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How Networks Topple Scientific Dogmas – Article by Max Borders

How Networks Topple Scientific Dogmas – Article by Max Borders

The New Renaissance HatMax Borders

The Peer-to-Peer Republic of Science

Science is undergoing a wrenching evolutionary change.

In fact, most of what we consider to be carried out in the name of science is dubious at best, flat wrong at worst. It appears we’re putting too much faith in science — particularly the kind of science that relies on reproducibility.

In a University of Virginia meta-study, half of 100 psychology study results could not be reproduced.

Experts making social science prognostications turned out to be mostly wrong, according to political science writer Philip Tetlock’s decades-long review of expert forecasts.

But there is perhaps no more egregious example of bad expert advice than in the area of health and nutrition. As I wrote last year for Voice & Exit:

For most of our lives, we’ve been taught some variation on the food pyramid. The advice? Eat mostly breads and cereals, then fruits and vegetables, and very little fat and protein. Do so and you’ll be thinner and healthier. Animal fat and butter were considered unhealthy. Certain carbohydrate-rich foods were good for you as long as they were whole grain. Most of us anchored our understanding about food to that idea.

“Measures used to lower the plasma lipids in patients with hyperlipidemia will lead to reductions in new events of coronary heart disease,” said the National Institutes of Health (NIH) in 1971. (“How Networks Bring Down Experts (The Paleo Example),” March 12, 2015)

The so-called “lipid theory” had the support of the US surgeon general. Doctors everywhere fell in line behind the advice. Saturated fats like butter and bacon became public enemy number one. People flocked to the supermarket to buy up “heart healthy” margarines. And yet, Americans were getting fatter.

But early in the 21st century something interesting happened: people began to go against the grain (no pun) and they started talking about their small experiments eating saturated fat. By 2010, the lipid hypothesis — not to mention the USDA food pyramid — was dead. Forty years of nutrition orthodoxy had been upended. Now the experts are joining the chorus from the rear.

The Problem Goes Deeper

But the problem doesn’t just affect the soft sciences, according to science writer Ron Bailey:

The Stanford statistician John Ioannidis sounded the alarm about our science crisis 10 years ago. “Most published research findings are false,” Ioannidis boldly declared in a seminal 2005 PLOS Medicine article. What’s worse, he found that in most fields of research, including biomedicine, genetics, and epidemiology, the research community has been terrible at weeding out the shoddy work largely due to perfunctory peer review and a paucity of attempts at experimental replication.

Richard Horton of the Lancet writes, “The case against science is straightforward: much of the scientific literature, perhaps half, may simply be untrue.” And according Julia Belluz and Steven Hoffman, writing in Vox,

Another review found that researchers at Amgen were unable to reproduce 89 percent of landmark cancer research findings for potential drug targets. (The problem even inspired a satirical publication called the Journal of Irreproducible Results.)

Contrast the progress of science in these areas with that of applied sciences such as computer science and engineering, where more market feedback mechanisms are in place. It’s the difference between Moore’s Law and Murphy’s Law.

So what’s happening?

Science’s Evolution

Three major catalysts are responsible for the current upheaval in the sciences. First, a few intrepid experts have started looking around to see whether studies in their respective fields are holding up. Second, competition among scientists to grab headlines is becoming more intense. Third, informal networks of checkers — “amateurs” — have started questioning expert opinion and talking to each other. And the real action is in this third catalyst, creating as it does a kind of evolutionary fitness landscape for scientific claims.

In other words, for the first time, the cost of checking science is going down as the price of being wrong is going up.

Now, let’s be clear. Experts don’t like having their expertise checked and rechecked, because their dogmas get called into question. When dogmas are challenged, fame, funding, and cushy jobs are at stake. Most will fight tooth and nail to stay on the gravy train, which can translate into coming under the sway of certain biases. It could mean they’re more likely to cherry-pick their data, exaggerate their results, or ignore counterexamples. Far more rarely, it can mean they’re motivated to engage in outright fraud.

Method and Madness

Not all of the fault for scientific error lies with scientists, per se. Some of it lies with methodologies and assumptions most of us have taken for granted for years. Social and research scientists have far too much faith in data aggregation, a process that can drop the important circumstances of time and place. Many researchers make inappropriate inferences and predictions based on a narrow band of observed data points that are plucked from wider phenomena in a complex system. And, of course, scientists are notoriously good at getting statistics to paint a picture that looks like their pet theories.

Some sciences even have their own holy scriptures, like psychology’s Diagnostic and Statistical Manual. These guidelines, when married with government funding, lobbyist influence, or insurance payouts, can protect incomes but corrupt practice.

But perhaps the most significant methodological problem with science is overreliance on the peer-review process. Peer review can perpetuate groupthink, the cartelization of knowledge, and the compounding of biases.

The Problem with Expert Opinion

The problem with expert opinion is that it is often cloistered and restrictive. When science starts to seem like a walled system built around a small group of elites (many of whom are only sharing ideas with each other) — hubris can take hold. No amount of training or smarts can keep up with an expansive network of people who have a bigger stake in finding the truth than in shoring up the walls of a guild or cartel.

It’s true that to some degree, we have to rely on experts and scientists. It’s a perfectly natural part of specialization and division of labor that some people will know more about some things than you, and that you are likely to need their help at some point. (I try to stay away from accounting, and I am probably not very good at brain surgery, either.) But that doesn’t mean that we shouldn’t question authority, even when the authority knows more about their field than we do.

The Power of Networks

But when you get an army of networked people — sometimes amateurs — thinking, talking, tinkering, and toying with ideas — you can hasten a proverbial paradigm shift. And this is exactly what we are seeing.

It’s becoming harder for experts to count on the vagaries and denseness of their disciplines to keep their power. But it’s in cross-disciplinary pollination of the network that so many different good ideas can sprout and be tested.

The best thing that can happen to science is that it opens itself up to everyone, even people who are not credentialed experts. Then, let the checkers start to talk to each other. Leaders, influencers, and force-multipliers will emerge. You might think of them as communications hubs or bigger nodes in a network. Some will be cranks and hacks. But the best will emerge, and the cranks will be worked out of the system in time.

The network might include a million amateurs willing to give a pair of eyes or a different perspective. Most in this army of experimenters get results and share their experiences with others in the network. What follows is a wisdom-of-crowds phenomenon. Millions of people not only share results, but challenge the orthodoxy.

How Networks Contribute to the Republic of Science

In his legendary 1962 essay, “The Republic of Science,” scientist and philosopher Michael Polanyi wrote the following passage. It beautifully illustrates the problems of science and of society, and it explains how they will be solved in the peer-to-peer age:

Imagine that we are given the pieces of a very large jigsaw puzzle, and suppose that for some reason it is important that our giant puzzle be put together in the shortest possible time. We would naturally try to speed this up by engaging a number of helpers; the question is in what manner these could be best employed.

Polanyi says you could progress through multiple parallel-but-individual processes. But the way to cooperate more effectively

is to let them work on putting the puzzle together in sight of the others so that every time a piece of it is fitted in by one helper, all the others will immediately watch out for the next step that becomes possible in consequence. Under this system, each helper will act on his own initiative, by responding to the latest achievements of the others, and the completion of their joint task will be greatly accelerated. We have here in a nutshell the way in which a series of independent initiatives are organized to a joint achievement by mutually adjusting themselves at every successive stage to the situation created by all the others who are acting likewise.

Just imagine if Polanyi had lived to see the Internet.

This is the Republic of Science. This is how smart people with different interests and skill sets can help put together life’s great puzzles.

In the Republic of Science, there is certainly room for experts. But they are hubs among nodes. And in this network, leadership is earned not by sitting atop an institutional hierarchy with the plumage of a postdoc, but by contributing, experimenting, communicating, and learning with the rest of a larger hive mind. This is science in the peer-to-peer age.

Max Borders is Director of Idea Accounts and Creative Development for Emergent Order. He was previously the editor of the Freeman and director of content for FEE. He is also cofounder of the event experience Voice & Exit.

This article was published by The Foundation for Economic Education and may be freely distributed, subject to a Creative Commons Attribution 4.0 International License, which requires that credit be given to the author.

A Speculative Order of Arrival for Important Rejuvenation Therapies – Article by Reason

A Speculative Order of Arrival for Important Rejuvenation Therapies – Article by Reason

The New Renaissance Hat
October 6, 2012

A toolkit for producing true rejuvenation in humans will require a range of different therapies, each of which can repair or reverse one of the varied root causes of degenerative aging. Research is underway for all of these classes of therapy, but very slowly and with very little funding in some cases. The funding situation spans the gamut from that of the stem cell research community, where researchers are afloat in money and interest, to the search for ways to break down advanced glycation endproducts (AGEs), which is a funding desert by comparison, little known or appreciated outside the small scientific community that works in that field.

While bearing in mind that progress in projects with little funding is unpredictable in comparison to that of well-funded projects, I think that we can still take a stab at a likely order of arrival for various important therapies needed to reverse aging. Thus an incomplete list follows, running from the earliest to the latest arrival, with the caveat that it is based on the present funding and publicity situation. If any one of the weakly funded and unappreciated lines of research suddenly became popular and awash with resources, it would probably move up in the ordering:

1) Destruction of Senescent Cells

Destroying specific cells without harming surrounding cells is a well-funded line of research thanks to the cancer community, and the technology platforms under development can be adapted to target any type of cell once it is understood how to target its distinctive features.

The research community has already demonstrated benefits from senescent cell destruction, and there are research groups working on this problem from a number of angles. A method of targeting senescent cells for destruction was recently published, and we can expect to see more diverse attempts at this in the next few years. As soon as one of these can be shown to produce benefits in mice that are similar to the early demonstrations, then senescent cell clearance becomes a going concern: something to be lifted from the deadlocked US regulatory process and hopefully developed quickly into a therapy in Asia, accessed via medical tourism.

2) Selective Pruning and Support of the Immune System

One of the reasons for immune system decline is crowding out of useful immune cells by memory immune cells that serve little useful purpose. Here, targeted cell destruction can also produce benefits, and early technology demonstrations support this view. Again, the vital component is the array of mechanisms needed to target the various forms of immune cell that must be pruned. I expect the same rising tide of technology and knowledge that enables senescent cell targeting will lead to the arrival of immune cell targeting on much the same schedule.

Culling the immune system will likely have to be supported with some form of repopulation of cells. It is already possible to repopulate a patient’s immune system with immune cells cultivated from their own tissues, as demonstrated by the limited number of full immune system reboots carried out to cure autoimmune disorders. Alternatives to this process include some form of tissue engineering to recreate the dynamic, youthful thymus as a source of immune cells – or more adventurous processes such as cultivating thymic cells in a patient’s lymph nodes.

3) Mitochondrial Repair

Our mitochondria sabotage us. There’s a flaw in their structure and operation that causes a small but steadily increasing fraction of our cells to descend into a malfunctioning state that is destructive to bodily tissues and systems.

There are any number of proposed methods for dealing with this component of the aging process – either repairing or making it irrelevant – and a couple are in that precarious state of being just a little more solidity and work away from the point at which they could begin clinical development. The diversity of potential approaches in increasing too. Practical methods are now showing up for ways to put new mitochondria into cells, or target arbitrary therapies to the interior or mitochondria. It all looks very promising.

Further, the study of mitochondria is very broad and energetic, and has a strong presence in many areas of medicine and life science research. While few groups in the field are currently engaged in work on mitochondrial repair, there is an enormous reservoir of potential funding and workers awaiting any method of repair shown to produce solid results.

4) Reversing Stem Cell Aging

The stem cell research field is on a collision course with the issue of stem cell aging. Most of the medical conditions that are best suited to regenerative medicine, tissue engineering, and similar cell based therapies are age-related, and thus most of the patients are old. In order for therapies to work well, there must be ways to work around the issues caused by the aged biochemistry of the patient. To achieve this end, the research community will essentially have to enumerate the mechanisms by which stem cell populations decline and fail with age, and then reverse their effects.

Where stem cells themselves are damaged by age, stem cell populations will have to be replaced. This is already possible for many different types of stem cell, but there are potentially hundreds of different types of adult stem cell – and it is too much to expect for the processes and biochemistry to be very similar in all cases. A great deal of work will remain to be accomplished here even after the first triumphs involving hearts, livers, and kidneys.

Much of the problem, however, is not the stem cells but rather the environment they operate within. This is the bigger challenge: picking out all the threads of signalling, epigenetic change, and cause and effect that leads to quieted and diminished stem cell populations – and the resulting frailty as tissues are increasingly poorly supported. This is a fair sized task, and little more than inroads have been made to date – a few demonstrations in which one stem cell type has been coerced into acting with youthful vigor, and a range of research on possible processes and mechanisms to explain how an aging metabolism causes stem cells to slow down and stop their work.

The stem cell research community is, however, one of the largest in the world, and very well funded. This is a problem that they have to solve on the way to their declared goals. What I would expect to see here is for a range of intermediary stopgap solutions to emerge in the laboratory and early trials over the next decade. These will be limited ways to invigorate a few aged stem cell populations, intended to be used to boost the effectiveness of stem cell therapies for diseases of aging.

Any more complete or comprehensive solution for stem cell aging seems like a longer-term prospect, given that it involves many different stem cell populations with very different characteristics.

5) Clearing Advanced Glycation Endproducts (AGEs)

AGEs cause inflammation and other sorts of mischief through their presence, and this builds up with age. Unfortunately, research on breaking down AGEs to remove their contribution to degenerative aging has been a very thin thread indeed over the past few decades: next to no-one works on it, despite its importance, and very little funding is devoted to this research.

Now on the one hand it seems to be the case that one particular type of AGE – glucosepane – makes up 90% or more the AGEs in human tissues. On the other hand, efforts to find a safe way to break it down haven’t made any progress in the past decade, though a new initiative was launched comparatively recently. This is an excellent example of how minimally funded research can be frustrating: a field can hover just that one, single advance away from largely solving a major problem for years on end. All it takes is the one breakthrough, but the chances of that occurring depend heavily on the resources put into the problem: how many parallel lines of investigation can be followed, how many researchers are working away at it.

This is an excellent candidate for a line of research that could move upward in the order of arrival if either a large source of funding emerged or a plausible compound was demonstrated to safely and aggressively break down glucospane in cell cultures. There is far less work to be done here than to reverse stem cell aging, for example.

6) Clearing Aggregates and Lysomal Garbage

All sorts of aggregates build up within and around cells as a result of normal metabolic processes, causing harm as they grow, and the sheer variety of these waste byproducts is the real challenge. They range from the amyloid that features prominently in Alzheimer’s disease through to the many constituents of lipofuscin that clog up lysosomes and degrade cellular housekeeping processes. At this point in the advance of biotechnology it remains the case that dealing with each of the many forms of harmful aggregate must be its own project, and so there is a great deal of work involved in moving from where we stand today to a situation in which even a majority of the aggregates that build up with age can be removed.

The most promising lines of research to remove aggregates are immunotherapy, in which the immune system is trained or given the tools to to consume and destroy a particular aggregate, and medical bioremediation, which is the search for bacterial enzymes that can be repurposed as drugs to break down aggregates within cells. Immunotherapy to attack amyloid as a treatment for Alzheimer’s is a going concern, for example. Biomedical remediation is a younger and far less funded endeavor, however.

My expectation here is that some viable therapies for some forms of unwanted and harmful metabolic byproducts will emerge in the laboratory over the next decade, but that will prove to be just the start on a long road indeed. From here it’s hard for me to guess at where the 80/20 point might be in clearing aggregates: successfully clearing the five most common different compounds? Or the ten most common? Or twenty? Lipofuscin alone has dozens of different constituent chemicals and proteins, never mind the various other forms of aggregate involved in specific diseases such as Alzheimer’s.

But work is work: it can be surmounted. Pertinently, and again, the dominant issue in timing here is the lack of funding and support for biomedical remediation and similar approaches to clearing aggregates.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries.  

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