Better health through better lifestyle

Bandolier gives sound advice to improve health through simple life style changes. Do not miss the 10 point plan pdf. By following them you will be well at the tail of the distribution!

What are YOU doing to get there?

During these last days I have been browsing across a number of transhumanist blogs and websites. The funny thing is that most of what can be found is just hype and unrealistic babble. Most of the people are just supporters. Transhumanism seems to be a heavily backed ideology, at least in verbal terms. However, there doesn't seem to be much real activity, at least from these enthusiastic supporters that seem to abound. It's okay not to be able to help. It's okay even to only do advocacy. But it would be much more useful and satisfying to contribute in more substantial ways to make true one's beliefs. Some substantial contributions can be:

• Economical (money donations, if you have no ideas you can try the Methuselah Mouse Prize)
• Intellectual (sound ideas for feasible developments)
• Service (direct work on scientific or technologic advances)

So, if you say that you are a transhumanist, which kind of transhumanist are you? And, if you are the kind of transhumanist that is less effective, which can you do to change this situation?

YOU can make the difference, but only if you go and do what has to be done. Don't wait for someone else to do it.

If you believe that something needs to be done, go and do it.

And, if you are one of those most effective transhumanists, be sure that you are not alone, and that you count with my sincere respect.

A radical proposal: body donors for drug testing

As you probably know, at the beginning of this week there was a clinical trial that ended badly.

An antibody called TGN1412, from a Biotech called TeGenero was tested on six healthy men. All of them fell very ill. At this moment, it is not clear if the violent reaction that the biological induced in the volunteers was due to a contaminated batch or to the drug itself. The drug, an anti CD28, was thought to be useful to treat leukaemias and rheumatoid arthritis. Although some experts say that such a violent reaction is not something totally unexpected, others believe that this effect couldn't be anticipated.

This kind of situation shows us one of the biggest problems of drug research and development. By definition, new drugs may have unforeseen effects. They may not have any therapeutic value, regardless of the hypothesis that fostered the work on them. Moreover, they can even be dangerous because of pleiotropy at the target (i.e., the target is involved in other functions that are needed for maintain health), or they can be harmful because they have off target effects (toxic metabolites, lack of enough selectivity, and many other possibilities). The absolute truth is that there is no reliable way to predict with 100% of certainty what will do a new molecule to humans. There are many ways to reduce the risk: in vivo (animal) tests, in vitro (e.g., cellular), and in silico (e.g., structural alerts). But, in the end, the real "smoke test" will be the first administration in humans. That's why I would like to make a radical (and humble) proposal:

Les't enroll body donors to make the First In Man drug development step

What do I mean? As there are donors for organ transplant, there could be body donors. A body donor would be a person that, in case of brain death, would allow to assay innovative drugs in their artificially sustained body. The person would be no longer there. His brain would be dead, but the rest of his body would be kept alive for a while to make possible studies that would be too risky to perform in living humans. I regard this solution as technically possible and ethically acceptable.

Telomere shortening and cosmetic creams (cancer and aging, part 2)

I have read in betterhumans that there is some interest in making cosmetic creams that would avoid telomer shortening, or that may be able to recover shortened telomeres in skin cells.

Well, I do believe that there is a high probability of a company going bust if the only thing it can offer is a cosmetic cream based in telomer repair/maintenance.

Telomer shortening is not some disgusting process that Satan put into our bodies to make them age and die. Telomer shortening is a life saving device that prevents aberrant cells to go out of control.

If we remove this control without doing anything else, we will elevate enormously the frequency of malignancies. For sure we will have better wound healing, and this may reflect a niche market for that product, but the price (in terms of health risk) would be too high for being used as a cosmetic cream.

The telomerase problem is a very good example of the delicate processes that are running silently inside us. We are the product of many cycles of evolutionary refinement. We are sat on a nice hill of the fitness landscape. Of course, we are not in the absolute maximum, neither we are in any of the many local maxima that represent highly desired situations (e.g., we don't grow limbs when we get the original severed). But we are in a local maximum, so we should keep in mind that most single target interventions (which are quick fixes, no matter which technology is involved) were probably tried and discarded by the blind watchmaker many years ago.

I am very optimistic about our future prospects as a species, and I do believe that our generation has a chance to reap enormous rewards from the technologies that are emerging, but things are far more difficult to get done than what it seems by reading press releases of cash hungry startups.

Manna: a possible future

Marshall Brain's Manna is a very interesting story about how technology can either slave us or free us. It's a very good reminder of some powerful ideas:

• Technology can make heaven in earth. Certain degrees of prosperity can only be attained in extremely high tech environments.
  
• Technology can make hell in earth, although low tech settings are also quite appropriate for spreading suffering.
  
• We are responsible of the outcome of technology. If we don't want the way things are going, we better start doing something about it.
  
• Advanced robotics is going to be a very disruptive technology. Our current socio-economic structure will need profound modifications to adapt to it.

Fusion power out of our reach? (part 2)

Some hours ago I went to the Nature website. To my surprise, I found a news article called "Fusion power gets slammed". In it, Nature's reporter Mark Peplow comments on the Science's policy forum I talked about in a previous post.

It's always fun to watch a battle between Nature and Science.

It seems pretty clear that a number of fusion experts don't agree with Parkins' ideas. There are statements as strong as "It's complete rubbish from beginning to end [...] He knows nothing about what's happened in the past 15 years" (Ian Cook). Other people in the report agree with Parkins, though.

To me, as for any other layman in the fusion field, there is no way to know where lies the truth.

The Universe as a Computer and the Omega Point

A book by Charles Seife, entitled "Decoding the Universe: How the New Science of Information Is Explaining Everything in the Cosmos, from Our Brains to Black Holes", was commented in Betterhumans. In particular, the concept of the Cosmos as a big computer was highlighted.

I don't know about the other ideas of the book, but at this moment of cosmic evolution I don't regard the "Universe as a computer" concept very interesting.

We know that the Universe makes computations, because we and our machines are members of it. Besides that, almost any physical process entails a computation. The real question is if the Universe is computing something really big and not obvious. I believe that the probability of that going on at this moment of the cosmic history is almost zero.

There are many non-sentient processes and objects in the Universe. Perhaps there are some other civilizations, apart from ours. All this equals to a very big number crunching process. It may be an extremely massive computation, but today’s situation is a not too clever one: pure consequence of randomness and selection of stable patterns. Being it so simple and gross, the idea of the Universe as a computer doesn't seem a powerful concept.

An Omega situation, even if it were loosely related to Teilhard de Chardin* or Tipler** ideas, would give a clear purpose to the whole computation, making it relevant as a concept. But, at this moment, these kind of grandiose ideas are no more than mind candy.

*(A good introduction to the original Teilhard de Chardin's concept of the Omega Point can be read at The Phenomenon of Man)
**(Tipler's modern approach to Omega can be read at The Physics of Immortality)

The Matrix: reality and relevance

A key question that appears in movies like "The Matrix" and alike is: What is real?, or What is reality? . An answer to that question is totally out of our reach, and not really useful. The appropriate question for me is:

What is relevant?

This question will always give us light about where we are and will lead us to a definite and suitable course of action. In the end, it doesn't matter if we are living in a selaed simulation. It only matters what is at our reach. It only matters what we can understand and influence.

Fusion power out of our reach?

You may remember the movie "Back to the Future". At the end of it, "Doc" Brown returns from the future with his time machine, asking Marty to join in. As the car needs refueling for the flux capacitor, Doc puts some organic rubbish into the new Mr Fusion. They are ready to return to 2015.

We already know that 2000 was far away from what most of us expected to be when we were kids (and from what our parents expected too!). It's not surprising that nobody believes that Mr Fusion will be here in 9 years from now. But, sincerely, does anyone believe that we will have a single fusion plant in operation by 2015?

It's sad that expert people on this matter believe that usable fusion power is out of our reach.

This week we could read two discouraging comments on fusion power in top level scientific journals. Science has published a policy forum article titled "Fusion Power: Will It Ever Come?" that, at least for me, gives a devastating overview about the prospects of energy production through hot fusion. The report states that, contrarily to the reasonably fast transition to power plants in the case of fission power, fusion seems now almost as far from practical use as it was in the 1950's. Even for deuterium-tritium fusion, the combination that requires less energy, temperatures of 100 million Kelvin are required. Apart from the temperature requirements, a lot of tough technical needs have to be met together:

• Massive absorbing blankets (to generate tritium and filter neutrons).
• Tolerance to structural damage.
  
• Extremely high vacuum.
• Radiation shielding.
• Tolerance to stresses from thermal cycling.
• High performance remotely controlled equipment.
• Magnetic field windings.
  
• Cryogenic system to keep the superconductivity of the magnetic system.

To meet all this requirements in a practical way doesn't seem reasonable. All the fusion plant designs that have been made use extrapolations to calculate output. Even worse, the cost of the energy generated would be far from current prices, even if those extrapolations prove true.
Others may keep their hope, but hot fusion is something I don't expect to work anymore.

So what about bubble fusion?

Nature has published a report on bubble fusion that is as devastating as the policy forum published in Science. It says that since the publication in 2002 of Rusi Taleryarkhan's claims of successful table-top fusion through sonoluminescence, there have been no independent confirmation of those results. It seems now that an independent investigation performed by Nature raises serious doubts about the value of the original results. Apart from this, most scientists closely related to this kind of research do not have any hope of achieving energy generation through sonoluminescence bubble fusion.

As far as it is, it seems in the end that there is only one practical way to exploit hydrogen fusion: solar power.

In defense of Craig Venter

Browsing through BetterHumans, I came across a blog entry (Who's who in biotech), which commented on a feature with the same name published in Nature Biotechnology.

After reading the blog entry and the original feature, I couldn't help but to write this comment at that blog:

Someone who changed everything was Craig Venter. He was enormously influencial before Celera, during his time at Celera, and after it. His push with ESTs and genome sequencing moved the whole community. If it wasn't for Venter and the rush that Celera made for the human genome, we would be still waiting for the public assembly. Almost ANY biotech has profited from the treasure chest that the human genome sequence is. The hype has dissipated, the crazy promises didn't materialize, but biologists have a sound tool that enhances enormously their daily work.

I have a lot of hope in his plans to make a minimal synthetic organism. I bet it will become an extraordinary asset for biotechnology.

The more, the better: N-Acetylcysteine and pharmacokinetics

As you probably know, N-acetylcysteine (NAC) is a highly used antioxidant. NAC is not a bogus medicine. Its reducing capacity makes it a valuable antidote of acetaminophen poisoning. Apart from its utility as mucolytic, NAC is a common ingredient of many “anti-aging pills”. The idea behind NAC as anti-aging agent is that it would protect the cells from oxidative stress. NAC is pretty safe, so it can be administered for long periods at significant doses without visible side effects. It would be nice, however, to know how much and how often it should be administered. This leads us to NAC pharmacokinetics. It is not our today’s objective to write a treatise on pharmacokinetics, so we will go through a couple of concepts to illustrate where is the point. A simple definition will suffice: Pharmacokinetics is what the body does to the drug. Being so, it implies:

• The absorption of the drug.
• The distribution of the drug among all its organs.
• The metabolism of the drug.
• The elimination of the drug and its metabolites.

A simple and informative way to have a gross view of what happens to a drug in humans it to administer it and take blood samples at defined intervals. In the case of NAC, if it is administered orally we will be able to know how much of it enters the blood stream, and how long it stays there.

We are in 2006 at the time I am writing this, and it may seem that any study on NAC that is 15 years old is probably irrelevant. After all, a blog is about hectic news, isn’t it?

In fact, by 1991 there were even reviews published about NAC pharmacokinetics. A fast search in PubMed shows a very interesting piece of information. The terminal half life of NAC if of 6.25 hours. That means that, excluding absorption effects, NAC levels decrease to 50% of its initial concentration in 6.25 hours. Translated to practical words, it implies that a single dose of 200 mg of NAC will be like a 50 mg dose after 12 hours. We don’t know how much NAC is needed to protect from aging. We don’t even know if NAC has any real anti‑aging effect. But it is clear that if we bet for the protective effects of NAC, it is reasonable to expect that high blood levels of NAC will have better chances of showing anti‑aging effects. Given its high safety window, its not probable that maximizing exposure will yield any undesired effects.

Having said all that, the question is: How can we increase exposure with this kind of pharmacokinetics profile? We can increase exposure by dividing the daily dose in as many takes as reasonable. This will ensure an almost constant level of NAC. For this purpose, it is better to take two doses of X mg every 12 hours than taking 2X mg every 24 hours. This assumes that X mg orally is enough for its desired effects.

How can we do this in a practical way?

• We can buy NAC in small doses and take them more often.
• We can divide a big dose in small ones (I don’t like this one, it is cumbersome).
• If NAC is included in a multivitamin complex, we can split the pill of the day and take each half in different moments.

As you can imagine, this analysis applies to any molecule that has a short half life, so it is probably a good idea to divide any anti‑aging complex in fragments, so they can be taken along the day. For the components that have long half lives, it won’t make any difference to take them in more than one dose along the day.

I only know about one of those supplements that are already fragmented. The Kurzweil’s & Grossman’s “Total Care Daily Formula” has a serving size of 6 tablets (yes, I know… quite difficult to swallow). Those six tablets can be taken one by one along the day*. I will be happy to know about other supplements that can have a daily dosage of more than one pill. Do not hesitate to comment on it (or any other issue about this post) if you want to do so.

In fact, I wish there were vitamin/antioxidant supplements formulated like small candies, so I could take one every time I have a craving for something sweet…

Next time we will talk about vitamin C and its pharmacokinetics.

*(I don’t have any relationship with Ray & Terry’s)

What is the relationship between cancer and aging? (part 1)

Life is possible because the millions of cells that compose our bodies agree to perform their roles. They do what they have to do at the precise place, and only at the right moment. Some important tasks that have to be precisely regulated are:

• Cell division: If a cell divides when it is not required, it may form an imbalance, leading to physical problems (as with solid tumours), metabolic changes (as in cachexia), or functional disturbances (as in leukaemias).
• Cell migration: If a cell migrates to a place where it should not be, it is almost guaranteed that there will appear disturbances similar to the ones produced by uncontrolled cell division. Moreover, cells that fail to control both cell division and migration usually lead to metastatic tumours.
• Cell differentiation: If a cell changes its differentiation when it should not do it, it will not perform its intended function. Besides its lack of functionality, its new physiological state may itself lead to further problems.

As we live, some of our cells divide, while others perform their tasks in a non dividing state. Both groups of cells, dividing and not dividing, are exposed to aggressions through their life. Some examples of these damaging influences are exogenous toxins, reactive molecules generated by the body metabolism, and cosmic rays. Our body has many protective systems to cope with these attacks. However, as powerful as those systems are, in some cases a cell does not fully revert to its original state. Those altered cells are a potential security risk for the body. If the damages are located in processes that control any of the tasks indicated above, the cell is getting closer to a malignant state. There are two ways to stop this dangerous progression: cell senescence and apoptosis. Cell senescence makes a cell unable to divide, protecting the organism from cancer. Apoptosis induces the cell to commit suicide, protecting the organism from what may happen if the cell stays alive.

As we age, more and more cells enter apoptosis to protect the organism, and more and more cells get senescent. Senescent cells are less functional than normal cells, and do not contribute to the pool of dividing progenitors. The tissues have less and less cells that work at peak efficiency, so the function degrades progressively. The regeneration capacity decreases with age. Our defences decrease with age. In the end, any random strike can blow us away.

Cancer cells are cells that escape controls. Senescent cells are cells that do not escape controls, but who are not healthy enough to divide and work as young cells. The only way to have a long and healthy life is to have good repair systems to keep every cell in good condition for as long as possible, and to have good premalignant cell removal systems (apoptosis and senescence).

What is the relationship between syndromes as HGPS and normal aging?

In the past I was very hopeful about results coming from studies performed with progeroid syndromes. I expected them to shed some light into the processes that are involved in normal senescence. Nowadays, however, I believe that they have taught us all that the could. I think that aging is due to two different causes:

• Cancer avoidance systems: Cell cycle arrest, and preventive apoptosis.

• Imperfect repair systems: Accumulation of errors that induce cancer avoidance systems in damaged cells. They either die or stop dividing/working properly.

In all the progeroid syndromes there is at least one of these situations:

1. The repair systems do not work at peak efficiency.
2. There is a disturbing factor that increases the amount of damage to the organism.

So far, we have found no clue of a senescence regulating system. There are ways to slow aging, of course (we will talk about them in later entries), but all of them seem not to clearly increase the overall fitness of the individual.

I rather prefer to die at 75 of an infection that I could easily cope with if I am only 30, than not getting to 75 because I die of cancer at 40. I believe that natural selection thinks the same as me in this case, so it has optimised our repair/kill/arrest systems to get the most of them.

If we want to live significantly longer we have to reengineer both our repair and anticancer systems.

News: Farnesyl transferase inhibitors may help children with Hutchinson-Gilford progeria

Kids with of Hutchinson-Gilford progeria (HGPS) suffer a fast and devastating kind of accelerating aging syndrome. They experience many symptoms common to normal senility, as atherosclerosis, osteoporosis and hair loss. The life expectancy of HGPS children is extremely short. Most of them die in their early teens. The gene responsible of typical HGPS has been identified in 2003. HGPS is due to mutations in the lamin A gene.

Lamins are proteins that belong to the nuclear lamina, a network of proteins underlying the inner nuclear membrane. In normal cells, prelamin A attaches to the inner nucleus membrane. The attachment to the membrane is done by adding a farnesyl group to the prelamin A. This modification is done by an enzyme called farnesyl transferase (FT). Once farnesylated prelamin A is bound to the nucleus membrane, another enzyme called ZMPSTE24 trims it to render functional lamin.

HGPS patients have prelamin versions that are not cut by ZMPSTE24, so the non functional farnesylated prelamin accumulates, leading to problems in nucleus morphology and function.

A group from an UCLA team has raised hopes of having a treatment to alleviate HGPS kids. They used mice deficient in ZMPSTE24 to determine if FT inhibitors could ameliorate the progression of HGPS. Treated with ABT-100 (a FT inhibitor), mice mutant of ZMPSTE24 had less osteoporosis, better growth and, less drop in grip strength than mutant mice not treated with ABT-100.

FT inhibitors were developed in the past as anticancer drugs, though they revealed disappointing in the clinic. Being FT inhibitors not too toxic, they could be used to treat HGPS. The results obtained with ABT-100 are expected to boost clinical trials with HGPS kids.

To know more about ZMPSTE24, you can start here.
To know more about HGPS, you can start here.
To know more about lamin, you can start here.

Which authority do you have to talk about the future?

None. And all.

The same as anyone out there. If you are talking about academic credentials, you may be interested in going through my profile. Apart from what appears there, I have read quite a number of papers and books of almost anything relevant to the issue, and played with some of the most exciting technologies that are around the corner.

But, of course, in the end nobody can predict what will happen, so please take my words with a grain of salt.

What is DeltaBoost?

DeltaBoost is about the future.

In a very simple format –relevant news, plus short essays and comments on relevant topics- this blog goes through any aspect related to the next hundred years counting from now. In DeltaBoost you can expect...

1. ... to find news on relevant inventions, events or discoveries. The news will be always commented. Not all relevant news will be presented here. The more I feel that other sources don't get the point about an event, the more probable that it will appear commented here.
   
2. ... comments on topics that I regard as important, independently on how hot they are.
3. ...a personal point of view. I am the only responsible of the content. I will always try to be as informed and objective as I can. In the end, however, I won't have any problem to express educated guesses.

If you don't agree with any of my posts, you are more than welcome to express your opinion, as long as you do it with a constructive intent.