Aubrey de Grey – Towards the Future of Regenerative Medicine

Why is aging research important? Biological aging causes suffering, however in recent times there as been surprising progress in stem cell research and in regenerative medicine that will likely disrupt the way we think about aging, and in the longer term, substantially mitigate some of the suffering involved in growing old.
Aubrey de Grey is the Chief Science Officer of SENS Foundation – an organisation focused on going beyond ageing and leading the journey towards  the future of regenerative medicine!  
What will it take to get there?

You might wonder why pursue  regenerative medicine ?
Historically, doctors have been racing against time to find cures for specific illnesses, making temporary victories by tackling diseases one by one – solve one disease and another urgency beacons – once your body becomes frail, if you survive one major illness, you may not be so lucky with the next one – the older you get the less capable your body becomes to staving off new illnesses – you can imagine a long line of other ailments fading beyond view into the distance, and eventually one of them will do you in.  If we are to achieve  radical healthy longevity , we need to strike at the fundamental technical problems of why we get frail and more disease prone as we get older.  Every technical problem has a technical solution – regenerative medicine is a class of solutions that seek to keep turning the ‘biological clock’ back rather than achieve short-term palliatives.

The damage repair methodology has gained in popularity over the last two decades, though it’s still not popular enough to attract huge amounts of funding – what might tip the scales of advocacy in damage-repair’s favor?
A clear existence proof such as achieving…

Robust Mouse Rejuvenation

In this interview, Aubrey de Grey reveals the most amount of optimism I have heard him express about the near term achievement of Robust Mouse Rejuvenation.  Previously it’s been 10 years away subject to adequate funding (which was not realised) – now Aubrey predicts it might happen within only 5-6 years (subject to funding of course).  So, what is Robust Mouse Rejuvenation – and why should we care?

For those who have seen Aubrey speak on this, he used to say RMR within 10 years (subject to funding)

Specifically, the goal of RBR is this:  Make normal, healthy two-year old mice (expected to live one more year) live three further years. 

  • What’s the ideal type of mouse to test on and why?  The ideal mouse to trail on is one that doesn’t naturally have a certain kind of congenital disease (that might on average only live 1.5 or 2 years) – because increasing their lifespan might only be a sign that you have solved their particular congenital disease.  The ideal type of mouse is one which lives to 3 years on average, which could die of various things.
  • How many extra years is significant? Consistently increasing mouse lifespan for an extra two years on top of their normal three year lifespans – essentially tripling their remaining lifespan.
  • When, or at what stage of the mice’s life to begin the treatment? Don’t start treating the mice until they are already 2 years old – at a time where they would normally be 2 thirds of the way though their life (at or past middle age) and they would have one more year to live.

Why not start treating the mice earlier?  The goal is to produce sufficiently dramatic results in a laboratory to convince the main-stream gerontology community, such that they would willingly publicly endorse the idea that it is not impossible, but indeed it is only a matter of time before rejuvenation therapy will work in humans – that is to get out there on talk shows and in front of cameras and say all this.

Arguably, the mainstream gerontology community are generally a bit conservative – they have vested interests in being successful in publishing papers, they get grants they have worries around peer review, they want tenure, and have a reputation to uphold.   Gerontologists hold the keys to public trust – they are considered to be the authorities on aging.
When gerontologists are convinced and let the world know about it, a lot of other people in the scientific community and in the general community will also then become convinced.  Once that happens, here’s what’s likely to happen next – longevity through rejuvenation medicine will become a big issue, there will be domino effects – there will be a war on aging, experts will appear on Oprah Winfrey, politicians will have to include the war on aging in their political manifesto if they want to get elected.

Yoda - the oldest mouse ever to have lived?
Yoda, a cute dwarf mouse, was named as the oldest mouse in 2004 at age 4 who lived with the much larger Princess Leia, in ‘a pathogen-free rest home for geriatric mice’ belonging to Dr. Richard Miller, professor of pathology in the Geriatrics Center of the Medical School. “Yoda is only the second mouse I know to have made it to his fourth birthday without the rigors of a severe calorie-restricted diet,” Miller says. “He’s the oldest mouse we’ve seen in 14 years of research on aged mice at U-M. The previous record-holder in our colony died nine days short of his 4th birthday; 100-year-old people are much more common than 4-year-old mice.” (ref)

What about Auto-Immune Diseases?

Auto-immune diseases (considered incurable to some) – they get worse with aging for the same reason we loose general ability to fight off infections and attack cancer. Essentially the immune system looses it’s precision – it has two arms: the innate system and the adaptive – the adaptive side works by having polyclonality – a very wide diversity of cells with different rearrangements of parts of the genome that confer specificity of the immune cell to a particular target (which it may or may not encounter at some time in the future) – this polyclonality diminishes over life such that the cells which are targeted towards a given problem with the immune system are on average less precisely adapted towards it – so the immune system takes longer to do it’s job or doesn’t do it effectively – so with autoimmune system it looses it’s ability to distinguish between things that are foreign and things that are part of the body. So this could be powerfully addressed by the same
measures taken to rejuvenate the immune system generally – regenerating the thyamis and illuminating senescent cells that are accumulating in the blood.

Big Bottlenecks

See Aubrey discuss this at timepoint: 38:50
Bottlenecks: which bottlenecks does Aubrey believes need most attention from the community of people who already believe aging is a problem that needs to be solved? The first thing: Funding. The shortage of funding is still the biggest bottleneck. The second thing: The need for policy makers to get on board with the ideas and understand what is coming – so it’s not only developing the therapies as quickly as possible, it’s also important that once they are developed, the therapies get disseminated as quick as possible to avoid complete chaos. It’s very urgent to have proper discussions about this. Anticipating the anticipation – getting ready for the public anticipating these therapies instead of thinking that it’s all science fiction and is never going to happen.


Effective Advocacy

See Aubrey discuss this at timepoint: 42:47
Advocacy, it’s a big ask to get people from extreme opposition to supporting regenerative medicine. Nudging people a bit sideways – that is getting them from complete offense to less offense,
or getting people who are un-decided to be in favor of it.

Here are 2 of the main aspects of advocacy:
1) feasibility / importance – emphasise progress, embracement by the scientific community (see paper hallmarks of aging – single most highly cited paper on the biology of aging this decade) – defining the legitimacy of the damage repair approach – it’s not just a crazy hair brained idea …
2) desirability – concerns about (bad arguments : on overpopulation – oh don’t worry we will immagrate into space – the people who are conerned about this problem aren’t the ones who would like to go to space) – focus on more of the things that can generalize to desirable outcomes – so regerative medicine will have side effects, like a longer lifespan, but also people will be more healthy at any given age compared to what they would be in they hadn’t had regenerative theroapy – no body wants alsimers, or heart disease – if the oucome of rejereative medicine is that then it’s easier to sell.
a sense of proportion on possible future problems – will they generally be more serious than they are today?
Talking about uploading, substrate independence, etc one is actively alienating the public – it’s better to create a foundation of credibility in the conversation before you decide to persuade anyone of anything. If we are going to get from here to the long term future we need advocacy now, so the short term matters as well.

More on Advocacy here:

And here

Other Stuff

This interview covers a fair bit of ground, so here are some other points covered:

– Updates & progress at SENS
– Highlights of promising progress in regenerative medicine in general
– Recent funding successes, what can be achieved with this?
– Discussion on getting the message across
– desirability & feasibility of rejuvenation therapy
– What could be the future of regenerative medicine?
– Given progress so far, what can people alive today look forward to?
– Multi-factorial diseases – Fixing amyloid plaque buildup alone won’t cure Alzheimer’s – getting rid of amyloid plaque alone only produced mild cognitive benefits in Alzheimer’s patients. There is still the unaddressed issue of tangles… If you only get rid of one component in a multi-component problem then you don’t get to see much improvement of pathology – in just he same way one shouldn’t expect to see much of an overall increase in health & longevity if you only fix 5 of 7 things that need fixing (i.e. 5 of the 7 strands of SENS)
– moth-balling anti-telomerase approach to fighting cancer in favor of cancer immunotherapy (for the time being) as it’s side effects need to be compensated against…
– Cancer immunotherapy – stimulating the bodies natural ability to attack cancer with it’s immune system -2 approaches – car-T (Chimeric Antigen Receptors and T cells), and checkpoint inhibiting drugs.. then there is training the immune system to identify neoantegens (stuff that all cancers produce)


Chief Science Officer, SENS Research Foundation, Mountain View, CA –

AgeX Therapeutics –

Dr. Aubrey de Grey is a biomedical gerontologist based in Mountain View, California, USA, and is the Chief Science Officer of SENS Research Foundation, a California-based 501(c)(3) biomedical research charity that performs and funds laboratory research dedicated to combating the aging process. He is also VP of New Technology Discovery at AgeX Therapeutics, a biotechnology startup developing new therapies in the field of biomedical gerontology. In addition, he is Editor-in-Chief of Rejuvenation Research, the world’s highest-impact peer-reviewed journal focused on intervention in aging. He received his BA in computer science and Ph.D. in biology from the University of Cambridge. His research interests encompass the characterisation of all the types of self-inflicted cellular and molecular damage that constitute mammalian aging and the design of interventions to repair and/or obviate that damage. Dr. de Grey is a Fellow of both the Gerontological Society of America and the American Aging Association, and sits on the editorial and scientific advisory boards of numerous journals and organisations. He is a highly sought-after speaker who gives 40-50 invited talks per year at scientific conferences, universities, companies in areas ranging from pharma to life insurance, and to the public.


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Surviving the Zombie Cell Apocalypse – Oisín Biotechs Stephen Hilbert

Oisín Biotechnologies ground-breaking research and technology is demonstrating that the solution to mitigating the effects of age-related diseases is to address the damage created by the aging process itself. We have recently successfully launched our first subsidiary, Oisin Oncology, focusing in combating multiple cancers.

Interview with Stephen Hilbert

We cover the exciting scientific progress at Oisín, targeting senescent cells (dubbed ‘zombie cells’) to help them to die properly, rejuvenation therapy vs traditional approaches to combating disease, Oisín’s potential for aiding astronauts survive high levels of radiation in space, funding for the research and therapy/drug development and specifically Stephen’s background in corporate development in helping raise capital for Oisín and it’s research.

Are we close to achieving Robust Mouse Rejuvenation?

According to Aubrey de Grey we are about 5-6 years away from  robust mouse rejuvenation   (RBR) subject to the kind of funding SENS has received this year and the previous year (2017-2018). There has been progress in developing certain therapies .

Specifically, the goal of RBR is this:

  • Make normal, healthy two-year old mice (expected to live one more year) live three further years.
    • The type of mice: The ideal mouse to trail on is one that doesn’t naturally have a certain kind of congenital disease (that might on average only live 1.5 or 2 years) – because increasing their lifespan might only be a sign that you have solved their particular congenital disease.
    • Number of extra years: Consistently increasing mouse lifespan for an extra two years on top of their normal three year lifespans – essentially tripling their remaining lifespan.
    • When to begin the treatment: Don’t start treating the mice until they are already 2 years old – at a time where they would normally be 2 thirds of the way though their life (at or past middle age) and they would have one more year to live.

Why not start treating the mice earlier?  The goal is to produce sufficiently dramatic results in a laboratory to convince the main-stream gerontology community such that they would willingly publicly endorse the idea that it is not impossible, but indeed it is only a matter of time before rejuvenation therapy will work in humans – that is to get out there on talk shows and in front of cameras and say all this.

The mainstream gerontology community are generally a bit conservative – they have vested interests in being successful in publishing papers, they get grants they have worries around peer review, they want tenure, and have a reputation to uphold.   Gerontologists hold the keys to public trust – they are considered to be the authorities on aging.


For the lowdown on progress towards Robust Mouse Rejuvenation see partway through this interview with Aubrey de Grey!

Preliminary results from study showing normalized mouse survival at 140 weeks

Stephen heads up corporate development for Oisín Biotechnologies. He has served as a business advisor to Oisín since its inception and has served on several biotechnology company advisory boards, specializing in business strategy and capital formation. Prior to Oisín, his career spanned over 15 years in the banking industry where he served as trusted advisor to accredited investors around the globe. Most recently he headed up a specialty alternative investment for a company in San Diego, focusing in tax and insurance strategies for family offices and investment advisors. Stephen is the founder of several ventures in the areas of real estate small manufacturing of novelty gifts and strategic consulting. He serves on the Overlake Hospital’s Pulse Board, assists with Children’s Hospital Guild and is the incoming Chairman at the Columbia Tower Club, a member’s club in Seattle.
LinkedIn Profile

Head of Corporate Strategy/Development Pre-Clinical Oisin Biotechnologies and OncoSenX
FightAging - Oisin Biotechnologies Produces Impressive Mouse Life Span Data from an Ongoing Study of Senescent Cell Clearance
FightAging reported:
Oisin Biotechnologies is the company working on what is, to my eyes, the best of the best when it comes to the current crop of senolytic technologies, approaches capable of selectively destroying senescent cells in old tissues. Adding senescent cells to young mice has been shown to produce pathologies of aging, and removal of senescent cells can reverse those pathologies, and also extend life span. It is a very robust and reliable approach, with these observations repeated by numerous different groups using numerous different methodologies of senescent cell destruction. Most of the current senolytic development programs focus on small molecules, peptides, and the like. These are expensive to adjust, and will be tissue specific in ways that are probably challenging and expensive to alter, where such alteration is possible at all. In comparison, Oisin Biotechnologies builds their treatments atop a programmable suicide gene therapy; they can kill cells based on the presence of any arbitrary protein expressed within those cells. Right now the company is focused on p53 and p16, as these are noteworthy markers of cancerous and senescent cells. As further investigation of cellular senescence improves the understanding of senescent biochemistry, Oisin staff could quickly adapt their approach to target any other potential signal of senescence – or of any other type of cell that is best destroyed rather than left alone. Adaptability is a very valuable characteristic. The Oisin Biotechnologies staff are currently more than six months in to a long-term mouse life span study, using cohorts in which the gene therapy is deployed against either p16, p53, or both p16 and p53, plus a control group injected with phosphate buffered saline (PBS). The study commenced more than six months ago with mice that were at the time two years (104 weeks) old. When running a life span study, there is a lot to be said for starting with mice that are already old; it saves a lot of time and effort. The mice were randomly put into one of the four treatment groups, and then dosed once a month. As it turns out, the mice in which both p16 and p53 expressing cells are destroyed are doing very well indeed so far, in comparison to their peers. This is quite impressive data, even given the fact that the trial is nowhere near done yet.
Considering investing/supporting this research?  Get in contact with Oisin here.

One Big Misconception About Consciousness – Christof Koch

Christof Koch (Allen Institute for Brain Science) discusses Shannon information and it’s theoretical limitations in explaining consciousness –

Information Theory misses a critical aspect of consciousnessChristof Koch

Christof argues that we don’t need observers to have conscious experiences (other poeple, god, etc), the underlying assumptions behind traditional information theory assumes Shannon information – and that a big misconception about the structure of consciousness stems from this idea – assuming that Shannon information is enough to explain consciousness.  Shannon information is about “sending information from a channel to a receiver – consciousness isn’t about sending anything to anybody.”  So what other kind of information is there?

The ‘information’ in Integrated Information Theory (IIT) does not refer to Shannon information.  Etymologically, the word ‘information’ derives from ‘informare’ – “it refers to information in the original sense of the word ‘Informare’ – to give form to” – that is to give form to a high dimensional structure.



It’s worth noting that many disagree with Integrated Information Theory – including Scott Aaronson – see here, here and here.


See interview below:

“It’s a theory that proceeds from phenomenology to as it were mechanisms in physics”.

IIT is also described in Christof Koch’s Consciousness: Confessions of a Romantic Reductionist’.

Axioms and postulates of integrated information theory

5 axioms / essential properties of experience of consciousness that are foundation to IIT – the intent is to capture the essential aspects of all conscious experience. Each axiom should apply to every possible experience.

  • Intrinsic existence: Consciousness exists: each experience is actual—indeed, that my experience here and now exists (it is real) is the only fact I can be sure of immediately and absolutely. Moreover, my experience exists from its own intrinsic perspective, independent of external observers (it is intrinsically real or actual).
  • Composition: Consciousness is structured: each experience is composed of multiple phenomenological distinctions, elementary or higher-order. For example, within one experience I may distinguish a book, a blue color, a blue book, the left side, a blue book on the left, and so on.
  • Information: Consciousness is specific: each experience is the particular way it is—being composed of a specific set of specific phenomenal distinctions—thereby differing from other possible experiences (differentiation). For example, an experience may include phenomenal distinctions specifying a large number of spatial locations, several positive concepts, such as a bedroom (as opposed to no bedroom), a bed (as opposed to no bed), a book (as opposed to no book), a blue color (as opposed to no blue), higher-order “bindings” of first-order distinctions, such as a blue book (as opposed to no blue book), as well as many negative concepts, such as no bird (as opposed to a bird), no bicycle (as opposed to a bicycle), no bush (as opposed to a bush), and so on. Similarly, an experience of pure darkness and silence is the particular way it is—it has the specific quality it has (no bedroom, no bed, no book, no blue, nor any other object, color, sound, thought, and so on). And being that way, it necessarily differs from a large number of alternative experiences I could have had but I am not actually having.
  • Integration: Consciousness is unified: each experience is irreducible to non-interdependent, disjoint subsets of phenomenal distinctions. Thus, I experience a whole visual scene, not the left side of the visual field independent of the right side (and vice versa). For example, the experience of seeing the word “BECAUSE” written in the middle of a blank page is irreducible to an experience of seeing “BE” on the left plus an experience of seeing “CAUSE” on the right. Similarly, seeing a blue book is irreducible to seeing a book without the color blue, plus the color blue without the book.
  • Exclusion: Consciousness is definite, in content and spatio-temporal grain: each experience has the set of phenomenal distinctions it has, neither less (a subset) nor more (a superset), and it flows at the speed it flows, neither faster nor slower. For example, the experience I am having is of seeing a body on a bed in a bedroom, a bookcase with books, one of which is a blue book, but I am not having an experience with less content—say, one lacking the phenomenal distinction blue/not blue, or colored/not colored; or with more content—say, one endowed with the additional phenomenal distinction high/low blood pressure. Moreover, my experience flows at a particular speed—each experience encompassing say a hundred milliseconds or so—but I am not having an experience that encompasses just a few milliseconds or instead minutes or hours.

So, does IIT solve what David Chalmers calls the “Hard Problem of consciousness”?

Christof Koch  is an American neuroscientist best known for his work on the neural bases of consciousness. He is the President and Chief Scientific Officer of the Allen Institute for Brain Science in Seattle. From 1986 until 2013, he was a professor at the California Institute of Technology.

This interview is a short section of a larger interview which will be released at a later date.

The long-term future of AI (and what we can do about it) : Daniel Dewey at TEDxVienna

daniel deweyThis has been one of my favourite simple talks on AI Impacts – Simple, clear and straight to the point. Recommended as an introduction to the ideas (referred to in the title).

I couldn’t find the audio of this talk at TED – it has been added to


Daniel Dewey is a research fellow in the Oxford Martin Programme on the Impacts of Future Technology at the Future of Humanity Institute, University of Oxford. His research includes paths and timelines to machine superintelligence, the possibility of intelligence explosion, and the strategic and technical challenges arising from these possibilities. Previously, Daniel worked as a software engineer at Google, did research at Intel Research Pittsburgh, and studied computer science and philosophy at Carnegie Mellon University. He is also a research associate at the Machine Intelligence Research Institute.


Brian Greene on Artificial Intelligence, the Importance of Fundamental Physics, Alien Life, and the Possible Future of Our Civilization

March 14th was Albert Einstein’s birthday, and also PI day, so it was a fitting day to be interviewing well known theoretical physicist and string theorist Brian Greene – the author of a number of books including, The Elegant Universe, Icarus at the Edge of Time, The Fabric of the Cosmos, and The Hidden Reality!
Think-Inc-logo2Many thanks to Suzi and Desh at THINKINC for helping organize this interview & for bringing Brian Greene to Australia for a number of shows (March 16 in Perth, March 18 in Sydney and March 19 in Melbourne) – check out for more info!

Audio recording of the interview:

About the Interview with Brian Greene

Brian Greene discusses implications Artificial Intelligence and news of DeepMind AI (AlphaGo) beating the world grand champion in the board game Go.  He then discusses physics string theory, the territory of opinion on grand unifying theories of physics, the importance of supporting fundamental science, the possibility of alien life, the possible future of our space-faring civilization and of course gravitational waves!

In answer to the question on the importance of supporting fundamental research in science, Brain Greene said:

I tell them to wake up! Wake up and recognize that fundamental science has radically changed the way they live their lives today. If any of these individuals have a cell phone, or a personal computer, or perhaps they themselves or loved ones has been saved by an MRI machine.. I mean any of these devices rely on integrated circuits, which they themselves rely on quantum physics – so IF those folks who were in charge in the 1920s had have said, ‘hey you guys working on quantum physics, that doesn’t seem to be relevant to anything in the world around as so were going to cut your funding – well those people would have short circuited on of the greatest revolutions that our species has gone through – the information age, the technological age – so the bottom line is we need to support fundamental research because we know historically that when you gain a deep understanding of how things work – we can often leverage that to then manipulate the world around us in spectacular ways! And that needs to be where our fundamental focus remains – in science!


Layered art of Brian Greene, background and series titleBrian Randolph Greene is an American theoretical physicist and string theorist. He has been a professor at Columbia University since 1996 and chairman of the World Science Festival since co-founding it in 2008. Greene has worked on mirror symmetry, relating two different Calabi–Yau manifolds (concretely, relating the conifold to one of its orbifolds). He also described the flop transition, a mild form of topology change, showing that topology in string theory can change at the conifold point.

Greene has become known to a wider audience through his books for the general public, The Elegant Universe, Icarus at the Edge of Time, The Fabric of the Cosmos, The Hidden Reality, and related PBS television specials. He also appeared on The Big Bang Theory episode “The Herb Garden Germination“, as well as the films Frequency and The Last Mimzy. He is currently a member of the Board of Sponsors of the Bulletin of the Atomic Scientists.


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Peter Singer – Ethics, Utilitarianism & Effective Altruism

Peter Singer at UMMS - Ethics Utilitarianism Effective Altruism
Peter Singer discusses Effective Altruism, including Utilitarianism as a branch of Ethics. Talk was held as a joint event between the University of Melbourne Secular Society and Melbourne University Philosophy Community.

Is philosophy, as a grounds to help decide how good an action is, something you spend time thinking about?

Audio of Peter’s talk can be found here at the Internet Archive.

In his 2009 book ‘The Life You Can Save’, Singer presented the thought experiment of a child drowning in a pond before our eyes, something we would all readily intervene to prevent, even if it meant ruining an expensive pair of shoes we were wearing. He argued that, in fact, we are in a very similar ethical situation with respect to many people in the developing world: there are life-saving interventions, such as vaccinations and clean water, that can be provided at only a relatively small cost to ourselves. Given this, Singer argues that we in the west should give up some of our luxuries to help those in the world who are most in need.

If you want to do good, and want to be effective at doing good, how do you go about getting better at it?

UMMS - James Fodor - Peter Singer

Nick, James, and Peter Singer during Q&A

Around this central idea a new movement has emerged over the past few years known as Effective Altruism, which seeks to use the best evidence available in order to help the most people and do the most good with the limited resources that we have available. Associated with this movement are organisations such as GiveWell, which evaluates the relative effectiveness of different charities, and Giving What We Can, which encourages members to pledge to donate 10% or more of their income to effective poverty relief programs.

Peter-Singer--Adam-Ford-1I was happy to get a photo with Peter Singer on the day – we organised to do an interview, and for Peter to come and speak at the Effective Altruism Global conference later in 2015.
Here you can find number of videos I have taken at various events where Peter Singer has addressed Effective Altruism and associated philosophical angles.

New Book ‘The Point of View of the Universe – Sidgwick and Contemporary Ethics‘ – by Katarzyna de Lazari-Radek and Peter Singer

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My students often ask me if I think their parents did wrong to pay the $44,000 per year that it costs to send them to Princeton. I respond that paying that much for a place at an elite university is not justified unless it is seen as an investment in the future that will benefit not only one’s child, but others as well. An outstanding education provides students with the skills, qualifications, and understanding to do more for the world than would otherwise be the case. It is good for the world as a whole if there are more people with these qualities. Even if going to Princeton does no more than open doors to jobs with higher salaries, that, too, is a benefit that can be spread to others, as long as after graduating you remain firm in the resolve to contribute a percentage of that salary to organizations working for the poor, and spread this idea among your highly paid colleagues. The danger, of course, is that your colleagues will instead persuade you that you can’t possibly drive anything less expensive than a BMW and that you absolutely must live in an impressively large apartment in one of the most expensive parts of town.Peter Singer, The Life You Can Save: Acting Now to End World Poverty, London, 2009, pp. 138-139


Playlist of video interviews and talks by Peter Singer:


Science, Technology & the Future