A term invented by Naira, the TBO is interpreted in medical, legal, regulatory, and policy environments.

1. TECHNO-BORNEORGANS
HLTH952:
HLTH952: BIOTECHNOLOGY & LAW
BIOTECHNOLOGY & LAW
Naira Roland Matevosyan, MD, MSJ, PhD
Naira Roland Matevosyan, MD, MSJ, PhD
Copyright
Copyright © 2015. All rights reserved.
© 2015. All rights reserved.
The author has published an expanded article in Springer Verlag:
The author has published an expanded article in Springer Verlag:
Matevosyan, Naira R. (2016). Techno-borne organs: Medical, legal, and
policy concerns. Journal of the Knowledge Economy; 9: 544–560.
https://link.springer.com/article/10.1007/s13132-015-0346-4

2. CONTENTS
I
INTRODUCTION
NTRODUCTION - 3
● Demand and supply – 4
● Risks intrinsic to organ donations – 4
● Donor organ storage and transport - 5
● Donor organ costs and transplantation coverage – 6, 7
SYNTHETIC BIOLOGISTS CREATE HUMAN ORGANS
SYNTHETIC BIOLOGISTS CREATE HUMAN ORGANS - 8 -11
MEDICAL ADVANTAGES
MEDICAL ADVANTAGES - 12, 13
MEDICAL RISKS
MEDICAL RISKS - 14
PSYCHOSOCIAL ADJUSTMENT
PSYCHOSOCIAL ADJUSTMENT - 15
TRANSPLANTATION POLICIES
TRANSPLANTATION POLICIES - 16
● Coordination Framework and Committee - 16
● Licensing and “march-in rights” - 17
LEGAL ISSUES
LEGAL ISSUES - 18
● Patenting rights and trade secrets - 19
● Property rights - 20
● Patient privacy – 21, 22
● Advance directives for autopsy – 23, 24
● Research integrity – 25, 26
● Publishing an invention – 27
DISCLAIMER
DISCLAIMER - 28

3. INTRODUCTION
● Organ transplantation is an effective (often ultimate)
therapy for end-stage organ failure. Cornea, skin, bone
marrow, kidneys, lungs, liver, heart, and pancreatic islet
are the most demanded organs.
● Nearly 28,000 organ replacements are performed
annually in the United States, with 120,000 people on
the waiting lists. The majority of the organ subscribers
die before the donor organ becomes available.
● The growing organ shortage has led to an international organ
trade, named “transplantation tourism,” raising ethical and legal
concerns. Most of the donor organs are alleged to be procured
from the executed prisoners [1, 2].
(1) Tianjin, K.C. (2005). A transplant Mecca' that attracts patients from 19 Asian countries.
http://www.chosunonline.com/article/20050130000046
(2) Ghods, A.J. & Nasrollahzadeh, D. (2005). Transplant tourism and the Iranian model of renal
transplantation program: ethical considerations. Experimental & Clinical Transplantology, 3:351-4
3

4. DEMAND&SUPPLY
● According to the “Organs Watch,” major
organ importers are Australia, Canada,
Costa Rica, Israel, Japan, Oman, Saudi
Arabia, and the United States.
● Commonly known organ exporters are Bolivia, Brazil, China, Colombia,
India, Iran, Iraq, Israel, Moldova, Pakistan, Peru, and Turkey.
● The consistently reported medical complications include: transmissions
of the HIV, hepatitis B and C, and tuberculosis [3-5]. Many organ
recipients embrace a path of lifetime immunosuppression to stave-off
the organ rejection at the cost of lowering their overall immune defense.
(3) Inston N.G., Gill D., Al-Hakim A., Ready A.R. (2005). Living paid ordgan transplantation results in unacceptably
high recipient morbidity and mortality. Transplant Proceedings; 37: 560-2.
(4) Ivanovski N., Popov Z., Cakalaroski K., et al (2005). Living-unrelated (paid) renal transplantation – Ten years
later. Transplant Proceedings; 37: 563-4.
(5) Kennedy S.E., Shen Y., Charlesworth J.A., et al (2005). Outcome of overseas commercial kidney
transplantation: an Australian perspective. Medical Journal of Australia; 182: 224-7 4

5. STORAGE&TRANSPORTATION
Currently, there are two preservation methods:
● Static - simple static cold storage (SCS);
● Dynamic - hypothermic machine perfusion
(HMP), normothermic machine perfusion
(NPM), and oxygen persufflation [6].
Both SCS and HMP are clinically approved for kidneys. Only SCS is approved
for the liver, lungs, pancreas, and heart. The remaining methods are in the
various stages of preclinical studies. SCS relies on the cooling effect alone
[7]. By contrast, HMP depends on activating residual metabolism, largely
dependent on energy generation for oxygen supply in aerobic metabolism
delivered by the vascular perfusion [8]. Technically, SCS is simpler and
cheaper than HMP that costs around $3,000 in the U.S.[8, 9].
(6) Semenza, G.L. (2000). Surviving ischemia: adaptive responses mediated by hypoxia-inducible factor 1. Journal of
Clinical Investigation; 106:809 -811.
(7) Lee, C.Y. & Mangino, M.J. (2009). Preservation methods for kidney and liver. Organogenesis; 5:105-112.
(8) McAnulty, J, (2010). Hypothermic organ preservation by static cold storage methods: Current status and a view to the
future. Cryobiology; 60(3 suppl):S13- S19. 5

6. DONORORGAN&TRANSPLANTATIONCOSTS
6

7. TRANSPLANTATIONCOVERAGEBYTHEGOVERNMENT
Federal and state governments may fund organ transplant under Medicare or
Medicaid. Pursuing a Social Security Disability (SSAD) pre-approval is a good idea
for seeking full coverage under Medicare. Since W. J. Clinton's Administration,
Medicare paid for post-transplant anti-rejection therapy at 100% for the life of
organ-recipient. After the enactment of the 2010's Patient Protection &
Affordable Care Act, Medicare remains available to retirees over 65 years of age,
disabled people, and those with End-Stage Renal Disease (ESRD).
Medicaid covers transplants only for approved, select diagnoses and only when
performed by the recognized Centers of Excellence. Medicaid services are
reimbursable only if the recipient is eligible for Medicaid during the month of
service. Proof of donor eligibility and Treatment Authorization Requests (TAR)
from the DHHS are required for major solid organs and bone marrow
transplants. Providers must submit a Service Authorization Request (SAR) for <
21-year old patents who are eligible for the Genetically Handicapped Persons
Program (GHPP).
Donor/recipient services are billed on separate claims. When the living donor
and recipient are at different hospitals, both hospitals must be designated as
Medicaid Centers of Excellence for the specific organ transplant involved. 7

8. SYNTHETICBIOLOGISTSCREATEHUMANORGANS
11]. With the advances of nanotechnology and regenerative medicine, a
number of solutions are available: regeneration of the whole organs
using stem cells, bioprint tissues; creation (harvesting, cloning) of organs,
and even “Petri-dish steak.” Custom-designed human organs/tissues
(cornea, heart, kidneys, liver, lungs, teeth) are becoming 'off the shelf.'
(10) Endy, D. (2005). Foundations for Engineering Biology. A, C, T, and G refer to the four essential nucleotide base
pairs that make up DNA: adenine, cytosine, thymine, and guanine. Nature, 438: 449-53
(11) Paradise J.J & Fitzpatrick, E. (2014). Synthetic biology: Does re-writing nature require re-writing regulation?
Penn State Law Review, 88 (117):53-87
Techno-borne organs (TBO) are
promising organ-repair strategies in a
vast spectrum of terminal diseases.
Synthetic biology utilizes “biological
parts” to build cells or entire
organisms that can either mimic what
occurs in nature or be programmed
with wholly novel characteristics [10,

9. MAKINGANORGAN
Currently, there are three main
techniques of a TBO creation (from the
autologous, syngenic, isogenic cells):
I. Organ Harvesting: Isolation of a three-
dimensional (3D) bio-scaffold material
vacant of any cells, then using stem cell
technique to plant the patient's own cells
unto the scaffold. A stem is coaxed into,
becoming a mature hepatocyte,
osteocyte, or myocyte. About $10-$30
million U.S. dollars is needed to harvest
one organ [12].
(12) Badylak, S. (2015). Grow your own. McGowan Institute
for Regenerative Medicine, University of Pittsburgh and
UPMC.
9

10. MAKINGANORGAN
sustaining a regeneration process, are “switched on” through growth
factors so that they generate new functional tissue of the required
variety. Collagen-based biopolymers, combined with synthetic
crosslinkers or copolymers, form effective scaffolds for developing
prototype artificial corneas, skin, or cartilage for replacements [13]. The
tissue engineering strategy is cheaper in both investment and recurring
costs. Endothelial keratoplasty sham, for example, costs $880 per
transplant. By contrast, utilizing donor tissue procured from the eye
banks for keratoplasty requires U.S. $3,710 per transplant [14].
II. Tissue Engineering & Polymerization:
Modified natural and synthetic polymers are
used to replace damaged portions of the organs
or tissues. Those cells, capable of initiating and
(13) Griffith M., Hakim, M.A., Shimmura, S.M. et al (2002). Artificial human corneas: Scaffolds for
transplantation and host regeneration. Cornea; 21 (p): S54-S61
(14) Tan T-E., Peh, G.S.L., George, B.L., et al (2014.) A Cost-minimization analysis of tissue-engineered
constructs for corneal endothelial transplantation. PLoS ONE; 9(6): e100563

11. MAKINGANORGAN
III. DNA Synthesis: This is either natural
or artificial creation of deoxyribonucleic
acid (DNA) molecules in various
contexts: DNA replication (in vivo
amplification), polymerase chain
reaction (enzymatic synthesis), and gene synthesis (physically
creating artificial gene sequences). Emerging techniques promise a
creation of new nucleobase pairs in addition to the naturally
occurring pairs, A-T (adenine-thymine) and G-C (guanine-cytosine).
A third base pair could dramatically expand the number of amino
acids that can be encoded by DNA, from existing 20 amino acids to
a theoretically possible 172 [15].
(15) Bradley, F.J. (2014). Life engineered with expanded genetic code. San Diego Union
Tribune.
11

12. T.B.O.ADVANTAGES
Absence of risk of infection-transmission by the donor organ,
Absence of risk of histocompatibility or other conflicts,
No need for expensive immunosuppression therapy,
Absence of risk of microbiological contamination in the donor
organ (by latent viruses or fungi),
Absence of risk of delivering mixed-up organs or wrong cells,
Absence of side effects from the artificial preservants and
donor organs' histological changes during the preservation or
transport (ischemia and reperfusion injury, oxidative stress and
inflammation, inhibition of Na+/K+ATPase causing oedema,
increase of cytosolic Ca2+, anaerobic glycolysis, magnesium
crystal precipitation, redox reaction). 12

13. T.B.O.ADVANTAGES(continued)
Patients' independence from long waiting lists
Combating “transplant tourism”
Reduction of healthcare costs
Organ customization for recipient's age, gender, race,
metabolism or energy level, HLA, blood group and Rh factor
Time management - reduced time between the organ
prescription and transplant surgery
Peace of mind in the patient
Peace of mind in patient's family or relatives
Reduction of malpractice suits for transplantation failures
Others. 13

14. MEDICALRISKS
Tissue modification during the cell amplification, differentiation, or genetic
manipulation: gene transfer of the anti-oxidative molecules, anti-apoptotic
molecules, cytoprotective (heat shock) proteins, HO-1-inducing molecules,
cytokines and cytokine antagonist; blockade of T-cell co-stimulation
Scaffold interaction
Low quality and biocompatibility of the synthesized or regenerated tissue,
Potential toxicity of the process additives, residues, as well as patient-specific
responses (allergies)
The regeneration process is not yielding a tissue with adequate mechanical or
physical properties (especially in engineered blood vessels or valves)
Risks associated with maintenance of created organs in vivo. In a traditional
transplant scenario, the post-surgical screening at a minimum includes the white
blood cell (WBC) count, blood gases, hematocrit, coagulation cascade, creatinine
index, electrolytes, phosphates, chlorides, and imaging techniques. Having no
observational data on the side effects from a created organ cannot inform default
physiological cutoffs indicative of transplantation success or failure.
Products of synthetic biology have the ability to self replicate when released into
the environment.

15. PSYCHOLOGICALADJUSTMENT
In traditional transplantation, both donors and recipients may
encounter issues of adjustment, ability to adhere to post-transplant
medical directives, sexual dysfunction, and job resuming difficulties
[17, 18]. While donors may suffer hypochondriac phobia, the recipients
may suffer intrusive resistance to the “newcomer” in their body.
Preparing to die is easy for some, and grueling for others.
Additionally, wait-listed candidates may develop medical
contraindications to transplantation (sudden infection, serious stroke,
hemodynamic instability).
Such issues could be eliminated by transplanting a TBO with the
patient's own genetic package. This situation, however, can also
trigger psychological limbo, similar to the “iron-man-3 syndrome.”
(17) Engle, D. (2001). Psychosocial aspects of the organ transplant experience: What has been
established and what we need for the future. Journal of Clinical Psychology; 57(4):521-49.
(18) DiMartini, C. C., Fireman M., et al (2009). Psychiatric aspects of organ transplantation In
critical care. Critical Care Clinics; 24(4): 949-x 15

16. POLICYSPECIFICS
In 1986, the U.S. Coordinated Framework established a biotechnology oversight
by the Environmental Protection Agency (EPA), Department of Agriculture &
Animals (USDA), Food & Drug Administration (FDA), National Institutes of Health
(NIH), National Science Foundation (NSF), and Occupational Safety & Health
Administration (OSHA) – to monitor the genetic engineering sector. The
Framework established a Coordinating Committee to ensure timely decision
making, inter-agency communication, jurisprudence over the biotechnology
products, and keeping track of the changing scene in biotechnology [19]. The
narrowed Committee (USDA, APHIS, EPA, FDA) has a limited regulatory scope [20]:
● it only applies to entities receiving federally funded research grants;
● federal oversight is not triggered until the development of a commercial
product;
● some laboratory or animal studies are not regulated because they do not
result in a product of commercial interest.
(19) Stepp, D.L. (1999). The history of FDA regulation of biotechnology in the twentieth century.
Food Drug Law; 46:1 -16.
(20) Wozniak C.A., Waggoner, A.F., Reilly, S. (2012). An introduction to Agricultural Biotechnology
Regulation in the U.S. Biopesticides and Pollution Prevention Division, Office of Pesticide
Programs. The U.S. Environmental Protection Agency.
16

17. POLICYSPECIFICS(continued)
● With remarkable promises on the way, we need to determine whether a
man-made organ, with the identical genetic package as that in the
recipient, is a subject of scientific novelty, commercial interest, or public
health interest? It could be one, both, or all. Additional hurdles are
debated as to the NIH and NSF rejoining the Coordinating Committee to
to monitor the scientific process and non-commercial products as well.
● Licensing an invention is another bailiwick. The Bayh-Dole Act (1980)
and Stevenson-Wydler Act (1980) not only have enabled collaborations
between the federally funded researchers but also commercialization of
the institutions. Such an influx of economic success drives the institution
to focus on funding an invention for a financial benefit - as opposed to
altruistic brainstorming. This may negate the “upstream research”.
● Under certain circumstances, the government can require a university to
grant a license to a third party, or the government may take title and
grant licenses itself (using its "march-in rights"). This may occur if an
invention isn't brought to practical use within a reasonable time, if
health or safety issues arise if public use of the invention is in jeopardy.
17

18. LEGALISSUES
In the traditional donor-organ transplantation practices, tort or
malpractice claims include fraud and misrepresentation, deficient
informed consent, conspiracy, breach of the patient's privacy, or health
insurance constraints. The overwhelming majority of claims concern to
the health insurance coverage (Fig. 1):
By contrast, the
TBO transplant
eliminates
grounds for
claims about
misusing unfit
donor organs, or
waiting list
discrimination.
Anticipated legal
issues are
discussed further.
18

19. PATENTINGRIGHTS&TRADESECRETS
An invention can be patentable if it presents:
(1) Patentable subject matter [35 U.S. Code §101 ]
(2) Utility [35 U.S. Code §102]
(3) Novelty [35 U.S. Code § 103]
(4) Nonobviousness [MPEP Guide 2141]
(5) Specification [35 U.S. Code §112].
Under the Subject Matter Eligibility [R-11.2013] requirement, there are two
matter determinations and both must be satisfied. The claimed invention:
● must be directed to one of the four statutory categories (process,
machine, manufacture, composition of matter), and
● must not be wholly directed to subject matter encompassing judicially
recognized exceptions: laws of nature, physical phenomena, abstract
ideas, theories, mathematical algorithms [21-23].
(21) Bilski v. Kappos, 561 US 593 (2010)
(22) Diamond v. Ananda M. Chakrabarty, 447 U.S. 303 (1980)
(23) Parker v. Flook, 437 US 584 (1978) 19

20. PATENTINGRIGHTS(continued)
In addition, under the PTO 2164.01, the patent should allow
enablement: “Any analysis of disclosure requires a determination of
whether the filed disclosure contained sufficient information
regarding the subject matter of the claims as to enable one skilled in
the pertinent art to make and use the claimed invention” [24].
Several questions raise of the TBO patentability under the matter,
process, and novelty criteria. Isn't the TBO a natural phenomenon
even though it is man-made? Where each organ or transplant is
unique, does it grant the TBO a novelty status?
Creating a TBO is a process of genetic engineering that includes DNA
isolation, random digestion (DNA with restriction enzymes), or
recombination. Ergo, succeeding in a patent claim greatly depends on
how skillfully the matter and process are separated and specified in
the patent application.
(24) Minerals Separation, Ltd. v. Hyde, 242 U.S. 261 (1916) 20

21. PROPERTYRIGHTS
The TBO is both inventor's intellectual property and the recipient's
private property. Such a dual-status may trigger extensive legal
conflict.
In resonance to the Myriad's decision, the American College of
Medical Genetics and Genomics (ACMG) raised an issue of
property rights, reflecting that the DNA (whether native or cDNA)
conveys special genetic information that “should not be anyone's
private property, and that developing a patent thicket of gene
sequences could prevent easy commercialization of genetic
diagnostics” [25, 26].
(25) Association for Molecular Pathology v. Myriad Genetics, 569 U.S. 12--398 (2013)
(26) ACMG Applauds Supreme Court Decision on GenePatents (2013).
www.acmg.net/docs//GenePatientsDecision.pdf
21

22. PATIENTPRIVACY
A successful TBO transplant could become a risk to the patient's
privacy. The recipient may become a subject of mass-media
monitor and a target by research studies for public benefit. To be
protected from the privacy breaches, the patient may exercise his
1st and 14th Amendment rights, Health Insurance Portability and
Accountability Act of 1996 (HIPPA), or Patient Safety & Quality
Improvement Act of 2005 (PSQIA) privileges.
The patient or his representative should
carefully study the Informed Consent Form
prior to the surgery, and decide whether to
agree to informed obligations to participate
in post-surgical scientific studies for the
public good.
22

23. ADVANCEDIRECTIVES
Advance Directives, Uniform Anatomical Gift
Acts, Living Will, or Durable Power of Attorney
(DPOA) vary from state to state and are
designated to protect an adult person's rights
by communicating his/her medical choices in
advance, would s/he become unable to do so
in the future by reason of a terminal illness or
mental incapacity.
The principal competing interests are: (1) the
wishes of the deceased during his lifetime
concerning the disposition of his body; (2) the
desires of the surviving spouse or next of kin; (3)
the interest of the state in determining by
23
autopsy, the cause of death in cases involving crime or violence; (4) the need for
autopsy to determine the cause of death when private legal rights are dependent
upon such cause, and (5) the need of society for bodies, tissues, and organs for
medical education, research, therapy and transplantation. Continued on the next slide.

24. ADVANCEDIRECTIVESFORAUTOPSY
● The formerly discussed competing interests [26-29] most
frequently concern cornea donations.
● In any event, it is wiser to complete both documents (Living
Will and DPOA) to provide comprehensive guidance regarding
the postmortem autopsy and the TBO “recycling.” Examples
of combined documents include Five Wishes and
MyDirectives. Department of Pastoral Care may be available
to assist with the choice and with preparing an advance
directive for the TBO carriers.
(26) Brotherton v. Cleveland, 923 F. 2d 477 (6th Cir. 1991)
(27) Brown v. Delaware Val. Trans. Program, 420 Pa. Superior Ct. 84 (1992)
(28) Lyon v. United States, 843 F. Supp. 531 (D. Minn. 1994)
(29) Perry v. Saint Francis Hosp. & Medical Center, 886 F. Supp. 1551 (1995)
24

25. RESEARCHINTEGRITY
The National Science Advisory Board for Biosecurity (NSABB) is a
federal agency designated to provide guidance and leadership in
research in biosafety and biosecurity. Expert of the NSABB are selected
by the Department of Health and Human Services (DHHS) on a 4-year
run. The key role players in safe biotechnology, as defined by the
National Research Council (NRC), are the NSABB, NIH, DHHS,
Institutional Biosafety Committee (IBC), Biological Toxins and Weapon
Convention (BWC) of 1975, and the U.S. Patriot Act of 2001. The NIH,
NSF, FDA, EPA, USDA, Department of Justice, Department of
Commerce, Department of Education, Department of Housing, the
Veteran Administration (VA), Consumer Products Safety Commission,
Social Security Administration (SSA), the Homeland Security and
Recombinant DNA Advisory Committee (RAC) are concerned of the
ethics of rDNA. These are entities that directly or indirectly monitor the
provision of the Common Rule. Under a federal statute (42 USC 282),
the RAC governs bioethics, human subject research, biotechnology.
25

26. RESEARCHINTEGRITY (continued)
● The Common Rule also identifies the Dual Use Research of
Concern (DURC). In life sciences, the DURC is reasonably
anticipated to provide information about products or technologies
that could be directly misapplied to pose a significant threat with
broad consequences to public health and safety, environment,
materiel, or national security.
● The U.S. Government’s oversight of DURC is aimed at preserving
the benefits of life sciences while minimizing the risk of misuse of
knowledge, information, products, or technologies provided by
such research [30].
● In extreme cases, the synthetic biology products may be reviewed
under the DURC category and monitored by the NRC and RAC.
(30) Kraemer, J. D. & Gostin, L. O. (2012). The limits of government regulation of
science. Georgetown Law Faculty Publications and Other Works; 776: 1047-
1049https://scholarship.law.georgetown.edu/facpub/776 26

27. PUBLISHINGANINVENTION
The synthetic biologists who create TBO should consider striking a
balance between publishing an invention of national interest and
patient privacy.
Disclosure of private health information poses economic and
psychosocial harm. The affected individuals could lose their jobs,
health insurance, housing, suffer emotional distress if sensitive
information becomes public knowledge.
Despite the 1st Amendment rights, the government strongly
discourages the publishers from exposing scientific information about
issues linked to bioterrorism (Lassa fever, Cholera, Anthrax, Ebola,
Nipah virus, Hantavirus, Marburg virus, Plague, Botulism,
Coronavirus, others) and defense strategies involved. The 1st
Amendment comes with limitations as to the scientific secrets.
Restraints include: scientific expression, prior restrains on publication,
classification and security clearance. 27

28. DISCLAIMER
This presentation shall not be utilized
as medical or legal advice.
The author declares no commercial,
fiduciary, or strategic interest (or a
conflict thereof) with the names,
entities, or publications mentioned or
omitted herein.
28