Medicine, F.D.A, and controversies feeding the Big-Data-Driven Stem Cell Science- A case of Ethical and Legal predicament

For the past decade Stem cell therapy, research and its applications in medicine have been the topic of prodigious controversy, not only in the medical showground but also among the political activists, and media.

“Their costly, unproven treatments can be risky. However, for-profit stem cell clinics are flourishing” said Erin Allday In miracle cell publication.

According to a study published in Journal of Regenerative Medicine, public media plays a significant role in swaying the civic opinion of policy issues such as stem cell research and offers officialdoms a better understanding of how to more effectively apply social media to advance their stem cell course of actions. On the other hand, The Official Blog of CIRM, California's Stem Cell Agency in one blog states:

 “Why are we concerned about these clinics? Well, they claim their therapies, which usually involve the patient’s own fat or blood cells, can cure everything from arthritis to Alzheimer’s. However, they offer no scientific proof, have no studies to back up their claims and charge patients thousands, sometimes tens of thousands of dollars”

It is evident that despite all the inherent potential medical benefits, stem cell therapy is being disputed due to the lack of well-defined clinical trials, so that recently a federal court Judge Rules against U.S. Stem Cell, a private clinic in Sunrise, Florida that officials have the authority to regulate stem-cell treatments made from “patients’ own fat.” In the ruling, Judge Ursula Ungaro agreed with The Food and Drug Administration (F.D.A) that extracting stem cells from fat requires “so many” (Remember these II words!) processing that it essentially transforms them into a "drug"!- And further elaborated that “alteration” firmly places such treatments under the jurisdiction of the F.D.A, which has the authority to regulate drugs. The U.S. Department of Justice, on F.D.A’s behalf, initiated this action against US Stem Cell Clinic LLC and US Stem Cell Inc., and Comella in May 2018, seeking a permanent injunction to stop the entities’ illegal behavior after several attempts to provide the clinic and the individual defendants the opportunity to work with the agency to come into compliance with F.D.A regulations and protect patients from harm.

Before we plunge into the details let’s agree upon a few facts that

1) The stem cell science is particularly diverse and using it within a two-word perspective is beyond the scope of legal and political rhetoric

2) There are unanswered questions in stem cell science just as is with most other treatments

3)An authoritative agency such as F.D.A and many other branches of the federal government has enough authority, and since they are the originator of their own policies, nevertheless is fair to stipulate that they also have the power of rationalization over such regulations in the court of law.

4) Patients have the right to treatments to diseases that they have failed by the means of a conventional way.

5) As it was being contended in the case of F.D.A vs US stem cell, one needs to be able to define what manipulation of tissue is and what would be the outcome of such intervention. Therefore, it is also reasonable to assume that there is more to the argument that the safety of the treatments in clinical footings vs legal terminology- after all medical science must at all times consider the notion of risk and benefit ratio, where legal and regulatory languages are neither a valid comprehension nor carry any form of validity.

What is a stem cell?

Stem cells are the units of tissue with the potential to develop into many different types of cells in the body. Stem cells and derivative offer boundless aptitude for new medical treatments. They merely function as the restoration scheme for the body. There are two main types of stem cells: Embryonic stem cells and Adult stem cells. Embryonic stem cells come from embryos that are three to five days old. At this stage, an embryo is called a blastocyst and has about 150 cells. These are pluripotent stem cells, the importance they are able to divide into additional stem cells or can become any sort of cell in the body. Adult stem cells are found in small numbers in the majority of the adult tissues, such as bone marrow or fat. In contrast to embryonic stem cells, adult stem cells have a more limited ability to give rise to various cells of the body. However, until recently, scientists assumed adult stem cells could create just similar types of cells as to their host. For instance, those stem cells inherent in the bone marrow could give rise at most to blood cells. However, evolving indication suggests that adult stem cells may be adept to create innumerable types of cells. As an illustration, bone marrow stem cells may be capable to create bone or heart muscle cells. Adult cells, if transformed can have properties of embryonic stem cells (induced pluripotent stem cells- a procedure that is not currently practiced legally within the independent medical clinic within the United States). Scientists have successfully transformed regular adult cells into stem cells using genetic reprogramming. By modifying the genes in the adult cells, researchers can reprogram the cells to act similarly to embryonic stem cells. This new technique may allow researchers to use reprogrammed cells as an alternative of embryonic stem cells and in tandem prevent immune system rejection of the new stem cells. Nonetheless, experts don't yet know whether using altered adult cells will cause adverse effects in humans. Researchers also have been able to take regular connective tissue cells and reprogram them to become functional heart cells. Concurrently, they have discovered that perinatal stem cells in amniotic fluid, as well as umbilical cord blood, have the ability to change into specialized cells.

Most of the major stem cell polemics are focused around embryonic or pluripotent stem cells, as they are more undifferentiated and potential to form a diverse lineage of cells. Embryonic stem cell use is legally outlawed in most countries as well as within the United States with only a hardly any exceptions. What we hear or read on the social media and what has been pragmatic by the medical community is the adult stem cell which is primarily harvested from the bone marrow and adipose tissue of the patient self. Hence, in today's healthcare space the dispensation of the adult stem cell is primarily limited to utilizing collagenase enzyme to release the stem cell to render it separable from its collagenous framework and as concentrated through centrifugation. In a selection of cases patients own Platelet is also made use of as the source of “platelet growth factors”. By no means has such process entails tortuous manipulation of the cells in the morphological lucidity.

Over recent decades, the adipose tissue has become a highly prevalent source of adult stem cells for plastic surgery and regenerative medicine. The isolated stromal vascular fraction (SVF) is a heterogeneous cell population, including the adipose-derived stromal/stem cells (ASC), which showed regenerative potential previously in a few clinical studies and trials. However, because the stem cells within the adipose tissues are bound within the fibrous attached environs, it necessitates marginal handling under sterile environment, to sequester SVF from adipose tissue, with or without the use of enzymes such as collagenase in conjunction with isolation systems using physical forces like the centrifuge. Analogous types of processes are regularly practiced in operating rooms such as bone and skin grafting procedures without direct F.D.A statutory intervention.

Uses of stem cell

Note: The utility of the word “Stem cell” in the rest of this article exclusively refers to adult stem cell, unless specifically mentioned as “embryonic stem cell” is not the main focus of this argument.

An adult stem cell has significant regenerative potential by inoculating itself into the degenerating tissues in the body and utilizing the milieu to differentiate to the type of cells customary of its new habitat. In contrast to their embryonic counterpart, since adult stem cells are more segregated along the chain of the development, they have lesser propensity to swerve in less predictable lineage of maturation within their fresh environment, if not they are further enzymatically manipulated in the laboratory setting, where adult cells altered to have properties of embryonic foils, (also called induced pluripotent stem cells) which by themselves are sophisticated. Contemporary Stem cell researchers are within those lines of being able to improve the efficiency of stem cell therapy via controlled phenotypic manipulation of those cells to render them more potent and effective; the phenomena that present techniques are struggling to openly demonstrate. The application of stem cell therapy may seem diverse as it is used for various health conditions such as Degenerative Arthritis, Heart failure, Chronic Obstructive Pulmonary Disease (COPD) or even some beneficial effect in Attention deficit and hyperactivity disorder (ADHD), Autism and Dementia, but they all follow the same line of principle like “making the host regenerate new and healthy tissue” hence functions. Same regenerative principle moreover applies to cosmetic procedures.

What is the Trend?

There is undoubtedly consumers under particular circumstances are willingly interested in stem cell treatments, and they are correspondingly willing to spend thousands of dollars if it even means there is a small chance, few successes-more so to treat diseases as devastating as dementia or torturous as Amyotrophic lateral sclerosis (ALS). Granting criticism of current administration and media over the corporate business of stem cell holds validity and as regulation is a matter of necessity, but the extravagance of the necessity is without doubt toxic.

We are living in an age when patients have access to the ocean of information and reckoned more sophisticated. They understand the theory of risk and benefit ratio in their own unequaled way, and may even remarkably make choices based on those unique personae, but they will furthermore trust their physician and are able to lead them in the veracious course. Meddling with such autonomy in the 21st century over and done with media scares tactics and political rhetoric by means of the sustenance of administration will lead to a toxic outcome. Medical tourism for stem cell treatment is one such an example by way of Internet sites for clinics all around the world, including the U.S., but particularly in China, India, the Caribbean, Latin America, and the nations of the former Soviet Union offer stem-cell-based therapies for patients suffering from a copious selection of grim disorders where many who are despairing and in need of a second chance to travel abroad and spend thousands of dollars to seek treatment. But does that imply patients are blinded by stem cell therapy?! - Or is it fair-minded to state, the particular procedure may not turn out fruitful, as even under conventional treatment protocols, not every case is a success?!

Regulations and guidelines governing stem cell-based products and Clinical considerations

“Stem cells, like other medical products intended to treat, cure or prevent disease, require F.D.A approval before they can be marketed. It is important for F.D.A to maintain a sound regulatory science research program to promote the development of safe and effective products in emerging areas that hold great promise,” says Steven R. Bauer, Ph.D., chief of the Cellular and Tissue Therapy Branch in F.D.A’s Office of Cellular Tissue and Gene Therapies.

Why it matters?

"I think the F.D.A is taking on industries where there is a potent political constituency trying to resist regulation. And that's hard," former F.D.A Commissioner Scott Gottlieb said. Nevertheless, Controversial clinics still recruiting patients

“Stem cell clinics co-opt clinical-trials registry to market unproven therapies”, critics say. On the one hand, the Food and Drug Administration issued a letter stating that “what an Arizona distributor was selling as stem cell therapies were “unapproved” and posed “safety concerns”

On the other, a National Institute of Health database — clinicaltrials.gov — went right on listing the same merchant’s studies, with a link to the company’s website and the word “Recruiting” displayed invitingly in green.

Big data, Stem cell genomics

Stem cell genomics is a science that analyzes the genome of stem cell. Currently, this branch of discipline is rapidly expanding due to the melodramatic decline in the cost of genome sequencing. The study of stem cell genomics has wide-reaching repercussions in the study of stem cell biology and possible therapeutic uses of stem cells. Based on those utilities Stemformatics has industrialized a visible and downloadable curated stem cell database. The company has executed a gene expression data portal containing over 420 public gene expression datasets resulting from microarray of RNA sequencing and single cell profiling technologies. Big-Data-Driven Stem Cell Science and Tissue Engineering have been recognized as one of the increasing numbers of edges that are pressing the need to generate high-quality, curated pheno-genomic stem cell data sets for use by the community.

Between the lines

There is no doubt stem cell has a way to go to perfection, and without question F.D.A's duty is to protect the public health by guaranteeing the safety, efficacy, and security of drugs, biological products, medical devices; food supply, cosmetics, and products that emit radiation. But with respect to stem cell polemic, the scope of F.D.A’s authority is apparently broad, nevertheless, selective.

Historically, the regulations have typically been categorized as, if it is not for radiation device and does not reason imminent harm it is to be treated as unregulated. For instance, there are numerous counts of dietary supplements and products on the shelves of the health stores that are significantly modified by enzymatic processes (such as sports protein shakes) that are less of a concern for the F.D.A.

What tends to raise a red flag for the agency is multifaceted and complex. Few examples are a safety concern, scale by which the business behind the particular product is growing; pursuance to secondarily feed an alternate mission whom I will touch on further down this piece, equally if the company is growing over a particular capacity, then it must be too influential to be left unregulated. A trend which is being strategically exercised today to the point of shortcoming with enterprises like Google, Facebook, Amazon, Apple, and Twitter. Labeling a product as F.D.A jurisdiction is more of an opportunity than an interdict and regulating it accordingly is the matter of political and economic inspiration. There are simply too many open ambiguities as what makes a stem cell harvested from fat a drug rendering it a philosophy rather than a science. Even so, does it matter what we call it?!- Isn’t it about safety in the end?!- What makes enzymatically processed protein shakes any less of a drug than enzymatically processed fat? Conversely, if it is about sterility and infection, the agency does not have to regulate that, because many surgical procedures are performed with a high risk of infections that don’t fall under the F.D.A’s responsibilities.

There are simply too many bogus supplements out there in the market, but whether F.D.A cares about every single element, is the matter of argument. F.D.A’s pragmatic position has continually mirrored as “you may sell snake oil to the public, as long as there is no direct harm reported in a large-scale and/ or you pay your administrative levies.

With respect to “Adult stem cell” 

As we already know there are a variety of stem cell sources with multiple differentiation levels and completely different behaviors. However, one thing we are learning today is the F.D.A’s tendency to profile and bundle those phenotypes (at least bureaucratically) under the single regulatory umbrella or at least giving such an imprint to the public, that contaminated adult stem cell is just as risky as its embryonic counterpart. Based on such postulation in association with the element that the F.D.A is one of the most authoritative branches of the government, makes it convenient to presume, there are different layers of targets for the administration to shadow within the medical arena, which may or may not be exclusively related to the actual safety of stem cell therapy. To be more explicit, the big data industry and data mining are the gold rushes of the 21st century. It serves as the basic ingredient and prime inventory for all trades. Traditionally if a government envisioned controlling a market, they were prone to implement various levels of regulations through import, inspection, tariffs or licensing. Today big data industry joins the government list and subject to inspection and usage by the corporate entities, including the governments. There are a couple of entities such as 23 and me, ancestry.com, etc. which serve as genetic data banks. US stem cell may be the first in line for the stem cell industry to join the rest. Despite the US stem cells court battle to decline sharing stem cell data with the agency, the court ruling was still a win for the F.D.A. Thus, is it about safety, micro-management, regulation, money or simply invasion of individual privacy? — Probably all of the about right?!

Utilizing data, especially the genetic building block of an individual is the gateway for its utility by other branches of the Administration as well as personal entities. To gather this information using a committed public fund is an expensive task, to begin with, besides the constitutional barriers that may hinder access to individual personal information. The F.D.A’s move towards creating the clinical-trials registry and its conditional permission of regenerative physicians offer “unproven stem cell therapeutics” exclusively under such a circumstance is a hypocrite and only points to the administration's mission to use private clinic efforts and funds to achieve the administrative goal of accessing the valuable patient data that would be otherwise harder to access. As in the case of clinical services that are reimbursed through insurance entities and Medicare such as data is easily available to the government, but with regards to cash-based services, the agency must explore other stratagems to collect relevant information without raising public funds, henceforth ensuring another conquest for the F.D.A. One similar example is Biopharmaceutical Industry Provides 75% Of the F.D.A's Drug Review Budget.

Corporative system anti-Independent physicians

Independent physician's practices are practically fated by the restricted policies around stem cell therapy. As junior entities such as US stem cell will be pressed to partner with the government and share data, consequently independent physicians would be forced to be funneled through the stem cell entities to provide clinical services.

Recently, I published an article about how licensing and regulations influence the economy of a particular industry. While the stem cell industry is at its early stages, the regulatory monopolies are equally evolving. Fishing from murky waters is not new in today’s political scenery, as it is efficient, fast and convenient to every government agency, which can be applied to any industry and organization without following the constitutional path. Partisan politics of science like stem cell uses common ethical dilemmas around each theme and make it weaponized as it conquers its undertakings, which frequently have been little to do with the fundamentals of that particular scientific discipline. Within the process, the citizens and patient's welfares and privileges are forfeited. Regulation is a good thing, but too much of a good thing is just as harmful as no regulation, if not more!

The legality of a good or service neither renders it safer nor is the proof of its legitimacy, but then again prohibiting a reasonably safe product or service irrespective of its effectiveness for sure renders it harmful in many ways.

Regardless of the scope of the efficacy of stem cell therapy, it is extremely vital to apply and maintain the concept of risk vs benefits ratio in every circumstance. However, across the board over-regulation and needless mandates will only create pushback against quality physician practice and patient sovereignty hence will corporatize the “Cookie Cutter” medical services. Patients, especially those with medical issues that have persistently failed to respond to the conventional treatment modalities have the Right to try other options that are reasonably safe, even if those alternatives seem contentious.

Effective high levels of regulations are fundamental to safety and autonomy of the state, as far as it is focused and coherent with the actual ethical and interest of the mission it is aimed at, hence individual choice, reasonable safety, and informed consent.