (see Interview “I want to put your death on ice so that you can live again“). “Some people say they are de-animated.”

This article appeared in print under the headline “The big freeze”

from Health – New Scientist http://ift.tt/293zXna

https://www.newscientist.com/article/mg23130800-200-the-big-freeze-welcome-to-the-cryogenic-revolution/