The Adventures of Professor EinsZwei verses 1-2

Posting serious thoughts on science can wear thin. So with that, I shall periodically provide updates on the continuing adventures of a super-genius professor who applied stem cell engineering to render himself both immortal and hyperintelligent, before developing a wormhole machine to travel through space-time forever.....




From Dusseldorf he came, his hair like a mane,
All grey and disheveled, his nose so beveled,
He even looked troubled - perhaps in pain,
His back bent doubled when walking at pace,
But that didn't matter given his aim:
To travel up there, through deepest space.

Professor EinsZwei (pronounced 'irons tsfie')
Was a genius, though that wasn't enough,
For he wanted to travel through the space-time continuum,
A challenge so amazingly tough:
Immortality; hyperintelligence; a wormhole machine,
Demanding requirements - and technical stuff!

SCIENCE vs. RELIGION - Interdependence not Opposition, Part I

Much has been debated on the topic of science vs. religion. What disappoints me however, is the frequent assumption that science equates to atheism, so that the argument is more about atheism vs. faith, in which science is allied to atheism. As an agnostic scientist, I prefer the open-minded approach in which there exists no conflict between science and religion but rather a complement that helps advance Man's knowledge and understanding of the existence and function of the cosmos.

There was a time in Man's prehistory when he simply did not have the intellect to adequately rationalise on the nature or existence of all he saw. As he continued to evolve however, so developed his ability to reason and seek explanation. Now he could start applying rationalistic thought to reconcile with his fear of Mother Nature's might. Indeed, his early cogitations (albeit limited) led to the conclusion that Nature and the cosmos - as visible through the tiny vista of his naked eye - were created and governed by an all powerful collective of gods and demigods. More time gave way to further intellectual evolution and learning, until there emerged a divergence of two seemingly opposing approaches to the rationalisation of Man's visible surroundings: science and religion. Unfortunately for the early scientist, religion became enmeshed with the ruling classes and he was regarded more often than not, as an atheistic challenger to the Church's (ruling power) authority.

In reality, science and religion were not and are still not, mutually exclusive. I prefer to consider the premise of whether a scientist has faith or not, and to gauge this using a scale that spans from extreme atheistic science through to extreme religious fanaticism, connected by intermediate blends of scientific reasoning and religious belief. I suggest a scale of 1 to 6, starting at 1 for the atheistic scientists who scoff at the existence of an all-powerful being, then 2 for the agnostic scientists, 3 for religious scientists, 4 for faiths tolerant of science, 5 representing faiths sceptical of science, and finally, 6 for the other extreme: faiths abhorrent of anything that seeks to challenge the existence of their God. Note that a scientist may still be able to rate a 6, however, they simply carry out their profession without questioning or seeking to disprove the might of their god - indeed they may use it to help exert their faith upon the oppressed.

This leads to the point of my discussion on why science and religion have common ground: the scale proposed previously demonstrates that science is not disconnected from or in opposition to religion. Science is not a religion or faith and even someone rated a 1 on the scale doesn't have to be a scientist. It is the religious outlook of the individual that matters - not their profession. They may just happen to be a scientist, affording them the appropriate skills that enable them, should they wish, to challenge religion with a more advanced scientific rationale. For example, an atheistic scientist might use their skills to prove (in their mind) that God can't exist (as with Richard Dawkins and his book, the God Delusion, which we'll revisit in a later posting). Alternatively, a once-agnostic scientist may apply their skills to draw up sufficient evidence with well-reasoned inference to refute the existence of a God, leading the agnostic to switch allegiance to atheism. Or perhaps the agnostic might draw the conclusion that the scientist is simply using the best technology, analysis, and deductive skills possible to study and understand all that he sees of physical matter, whose shear existence can't possibly be random and therefore must be the product of an all-powerful being (a conclusion akin to Man's more primitive and wholly subjective conclusions!).

This means science is complimentary to religion: it enables the skilled practitioner (should they wish) to scientifically challenge and rationalise over whether an all-powerful entity (to which some refer to as a god) exists and hence reaffirm or refute one's faith or lack of.

However, there is much more to my argument that science and religion actually depend on each other for the advancement of Man's understanding of the Universe and everything. Historically there was neither commonality nor complement. Instead the Church virtually governed with a blend of religion and power, not unlike that still seen in some countries today (and scoring a 6 on the science-religion scale). So long as the scientist was developed techniques or discovered physical or biological processes that would not challenge the Church's standing or authority, he could continue his work. However, if the work did challenge the religious mandates of the day, the scientist, too concerned for their own safety or reputation, withheld publication. Darwin and Copernicus were prime examples. Thankfully most countries have emerged from oppression to democracy and free speech and indeed the church understands better what the scientist is simply doing. In fact it should welcome the latest challenges that help test their religious resolve.

In subsequent blogs I'll consider the thorny notion that the degree and mode of scientific advancement has often depended on wars sparked by religious disagreement (accepting that historically, religion was inextricably linked to the governing power of the day). I'll look at the God Spot and how this signifies common ground between religion and science. I'll also review the impact of Darwin and Copernicus on the science vs. religion argument and relate this to the effect of modern scientific advances on religion, such as pre-Big Bang physics, Einstein's theory of relativity, and time travel. And for a real challenge, I'll try to ponder over the stance of science vs. religion as it might exist in the year 2500. In the meantime, I welcome comments for discussion.

http://news.aol.com/newsbloggers/2008/04/07/atheism-masquerading-as-science/

http://atheism.about.com/od/philosophyofscience/p/GodlessScience.htm

DRUG SAFETY TESTING - a Bittersweet Pill, Part I

For the pharmaceutical industry, the topic of drug safety testing tends to be a case of 'damned if you do and damned if you don't'. It certainly isn't easy going from the decision to jump on board a new therapeutic area, selecting an appropriate drug candidate, to (if the company is lucky) finally obtaining a license to market that potential blockbuster! Part of this process is showing that a new drug is safe for the patient. This exercise alone requires a massive effort that, however unpleasant, is a mandatory requirement by the various regulatory authorities that govern national and international therapeutic markets. Such agencies as the Medicines and Healthcare products Regulatory Agency (MHRA), the European Medicines Agency (EMEA), and the U.S. Food and Drug Administration (FDA) therefore have an important responsibility in issuing drug licenses. Even then, this is not a guarantee against severe side effects and sometimes it all goes wrong only after the drug is launched - patients may end up suffering from drug toxicity that even causes death. So what might have happened on those occasions? Why didn't preclinical animal safety studies and clinical trials pick up any signs of toxicity?

I intend to break down the whole process of drug safety assessment in a series of postings, in which consideration will be given to those particularly challenging avenues such as the predictivity of animal studies and clinical trials and that inextricable issue of human vs. animal rights. I'll give attention to advances in in vitro screens (cell models), the balance between cost and benefit, and the interplay between safety and efficacy (how well a drug works).

For now, let's remember that our bodies do try their best to battle the many ailments that strike us through our lifetime. It's just that on occasion it isn't enough, so we turn instead to various concoctions to speed up the healing process, alleviate our suffering, or tackle the diseases that our bodies' defence systems simply can't cope with. We also take these remedies with the hope that we are cured quickly and safely, when few actually meet both expectations. For those of us who prefer to seek our GP's advice and accept recommended prescription drugs, we also often (and naively) presume that these will do the job to great aplomb - a preceding faith that may actually afford an important placebo effect (something to look at in later postings).

These expectations are of course the crunch point for all pharmaceutical companies. In order to solicit approval from the regulatory authorities, a drug candidate must indeed be demonstrated convincingly to work effectively and safely. In reality this is a multifaceted statement underlined with assumptions. For example, the claim that a drug works can be interpreted as 'we showed in our studies that so long as the patient conforms to the appropriate dosing regimen, the drug reaches the target site(s) in the body in sufficient quantities to be effective, remains there long enough to do the job and other diseases or conditions do not interfere with this process, only a few and tolerable side effects may occur, and the resulting benefit of taking the drug is worth the risk and the financial cost.'

So, there we have it - a drug must work (be efficacious) and be safe. Sounds obvious, except generating the data to prove this to the authorities can be a major headache and even end in disaster. Look out for future postings on drug safety assessment. In the meantime, keep taking the pills - or should you?????

STEM CELLS - the Future Regeneration, Part II

In Part I we looked at the basics of stem cell research and some of the technical and ethical challenges. Let's now ponder a little more on these avenues. As their knowledge expands, scientists continue to develop the variety of techniques required for isolating, culturing, and growing (expanding) stem cell populations in the laboratory for storage and future use. These more readily-available cells can be retrieved for further study, transplantation procedures, tissue production and so on. Further expansion of stem cell populations in vitro (meaning 'within the glass' or in other words, in the laboratory) is important for overcoming the problem of obtaining sufficient cells to work on - in vivo (meaning 'within a living body') stem cells are few and far between!

Taking a look at stem cell transplantation, recall that in disease or injury, damaged tissue sends a variety of chemical signals to local stem cells, instructing them to replicate and differentiate into specific cells that will replace old tissue cleared away by the immune system. This process can be greatly speeded up by transplanting stem cells directly into the patient. Alternatively reproduction of such processes in vitro enables medical researchers to ultimately grow complex tissues and even organs in the laboratory for subsequent transplantation. The advantage of transplanting stem cells over tissue however, is that you don't worry about the chemical signals required for differentiation - the body does that bit.

A great example of advances in stem cell transplantation was the recent study by JC Voltarelli and colleagues in Brazil, in which a small number of diabetics were treated with their own stem cells to regenerate pancreatic tissue. These patients had the type I form of diabetes, in which the immune system attacks the specialised cells in the pancreas that produce insulin (beta cells). With few available beta cells, little or no insulin is produced and glucose levels in the blood stream can't be controlled. Type I diabetics must therefore regularly inject themselves with insulin. In the stem cell trial, medics first treated the patients with drugs to stimulate the bone marrow to generate large numbers of a particular stem cell - the so-called CD34+ haematopoietic stem cell. As this cell is subsequently released into the blood stream, doctors only had to collect blood to harvest what is effectively a bone marrow-derived cell. Patients were then treated with drugs to knock out the immune cells that were attacking the pancreas. Shortly after this treatment was commenced, the patients were transplanted with the CD34+ cells, which in turn received the appropriate signals in the pancreas to generate replacement beta cells. This procedure resulted in the majority of treated patients no longer requiring insulin injections. You can see how this approach might pave the way for the treatment of any disease by simply transplanting the right stem cells (that's the tricky bit - checking that the cell you use is able to differentiate into the desired terminal cell). Treatment of neurodegerative diseases is high up on the list because neuronal tissue is notorious for its poor regenerative capacity. Similarly, much research exists in the use of stem cells to treat liver diseases. Success here would greatly reduce the need for liver donors.

In the meantime there have been other achievements. Do you recall the recent treatment of the Spanish lady whose bronchus was damaged by TB? In this case, a donor piece of bronchus was stripped of donor cells and the remaining cartilage used to provide a scaffold for rebuilding tissue from cells taken from the TB patient. Risk of tissue rejection and the need for unpleasant immunosuppressive drugs are again avoided. So now you have it. First remove stem cells from an individual, generate a bank of different stem cell types from the ones you removed, then when disease or injury strikes, select the most appropriate stem cell type and transplant into the patient (this applies to both human and animal patients - yes you can have your pet saved from disease by stem cell transplantation too). Or if more appropriate, use a donor or synthetic scaffold to grow a basic tissue construct and transplant that.

So, how long before limbs are replaced in this way? When might the first heart transplant with a laboratory-grown organ occur? This whole field of repairing damaged or diseased tissue with stem cells or stem cell-derived tissue is known as regenerative medicine. This area is in hot pursuit by the pharmaceutical industry - much money is to be made. Indeed, I would suspect that the military would also be actively involved or at least monitoring events in regenerative medicine. Rapid repair of injured soldiers, particularly so that they are able to resume combat duties, would offer a substantive military advantage. Mind you, physical repair is one thing and mental recovery another....

Now here are some further thoughts. Eventually it will be possible to repair damaged areas of brain - so does this mean that you would be able to increase intelligence by stimulating further growth of a particular area of brain in a normal person? Tissue growth is also controlled by chemical factors that inhibit further growth once the appropriate volume is achieved. For example, myostatin prevents excessive growth of skeletal muscle. This ensures that mescle growth doesn't continue after the young adult has reached their full size. Without growth inhibition, you would end up with muscle-bound and distorted figures, as seen in a rare genetic disorder in which myostatin production is reduced or absent. A desire for bodybuilders perhaps, but not for the average person. What of applying this principle to the brain? Physicians could simply transplant stem cells, then treat with inhibitors of the biochemicals that control the level of tissue growth. And there you have a potential genius. Don't believe this principle? Then take a look at the discussions over the studies of Einstein's brain. Evidence suggests that if a specific area of the brain is larger than normal then the function attributable to that area is significantly enhanced. Mind you, the skull will limit growth so you may need surgery to provide more growth space.

Staying with future perspectives, I also believe that we shall see the advent of the true bionic man in around 50 to 100 years. The reason is simple. Man's scientific advances are often based on a specific principle: he wonders how nature works, unravels it's secrets, then exploits and refines them. Look at metals: he learns to extract metals such as iron and copper from different ores. Then he learns to mix them to produce alloys that offer new physical qualities. He continues to discover and extract other metals and produce more sophisticated alloys for even more refined applications. This evolutionary trend is repeated everywhere. Indeed we now understand the structure and physical properties of many of Nature's natural and biological materials. We refine them to taylor the physicochemical properties or we produce completely new materials such as the various polymers (polyethylene, polyvinyl chloride etc). And each time we realise that we have a new advancement in specific physicochemical properties, we exploit it.

Well, this all paves the way for bionic man. The Terminator technology. Astrobionics (which for me sounds more like that branch of science that deals with the advancement of Man’s physico-psycho constitution for deep space travel rather than how NASA describes it). The era of medical and materials technology in which tissue is grown on advanced materials and embedded with electronic devices that can be wired to the central nervous system. Engineered super-muscle. Engineered super-brain. Engineered super-bone. This is where today's science fiction becomes tomorrow's reality. But this is also where we must learn to draw the line and continue to challenge our ethical status. Just as the splitting of the atom gave way to the nuclear weapon, so regenerative medicine could herald new biological weapons in the form of the characters we see in science fiction films. Perhaps it will be the unscrupulous regimes of the future on whom we must keep our eyes focussed.

Signing off on Man's regenerative future,

The Senile Scientist

PS I'll revisit this area because there is still much more to discuss

STEM CELLS - the Future Regeneration, Part I

As a scientist pondering over the merging of regenerative medicine and astrobionics, how could I not take a look at the advent of stem cell research. It encapsulates all that is exciting about science: it's new, it's controversial, research is increasing exponentially, the variety of applications is expanding, promises of great magnitude abound, expectations are high, and yes, there are politics and shame. But most exciting are the early successes, since these herald achievements to come. Think of powered flight. At first it was all theory and ridicule. Then a few brave pioneers risked all to prove that is was possible. And before you knew it, exponential advances (particularly through massive war-driven investment) have thus far culminated in moon landings, Mars explorers, deep space probes, the rise and fall of Concorde, and now the gargantuan people carrier, the Airbus A380. So perhaps stem cells will become another powered flight success story. What we must avoid however, is the potential run-away effect of any success. For flight it is crowded skies and pollution. For stem cells it appears to be risk of cancer and dodgy clinics offering suspect miracle cures. The problem with new biological advances is that we often get caught off guard. Let's hope therefore that we keep our eyes open with this one and not turn a blind eye to issues that arise.

OK then, let's do an overview of the basics. First we must realise the importance of understanding the principles of any new avenue of scientific research lest we misguidedly slam new advances as being unethical, dangerous, or immoral. Just look at what Darwin and Copernicus had to deal with when they upset the Church (later topic perhaps). Stem cell research is already under scrutiny, so let's see why. In essence a stem cell is rather boring and non-descript: a tiny see-through football just ticking over. When given the right chemical instructions however, this little entity will start dividing to produce new cells that have a specific function, such as a liver cell (hepatocyte) or nerve cell (neuron). This process is called differentiation. Thus the stem cell may differentiate into specific cell types. It is highly complex but the principle remains. Stem cells can self-renew and may generate many different types of cells that in turn make up the various forms of tissues that constitute the body. And hence you see a truly great potential for stem cells. One can instruct them to generate required cell types or tissues that could be used to replace damaged tissue (e.g.; from severe burns or disease) or use them to grow organs in the laboratory for transplantation and medical research.

Now the controversial bit and how we get round it. There are essentially two classes of stem cells: those derived from the early embryo (embryonic stem cells - ESC) and those found in tissues in the adult (so-called adult stem cells). An additional and very useful source of stem cells is cord blood - after a baby is born, blood can be removed from the umbilical cord and stem cells isolated from the blood and frozen for storage (cryopreservation). This process has a great advantage since cells isolated from cord blood can be used to generate tissues for that person from which the cord blood was taken, hence obviating the risk of rejection. In the early days, the majority of stem cell research was done with ESC which meant that a (usually) five-day old embryo would be required and therefore destroyed, to provide a source of such cells. Why ESC? Because they have the ability to generate any cell type (except a fertilised egg - zygote ) after all, their role is to generate a new organism. Importantly, little was known about adult stem cells either. The use of ESC in research however, is not acceptable to the pro-life group who regard even the primitive, 5-day embryo and what it represents as sacrosanct. Furthermore, there is concern that ESC could be used for reproductive cloning of humans. Perish the thought of producing more of me! One way round this problem is to use mouse ESC and indeed mouse models have helped much with our learning. They are not human of course and we still eventually need to jump to human models to verify translatability and to generate cells for therapies. The way round this is to concentrate on those stem cells that come from adult tissue (cord blood or tissues directly from the adult body).

There exist different types of adult stem cells that vary in their capacity to produce ranges of differentiated progeny. Indeed, imagine a heirarchy of stem cells in which the pluripotent ESC can produce any type of cell (although the fertilised egg is the ultimate, totipotent cell because it gives rise to ESC) and then down the tree are stem cells that can produce a broad range of other cell types (multipotent). Finally, at the bottom of the tree we find those cells that are only able to produce a few different types of differentiated progeny (oligopotent). This last type of stem cell is usually confined to a specific tissue and is responsible for generating new local tissue in response to loss from disease or injury. In the liver, for example, the local stem cell is known as the oval cell and generates the two key differentiated cells that make up the liver: hepatocytes and cholangiocytes. Nonetheless, it is likely that scientists could learn to provide the right signals to instruct such cells to revert back to an embryonic-like stem cell and therefore acquire the potential to generate any cell type from an adult stem cell. It is all down to gaining an understanding of the complex mix of biochemicals and the type of local environment (milieu) that instruct and allow the stem cell to differentiate.

We'll move on to deeper consideration in Part II.

Signing off on stem cells for now,

The Senile Scientist

INTRODUCTION - the Outpost

So, let us begin by first allowing me to introduce myself. Having been around the science block a few times, I, the Senile Scientist, must now sit down and take a break from my once busy professional life and pontificate over what it's all about in the World of Science.

I shall be taking a look at the latest scientific advances (as I am a biological scientist this will be mostly in the biological and medical fields) and slapping on a Post-it of my personal view. Expect some excitement, cynicism, uncertainty, worry, pessimism, astonishment, mirth, misunderstanding, and schoolboy thrills. My wild and sometimes worrying imagination helps me stretch my visionary outlook on how science and technology may advance and what their potential impact on Planet Earth, Her biomass, and that weird species Homo sapiens might be. Much of this is of course unpredictable, but then speculation (a dirty word in science) is often fun and helps feed the creative and imaginative mind.

Scientists often try to promote themselves as being just another Joe Blogs and not the archetypal egg-headed sort often portrayed in the entertainment industry. As an ex-industrial scientist, I thoroughly support the need to point this out. Indeed, scientists, both academic and industrial, play out their professional lives just as in any other sector - politics are rife, money is always an issue, bias abounds (a great and awful weakness of human nature), there are deadline-induced shortcuts and assumptions - I could go on and on. Take the pharmaceutical industry. There have been many ugly legal battles as a result of toxic side effects of newly-launched drugs. How did they manage to get clearance in the first place? Were some of those aforementioned factors perhaps embedded in the company's drive to maintain it's portfolio? We shall look at this pressured world and how money and deadlines act as a deadly disease (probably existing in all industrial sectors) in a later posting. And what of academia? Pressure to publish and to secure that next research grant can attract bias and promote publication of suspect scientific articles associated with bold or exaggerated claims. 'More research needs to be done' is a classic call for another grant (of course this is more often a genuine claim). As with newspapers, scientists don't believe all they read in the scientific literature.

On a brighter note and rising above the messiness that sometimes surrounds Man's scientific quests, there have of course been many wonderful advances, including those in sciences' dependable sister, the field of technology. Just look at the Space Station. Expensive, yes, but one must look beyond the obvious. Man's great attribute is his risk-taking and unrelenting drive to acquire and apply new-found knowledge. Why? When? How? What limits? What value? What mathematical model best describes this? I am a proponent of the notion that Man must sometimes be given a toy and be left to play with it in his little world of theories and hypotheses testing, along with the obligatory bundle of pound notes of course - because when mixed together, this may culminate in an important scientific advance. Oh yes, and let's not forget serendipity. This wonderful star has sparked many a great discovery. Penicillin, superglue, the Post-it, and polymers such as nylon are but a few examples. Scientific Man therefore thrives best on a mix of key basic ingredients: a toy, time, some serendipity and money, and his schoolboy enthusiasm. And at the end of it all he then needs credence! Credibility in the eyes of scientific peers and/or big purse holders is mandatory if Dr Scientist is going anywhere with his or her new discovery. Any new invention or concept needs developing, which means support and money and where appropriate, good marketing of any ensuing commercial product.

And finally ...... the underdog. Yes, we Brits love the underdog. Professor Colin Pillinger and his failed Beagle II Mars mission immediately comes to mind. But let's get the context correctly positioned here. This chap is courageous and tenacious. Such qualities are no less better exemplified by the stalwarts of space travel. Not only are space missions incredibly expensive, but they require a great deal of bravery. And I don't just refer to the astronauts who risk their lives. I mean all of those scientists, engineers, and technicians like Prof. Pillinger and his colleagues who are brave enough to risk investing many years of their professional lives on one programme (because it requires that degree of effort!). I also take off my hat to the visionary benefactors who believe and support these people. And if a mission fails, that should be no big deal. It is both fortunate and unfortunate that space travel is very much in the public eye. Failure of such missions therefore receives much public tut-tutting upon disclosure of the amount of money invested. On the other hand, success generates heroes. We must remember, however, that the principle is the same as with a small university undergraduate project. It is simply on a colossal scale and therefore requires much grit to accept the associated pressure of risk. Importantly, such dedicated scientists and technologists must be supported upon failure - although they must still be slapped if this was due to a silly oversight, like the mixing up of units of measurement that resulted in the loss of a NASA Mars orbiter. But money (lack of it and the usual pressure to cut corners) is often the cause of failure since it forces poor workmanship and selection of suboptimal processes. Fiscal limitations will inevitably continue for ever and ever amen, a cog that will always remain in Man's machinery of scientific advancement. But I am getting negative again....

So hopefully I have given you a taster of how I shall post my thoughts on science. I shall also conduct polls to help me and you gauge public opinion on thorny topics relating to the scientific world which in turn should generate discussion.

Pleased to meet you....

The Senile Scientist