Over the past few decades, the medical field has been revolutionized by new developments in science and technology. One important innovative technology that is likely to be a game-changer in the medical field is the printing of human organs using 3D printers, also known as “bioprinting.” Bioprinting represents an enormous step forward in personalized medicine, and it may also eliminate waiting lists for organ transplants and prevent preclinical research on non-human animals.

Bioprinting is essentially the layer-by-layer positioning of living cells and other biomaterials to create functioning living organs, ranging from the kidney to liver and heart. The ultimate goal is to transplant these organs into humans.

Bioprinting is currently in its infancy; however, several years from now, scientists may be able to print organs customized to an individual’s structure, size, and complexity. To this point, there have been significant developments in cartilage, bone, and skin tissue bioprinting[1]; a human ear[2] and a miniature human heart[3] have also been successfully bioprinted by researchers; and significant progress has been made toward the ultimate objective of supplying larger human organs with blood vessels and capillaries.[4]

This emerging technology raises several intriguing questions that require attention. For example, what would be the effects on extending the life expectancy of individuals? Which bioprinting applications constitute treatment versus enhancement, and should we care about the difference between these two categories?[5] How should 3D-bioprinted organs be distributed across the population? What are the implications for the definition of a “human”?

In this blog post, I will examine two legal issues raised by bioprinting: 1) how to legally classify 3D-bioprinted organs; 2) what it would mean to treat 3D-bioprinted organs as “property.”

How Does Bioprinting Work?

Bioprinting operates according to a simple principle that we are all familiar with in the world of computers. Ink is used whenever you print a document on your home printer; similarly, scientists use ink to print organs. However, in bioprinting, scientists use “bio-ink” (i.e., cell-laden fluid materials) that mimics the extracellular environment of the human body. So, unlike a document you print on your home printer, a 3D-bioprinted organ contains living cells.

Bioprinting consists of three main stages. In the first stage, the organ that needs to be replaced is scanned using instruments such as CT and MRI. In the second stage, the new organ is bioprinted. Bioprinting a three-dimensional organ entails placing one layer of material on top of another. The positioning of the layers is determined by a digital image stored on a computer, which was created after scanning the organ to be replaced. Finally, after the bioprinting process, the organ is placed in an incubator in order to develop and grow appropriately. The incubator is necessary because although some bio-inks will quickly stiffen, others may require more treatment. If the bioprinting procedure is successful, the cells of the 3D-bioprinted organ will begin to act similarly to natural cells inside an organ.

Classification Matters: What Are 3D-Bioprinted Organs?

How 3D-bioprinted organs would be classified will undoubtedly be one of the most pressing legal issues concerning bioprinting. Some classifications are important from a legal perspective because how the material is classified influences the body of legislation that applies to it. Two existing categories of classification might work for 3D-bioprinted organs: “human organs” or “products.”

Human organs

One of the primary goals of 3D-bioprinted organs is to be able to replace donated organs; therefore, they may be considered “human organs” themselves. In this instance, the applicable law is the National Organ Transplant Act (NOTA).[6] NOTA defines “human organs” as: “human (including fetal) kidney, liver, heart, lung, pancreas, bone marrow, cornea, eye, bone, and skin or any subpart thereof and any other human organ (or any subpart thereof, including that derived from a fetus) specified by the Secretary of Health and Human Services by regulation.”

On the one hand, the biological and functional similarity to human organs, as well as the fact that they are created from (manipulated) cells that might be thought of as “subparts,” are two possible arguments for classifying 3D-bioprinted organs as “human organs” under NOTA. On the other hand, NOTA appears to cover primarily naturally existing compositions of matter. The reason for this pertains to the initial purpose of NOTA, which was to begin addressing the scarcity of human organ donations and to make organ transplantation more efficient and effective. Moreover, considering that 3D-bioprinted organs do not pose the same ethical, social, and legal issues as donated human organs–after all, the organs are produced and not harvested from another human being–there may be compelling reasons not to classify them as “human organs.”

Notably, NOTA empowers the Secretary of Health and Human Services to add additional organs to the definition of a “human organ,” which means that once 3D-bioprinted organs are ready to be transplanted into humans, the Secretary can explicitly determine whether a 3D-bioprinted organ falls under the category of “human organ.”

It is worth mentioning that NOTA determines that “[i]t shall be unlawful for any person to knowingly acquire, receive, or otherwise transfer any human organ for valuable consideration for use in human transplantation if the transfer affects interstate commerce” (NOTA, though, does not prohibit reimbursement payments for organ-related expenses). This means that if 3D-bioprinted organs are deemed to be “human organs,” it will be a violation of NOTA to either pay money to obtain them or generate profit from them. This ban on the sale of human organs for transplant is especially significant for scientists working toward commercializing 3D-bioprinted organs.

Products

An alternative option would be to classify 3D-bioprinted organs as “products.” In that case, the relevant laws are the Food, Drug, and Cosmetic Act (FDCA)[7] and the Public Health Service Act (PHSA).[8] Under these laws, a 3D-bioprinted organ could potentially be regulated as a drug, device, biologic product, or combination product.

Section 201(g) of the FDCA defines a “drug” as follows:

“(A) articles recognized in the official United States Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure or any function of the body of man or other animals; and (D) articles intended for use as a component of any article specified in clause (A), (B), or (C).”[9]

Section 201(h) of the FDCA defines a “device” as follows:

“An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is—(A) recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them, (B) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or (C) intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes.”[10]

Section 351 of the PHSA defines “biological product” as follows:

“A virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein, or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings.”[11]

Sometimes, a product will be regulated as a “combination product.” This means the product comprises any combination of the above categories (i.e., drug, device, or biological product). Under 21 CFR 3.2(e), a combination product is defined as follows:

“A product comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity.”[12]

Based on the definitions above, a “combination product” seems to be the best fit for a 3D-bioprinted organ. First, a 3D-bioprinted organ could be considered a “drug.” Although it may sound strange to refer to an organ as a drug, a 3D-bioprinted organ performs, after all, the same goal as a drug: such an organ is intended for use in the cure, mitigation, treatment, or prevention of a disease, as well as to influence body function. In fact, because of the expansive definition of “drug,” theoretically, all FDA-regulated medical items fit the meaning of the term. Second, a 3D-bioprinted organ could also be considered a “biological product.” A 3D-bioprinted organ will contain human proteins (as a reminder, bio-ink contains living cells made from proteins) applicable to the prevention, treatment, or cure of a disease or condition of human beings.

It should be emphasized that even while the definition of a “device” shares the two provisions in the definition of a “drug,” I do not think that a 3D-bioprinted organ is likely to be classified as such. According to the definition, a device “does not achieve its primary intended purposes through chemical action within or on the body of man” [my emphasis]. A product exhibits “chemical action” if it interacts at the molecular level with biological components to mediate a bodily reaction, or with foreign entities to affect the interaction of that foreign entity with the body.[13] Because the human body functions through the chemical reactions that occur within its organs, and a transplanted 3D-printed organ’s primary aim would be to perform these reactions more effectively, then a 3D-printed organ might not fit within the parameters of what constitutes a “device.” Moreover, unlike most devices, which are made of non-bioabsorbable metallic material, most of the 3D-bioprinted organs are made of bio-ink (in some cases, however, bioprinting may involve the use of synthetic substances, such as synthetic polymers[14]).

A 3D-Bioprinted Organ as “Property”

Various questions regarding 3D-bioprinted organs hinge on whether they can be treated as “property.” There are a few different ways in which individuals might claim ownership of 3D-bioprinted organs, and in this section, I will be discussing intellectual property rights and personal ownership.

Can 3D-bioprinted organs be patented?

35 U.S.C. § 101 determines the requirements necessary to secure intellectual property rights. This provision states that “[w]hoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvements thereof, may obtain a patent, subject to the conditions and requirements of this title.”

Before I proceed, I would like to make two clarifications. First, I am interested in the patentability of 3D-bioprinted organs, not the process of creating them or the components that are used to make them. I think that even if 3D-bioprinted organs themselves would not be eligible for patent protection, the method and components used to print the organs would most probably be patentable (providing that the requirement in 35 U.S.C. § 101 are satisfied).[15] Second, while the majority of researchers will likely be interested in patenting the method or the components, it is possible that some may be interested in patenting the 3D-bioprinted organ itself. This may occur, for instance, if a researcher successfully creates a 3D-bioprinted organ with exceptional qualities (for example, a heart that might keep beating for hundreds of years or an ear with some improved capabilities).

Currently, “laws of nature, natural phenomena, and abstract ideas,” as well as “products of nature” are not patentable.[16] While the U.S. Supreme Court has made it apparent that “natural” forms of innovations are not patentable, it has also outlined some conditions under which inventors may still be granted patent protection. There are two relevant cases for our purposes.

The first case is Diamond v. Chakrabarty.[17] In this case, the U.S. Supreme Court upheld the patentability of human-made, genetically engineered bacterium. According to the Court, a modified bacterium is patentable since it is a “manufacture” or “composition of matter” within the meaning of 35 U.S.C. § 101. The Court held that Chakrabarty had created a novel, potentially beneficial bacterium that possessed traits not previously seen in nature.

The second case is Association for Molecular Pathology v. Myriad Genetics, Inc.[18] In this case, the U.S. Supreme Court ruled that synthetically exons-only strands of nucleotides, also known as complementary DNA (cDNA), are patentable, while naturally occurring DNA segments are not patentable. The Court explained that cDNA is patent eligible because it is not a product of nature, and the removal of introns created something new.[19]

On the one hand, one may use the ruling in Chakrabarty and Myriad to argue that a 3D-bioprinted organ is not patentable because it is unlikely to be significantly different from the natural form of an organ. In the case of 3D-bioprinted organs, unlike modified bacterium and cDNA, there is no transformation of the living organism into something altogether different; the 3D-bioprinted organ is not altered to exclude or include new properties.

On the other hand, although a 3D-bioprinted organ is composed of natural materials, it also incorporates human-made components. One may thus argue that a 3D-bioprinted organ is a “manufacture” or “composition of matter” and that it has markedly different properties than the organ that failed to operate properly in the individual’s body. Consequently, the existing limitation on patenting “natural” discoveries may not apply to 3D-bioprinted organs.

Can 3D-bioprinted organs be inherited?

Whether human organs should be treated as “personal property” is among the most controversial questions. Because addressing this question is outside the scope of this post, I will assume for our purposes that human organs can be treated as personal property.

Personal property is usually understood as various rights possessed by an individual. Freedom of alienation, whether by sale or other means, is commonly seen as one of the basic property rights.

In most jurisdictions, individuals are permitted (and even encouraged!) to donate organs for transplantation, but they are prohibited from selling them. The sale of human organs is met with opposition partly due to the belief that human organs should be regarded with a heightened level of reverence and should not be viewed in the same light as people’s cars, furniture, or clothes.

Even if human organs are not “tradable,” does that mean they cannot be inherited? Consider the following hypothetical scenario: Dan obtained a 3D-bioprinted kidney in its most excellent and improved version (imagine that a person with this kidney could have a life expectancy of roughly 150 years). This kidney is one of the most valuable things Dan has. Dan’s other organs fail to function correctly at a certain point, and he is about to die. Is it possible for his daughter, who is experiencing kidney failure, to inherit his kidney (for the purposes of this post, I assume that there is compatibility between Dan and his daughter)?

Wills and state laws of intestate succession govern the division of assets after a person’s death. The guiding premise of American estates law is testamentary freedom, which holds that people have the power to determine how their assets are distributed after their deaths.[20] Thus, testamentary freedom can be seen as one’s property right.

If Dan left explicit instructions in his will to pass on the kidney to his daughter, his request would likely be honored. The Uniform Anatomical Gift (UAGA)[21] and most state anatomical gift laws, which model themselves after the UAGA, provide legal protection for deceased-directed donation.[22] Such donation occurs when a donor expresses a desire to donate an organ to a specific individual after their death.

If Dan did not leave a will (similar to how few people leave instructions for the distribution of their assets), his daughter might still be able to inherit his kidney under the state’s anatomical gift law and intestate succession law. Under many anatomical gift laws, several individuals may make an anatomical gift of a deceased person’s body parts.[23] Those include the spouse, adult children, and parents of the deceased. This means that either Dan’s spouse (who may also be the daughter’s mother) or the daughter herself may be able to make an anatomical gift of Dan’s kidney to the daughter.

Another possible option is to distribute Dan’s kidney under the state’s intestate succession law (again, assuming that human organs were to be treated as property). For instance, in re Daniel Thomas Christie, the Iowa District Court relied exclusively on intestate succession law to allow the parents of a person who died as a result of a motorcycle accident to retrieve and use his sperm after his death, as well as make an “anatomical gift” of the sperm to that person’s fiancé.[24] In Matter of Zhu, the New York Supreme Court reached a similar conclusion using New York’s Estate, Powers and Trusts law. The court decided to “place no restrictions on the use to which Peter’s parents may ultimately put their son’s sperm, including its potential use for procreative purpose.”[25] In both cases, the deceased person left no explicit instructions regarding the posthumous disposition or use of his sperm.

According to many intestate succession laws, any portion of the decedent’s property not given to a surviving spouse is usually distributed to the decedent’s children.[26] Principles of succession typically “reflect the desires of the ‘typical person,’ both with regard to protecting expressions of desire and anticipating situations where those expressions are inadequately presented.”[27] Therefore, Dan’s daughter might be eligible to inherit his kidney as long as the state’s intestate succession law does not determine otherwise.

***

Bioprinting is rapidly approaching and bringing up many interesting and complicated questions. In this blog post, I explored two legal questions raised by bioprinting that will require our attention in the coming years. As you have probably figured out by now, I had no intention in this blog post to answer these questions, and you likely have been left with more questions than answers.

Shelly Simana is a fellow at the Center for Law and the Biosciences.

[1] Swarnima Agarwal et al., Current Developments in 3D Bioprinting for Tissue and Organ Regeneration–A Review, 6 Frontiers in Mech. Eng’g 1 (2020).

[2] Roni Caryn Rabin, Doctors Transplant Ear of Human Cells, Made by 3-D Printer, N.Y. Times (June 2, 2022). Available here.

[3] David Freeman, Israeli Scientists Create World’s First 3D-Printed Heart Using Human Cells, NBC News (Apr. 19, 2019). Available here.

[4] Kristen Rogers, When We’ll Be Able to 3D-Print Organs and Who Will Be Able to Afford Them, CNN (July 15, 2022). Available here.

[5] Not only may non-functioning organs be replaced, but healthy ones could also be enhanced. Researchers at Princeton University, for instance, developed a “bionic” ear that can pick up frequencies beyond the range of the human ear by mixing bio-ink with an antenna coil attached to electrodes. Together, bio-ink and electrical components could one day enable the development of a fully functional artificial ear with enhanced capabilities that could be implanted in humans. See Owain Vaughan, Printing Bionic Ears, Nature Nanotechnology (June 5, 2013). Available here.

[6] Codified at 42 U.S.C. pt. H.

[7] Codified at 21 U.S.C. ch. 9.

[8] Codified at 42 U.S.C. ch. 6A.

[9] Codified at 21 U.S.C. § 321(g).

[10] Codified at 21 U.S.C. § 321(h).

[11] Codified at 42 U.S.C. § 262.

[12] 21 C.F.R. § 3.2(e).

[13] U.S. Food & Drug Admin., Classification of Products as Drugs and Devices and Additional Product Classification Issues (2017). Available here.

[14] ‪Saeedeh Vanaei‬ et al., An Overview on Materials and Techniques in 3D Bioprinting Toward Biomedical Application, 2 Eng’r Regeneration 1 (2021).

[15] Indeed, some patents have already been granted. For example, ICO, a 3D bioprinting firm, has been issued two new patents for the 3D bioprinting of temperature-sensitive bio-inks. See Kubi Sertoglu, BICO Granted Two New Patents for 3D Bioprinting with Temperature-Densitive Bioinks, 3D Printing Indus. (October 20, 2021). Available here.

[16] Jacob S. Sherkow, The Natural Complexity of Patent Eligibility, 99 Iowa L. Rev. 1137 (2014).

[17] Diamond v. Chakrabarty, 447 U.S. 303 (1980).

[18] Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107 (2013).

[19] The court’s ruling is still being debated; various scholars maintain that cDNA exists naturally and that, similar to genes, it also contains exons.

[20] Lee-ford Tritt, Sperms and Estates: An Unadulterated Functionally Based Approach to Parent-Child Property Succession, 62 S.M.U. L. Rev. 367 (2009).

[21] The Act’s third and most recent revision was published in 2006.

[22] OPTN Information Regarding Deceased Directed Donation, Organ Procurement and Transplantation Network (OPTN) (May 29, 2009). Available here.

[23] The UAGA states: “(a) … an anatomical gift of a decedent’s body or part for purpose of transplantation, therapy, research, or education may be made by any member of the following classes of persons who is reasonably available, in the order of priority listed: … (2) the spouse of the decedent; (3) adult children of the decedent.” See Revised U.A.G.A. § 9 (2006).

[24] This case was covered in Matter of Zhu, 64 Misc. 3d 280 (N.Y. Sup. Ct. 2019).

[25] Id.

[26] While the laws governing intestate succession vary from state to state, most of them are partially based on the Uniform Probate Code (UPC). The UPC states: “Any part of the intestate estate not passing under Section 2-102 to the decedent’s surviving spouse passes to the decedent’s descendants or parents.” See Revised U.P.C § 2-103(b) (2019).

[27] Lawrence H. Averill, Jr., An Eclectic History and Analysis of the 1990 Uniform Probate Code, 55 Alb. L. Rev. 891, 912 (1992).